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HFpEF

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• Iron deficiency and cardiovascular disease - Eur Heart J 2022 Oct 25 - "Iron deficiency (ID) is common in patients with cardiovascular disease. Up to 60% of patients with coronary artery disease, and an even higher proportion of those with heart failure (HF) or pulmonary hypertension have ID; the evidence for cerebrovascular disease, aortic stenosis and atrial fibrillation is less robust. The prevalence of ID increases with the severity of cardiac and renal dysfunction and is probably more common amongst women. Insufficient dietary iron, reduced iron absorption due to increases in hepcidin secondary to the low-grade inflammation associated with atherosclerosis and congestion or reduced gastric acidity, and increased blood loss due to anti-thrombotic therapy or gastro-intestinal or renal disease may all cause ID. For older people in the general population and patients with HF with reduced ejection fraction (HFrEF), both anaemia and ID are associated with a poor prognosis; each may confer independent risk. There is growing evidence that ID is an important therapeutic target for patients with HFrEF, even if they do not have anaemia. Whether this is also true for other HF phenotypes or patients with cardiovascular disease in general is currently unknown. Randomized trials showed that intravenous ferric carboxymaltose improved symptoms, health-related quality of life and exercise capacity and reduced hospitalizations for worsening HF in patients with HFrEF and mildly reduced ejection fraction (<50%). Since ID is easy to treat and is effective for patients with HFrEF, such patients should be investigated for possible ID" - See iron supplements at Amazon.com.
• Empagliflozin and Elderly Patients With Preserved Ejection Fraction Heart Failure: Is Age Just a Number? - Medscape, 10/17/22 - "Major molecular regulators of cellular lifespan are sirtuin-1 (SIRT1) and mammalian target of rapamycin complex 1 (mTORC1). In a nutrient-deficient or calorie-restricted state, SIRT1 activation, along with adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) set forth a cascade of downstream target activations culminating in deceleration of cell aging. Suppression of the mTORC1 pathway further augments SIRT1-activated autophagy, the lysosome-utilizing process of clearing misfolded proteins from the cytosol. Without healthy autophagy, oxidative stress contributes to impaired endothelial nitric oxide (NO) pathways, inflammation, cell death, fibrosis, and cardiomyopathy (adapted from Gevaert et al1). SGLT2 inhibitors are hypothesized to contribute to activation of SIRT1 and suppression of mTORC1 pathways.10 Akt = protein kinase B; HFpEF = heart failure with preserved ejection fraction; ROS = reactive oxygen species ... Aside from the obvious bedside clinical implications, the findings of Bohm et al[7] cause us to wonder more about the mechanistic impact of SGLT2 inhibition on multiple cardiovascular and noncardiovascular therapeutic targets. SGLT2 inhibitors induce glycosuria and reduce insulin levels, which promotes a ketogenic and fatty acid oxidation state, mimicking calorie restriction physiology, which has been associated with cellular stress resistance, attenuation of cellular senescence, and reduced oxidative stress-induced tissue damage.[9] Such pathway activation is hypothesized to assuage metabolic disease, alleviate endothelial and vascular inflammation, and mitigate the clinically observed arterial stiffness associated with the HFpEF syndrome" - See empagliflozin inhousepharmacy.vu.
• Dose-Response to Sacubitril/Valsartan in Patients With Heart Failure and Reduced Ejection Fraction - J Am Coll Cardiol 2022 Oct 18 - "The average daily dose was 112 mg in Tertile 1 (low dose), 342 mg in Tertile 2 (moderate dose), and 379 mg in Tertile 3 (high dose). Similar changes in prognostic biomarkers were observed in all dose tertiles. Gains in Kansas City Cardiomyopathy Questionnaire-23 scores were comparable regardless of dose category. Consistent reverse cardiac remodeling in all dose categories occurred; the median absolute left ventricular EF improvement across HF dose groups was 9.3%, 8.7%, and 10.2%, for low, moderate, and high doses, respectively; similar improvements in left atrial and ventricular volumes and E/e' were also observed across dose categories"
• Vitamin D and heart failure: A two-sample mendelian randomization study - Nutr Metab Cardiovasc Dis 2022 Aug 11 - "In summary, we found a potential inverse association between elevated 25OHD levels and the risk of HF, which suggested that timely 25OHD supplementation or maintaining adequate 25OHD concentrations may be an essential measure for HF prevention in the general population" - See vitamin D at Amazon.com.
• Iron Deficiency in Heart Failure and Effect of Dapagliflozin: Findings From DAPA-HF - Circulation 2022 Aug 16 - "Iron deficiency is common in heart failure and associated with worse outcomes. We examined the prevalence and consequences of iron deficiency in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) and the effect of dapagliflozin on markers of iron metabolism ... Transferrin saturation, ferritin, and hepcidin were reduced and total iron-binding capacity and soluble transferrin receptor increased with dapagliflozin compared with placebo ... Iron deficiency was common in DAPA-HF and associated with worse outcomes. Dapagliflozin appeared to increase iron use but improved outcomes, irrespective of iron status at baseline" - See dapagliflozin at reliablerxpharmacy.com.
• Overly Tight Sodium Restriction May Worsen HFpEF Outcomes - Medscape, 7/18/22 - "Compared with patients with a cooking salt score of zero, patients with a cooking salt score greater than zero had significantly lower risks of the primary outcome (hazard ratio [HR] 0.760; P = .002) and HF hospitalization (HR, 0.737; P = .003) but not all-cause (HR, 0.838) or CV (HR, 0.782) death ... Results of subgroup analyses suggested that patients aged 70 years or younger (HR, 0.644) and those of Black and other ethnicities (HR, 0.574) were at greater risk of the primary outcome from aggressive restriction of cooking salt ... What limits the importance of the authors' findings, which they acknowledge, is that the sodium intake for each patient was self-reported ... No confirmatory testing was done and recall bias could clearly have played a role"
• Empagliflozin has favourable effect on frontal plane QRS-T angle in diabetic patients with cardiovascular disease - J Clin Pharm Ther 2022 Jul 15 - "Empagliflozin leads a significant narrowing in the fQRST angle in type 2 DM patients with known CVD" - See empagliflozin inhousepharmacy.vu.
• Effect of Levothyroxine Supplementation on the Cardiac Morphology and Function in Patients with Subclinical Hypothyroidism: A Systematic Review and Meta-analysis - J Clin Endocrinol Metab 2022 Jul 10 - "The impact of abnormal thyroid hormone levels on the cardiovascular system has been explored for decades. In recent years, emerging evidence has suggested that subclinical thyroid dysfunction, especially subclinical hypothyroidism (SCH), significantly affects cardiac indices ... Judging from the obvious changes in the CO, LVEF and E/A ratio, LT4 supplementation can effectively improve the cardiac systolic and diastolic dysfunction prevalent in SCH patients. This study provides evidence of the recommendation for LT4 supplementation in adult SCH patients"
• Dapagliflozin Early Benefit Explored in Reduced-EF Heart Failure - Medscape, 6/6/22 - "Functional capacity in heart failure with reduced ejection fraction (HFrEF) appears to improve within a few weeks of SGLT2-inhibitor initiation, suggests a small, randomized study that followed peak VO2 in patients with HFrEF assigned to take dapagliflozin (Farxiga). The benefit observed at 30 days held at a plateau for at least a few more months ... The new study, called DAPA-VO2 , has limitations but is consistent with a similar study of empagliflozin (Jardiance), investigators observed, and could help explain why clinical risk fell off so rapidly once patients started on SGLT2 inhibitors in major HFrEF trials of these drugs ... Peak VO2 in the study rose 8% further (P = .021) in patients on dapagliflozin compared with placebo a month into the trial, the gain persisting at least to 90 days" - See empagliflozin inhousepharmacy.vu.
• Effects of Ubiquinol and/or D-ribose in Patients With Heart Failure With Preserved Ejection Fraction - Am J Cardiol 2022 May 26 - "Patients with heart failure with preserved ejection fraction (HFpEF) have few pharmacologic therapies, and it is not known if supplementing with ubiquinol and/or d-ribose could improve outcomes ... Group 1 received placebo ubiquinol capsules and d-ribose powder, Group 2 received ubiquinol capsules (600 mg/d) and placebo d-ribose powder, Group 3 received placebo ubiquinol capsules with d-ribose powder (15 g/d), and Group 4 received ubiquinol capsules and d-ribose powder ... Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score ... Treatment with ubiquinol and/or d-ribose significantly improved the KCCQ clinical summary score (17.30 to 25.82 points), vigor score (7.65 to 8.15 points), and EF (7.08% to 8.03%) and reduced B-type natriuretic peptides (-72.02 to -47.51) and lactate/adenosine triphosphate ratio (-4.32 to -3.35 × 10-4). There were no significant increases in the septal E/e' or the 6-minute walk test. In conclusion, ubiquinol and d-ribose reduced the symptoms of HFpEF and increased the EF. These findings support the use of these supplements in addition to standard therapeutic treatments for patients with HFpEF" - See ubiquinol products at Amazon.com and D-ribose at Amazon.com.
• Arginine catabolism metabolites and atrial fibrillation or heart failure risk: two case-control studies within the PREDIMED trial - Am J Clin Nutr 2022 May 16 - "Inverse associations with incident AF were observed for arginine [OR per 1 SD (95% CI): 0.83 (0.73, 0.94)]) and homoarginine [0.87 (0.76, 0.98)], whereas positive associations were found for the asymmetric dimethylarginine/symmetric dimethylarginine ratio (ADMA/SDMA) [1.15 (1.01, 1.31)] and citrulline [1.19 (1.01, 1.39)]. For HF, inverse associations were found for arginine [0.82 (0.69, 0.97)] and homoarginine [0.81 (0.68, 0.96)], and positive associations for the ADMA/SDMA ratio [1.19 (1.02, 1.41)], N1-acetylspermidine [1.34 (1.12, 1.60)], and diacetylspermine [1.20 (1.02, 1.41)]. In the stratified analysis according to the dietary intervention, the lower HF risk associated with arginine was restricted to participants in the MedDiet groups" - See arginine products at Amazon.com.
• T cells: a ‘hidden corner’ to be explored for treating heart failure - European Heart Journal, ehac241 , 13 May 22 - Interesting article. I think it's saying that t-cells inhibit the repair of the heart. I've been taking rapamycin for anti-aging but I was worried because it inhibits t-cells but ever since I've been taking it, I've felt on top of the world. Maybe the t-cell inhibition and the subsequent heart repair is the reason. See rapamycin at ReliableRXPharmacy.
  • Adult T-cells impair neonatal cardiac regeneration - European Heart Journal, ehac188 13 Apr 22 - "Patients who survive a myocardial infarction (MI) often develop chronic heart failure due to the heart’s poor regeneration capacity. We hypothesized that the cardiac ‘regenerative-to-scarring’ transition might be driven by the perinatal shifts observed in the circulating T-cell compartment ... The perinatal loss of myocardial regenerative capacity was paralleled by a baseline increase in αβ-T cell (CD4+ and CD8+) numbers ... The perinatal loss of myocardial regenerative capacity was paralleled by a baseline increase in αβ-T cell (CD4+ and CD8+) numbers. Strikingly, P1-infarcted mice reconstituted with adult T-cells shifted to an adult-like healing phenotype, marked by irreversible cardiac functional impairment and increased fibrosis. Infarcted neonatal mice harbouring adult T-cells also had more monocyte-derived macrophage recruitment, as typically seen in adults. At the transcriptome level, infarcted P1 hearts that received isolated adult T-cells showed enriched gene sets linked to fibrosis, inflammation, and interferon-gamma (IFN-γ) signalling ... Physiological T-cell development or adoptive transfer of adult IFN-γ-producing T-cells into neonates contributed to impaired cardiac regeneration and promoted irreversible structural and functional cardiac damage. These findings reveal a trade-off between myocardial regenerative potential and the development of T-cell competence"
• Apple Watch ECG App, Still Experimental, Reveals Asymptomatic Low LVEF - Medscape, 5/2/22 - "Applied to 421 patients with recent, clinically indicated echocardiograms for comparison, the app-based technique identified 13 of the 16 with ejection fractions of 40% or lower, for a predictive accuracy of almost 88% based on area-under-the curve (AUC) assessment. Its sensitivity and specificity were both about 81% ... It's very promising and very impressive" that the AI-based system could pick up LV dysfunction from a single-lead ECG ... The system's predictive accuracy was "very similar to what you would get from a 12-lead, clinically done ECG" - See Apple watches at Amazon.com.
  • Take an ECG with the ECG app on Apple Watch - Apple.com - "An electrocardiogram (also called an ECG or EKG) is a test that records the timing and strength of the electrical signals that make the heart beat. By looking at an ECG, a doctor can gain insights about your heart rhythm and look for irregularities ... How to use the ECG app ... The ECG app can record your heartbeat and rhythm using the electrical heart sensor on Apple Watch Series 4, Series 5, Series 6, or Series 7* and then check the recording for atrial fibrillation (AFib), a form of irregular rhythm ... The ECG app records an electrocardiogram which represents the electrical pulses that make your heart beat. The ECG app checks these pulses to get your heart rate and see if the upper and lower chambers of your heart are in rhythm. If they’re out of rhythm, that could be AFib"
• Clinical implications of low estimated protein intake in patients with heart failure - J Cachexia Sarcopenia Muscle 2022 Apr 14 - "An estimated lower protein intake was associated with a lower BMI, but signs of congestion were more prevalent. A lower estimated protein intake was independently associated with a higher mortality risk"
• Low-Sodium Diet Did Not Cut Clinical Events in Heart Failure Trial - Medscape, 4/2/22 - "a greater reduction in sodium than achieved in this study or a longer follow-up may be required to show an effect on clinical events ... By 12 months, events comprising the primary outcome (hospitalization or emergency department visits due to cardiovascular causes or all-cause death) had occurred in 15% of patients in the low-sodium diet group and 17% of those in the usual care group (hazard ratio [HR], 0.89 ... All-cause death occurred in 6% of patients in the low-sodium diet group and 4% of those in the usual care group (HR, 1.38 ... All-cause death occurred in 6% of patients in the low-sodium diet group and 4% of those in the usual care group (HR, 1.38; P = .32). Cardiovascular-related hospitalization occurred in 10% of the low-sodium group and 12% of the usual care group (HR, 0.82; P = .36), and cardiovascular-related emergency department visits occurred in 4% of both groups (HR, 1.21 ... Quality-of-life measures on the Kansas City Cardiomyopathy Questionnaire (KCCQ) suggested a benefit in the low-sodium group, with mean between-group differences in the change from baseline to 12 months of 3.38 points in the overall summary score, 3.29 points in the clinical summary score, and 3.77 points in the physical limitation score (all differences were statistically significant)"
• Coenzyme Q10 as Adjunctive Therapy for Cardiovascular Disease and Hypertension: A Systematic Review - J Nutr 2022 Mar 28 - "CoQ10 supplementation in patients with heart failure improved functional capacity, increased CoQ10 serum levels, and led to fewer major adverse cardiovascular events (MACE). CoQ10 had positive quantifiable effects on inflammatory markers in patients with ischemic heart disease. Myocardial hemodynamics improved in patients who received CoQ10 supplementation prior to cardiac surgery. Effects on hypertension were inconclusive" - See ubiquinol products at Amazon.com.
• Beneficial cardiovascular and remodeling effects of SGLT2 inhibitors: pathophysiologic mechanisms - Expert Rev Cardiovasc Ther 2022 Mar 23 - "The analysis of data clearly demonstrated that the use of the SGLT2 inhibitors besides their antidiabetic effects, provide additional protection against CVD, CAD, and HFrEF and HFpEF, and death, but not stroke, in both diabetic and non-diabetic patients. Therefore, they should be preferably used for the treatment of patients with T2DM with preexisting CVD, CAD, and HFrEF and HFpEF"  - See empagliflozin at ihouseepharmacy.
• Effect of omega-3 polyunsaturated fatty acids on left ventricular remodeling in chronic heart failure: a systematic review and meta-analysis - Br J Nutr 2022 Mar 4 - "Accumulating evidence suggests that supplementation of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) was associated with reduction in risk of major cardiovascular event ... Compared with placebo groups, ω-3 PUFAs supplementation improved LV ejection fraction (LVEF) (11 trials, 2112 participants, WMD=2.52, 95%CI 1.25 to 3.80, I2=87.8%) and decreased LV end-systolic volume (LVESV) (5 studies, 905 participants, WMD=-3.22, 95%CI -3.67 to -2.77, I2=0.0%) by using the continuous variables analysis. Notably, the high accumulated ω-3 PUFAs dosage groups (≥600g) presented a prominent improvement in LVEF, while the low and middle accumulated dosage (≤300g and 300-600g) showed no effects on LVEF. In addition, ω-3 PUFAs supplementation decreased the levels of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and hypersensitive-c-reactive protein (Hs-CRP). Therefore, the present meta-analysis demonstrated that ω-3 PUFAs consumption was associated with a substantial improvement of LV function and remodeling in patients subjected to CHF. The accumulated dosage of ω-3 PUFAs intake is vital for its cardiac protective role" - See omega-3 supplements at Amazon.com.
• Is It Time to Redefine Iron Deficiency? - Medscape, 2/22/22 - "before you just say, "This is the heart failure getting worse," investigate the iron. I think we're going to find some very interesting relationships" - See iron supplements at Amazon.com.
• Scientists characterize the imbalanced gut bacteria of patients with myocardial infarction, angina and heart failure - Science Daily, 2/18/22 - "However, the early microbiome changes persisted in patients with heart disease who in addition showed specific heart disease related alterations in the composition and function of the gut microbiome. Both at the early dysmetabolic stage and at the later stages of diagnosed heart disease, the diseased microbiome was characterized by a loss of bacterial cells and bacterial competences. In addition, the patients showed a shift towards fewer types of bacteria known to produce health promoting compounds like short chain fatty acids and more bacteria types producing unhealthy compounds from the metabolism of certain dietary amino acids, choline and L-carnitine. Analyses of the blood compounds mirrored the imbalance of the gut microbiome ... Intervention in both humans and rodents have shown that an imbalanced gut microbiome at various stages of heart disease development can be modified and partly restored by eating a more plant-based and energy-controlled diet, avoidance of smoking and compliance with daily exercise" - See probiotic supplements at Amazon.com.
• Micronutrient Supplementation to Prevent, Improve HF? - Medscape, 2/29/22 - "A new review suggests that micronutrient supplementation — particularly a combination of coenzyme Q10 (CoQ10), zinc, copper, selenium, and iron — might be a potential strategy to improve myocardial function in patients with heart failure (HF) by improving mitochondrial function" - See ubiquinol products at Amazon.com, zinc supplements at Amazon.com, copper supplements at Amazon.com, Selenium at Amazon.com and iron supplements at Amazon.com.
• High vitamin K status is prospectively associated with decreased left ventricular mass in women: the Hoorn Study - Nutr J 2021 Oct 19 - "High vitamin K status is prospectively associated with decreased left ventricular mass in women: the Hoorn Study ... This study showed a high vitamin K status being associated with decreased LVMI only in women, while intakes of vitamin K were not associated with any cardiac structure or function measures. These results extend previous findings for a role of vitamin K status to decrease heart failure risk" - See vitamin K at Amazon.com and vitamin K at iHerb.com.
• One-Year Committed Exercise Training Reverses Abnormal Left Ventricular Myocardial Stiffness in Patients With Stage B Heart Failure With Preserved Ejection Fraction - Circulatio 2021 Sep 21 - "In patients with LV hypertrophy and elevated cardiac biomarkers (stage B heart failure with preserved ejection fraction), 1 year of exercise training reduced LV myocardial stiffness. Thus, exercise training may provide protection against the future risk of heart failure with preserved ejection fraction in such patients"
• Omega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients: the Aldo-DHF randomized controlled trial - Clin Res Cardiol 2021 Aug 28 - "Higher O3I was associated with a more favorable cardiometabolic risk profile and predictive of higher submaximal/maximal aerobic capacity and lower BMI/truncal adiposity in HFpEF patients. Omega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients. Higher O3I was associated with a more favorable cardiometabolic risk profile and aerobic capacity (left) but did not correlate with echocardiographic markers for left ventricular diastolic function or neurohumoral activation (right). An O3I-driven intervention trial might be warranted to answer the question whether O3-FA in therapeutic doses (with the target O3I 8-11%) impact on echocardiographic markers for left ventricular diastolic function and neurohumoral activation in patients with HFpEF" - See omega-3 supplements at Amazon.com and iHerb.
• Potential use of ubiquinol and d-ribose in patients with heart failure with preserved ejection fraction - Annals of Medicine and Surgery, Volume 55, July 2020, Pages 77-80 - "HFpEF is a common and often debilitating disease process that may be difficult to diagnose and has limited targeted therapeutic options. Mitochondrial dysfunction appears to play a significant role in the pathophysiologic processes of this clinical syndrome. Improved methods of diagnosis for HFpEF are needed, as are specific effective therapies. Active ongoing research into the roles of ubiquinol and d-ribose in HFpEF may provide clinicians with additional management opportunities" - [Nutra USA] - See D-ribose at Amazon.com and ubiquinol products at Amazon.com.

Other News:

• Effect of add-on sacubitril/valsartan on the left ventricular hypertrophy of a patient with hypertension - J Int Med Res 2022 Nov - "We treated a man in his late 40s who had undergone a percutaneous coronary intervention and had hypertension that was refractory to multiple anti-hypertensive medications. We initiated sacubitril/valsartan 200 mg/day as an add-on therapy, and 3 months later, his blood pressure had decreased from 154/78 mmHg to 134/70 mmHg, in the absence of any drug-related adverse events. Furthermore, his left ventricular mass index had improved from 135 g/m2 to 112 g/m2. Thus, sacubitril/valsartan might ameliorate hypertrophy in patients with hypertension"
• Impact of Inpatient Initiation of Sodium-Glucose Cotransporter-2 Inhibitors on Prescription Rates in Patients With Heart Failure With Reduced Ejection Fraction - Am J Cardiol 2022 Oct 22 - "The heart failure readmission rate in the first 30 days was significantly lower in those with inpatient initiation of SGLT2i compared with those who did not start during hospitalization. (9.3% vs 22.7%, p = 0.04). Cardiovascular mortality was numerically, but not significantly, different between groups (4% vs 10.7%, p = 0.21). Inpatient initiation of an SGLT2i was associated with a significantly higher postdischarge rate of SGLT2i prescriptions and significantly lower heart failure readmission rates at 30 days. In conclusion, these findings highlight the importance of initiating SGLT2i during inpatient hospitalization to improve the quality of care in patients with HFrEF" - See empagliflozin inhousepharmacy.vu.
• Atrial Fibrillation and Heart Failure: Novel Insights Into the Chicken and Egg Dilemma - Medscape, 10/24/22 - "In summary, clinical trials and our experimental investigations have shown that normofrequent AF per se has distinct detrimental effects on the human LV via adverse remodelling of cardiomyocyte excitation–contraction coupling causing LVSD. These findings could contribute to our understanding of the favourable effects of rhythm control via catheter ablation in patients with AF and concomitant heart failure. Our novel data may represent, however, only a first glimpse into this AF-induced condition, which exceeds the atria and may affect the whole heart as well as other organs"
• DELIVER May Demystify Med Therapy in Heart Failure With Improved LVEF - Medscape, 10/6/22 - "As recently reported, DELIVER entered HF patients with an LVEF greater than 40%, that is, HF with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively). Those assigned to dapagliflozin (Farxiga) vs placebo over 2 years overall showed an 18% drop (P = .0008) in risk for the primary endpoint, worsening HF or cardiovascular (CV) death ... The new analysis centered on the 18% of patients in the trial with an initial LVEF greater than 40%, per entry criteria, but who previously were symptomatic with an LVEF of 40% or lower, that is, HF with reduced ejection fraction (HFrEF) ... Their ostensible dapagliflozin benefit was comparable as well; they showed a significant 26% decrease in risk for worsening HF or CV death compared to the control group ... The HFimpEF patients in DELIVER benefited significantly from dapagliflozin for both the composite primary endpoint and the CV-death component, for which the risk reduction reached a significant 38%" - See dapagliflozin at reliablerxpharmacy.com.
• Heart Failure Medication: Moving From Evidence Generation to Implementation - Medscape, 8/11/22 - "Treating patients with heart failure (HF) and reduced ejection fraction (HFrEF) with renin–angiotensin–aldosterone system (RAAS) inhibitors, beta-blockers, and sodium–glucose co-transporter-2 (SGLT2) inhibitors at guideline-recommended dosages (GRD) improves quality of life and increases longevity ... mineralocorticoid receptor antagonists (MRAs) ... Sequences starting with an SGLT2 inhibitor, MRA, or both were associated with the most significant reduction in CV death, HF hospitalization, and all-cause death. Notably, up to half of the reduction in events was primarily attributed to shortening the time to reach target dose. This might partially explain why sequences starting with medications with fewer up-titration steps (i.e. SGLT2 inhibitors or MRAs) were associate"
  • Mineralocorticoid Receptor Antagonists for Treatment of Hypertension and Heart Failure - Methodist Debakey Cardiovasc J. 2015 Oct-Dec; 11(4) - "Spironolactone and eplerenone are both mineralocorticoid-receptor antagonists. These compounds block both the epithelial and nonepithelial actions of aldosterone, with the latter assuming increasing clinical relevance"
  • Renin Angiotensin Aldosterone System Inhibitors in Hypertension: Is There Evidence for Benefit Independent of Blood Pressure Reduction? - Prog Cardiovasc Dis 2016 Nov-Dec - "The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the pathogenesis of hypertension (HTN). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are first line anti-HTN drug classes that are potent, effective and largely safe"
• The Efficacy and Safety of Sacubitril-Valsartan for the Treatment of Heart Failure in Adults: A Meta-Analysis - Ann Pharmacother 2022 Aug 2 - "Data of included studies prove the efficacy and safety of SV for curing heart conditions. Therefore, the present evidence shows that SV is effective in the treatment of heart failure, reducing hospitalization and cardiovascular mortality, and that the adverse effects are comparable or fewer than those associated with other drugs used for this indication"
• Do ICDs Still 'Work' in Primary Prevention Given Today's Recommended HF Meds? - Medscape, 7/29/22 - "The cohort study of almost 5000 patients with HFrEF and such devices saw their all-cause mortality risk improve stepwise with each additional prescription they were given toward the full quadruple drug combo at the core of modern HFrEF guideline-directed medical therapy (GDMT). The four classes are SGLT2 inhibitors, beta blockers, mineralocorticoid receptor antagonists (MRA), and renin-angiotensin system (RAS) inhibitors."
• SGLT-2 Inhibitors for Patients with Heart Failure: What Have We Learned Recently? - Curr Atheroscler Rep 2022 Jun 2 - "Heart failure (HF); Heart failure with preserved ejection fraction (HFpEF); Heart failure with reduced ejection fraction (HFrEF); Sodium-glucose cotransporter-2 inhibitors (SGLT-2i)" - See empagliflozin inhousepharmacy.vu.
• Gout medicine improves survival for heart failure patients, study finds - Science Daily, 5/19/22 - "Researchers reviewed the records of more than 1,000 patients admitted to University of Virginia Medical Center between March 2011 and February 2020 for worsening heart failure. Patients who received colchicine for a gout flare had a survival rate of 97.9%, compared with a 93.5% survival rate for patients not receiving colchicine ... While colchicine is a well-established treatment for gout, the UVA research team believes the medication's anti-inflammatory properties may also be key to improving outcomes for heart failure patients. They think that colchicine may modulate inflammation in the heart and blood vessels with potential for improving outcomes, especially in the acute phases of heart failure hospitalizations"
• Accelerated and personalized therapy for heart failure with reduced ejection fraction - Eur Heart J 2022 Apr 25 - "The optimal alternative sequences included sodium-glucose cotransporter 2 inhibition and a mineralocorticoid receptor antagonist as the first two therapies" - See empagliflozin inhousepharmacy.vu.
  • Mineralocorticoid Receptor Antagonists for Treatment of Hypertension and Heart Failure - Methodist Debakey Cardiovasc J. 2015 Oct-Dec - "Spironolactone and eplerenone are both mineralocorticoid-receptor antagonists. These compounds block both the epithelial and nonepithelial actions of aldosterone, with the latter assuming increasing clinical relevance. Spironolactone and eplerenone both affect reductions in blood pressure either as mono- or add-on therapy; moreover, they each afford survival benefits in diverse circumstances of heart failure and the probability of renal protection in proteinuric chronic kidney disease. However, as use of mineralocorticoid-blocking agents has expanded, the hazards inherent in taking such drugs have become more apparent. Whereas the endocrine side effects of spironolactone are in most cases little more than a cosmetic annoyance, the potassium-sparing effects of both spironolactone and eplerenone can prove disastrous, even fatal, if sufficient degrees of hyperkalemia emerge. For most patients, however, the risk of developing hyperkalemia in and of itself should not discourage the sensible clinician from bringing these compounds into play. Hyperkalemia should always be considered a possibility in patients receiving either of these medications; therefore, anticipatory steps should be taken to minimize the likelihood of its occurrence if long-term therapy of these agents is being considered"
  • Spironolactone - dermcoll.edu.au - "Spironolactone is an anti-male hormone (anti-androgen) medication. It blocks the male hormone receptor and reduces the level of the male hormones, testosterone and DHEAS ... Spironolactone has a diuretic (“fluid tablet”) effect and increases urine production. This medication lowers blood pressure and reduces fluid retention seen in conditions such as heart failure and chronic liver disease. Spironolactone can be used to treat low potassium levels (hypokalaemia)" - Note: Lowering testosterone sounds like it would do more harm then good. I can cite studies to back if up. Maybe what needs to be lowered is SHBG:
  • Sex hormone-binding globulin: a new marker of disease severity and prognosis in men with chronic heart failure - Rev Esp Cardiol 2009 Dec - "Sex hormone-binding globulin (SHBG) is a key regulator of the actions of anabolic steroids. Chronic heart failure (HF) has been associated with anabolic steroid deficiency, but its relationship with SHBG is not known ... At enrolment, the SHBG level (median 34.5 nmol/L, IQR 27-50 nmol/L) was correlated with the N-terminal probrain natriuretic peptide level (r=0.271, P=.005), LVEF (r=-0.263, P=.007), body mass index (r=-0.199, P=.020) and total testosterone level (r=0.332, P=.001). The median SHBG level was higher in the 16 patients (15.4%) who died, at 48.5 nmol/L (IQR 36-69.5 nmol/L) vs. 33 nmol/L (IQR 25.3-48.7 nmol/L; P=.001), and a high level was associated with an increased risk of death (hazard ratio [HR]=1.045, 95% confidence interval [CI] 1.021-1.069; P< .001). The association remained significant after adjustment in Cox multivariate regression modeling, at HR=1.049 (95% CI 1.020-1.079; P=.001). Analysis by SHBG tertiles showed mortality was 30% in the third tertile, 14% in the second, and 4% in the first (log rank 0.007; HR=3.25 ... The SHBG level correlated with measures of HF severity and was associated with a higher risk of cardiac death"
• Substrate Ablation vs Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia - J Am Coll Cardiol 2022 Apr 19 - "Patients were 1:1 randomized to complete endocardial substrate-based catheter ablation or antiarrhythmic therapy (amiodarone + beta-blockers, amiodarone alone, or sotalol ± beta-blockers) ... After 24 months, the primary outcome occurred in 28.2% of patients in the ablation group and 46.6% of those in the AAD group (hazard ratio [HR]: 0.52; 95% CI: 0.30-0.90; P = 0.021). This difference was driven by a significant reduction in severe treatment-related complications (9.9% vs 28.8%, HR: 0.30; 95% CI: 0.13-0.71; P = 0.006). Eight patients were hospitalized for heart failure in the ablation group and 13 in the AAD group (HR: 0.56 ... In ICD patients with ischemic cardiomyopathy and symptomatic VT, catheter ablation reduced the composite endpoint of cardiovascular death, appropriate ICD shock, hospitalization due to heart failure, or severe treatment-related complications compared to AAD"
• Empagliflozin Rapidly Improves Acute Heart Failure Symptoms in Hospitalized Patients - Medscape, 4/14/22 - "The trial randomized patients hospitalized for acute heart failure after a brief period of stabilization regardless of their left ventricular ejection fraction or presence of diabetes to receive a single, daily dose of 10 mg of empagliflozin (Jardiance) or placebo starting a median of 3 days after admission ... Using a “win ratio” method for analyzing the composite endpoint, the primary analysis showed that treatment with empagliflozin for 90 days boosted the win ratio by a significant 36% relative to placebo (Nature Med. 2022 Mar;28[3]: 568-74) ... EMPULSE is the second trial to show that an SGLT2 inhibitor can safely and effectively treat patients hospitalized for acute heart failure. Previously, results from the SOLOIST-WHFpivotal trial, which enrolled 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure, showed that treatment with an investigational, combined SGLT2 and SGLT1 inhibitor, sotagliflozin, resulted in a significant, 33% relative reduction in the primary outcome compared with placebo after a median 9 months of treatment." - See empagliflozin inhousepharmacy.vu.
• Heart Failure With Preserved Ejection Fraction: New Treatments Provide 'Hope' - Medscape, 3/28/22 - "That is, those individuals in PARAGON-HF who had ejection fractions slightly on the lower end of "normal" tended to benefit more from this medication as well. That differentiated by sex. This is a controversial aspect of the field and it is something that's evolving on a day-to-day or month-to-month basis ... Sacubitril-valsartan, I think, would be a medicine that could be of particular benefit in this patient. That was the first of the next few trials in HFpEF that started to yield potential new drug classes for HFpEF. ... The next drug class is one with which all aspects of cardiology have become more and more aware, and the HFpEF field is no stranger. With the results of the EMPEROR-Preserved trial we have, in the history of HFpEF clinical trials, our first positive trial, and a monumental moment. A trial evaluating the efficacy of empagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) vs placebo in HFpEF. This is the ideal patient who may benefit from this medicine ... EMPEROR-Preserved demonstrated a reduction in a composite endpoint of heart failure hospitalization and cardiovascular death. As you mentioned, Clyde, this efficacy was driven by a reduction in heart failure hospitalization. The class of SGLT2 inhibitors would be, certainly, a medicine that would provide much benefit not only from a reduction in heart failure hospitalization perspective, but a marked improvement in symptoms" - See empagliflozin at ihouseepharmacy.
• Left Atrial Dysfunction Linked to Future Dementia Risk - Medscape, 3/27/22 - "Individuals with the lowest quintiles of various measures of left atrial function had a 43%-98% greater risk of developing dementia than those in the highest quintiles of the same measures ... The hazard ratios for the lowest vs highest quintile for reservoir strain were 1.98; conduit strain 1.50; contractile strain 1.57; emptying fraction 1.87; and for active emptying fraction 1.43, all values being statistically significant. Left atrial passive emptying fraction was not significantly associated with dementia ... diagnosed AF accounted for less than 2% of the association between left atrial dysfunction and dementia ... The editorialists suggest several mechanisms that may explain the association of atrial myopathy and dementia risk. These include an effect mediated through ischemic stroke, subclinical embolism, altered cardiac output causing a reduction in cerebral perfusion, a role of inflammatory markers, and shared risk factors between atrial myopathy and dementia"
• A Systematic Review and Network Meta-Analysis of Pharmacological Treatment of Heart Failure With Reduced Ejection Fraction - Medscape, 3/21/22 - "In patients with HF with reduced ejection fraction, the estimated aggregate benefit is greatest for a combination of ARNi, BB, MRA, and SGLT2i"
• Empagliflozin Improves Cognitive Impairment in Frail Older Adults With Type 2 Diabetes and Heart Failure With Preserved Ejection Fraction - Diabetes Care 2022 Mar 14 - "This study is the first to show significant beneficial effects of the SGLT2 inhibitor empagliflozin on cognitive and physical impairment in frail older adults with diabetes and HFpEF" - See empagliflozin inhousepharmacy.vu.
• FDA Okays Empagliflozin for HF Regardless of Ejection Fraction - Medscape, 2/24/22 - "That means the SGLT2 inhibitor, once considered primarily an antidiabetic agent, is approved for use in patients with HF per se without regard to ventricular function ... The study saw a significant 21% relative reduction in that composite endpoint over about 2 years in patients with NYHA class II-IV heart failure and an LVEF greater than 40% who received empagliflozin along with other standard care" - See empagliflozin at ihouseepharmacy.
• SGLT2 Inhibitors in Older Adults with Heart Failure with Preserved Ejection Fraction - Drugs Aging 2022 Feb 4 - "Until now, empagliflozin is the first therapy that has convincingly been shown to improve clinical outcome in HFpEF. Importantly, some key points should be considered to better understand the impact of empagliflozin on the patient trajectory, particularly in older adults with HFpEF. In this current opinion article, we have therefore provided more information on how to translate the findings of the EMPEROR-Preserved trial to the setting of older adults, with a focus on the impact of empagliflozin on hospitalizations, both heart failure-related and all-cause. To better understand the importance of EMPEROR-Preserved findings, we compared these findings with previous relevant HFpEF and heart failure with reduced ejection fraction (HFrEF) trials and provided information on ongoing trials in the HFpEF setting"
• Effect of empagliflozin in patients with heart failure across the spectrum of left ventricular ejection fraction - Eur Heart J 2021 Dec 8 - "The magnitude of the effect of empagliflozin on heart failure outcomes was clinically meaningful and similar in patients with ejection fractions <25% to <65%, but was attenuated in patients with an ejection fraction ≥ 65%"
• The effect of empagliflozin on the total burden of cardiovascular and hospitalization events in the Asian and non-Asian populations of the EMPA-REG OUTCOME trial of patients with type 2 diabetes and cardiovascular disease - Diabetes Obes Metab 2021 Dec 14 - "Among 1517 Asian participants, empagliflozin reduced relative risk of total events of the primary outcome by 38% versus placebo (rate ratio [95% CI]: 0.62 [0.427, 0.885]), the key secondary outcome by 33% (0.67 [0.479, 0.929]), the composite of cardiovascular death (excluding fatal stroke) and hospitalization for heart failure by 43% (0.57 [0.329, 0.996]), and all-cause hospitalization by 21% (0.79 [0.651, 0.967]). Empagliflozin's effects were consistent between Asian and non-Asian populations"
• Beta-Blocker Use in Hypertension and Heart Failure (A Secondary Analysis of the Systolic Blood Pressure Intervention Trial) - Am J Cardiol 2021 Dec 11 - "Given the concern that beta-blocker use may be associated with an increased risk for heart failure (HF) in populations with normal left ventricular systolic function, we evaluated the association between beta-blocker use and incident HF events, as well as loop diuretic initiation in the Systolic Blood Pressure Intervention Trial (SPRINT) ... Subjects on a beta blocker for the entire trial duration were compared with subjects who never received a beta blocker after 1:1 propensity score matching. A competing risk survival analysis by beta-blocker status was performed to estimate the effect of the drug on incident HF and was then repeated for a secondary end point of cardiovascular disease death. Among the 3,284 propensity score-matched subjects, beta-blocker exposure was associated with an increased HF risk (hazard ratio 5.86; 95% confidence interval 2.73 to 13.04; p <0.001). A sensitivity analysis of propensity score-matched cohorts with a history of coronary artery disease or atrial fibrillation revealed the same association (hazard ratio 3.49; 95% confidence interval 1.15 to 10.06; p = 0.028). In conclusion, beta-blocker exposure in this secondary analysis was associated with increased incident HF in subjects with hypertension without HF at baseline"
• Metformin Benefits Patients Hospitalized for Heart Failure - Medscape, 12/14/21 - "SGLT2 inhibitors must be part of the treatment regimen for patients with heart failure of any type. This report supports also using metformin in those with type 2 diabetes and heart failure, but not in place of an SGLT2 inhibitor or to delay start of an SGLT2 inhibitor ... Patients started on metformin had a significant 19% reduction in 12-month incidence of all-cause death or HHF relative to other patients in the study in an analysis that adjusted for 29 potential confounders ... HHF was reduced by 20% in those who started metformin compared with those who did not ... A more granular analysis that divided patients by LVEF during their index hospitalization showed metformin use was linked with a significant 42% lower incidence of HHF and a significant 32% lower rate of HHF or all-cause death in patients with an LVEF of more than 40%" - See metformin at ReliableRX.
• Are Long-Term Beta Blockers Following MI in the Absence of Angina and HF Indicated in the PCI Era? - Medscape, 12/8/21 - "Therefore, in older adults who are completely revascularized and have no LV dysfunction or residual angina, long term BB therapy should be reassessed after 3 months since these drugs may cause adverse effects with no appreciable long-term benefits"
• Clinical benefits of empagliflozin in very old patients with type 2 diabetes hospitalized for acute heart failure - J Am Geriatr Soc 2021 Nov 29 - "There is little evidence on the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors in older patients with heart failure. This work analyzed the clinical efficacy and safety of empagliflozin continuation in very old patients with type 2 diabetes hospitalized for acute decompensated heart failure ... In very old patients with type 2 diabetes hospitalized for acute heart failure, continuing preadmission empagliflozin reduced NT-proBNP levels and increased diuretic response and urine output compared to a basal-bolus insulin regimen. The empagliflozin regimen also showed a good safety profile" - See dapagliflozin at reliablerxpharmacy.com.  They don't carry empagliflozin.
• Beneficial Effect of Sodium-Glucose Co-transporter 2 Inhibitors on Left Ventricular Function - J Clin Endocrinol Metab 2021 Nov 15 - "Treatment with SGLT2 inhibitors can significantly improve LV function in patients with or without diabetes (especially those with HF or undergoing empagliflozin treatment)" - See dapagliflozin at reliablerxpharmacy.com.  They don't carry empagliflozin.
• The diabetes medication that could revolutionize heart failure treatment - Science Daily, 12/1/21 - "For many years there was not a single medicine that could improve the outcome in patients with the second type of heart failure -- those patients with preserved ejection fraction ... SGLT2 inhibitors are more commonly known under their trade-names Forxiga (Dapagliflozin), Invokana (Canagliflozin), and Jardiance (Empagliflozin) ... We found that patients taking SGLT2 inhibitors were 22 per cent less likely to die from heart-related causes or be hospitalised for heart failure exacerbation than those taking placebo" - See dapagliflozin at reliablerxpharmacy.com.
• Sacubitril/Valsartan May Alter Trajectory of Preclinical HFpEF - Medscape, 11/23/21 - "Sacubitril/valsartan (Entresto) appears to improve measures of cardiac structure and function compared with valsartan alone in asymptomatic preclinical heart failure with preserved ejection fraction ... Sacubitril/valsartan (Entresto) appears to improve measures of cardiac structure and function compared with valsartan alone in asymptomatic preclinical heart failure with preserved ejection fraction ... Preclinical heart failure with preserved ejection fraction (HFpEF), the dominant form of preclinical HF, is largely driven by CV compliance abnormalities. Sacubitril/valsartan, through preservation of natriuretic peptide (NP), may improve CV compliance, especially if introduced early in the disease process ... At baseline, the left atrial volume index (LAVI) was 33.2 mL/m2 using Doppler echocardiography and 50 mL/m2 using cardiac MRI. "The discrepancy you see with cardiac MRI is a notable feature in the literature, but maybe something that's not as widely appreciated as it should be," ... The primary outcome of change in maximal LAVI over 18 months by cardiac MRI was 6.9 mL/m2 with sacubitril/valsartan vs 0.7 mL/m2 with valsartan alone ... Sacubitril/valsartan was also associated with a significant change in left ventricular end-diastolic volume index (7.1 mL/m2 vs 1.4% mL/m2 ... Over a median 16.9 months of follow-up, sacubitril/valsartan reduced 24-hour pulse pressures by -4.2 mm Hg vs -1.2 mm Hg with valsartan alone ... Following the presentation, an audience member asked whether the results may endorse the use of sacubitril/valsartan as an antihypertensive — an indication already approved in some countries ... "That's a fascinating question," McDonald replied. "When you look at the mechanisms of action of this agent compared to other antihypertensive agents and, particularly its beneficial effect of vasoprotective peptides, there's good reason to suspect it may be of more benefit than standard therapies, especially in those people who've shown at risk for the development of cardiovascular events.""
• Empagliflozin, Health Status, and Quality of Life in Patients with Heart Failure and Preserved Ejection Fraction: The EMPEROR-Preserved Trial - Circulation 2021 Nov 15 - "Patients with heart failure and preserved ejection fraction (HFpEF) have significant impairment in health-related quality of life (HRQoL) ... The effect of empagliflozin on reducing the risk of time to cardiovascular death or HF hospitalization was consistent across baseline KCCQ-CSS tertiles (HR 0.83 [0.69-1.00], HR 0.70 [0.55-0.88] and HR 0.82 [0.62-1.08] for scores <62.5, 62.5-83.3 and ≥83.3, respectively; P trend=0.77). Similar results were seen for total HF hospitalizations. Patients treated with empagliflozin had significant improvement in KCCQ-CSS versus placebo (+1.03, +1.24 and +1.50 at 12, 32 and 52 weeks, respectively P<0.01); similar results were seen for TSS and OSS. At 12 weeks, patients on empagliflozin had higher odds of improvement ≥5 points (OR 1.23; 95%CI 1.10, 1.37), ≥10 points (1.15; 95%CI 1.03, 1.27), and ≥15 points (1.13; 95%CI 1.02, 1.26) and lower odds of deterioration ≥5 points in KCCQ-CSS (0.85; 95%CI 0.75, 0.97). A similar pattern was seen at 32 and 52 weeks, and results were consistent for TSS and OSS"
• EMPEROR-Preserved Findings Confirmed in 'True' HFpEF Patients - Medscape, 11/18/21 - "The demonstration that empagliflozin is an effective — and safe — treatment for patients with HFpEF not only provides a new treatment for a disorder that until now had no evidence-based intervention, but also streamlines the management approach for treating patients with heart failure with an agent from empagliflozin's class, the SGLT2 inhibitors ... The impact of empagliflozin, compared with placebo, for reducing both the study's combined, primary outcome as well as total HHF was statistically consistent across all strata of LVEF, from 50% to greater than 70% ... Patients' quality of life as measured by the Kansas City Cardiomyopathy Questionnaire showed a consistent benefit from empagliflozin treatment, compared with placebo, both in patients with an LVEF of at least 50% as well as in those with an LVEF of 41%-49% ... Deterioration of renal function on treatment slowed by an average 1.24 mL/min per 1.73 m2 per year in patients on empagliflozin, compared with placebo, in the subgroup with an LVEF of at least 50%"
• Empagliflozin a Winner in Challenging Arena of Stabilized Acute HF - Medscape, 11/16/21 - "Patients assigned to empagliflozin had a 36% greater likelihood of showing a benefit as reflected in the treatment's win ratio when opposed by placebo ... The trial also lends new weight to the strategy of "simultaneous or rapid-sequence initiation" of the so-called four pillars of guideline-directed medical therapy of HF with reduced ejection fraction (HFrEF) in patients hospitalized with HFrEF, once they are stabilized, Fonarow said. The four-pronged approach, he noted, consists of sacubitril/valsartan (Entresto), a beta blocker, a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor ... EMPULSE entered patients hospitalized for acute HF, which could be de novo or a decompensation of chronic HF, without regard to ejection fraction or whether they had diabetes, and who were clinically stable after at least one dose of loop diuretics. Their ejection fractions averaged 35% and exceeded 40% in about one third of the total cohort ... At 90 days in the win ratio analysis, the 265 patients assigned to empagliflozin 10 mg once daily were the "winners," that is, they were more likely to show a clinical benefit about 54% of the time in paired match-ups of patient outcomes, compared to about 40% for the 265 in the control group ... The empagliflozin group also benefited significantly for the endpoint of death from any cause or first HF event, with a hazard ratio (HR) of 0.65 (95% CI, 0.43 - 0.99, P = .042). They also were less likely to experience acute renal failure (7.7% vs 12.1% for the control group) or serious adverse events (32.3% vs 43.6%), Voors reported ... several ongoing trials are exploring dapagliflozin (Farxiga) in a similar clinical setting" - See dapagliflozin at reliablerxpharmacy.com.  They don't have empagliflozin.
• Ejection Fraction for Guiding HF Therapy: Forget About It? - Medscape, 9/29/21 - "For the first time in a major HFpEF trial, patients on a test medication — in this case a sodium-glucose transporter 2 (SGLT2) inhibitor — showed a clear-cut significant benefit for the primary endpoint. The agent was empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly), and the endpoint was cardiovascular (CV) death or HF hospitalization ... The preferential effect on HF hospitalization at lower LVEF values, Mann proposed, might be due to the non-neurohormonal SGLT2 inhibitor's mechanism of action. His "guess," he said, is that the drugs "have beneficial effects on renal function, which would cut across all ejection fractions." They seem to "make the kidneys better and help them deal with sick heart, whether it be HFpEF or HFrEF." ... That doesn't mean LVEF isn't helpful and shouldn't be measured. "I don't know that we need to throw out the baby with the bathwater [just] because the SGLT2 story has been so compelling,""
• Expanded Label for Sacubitril/Valsartan Makes 1.8 Million More HF Patients Eligible - Medscape, 9/28/21 - "The expanded indication was based on results of the PARAGON-HF trial. While the trial missed its primary endpoint, secondary subgroup analyses showed a significant interaction between LVEF and treatment efficacy, with patients with a mid-range (below-median) LVEF of 45% to 57% appearing to benefit from sacubitril/valsartan therapy"
• Empagliflozin's HFpEF Efficacy Catalyzes Redefinition of HF - Medscape, 9/22/21 - "This new consensus essentially throws out left ventricular ejection fraction (EF) as the key metric for matching patients to heart failure treatments. Experts have instead begun suggesting a more unified treatment approach for all heart failure patients regardless of their EF ... We encourage you to forget about ejection fraction ... We certainly encourage you to forget about an ejection fraction of less than 40%" as having special significance ... The 40% ejection fraction divide is artificial. It was created in 2003 as part of a trial design, but it has no physiological significance ... A much better way to distinguish systolic and diastolic heart failure is by strain assessment rather than by ejection fraction. "Strain is a measure of myocardial shortening, a measure of what the heart does. Ejection fraction is a measure of volume," ... Wouldn't it be easier if we said that every patient with heart failure needs to receive one agent from each of the four [pillar] drug classes, and put them in a polypill ... The four pillar drug classes, recently identified as essential for patients with HFrEF but until now not endorsed for patients with HFpEF, are the sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as empagliflozin (Jardiance); an angiotensin receptor blocker neprilysin inhibitor compound such as sacubitril/valsartan (Entresto); beta-blockers; and mineralocorticoid receptor antagonists such as spironolactone and eplerenone ... The consequence is that clinicians should feel comfortable prescribing empagliflozin to most patients with heart failure without regard to EF, even patients with EF values in the mid-60% range ... The EMPEROR-Preserved results showed a clear signal of attenuated benefit among patients with an EF of 65% or greater "on a population basis," ... Recently, data from a third trial that tested sacubitril/valsartan in patients with HFpEF, PARAGON-HF, showed benefit among patients with EFs below the study median of 57%"
• PRESERVED-HF: Dapagliflozin Improves Physical Limitations in Patients With HFpEF - Medscape, 9/14/21 - "These results in the PRESERVED-HF study follow closely on the heals of the initial report from the EMPEROR-Preserved trial that showed a benefit from a different sodium-glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin (Jardiance) in nearly 6,000 randomized patients for the primary endpoint of preventing cardiovascular death or hospitalizations for heart failure ... In PRESERVED-HF, patients with HFpEF who received a standard, once-daily dose of dapagliflozin (Farxiga) had an average 5.8-point improvement in their condition as measured by the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CS), the study's primary endpoint ... The impact of empagliflozin on KCCQ clinical summary score in EMPEROR-Preserved showed an average incremental improvement of 1.32 points compared with placebo, a significant difference, but more modest than the increment from dapagliflozin treatment seen in PRESERVED-HF. Kosiborod hypothesized that this difference might be mostly because of the different patient populations enrolled in the two studies" - See dapagliflozin at reliablerxpharmacy.com.
• Outcomes of patients with type 2 diabetes treated with SGLT-2 inhibitors versus DPP-4 inhibitors. An Italian real-world study in the context of other observational studies - Diabetes Res Clin Pract 2021 Aug 25 - "Patients with T2D who initiated SGLT2i under routine care had better cardio-renal outcomes and lower all-cause mortality than similar patients who initiated DPP4i"
• Outcome Benefits Seen With 1 Year of Optimized Sacubitril/Valsartan for the Treatment of Systolic Heart Failure Managed by Pharmacists in a Cardiology Practice - Ann Pharmacother 2021 Aug 28 - "patients with HF with reduced ejection fraction (HFrEF) on angiotensin receptor-neprilysin inhibitor (ARNi) therapy optimized within a pharmacist clinic ... Retrospective chart review of patients with HFrEF on sacubitril/valsartan ... For the primary outcome analysis, 70 patients with pre/post hospitalization data had a reduction in the rate of all-cause hospitalization from 45.7% in the 12 months prior to ARNi therapy initiation to 24.3% during the first year on optimized ARNi therapy (P = 0.004). The rate of hHF reduced from 24.3% to 8.6% (P = 0.003). For the secondary outcome analyses at the 6-month assessment point, which included 104 patients, ejection fraction improved from 26% to 34% (P < 0.001), NYHA FC improved or remained unchanged in 86.6% of patients, and weekly loop diuretic dosing requirements were significantly reduced"
• Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction - Eur Heart J 2021 Aug 15 - "Patients with heart failure and preserved ejection fraction (HFpEF) frequently have difficult-to-control hypertension. We examined the effect of neprilysin inhibition on 'apparent resistant hypertension' in patients with HFpEF in the PARAGON-HF trial, which compared the effect of sacubitril-valsartan with valsartan ... Sacubitril-valsartan may be useful in treating apparent resistant hypertension in patients with HFpEF, even in those who continue to have an elevated blood pressure despite treatment with at least four antihypertensive drug classes, including an MRA"
• EMPEROR-Preserved: Empagliflozin Scores HFpEF Breakthrough - Medscape, 8/27/21 - "The SGLT2 inhibitor empagliflozin achieved in EMPEROR-Preserved what no other agent could previously do: unequivocally cut the incidence of cardiovascular death or hospitalization in patients with heart failure and preserved ejection fraction (HFpEF) ... Treatment with empagliflozin (Jardiance) led to a significant 21% relative reduction in the rate of cardiovascular death or hospitalization for heart failure (HHF), compared with placebo, among 5,988 randomized patients with HFpEF during a median 26 months of follow-up, proving that patients with HFpEF finally have a treatment that gives them clinically meaningful benefit, and paving the way to an abrupt change in management of these patients, experts said ... A second sodium-glucose cotransporter 2 (SGLT2 ) inhibitor, dapagliflozin (Farxiga), is also an option for treating HFrEF based on results in the DAPA-HF trial, and the DELIVER trial, still in progress, is testing dapagliflozin as a HFpEF treatment in about 6,000 patients, with results expected in 2022 ... This showed a consistent and robust benefit from empagliflozin for reducing HHF across a wide spectrum of patients with heart failure, ranging from patients with left ventricular ejection fractions of less than 25% to patients with ejection fractions as high as 64% ... patients with reduced ejection fractions showed a significant 49% relative reduction in the incidence of serious renal outcomes" - Note:  If you can't get empagliflozin, ReliableRxPharmacy sells dapagliflozin.
• Dapagliflozin in HFrEF May Cut Arrhythmias, Sudden Death: DAPA-HF - Medscape, 8/27/21 - "The addition of dapagliflozin to standard therapy reduced the relative risk for the primary composite endpoint of any serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden death by 21%, compared with placebo" - See dapagliflozin at ReliableRxPharmacy.
• SGLT2 inhibitors: the story continues to unfold - European Heart Journal, 8/23/21 - "The sodium–glucose co-transport protein 2 inhibitors (SGLT2is) have had a huge impact on the clinical scene, such as for treatment of diabetes, chronic kidney disease (CKD), and heart failure. The renal protection provided by these agents has also been very impactful, with a potential delay in the time-related reduction of the glomerular filtration rate (GFR) that occurs in patients with CKD.1 However, to date, the true mechanism of SGLT2is, such as in the early and profound reduction in heart failure hospitalizations, still eludes us.2,3 Each new finding regarding an SGLT2i is met with enthusiasm as we unravel the whys and the hows. Certainly, a diuretic effect may be present, but this does not answer the question and neither does increased glucose excretion, since the effects in non-diabetics are equally impressive. Fortunately, the pharmaceutical industry has sponsored large randomized controlled trials of SGLT2is in various patient groups, providing the ideal arena for exploring effects by subgroups, asking critical questions, and establishing interesting hypotheses, yet to be proven."
• Sacubitril/valsartan for heart failure with preserved ejection fraction and resistant hypertension: one shot for a double strike? - European Heart Journal, 8/15/21 - "hypertension and HFpEF co-exist in >95% of subjects,5 and a large proportion of HFpEF patients have uncontrolled blood pressure (BP) levels despite the use of multiple antihypertensive drugs. Indeed, resistant hypertension, defined as the failure to achieve recommended BP targets despite appropriate lifestyle measures and treatment with optimal or best-tolerated doses of three or more drugs which should include a diuretic [typically an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) and a calcium channel blocker (CCB)]1,6, accounts for 10–20% of HFpEF patients ... Sac/Val appeared to be more effective than valsartan alone in treating resistant hypertension in HFpEF. Patients treated with Sac/Val achieved a 4.8 mmHg SBP reduction (–7.0 to –2.5 mmHg) compared with –3.9 mmHg (–6.6 to –1.3 mmHg) in the valsartan group. Consistent results were obtained in individuals with apparent MRA-resistant hypertension [–8.8 mmHg (–14.0 to –3.5 mmHg) vs. –6.3 (–12.5 to –0.1 mmHg) in the Sac/Val and valsartan groups, respectively]. Sac/Val improved the achievement of SBP control at 16 weeks by 22% compared with valsartan alone [47.9% vs. 34.3%; adjusted odds ratio (OR) 1.78; 95% CI 1.30–2.43]. In patients with apparent MRA-resistant hypertension, the proportions were 43.6% vs. 28.4%, respectively, with an adjusted OR of 2.63"
• FDA Okays Empagliflozin for HFrEF - Medscape, 8/19/21 - "The FDA based its decision on results from the EMPEROR-Reduced study, first reported in August 2020, that showed treatment of patients with HFrEF with empagliflozin on top of standard therapy for a median of 16 months cut the incidence of cardiovascular death or hospitalization for worsening heart failure by 25% relative to placebo, and by an absolute 5.3%, compared with placebo-treated patients ... Patients enrolled in EMPEROR-Reduced had chronic heart failure in New York Heart Association functional class II-IV and with a left ventricular ejection fraction of 40% or less, the standard ejection fraction criterion for defining HFrEF. Half the enrolled patients had diabetes, and analysis showed no heterogeneity in the primary outcome response based on diabetes status at enrollment ... Subsequent to the report of results from the EMPEROR-Reduced trial nearly a year ago, heart failure experts declared that treatment with an agent from the SGLT2 inhibitor class had become a "new pillar of foundational therapy for HFrEF," and they urged rapid initiation of an SGLT2 inhibitor (along with other appropriate medications) at the time of initial diagnosis of HFrEF"
• EU Approves Dapagliflozin for Kidney Disease, Regardless of Diabetes - Medscape, 8/10/21 - "We found that dapagliflozin delayed the initiation of dialysis and reduced the number of deaths ... treatment with dapagliflozin led to a 39% relative risk reduction in the incidence of a combined renal and cardiovascular endpoint during a median 2.4 years of follow-up, with an absolute risk reduction of 5.3%. The combined endpoint tallied the incidence of a 50% or greater drop in eGFR from baseline, onset of end-stage renal disease, or renal or cardiovascular death" - See dapagliflozin at reliablerxpharmacy.com.
• Evaluation of the effects of glycated hemoglobin on cardiac function in patients with short-duration type 2 diabetes mellitus: a cardiovascular magnetic resonance study - Diabetes Res Clin Pract 2021 Jul 14 - "Poor blood glucose control is an independent predictor of LV myocardial dysfunction for patients with short-term T2DM"
• Comparing cardiovascular benefits between GLP-1 receptor agonists and SGLT2 inhibitors as an add-on to metformin among patients with type 2 diabetes: A retrospective cohort study - J Diabetes Complications 2021 Jun 11 - "significantly lower CHF risks (HR: 0.47, 95% CI: 0.28-0.79) and cardiovascular composite (HR: 0.67, 95% CI: 0.47-0.97) were observed in SGLT2i users compared with GLP-1RA users, among individuals with established cardiovascular diseases ... Results suggest greater cardioprotective benefit from SGLT2i compared to GLP-1RA when used for secondary prevention among adults with T2D"
• Effectiveness of Sacubitril/Valsartan Versus Aldosterone Antagonists in Heart Failure with reduced Ejection Fraction: A Retrospective Cohort Study - Pharmacotherapy 2021 Jun 25 - "aldosterone antagonists (ARAs) ... Compared with ARAs, SAC/VAL was associated with lower risk of HF-related and all-cause hospitalizations"
• Iron-Clad Benefits of CRT Seen in Reduced-EF Heart Failure - Medscape, 7/2/21 - "a small randomized trial may highlight a potential mechanism for those benefits by demonstrating what appears to be a direct salutary effect of the injectable iron preparation ferric carboxymaltose (Ferinject / Injectafer), or FCM, on reverse remodeling in iron-deficient patients with HFrEF ... Its patients, who were already receiving "very robust background medical therapy and robust device therapy consisting of CRT," Martens observed, benefited with significant new cardiac reverse remodeling after 3 months of FCM treatment, compared to similar patients assigned to a standard-care control group. Their left-ventricular ejection fractions (LVEFs) went up and left-ventricular end-systolic volumes (LVESVs) went down. They also showed relative gains in exercise capacity and higher scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), which measures functional status ... Iron deficiency can impair the reverse-remodeling benefit of CRT and blunt the heart's positive force-frequency relationship (FFR) ― a measure of contractile mechanics that normally climbs exponentially with accelerating heart rate. Put another way, cardiac output at exercise testing tends to go up less in HFrEF patients with iron deficiency compared to those who aren't iron deficient ... The IRON-CRT trial suggests that FCM iron repletion in such patients "improves cardiac performance and is capable of transforming the negative FFR into a positive FFR," thereby boosting cardiac output and exercise capacity"
• The association between neurohormonal therapy and mortality in older adults with heart failure with reduced ejection fraction - J Am Geriatr Soc 2021 Jun 15 - "Neurohormonal therapy, which includes beta-blockers and angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (ACEi/ARBs), is the cornerstone of heart failure with reduced ejection fraction (HFrEF) treatment. While neurohormonal therapies have demonstrated efficacy in randomized clinical trials, older patients, which now comprise the majority of HFrEF patients, were underrepresented in those original trials ... Among those ≥85 years old, the hazard ratio for death within 30 days was 0.59 (95% confidence interval [CI] 0.56-0.62; p < 0.001) for beta-blockers and 0.47 (95% CI 0.44-0.49; p < 0.001) for ACEi/ARBs. The hazard ratio for death within 1 year was 0.37-0.56 (95% CI 0.35-0.58; p < 0.001) for beta-blockers and 0.38-0.53 (95% CI 0.37-0.55; p < 0.001) for ACEi/ARB"
• l -Arginine Can Enhance the Beneficial Effect of Losartan in Patients with Chronic Aortic Regurgitation and Isolated Systolic Hypertension - Int J Angiol 2021 Jun;30(2) - "chronic aortic regurgitation (CAR) and isolated systolic hypertension (ISH) ... Both groups had a significant reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP), left ventricular end-diastolic volume index (LVEDVI), LV end-systolic volume index (LVESVI), LV mass index (LVMI), and LV mean wall stress after 6- and 12-month treatment ( p <0.01 in all comparisons). Both groups had a significant increase in LV ejection fraction and exercise duration after 6- and 12-month treatment ( p < 0.01 in all comparisons). Using multivariate linear regression analysis, only losartan + l -arginine therapy achieved a significantly lower LVESVI (38.89 ± 0.23 mL/m 2 ), LVEDVI (102.3 ± 0.3 mL/m 2 ), LVMI (107.6 ± 0.3 g/m 2 ), SBP (123.5 ± 1.0 mm Hg), and greater exercise duration (7.38 ± 0.02 minutes) than those of the losartan-only treated groups ( p <0.01 in all comparisons). These findings suggest that early co-administrative strategy provides a beneficial approach to favorably influence the natural history of CAR" - See l-arginine products at Amazon.com.
• Cost-effectiveness of Dapagliflozin for Treatment of Patients With Heart Failure With Reduced Ejection Fraction - Medscape, 6/4/21
• Sotagliflozin's HFpEF Benefit Confirmed by New Analyses - Medscape, 5/24/21 - "The meta-analysis (Abstract 410-08) included 4,500 patients with type 2 diabetes and diagnosed heart failure at entry; its primary endpoint, which was the same in both trials, was the combined incidence of cardiovascular death and the total number of either hospitalization for heart failure or urgent outpatient visits for heart failure ... Compared with placebo, treatment with sotagliflozin for a median of about 15 months dropped this composite endpoint by a relative 33% among the 1,931 who began the study with a left ventricular ejection fraction (LVEF) of at least 50% (HFpEF), by a relative 22% in the 1,758 patients who entered with an LVEF of less than 40% (patients with heart failure with reduced ejection fraction), and by a relative 43% among the 811 patients who began with an LVEF of 40%-49% (patients with heart failure with mid-range ejection fraction). The relative risk reductions were significant for all three subgroups, Deepak L. Bhatt, MD, reported at the meeting"
• Usefulness of Sodium-Glucose Cotransporter 2 Inhibitors for Primary Prevention of Heart Failure in Patients With Type 2 Diabetes Mellitus - Am J Cardiol 2021 May 15 - "The sodium-glucose cotransporter 2 inhibitors (SGLT2i) empagliflozin, canagliflozin, and dapagliflozin reduce the risk of heart failure (HF) events in patients with diabetes mellitus (DM) at high risk for HF. Differences in HF outcomes between SGLT2i were demonstrated in a recent-published meta-analysis ... Our findings suggest that between the available SGLT2i, the cost of primary prevention of HF in patients with DM at high risk for HF is lowest with empagliflozin" - See dapagliflozin at ReliableRXPharmacy.  They don't carry empagliflozin, which in my view is better.  I read somewhere that India would no longer sell generic versions after a certain patent date until that drug goes generic.  I think that's the problem with buying generic empagliflozin from India.
• Effect of empagliflozin on cardiorenal outcomes and mortality according to body-mass index: A subgroup analysis of the EMPA-REG OUTCOME trial with a focus on Asia - Diabetes Obes Metab 2021 May 5 - "Overall, hazard ratios for empagliflozin versus placebo for all-cause mortality, HHF or CV death, and incident or worsening nephropathy were 0.68 (95% CI 0.57, 0.82), 0.66 (0.55, 0.79), and 0.61 (0.53, 0.70), respectively, and were consistent across BMI categories (P-values for interaction between treatment and BMI: 0.6772, 0.3087, and 0.6265, respectively). Results were similar in Asians using these BMI categories and < 24, 24 to <28, ≥28 kg/m2 categories. Thus, empagliflozin reduced cardiorenal and mortality risk regardless of BMI at baseline, including in Asians with lower BMI"
• Tips for Navigating Prior Authorization and Out-of-Pocket Costs for HFrEF Medications - Medscape, 5/11/21 - "Moreover, in the past decade, a series of large randomized trials have shown the efficacy of newer classes of medications in improving health outcomes of patients with HFrEF. These newer medications include the I f inhibitor ivabradine (SHiFT study); the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan (PARADIGM-HF and PIONEER-HF trials); the sodium-glucose transporter 2 (SGLT2) inhibitors dapagliflozin (DAPA-HF study) and empagliflozin (EMPEROR-Reduced trial); and the soluble guanylate cyclase activator vericiguat (VICTORIA trial) ... Although these new treatment options for HFrEF are proven to be safe and well tolerated across a wide range of patients, there are obstacles to their widespread use — namely, the high cost of these drugs, prior authorization requirements, and out-of-pocket fees. Not only must patients often first obtain approval from their insurance companies for these prescriptions, but they are also required to pay greater out-of-pocket costs for them than generic drugs. Perhaps not surprisingly, the use of generic ACE inhibitors and beta-blockers for HFrEF remains high, whereas uptake of ivabradine and sacubitril-valsartan continues to be slow and SGLT2 inhibitors are only just beginning to be prescribed." - See dapagliflozin at ReliableRXPharmacy.  They don't carry empagliflozin, which in my view is better.  I read somewhere that India would no longer sell generic versions after a certain patent date until that drug goes generic.  I think that's the problem with buying generic empagliflozin from India.
• Women, Black, and Asian Patients Least Likely to Get SGLT2 Inhibitors - Medscape, 4/23/21 - "If left unaddressed, these inequities in utilization will continue to widen well-documented disparities in cardiovascular and kidney outcomes in the [United States] ... Study after study, including large randomized trials, have demonstrated a cardio-protective and kidney-protective effect of this class of medications"
• Effects of Sacubitril/Valsartan on clinical symptoms, echocardiographic parameters, and outcomes in HFrEF and HFmrEF patients with coronary heart disease and chronic kidney disease - Curr Med Res Opin 2021 Mar 25 - "To compare the effects of Angiotensin Receptor-Neprilysin inhibitor (ARNI) on the clinical symptoms, echocardiographic parameters, and outcomes (cardiovascular death and hospitalization) in heart failure with reduced ejection fraction (HFrEF) and heart failure with mid-range ejection fraction (HFmrEF) patients with coronary heart disease and chronic kidney disease ... A statistically significant increase of 68.8% was observed in left ventricular ejection fraction (LVEF) in HFrEF patients compared to that in HFmrEF patients, with an increase of 27.2% at 8 months of follow-up. Sacubitril/valsartan significantly reduced left ventricular end-systolic volumes (LVESV) in HFrEF patients unlike in HFmrEF patients. The decrease in LVESV was 28.8% in HFrEF patients and 17.1% in HFmrEF patients. A significant reduction in the prevalence of severe secondary mitral regurgitation (EROA >0.4cm2) was observed in HFrEF compared to that in HFmrEF patients with the use of sacubitril/valsartan. A reduction of 15.6% was observed in HFrEF patients, whereas a reduction of 7.1% was observed in HFmrEF patients. Improvement in functional classification (NYHA) was observed during follow-up. The prevalence of (NYHA III) reduced from 50% to 15.7% in HFrEF patients, whereas a reduction from 21.1% to 8.8% was observed in HFmrEF patients. There was a significant reduction in NT-proBNP in HFrEF patients compared to that in HFmrEF patients. A reduction of 52% was observed in HFrEF patients, whereas a reduction of 28.7% was observed in HFmrEF pateints. Sacubitril/valsartan reduced primary endpoint events in both groups. The prevalence of HF-related hospitalization was higher in HFrEF than in HFmrEF patients: 12.1% vs 7.5%, respectively. The prevalence of CV death in HFrEF vs HFmrEF patients was 3.7% vs 0.5%, respectively. Cardiovascular (CV) was higher in patients with atrial fibrillation in both groups"
• Cardiac and Kidney Benefits of Empagliflozin in Heart Failure Across the Spectrum of Kidney Function - Medscape, 3/29/21 - "Empagliflozin reduced the primary outcome and total HF hospitalizations in patients with and without CKD: hazard ratio (HR)=0.78 (95% CI, 0.65–0.93) and HR=0.72 (95% CI, 0.58–0.90), respectively (interaction P=0.63). Empagliflozin slowed the slope of eGFR decline by 1.11 (0.23–1.98) ml/min/1.73 m2/yr in patients with CKD and by 2.41 (1.49–3.32) ml/min/1.73 m2/yr in patients without CKD. The risk of the composite kidney outcome was reduced similarly in patients with and without CKD: HR=0.53 (95% CI, 0.31–0.91) and HR=0.46 (95% CI, 0.22–0.99), respectively. The effect of empagliflozin on the primary composite outcome and key secondary outcomes was consistent across a broad range of baseline kidney function, measured by clinically relevant eGFR subgroups or by albuminuria, including patients with eGFR as low as 20 ml/min/1.73 m2. Empagliflozin was well tolerated in CKD patients ... In EMPEROR-Reduced, empagliflozin had a beneficial effect on the key efficacy outcomes and slowed the rate of kidney function decline in patients with and without CKD, and regardless of the severity of kidney impairment at baseline."
• SGLT-2 inhibitors for prevention of cardiorenal outcomes in type 2 diabetes: an updated meta-analysis - Diabetes Obes Metab 2021 Mar 12 - "A total of 8 cardiorenal outcomes trials of SGLT-2i (empagliflozin, canagliflozin, dapagliflozin, ertugliflozin, sotagliflozin) were identified, with 66 601 patients ... Overall, SGLT-2i were associated with a 12% reduced risk of major adverse cardiovascular events (MACE, HR = 0.88; 95% CI, 0.83-0.93; Q statistic, P = 0.19), with no significant heterogeneity (p for interaction = 0.465) between subgroups of patients with or without cardiovascular disease (CVD). The risk of the composite renal outcome was significantly reduced by treatment with SGLT-2i (HR = 0.61, 95% CI, 0.54-0.70), with no significant heterogeneity of associations with outcome (I2 = 37%, P = 0.11), and no difference in the risk between patients with or without CVD (p for interaction = 0.665). SGLT-2i have moderate benefits on MACE and major benefits on the progression of diabetic kidney disease"
• Dapagliflozin Reduces Systolic Blood Pressure and Modulates Vasoactive Factors - Diabetes Obes Metab 2021 Mar 17 - "24 and 23 patients receiving dapagliflozin and placebo, respectively, completed the 12 weeks' study. Systolic BP fell significantly, compared to placebo, both after a single dose (by 7 ± 3 mmHg) and 12-week (by 7 ± 2 mmHg) treatment with dapagliflozin. Dapagliflozin suppressed angiotensin II and angiotensinogen (by 10.5 ± 2.1 pg/mL and 1.45 ± 0.42 μg/mL, respectively) and increased ANP and cGMP (by 34 ± 11 pg/mL and 29 ± 11 pmol/mL, respectively) compared to placebo group. cGMP levels also increased acutely following a single dose of dapagliflozin. Dapagliflozin also suppressed PDE5 expression by 26 ± 11% in MNC. There was no change in the other vasoactive mediators investigated."
• Could Taking Viagra Come With an Extra Perk? - Medscape, 3/24/21 - "The researchers identified around 240,000 Swedish men who had a prior myocardial infarction or revascularization. Of that group, around 20,000 were receiving medication for ED — mostly PDE5 inhibitors but enough on alprostadil to do the analysis. ... Topline results: Men taking PDE5 inhibitors for ED were way less likely to have MIs, coronary revascularization, or heart failure than those taking alprostadil. In fact, over the course of up to 15 years of follow-up, 14% of men died of any cause in the PDE5 group compared with 26% in the alprostadil group" - Related study:
  • Erectile dysfunction drug 'effective' as heart failure treatment - Science Daily, 5/1/19 - "The study of Tadalafil -- which is in the same class as Viagra -- proves that the drug is biologically effective as a treatment for heart failure in sheep ... When the animals had heart failure -- induced by pace makers -- which was sufficiently advanced to need treatment, the team administered the drug. Within a short period the progressive worsening of the heart failure was stopped and, importantly the drug reversed the effects of heart failure ... And the biological cause of breathlessness in heart failure- the inability of the heart to respond to adrenaline was almost completely reversed" - See tadalafil at reliablerxpharmacy.com.
• Spironolactone in Patients With Heart Failure, Preserved Ejection Fraction, and Worsening Renal Function - J Am Coll Cardiol 2021 Mar 9 - "Treatment of heart failure with preserved ejection fraction (HFpEF) with spironolactone is associated with lower risk of heart failure hospitalization (HFH) but increased risk of worsening renal function (WRF) ... Among HFpEF patients enrolled in TOPCAT-Americas, spironolactone increased risk of WRF compared with placebo. Rates of CV death were lower with spironolactone in both patients with and without WRF"
• Hydrogel injection may change the way the heart muscle heals after a heart attack - Science Daily, 3/1/21 - "The international research team, which included researchers from Ireland, Spain, Sweden, France and Italy, were able to show that if their hydrogel was injected into the heart muscle shortly after a heart attack, it resulted in less fibrosis (scarring of the cardiac tissue) and an increase in the generation of new blood vessels in the area. They were also able to observe the rise in the preservation and survival of cardiomyocytes, a type of cell that allows the heart to beat, in the affected area"
• Nebivolol is more effective than atenolol for blood pressure variability attenuation and target organ damage prevention in L-NAME hypertensive rats - Hypertens Res 2021 Feb 22 - "β-Adrenergic blockers are no longer recommended as first-line therapy due to the reduced cardioprotection of traditional β-blockers compared with other antihypertensive drugs. It is unknown whether third-generation β-blockers share the limitations of traditional β-blocker ... Nebivolol had a greater ability than atenolol to decrease central SBP and mid-term and short-term blood pressure variability (BPV) in L-NAME rats. Echocardiographic analysis showed that nebivolol was more effective than atenolol on E/A wave ratio normalization. Compared with atenolol treatment, nebivolol had a greater protective effect on different TOD markers, inducing a decrease in collagen deposition and a reduction in the proinflammatory cytokines IL-6 and TNF-α in the left ventricle and aorta. Our findings suggest that the adverse hemodynamic profile and the reduced cardiovascular protection reported with traditional β-blockers must not be carried forward to third-generation β-blocker" - Note: For years cardiologists have put out that third-generation Nebivolol wouldn't work for heart failure and you had to use the first generation ones with unbearable side effects. That said, with Entresto and Jaridience or Farxiga, why do you even need a beta-blocker?
• Diabetes Drug Can Treat and Reverse Heart Failure and Reduce Hospitalizations - mountsinai.org - "Roughly 80 percent of the patients treated with empagliflozin showed significant improvement, and their hearts returned to near normal, the researchers found. This group had a 16.6 percent improvement in left ventricular ejection fraction at the six-month mark and their hearts pumped blood in a stronger way. Their hearts became smaller, less dilated because of less congestion and less fluid accumulation in the body, meaning that their heart failure became less severe, and the walls of the heart were less thick, meaning that the left ventricle could pump blood more easily"
• FDA Expands Sacubitril/Valsartan Indication to Embrace Some HFpEF - Medscape, 2/17/21 - "The US Food and Drug Administration (FDA) has approved a groundbreaking expanded indication for sacubitril/valsartan (Entresto), making it the first drug in the United States indicated for chronic heart failure (HF) not specifically characterized by ejection fraction ... PARAGON-HF had assigned more than 4800 patients whose LVEF was 45% or higher and were in NYHA class 2-4 to receive sacubitril/valsartan or valsartan only. Those taking the combo drug showed a 13% drop in risk for HF hospitalization or cardiovascular deaths over an average of 3 years, which narrowly missed significance (P = .059) ... But a subgroup analysis garnered attention for its hint of benefit for patients with "mid-range" LVEF, in this case, below the median of 57%. The finding was supported by a later PARAGON-HF and PARADIGM-HF meta-analysis that pointed to a significant benefit for patients with HFpEF at its lowest LVEF levels, especially in women"
• The role of SGLT-2 inhibitors in managing type 2 diabetes - Cleve Clin J Med 2020 Dec 31 - "Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are an exceptionally versatile class of medication, and their glycemic and nonglycemic benefits could help millions of patients with type 2 diabetes. Of note, they have been shown to improve cardiac and renal outcomes, much-needed benefits in patients with type 2 diabetes, who are at a higher risk for developing cardiac and renal dysfunction than those who do not have diabetes. The indications for SGLT-2 inhibitors may continue to expand as ongoing clinical trials provide more insight into these drugs"
• FDA Approval Adds Vericiguat (Verquvo) to HF Treatment Options - Medscape, 1/20/21 - "Vericiguat, which promotes vasodilation through stimulation of a nitric-oxide signaling enzyme pathway, was approved based primarily on the VICTORIA trial, which saw a 10% drop in adjusted risk for the primary end point, cardiovascular death, or first HF hospitalization (P = .019) in those who took the drug, compared with a placebo"
• Five Reasons Sacubitril/Valsartan Should NOT Be Approved for HFpEF - Medscape, 1/15/21
• FDA Panel Supports Expanded HF Role for Sacubitril/Valsartan - Medscape, 12/15/20 - "The U.S. Food and Drug Administration asked its Cardiovascular and Renal Drugs Advisory Committee to broadly consider whether new analyses of data from the PARAGON-HF trial, combined with other information, could support use of sacubitril/valsartan (Entresto, Novartis) in heart failure with preserved ejection fraction (HFpEF) ... The advisory committee voted 12-1 on this question"
• Sacubitril/Valsartan: Neprilysin Inhibition 5 Years After PARADIGM-HF - Medscape, 12/4/20 - "Sacubitril/valsartan is an efficacious, safe, and cost-effective therapy that improves quality of life and longevity in patients with chronic HFrEF and reduces hospital admission. An in-hospital initiation strategy offers a potentially new avenue to improve the clinical uptake of sacubitril/valsartan ... The recently completed PARAGON-HF trial showed that sacubitril/valsartan modestly reduced the risks of total heart failure hospitalizations and cardiovascular death than valsartan in patients with HFpEF, although this finding narrowly missed statistical significance,[18] Clinical benefits were observed in secondary endpoints including quality of life and kidney endpoints; women and patients at the lower end of the LVEF spectrum appeared to preferentially benefit. The safety profile of sacubitril/valsartan was largely consistent with prior trial experiences. Regulatory review of sacubitril/valsartan for the treatment of HFpEF is currently under way. Ongoing trials are evaluating the clinical utility of sacubitril/valsartan among patients with HFpEF (PARALLAX) and acute myocardial infarction ... In the last 5 years, sacubitril/valsartan has been established as a cornerstone component of comprehensive disease-modifying medical therapy in the management of chronic HFrEF. The next 5 years should see its wider implementation in practice and potential expansion of its therapeutic indications"
• Randomized Trial of Empagliflozin in Non-Diabetic Patients with Heart Failure and Reduced Ejection Fraction - J Am Coll Cardiol 2020 Nov 9 - "Empagliflozin administration to non-diabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for SGLT2 inhibitors in the treatment of HFrEF patients independently of their glycemic status"
• EMPEROR-Reduced: Empagliflozin's HFrEF Benefit Holds Steady on Top of Sacubitril/Valsartan - Medscape, 10/7/20 - "When there are two very effective treatments, it's common for people to ask: Which should I use?' The goal of my presentation was to emphasize that the answer is both. We shouldn't choose between neprilysin inhibition [sacubitril inhibits the enzyme neprilysin] and SGLT2 [sodium-glucose transporter 2] inhibition; we should use both"
• HFpEF: Gender Difference in Sacubitril/Valsartan Response Remains Mystery - Medscape, 4/20/20 - "In women, however, who comprised more than half of the study population, the benefit of sacubitril/valsartan was larger: a 27% relative risk reduction compared to valsartan alone. That's a statistically significant difference in a prespecified subgroup analysis, but according to the rules of clinical trials and statistics it must be considered hypothesis-generating and nondefinitive, since the overall trial was negative. Men randomized to sacubitril/valsartan had a modest 3% increased risk of the primary endpoint compared to men on valsartan."
• PARAGON-HF: Optimal Systolic Pressure in HFpEF is 120-129 mmHg - Medscape, 3/18/20 - "A target systolic blood pressure (SBP) of 120-129 mm Hg in patients with heart failure with preserved ejection fraction (HFpEF) proved to be the sweet spot with the lowest rates of major adverse cardiovascular and renal events in a new analysis from the landmark PARAGON-HF trial"