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  • 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"