|
|
Home > Health
Conditions > HFpEF
HFpEF
Alternative News:
-
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:
-
-
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"
-
|
|