Angiotensin Receptor Antagonists

Mineralocorticoid Receptor Antagonists

Sodium

PMID (1):

36107415

MeSH

Sodium-Glucose Transporter 2 Inhibitors

Milestones in Heart Failure: How Far We Have Come and How Far We Have Left to Go

Angioedema

Updated guidelines for management of congestive heart failure rom the American College of Cardiology and the American Heart Association. James W. Mold, MD, MPH

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GUIDELINE TITLE 2022 American College of Cardiology
(ACC)/American Heart Association AHA)/Heart Failure
Society of America (HFSA) Guidelines for the Management
of Heart Failure
RELEASE DATE April 1, 2022
PRIOR VERSIONS 2017 ACC/AHA/HFSA Focused Update
of the 2013 ACCF/AHA Guideline for the Management of
Heart Failure and 2013 ACCF/AHA Guideline for the
Management of Heart Failure
DEVELOPER AND FUNDING SOURCE ACC/AHA Joint
Committee on Clinical Practice Guidelines
TARGET POPULATION Adult patients with a diagnosis of
or at risk for heart failure (HF)
MAJOR RECOMMENDATIONS
• Classifications for HF are separated into 4 categories based
on ejection fraction (EF) and disease history: HF with
reduced EF (EF 40%), HF with mildly reduced EF
(EF 41%-49%), HF with preserved EF (EF 50%), and HF
with improved EF (EF previously 40% with improvement
to >40%).
• In patients with chronic HF with reduced EF, angiotensin
receptor–neprilysin inhibitors (ARNIs) are preferred over
angiotensin-converting enzyme inhibitors (ACEIs) and
angiotensin II receptor blockers (ARBs). If ARNI use is not
feasible, ACEIs are preferred over ARBs, unless there is
significant cough or angioedema (class 1, level of
evidence [LOE] A).
• Sodium-glucose cotransporter 2 (SGLT2) inhibitors should
be included across all HF categories (symptomatic HF with
reduced EF [class 1, LOE A]; HF with mildly reduced EF and
HF with preserved EF [class 2a, LOE B-R]).
• Patients with HF with improved EF should continue to
receive medical therapy originally indicated for HF with
reduced EF (class 1, LOE B-R).
• Evidence-based treatment of HF with preserved EF
includes blood pressure control (class 1, LOE C-LD),
SGLT2 inhibitors (class 2a, LOE B-R), mineralocorticoid
antagonists, ARBs, and ARNIs (class 2b, LOE B-R).

Author/s:

Belkin, M. N., Cifu, A. S., Pinney, S.

Milestones in Heart Failure: How Far We Have Come and How Far We Have Left to Go

Saige Blanchard — Mon, 03 Jan 2022 06:00:00 +0000

Date Added:

January 3, 2022

Journal/Publication:

Cureus Journal of Medical Science

Publication Date:

December 12, 2021

URL:

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.7759/cureus.20359

Keywords

MeSH

Angiotensin-converting-enzyme inhibitor–induced angioedema

Disease Progression

A nice summary of what we currently know about the pharmacologic treatment of congestive heart failure. James W. Mold, MD, MPH

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Heart failure is a clinically complex syndrome that results due to the failure of the ventricles to function as pump and oxygenate end organs. The repercussions of inadequate perfusion are seen in the form of sympathetic overactivation and third spacing, leading to clinical signs of increased blood pressure, dyspnea, fatigue, palpitations, etc. This article provided a brief overview of the clinical syndrome of heart failure; its epidemiology, risk factors, symptoms, and staging; and the mechanisms involved in disease progression. This article also described several landmark trials in heart failure that tested the efficacy of first-line drugs such as beta-blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and the latest drugs in the field of heart failure: angiotensin receptor neprilysin inhibitors. Most studies described in this article were guideline-setting trials that revolutionized the practice of medicine and cardiology.

Author/s:

H., Kela, I., Kakarlala, C., Hassan, M., Belavadi, R., Gudigopuram, S. V. R., Raguthu, C., Modi, S., Sange, I.

Angiotensin-converting-enzyme inhibitor–induced angioedema

Saige Blanchard — Tue, 18 May 2021 05:00:00 +0000

Date Added:

May 18, 2021

Journal/Publication:

CMAJ Joule Inc.

Publisher:

CMAJ Joule Inc.

Publication Date:

May 17, 2021

URL:

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Web Page

DOI (1):

10.1503/cmaj.202308

Keywords

inhibitor-induced angioedema

MeSH

Estimating Lifetime Benefits of Comprehensive Disease-Modifying Pharmacological Therapies in Patients With Heart Failure With Reduced Ejection Fraction: A Comparative Analysis of Three Randomised Controlled Trials

renin-angiotensin system

anesthesiology

A concise summary of what is known about angioedema caused by ACEIs. James W. Mold, MD, MPH

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Angiotensin-converting-enzyme (ACE) inhibitors are the leading cause of drug-induced angioedema Angiotensin-converting-enzyme (ACE) inhibitors are responsible for 20%–40% of emergency department visits for angioedema.1 The incidence of ACE inhibitor–induced angioedema is about 0.1%–0.7% in the first 5 years of treatment; symptoms occur within the first month in 10% of cases.1 Risk factors include concomitant use of dipeptidyl peptidase-4 inhibitors (e.g., sitagliptin), mammalian target of rapamycin (mTOR) inhibitors (e.g., sirolimus) and neprilysin inhibitors (e.g., sacubitril) (Appendix 1, available at www.cmaj.ca/lookup/doi/10.1503/ cmaj.202308/tab-related-content).1 Nonsteroidal anti-inflammatory drugs and statins can exacerbate angioedema, and the risk of ACE inhibitor–induced angioedema is fivefold higher in Black people.2

Author/s:

Quickfall, D., Jakubovic, B., Zipursky, J. S.

Estimating Lifetime Benefits of Comprehensive Disease-Modifying Pharmacological Therapies in Patients With Heart Failure With Reduced Ejection Fraction: A Comparative Analysis of Three Randomised Controlled Trials

John Bayhi — Tue, 26 May 2020 20:29:33 +0000

Date Added:

May 26, 2020

Journal/Publication:

Lancet

Publisher:

Elsevier Ltd

Publication Date:

May 21, 2020

Volume:

Online ahead of print

URL:

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/S0140-6736(20)30748-0

Keywords

CHF patients

pharmacologic management

PMID (1):

32446323

MeSH

Humans

Mineralocorticoid Receptor Antagonists

Sodium-Glucose Transporter 2 Inhibitors

Peptidyl-Dipeptidase A

Neprilysin

sodium-glucose transporter 2

SLC5A2 protein, human

Stroke Volume

Control Groups

Receptors, Drug

Progression-Free Survival

Receptors, Angiotensin

NR3C2 protein, human

For those of you who still initiate and manage CHF with reduced LV ejection fraction, this meta-analysis appears to support using combinations of the following five agents: 1) an ACEI or ARB, 2) a beta-blocker, 3) a mineralocorticoid receptor antagonist [MRA], 4) an angiotensin receptor–neprilysin inhibitor [ARNI], and 5) a sodium/glucose cotransporter 2 [SGLT2] inhibitor. They estimate that combined therapy could increase life expectancy for an 80-year-old 1.4 years and for a 55-year-old 6.3 years. If we are going to continue to manage these patients, it looks like we are going to have to develop specific CHF visits and protocols like those used in CHF clinics run by cardiology teams. James W. Mold, MD, MPH

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Background: Three drug classes (mineralocorticoid receptor antagonists [MRAs], angiotensin receptor-neprilysin inhibitors [ARNIs], and sodium/glucose cotransporter 2 [SGLT2] inhibitors) reduce mortality in patients with heart failure with reduced ejection fraction (HFrEF) beyond conventional therapy consisting of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and β blockers. Each class was previously studied with different background therapies and the expected treatment benefits with their combined use are not known. Here, we used data from three previously reported randomised controlled trials to estimate lifetime gains in event-free survival and overall survival with comprehensive therapy versus conventional therapy in patients with chronic HFrEF.

Methods: In this cross-trial analysis, we estimated treatment effects of comprehensive disease-modifying pharmacological therapy (ARNI, β blocker, MRA, and SGLT2 inhibitor) versus conventional therapy (ACE inhibitor or ARB and β blocker) in patients with chronic HFrEF by making indirect comparisons of three pivotal trials, EMPHASIS-HF (n=2737), PARADIGM-HF (n=8399), and DAPA-HF (n=4744). Our primary endpoint was a composite of cardiovascular death or first hospital admission for heart failure; we also assessed these endpoints individually and assessed all-cause mortality. Assuming these relative treatment effects are consistent over time, we then projected incremental long-term gains in event-free survival and overall survival with comprehensive disease-modifying therapy in the control group of the EMPHASIS-HF trial (ACE inhibitor or ARB and β blocker).

Findings: The hazard ratio (HR) for the imputed aggregate treatment effects of comprehensive disease-modifying therapy versus conventional therapy on the primary endpoint of cardiovascular death or hospital admission for heart failure was 0·38 (95% CI 0·30-0·47). HRs were also favourable for cardiovascular death alone (HR 0·50 [95% CI 0·37-0·67]), hospital admission for heart failure alone (0·32 [0·24-0·43]), and all-cause mortality (0·53 [0·40-0·70]). Treatment with comprehensive disease-modifying pharmacological therapy was estimated to afford 2·7 additional years (for an 80-year-old) to 8·3 additional years (for a 55-year-old) free from cardiovascular death or first hospital admission for heart failure and 1·4 additional years (for an 80-year-old) to 6·3 additional years (for a 55-year-old) of survival compared with conventional therapy.

Interpretation: Among patients with HFrEF, the anticipated aggregate treatment effects of early comprehensive disease-modifying pharmacological therapy are substantial and support the combination use of an ARNI, β blocker, MRA, and SGLT2 inhibitor as a new therapeutic standard.

Funding: None.

Author/s:

Vaduganathan, M., Claggett, BL, Jhund, PS, Cunningham, JW, Ferreira, JP, Zannad, F, Packer, M, Fonarow, GC, McMurray, JJV, Solomon, S.D.

Meta-Analysis Evaluating the Effects of Renin-Angiotensin-Aldosterone System Blockade on Outcomes of Heart Failure With Preserved Ejection Fraction

John Bayhi — Sat, 14 Mar 2020 20:03:18 +0000

Date Added:

March 14, 2020

Journal/Publication:

The American Journal of Cardiology

Publisher:

Elsevier Inc.

Publication Date:

January 30, 2020

URL:

Meta-Analysis Evaluating the Effects of Renin-Angiotensin-Aldosterone System Blockade on Outcomes of Heart Failure With Preserved Ejection Fraction

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/j.amjcard.2020.01.009

Keywords

RAAS Anatgonists

Identifying optimal doses of heart failure medications in men compared with women: a prospective, observational, cohort study

PMID (1):

32081366

ACEIs, ARBs, and spironolactone do not appear to reduce mortality or CHF hospitalizations in patients with CHF with preserved LV function. However, the combination of sacubitril (a neprilysin inhibitor) and valsartan may reduce CHF hospitalizations in those patients. James W. Mold, MD, MPH

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Clinical trials of renin-angiotensin-aldosterone system (RAAS) antagonists in heart failure with preserved ejection fraction (HFpEF) have suggested neutral results and treatment is focused on associated symptoms and comorbidities. MEDLINE and EMBASE were searched through October 2019 for randomized controlled studies investigating the effects of different RAAS antagonists in patients with HFpEF. The main outcomes were all-cause mortality, trial defined cardiovascular mortality, and heart failure (HF) hospitalizations. To compare different RAAS antagonists, a random-effects restricted-maximum-likelihood network meta-analysis based on a frequentist framework for indirect and mixed comparisons was used. We used p scores to rank best treatments per outcome. Our search identified 5 eligible clinical trials (PEP-CHF, perindopril; CHARM-preserved, candesartan; I-PRESERVE, irbesartan; TOPCAT, spironolactone; PARAGON-HF, sacubitril-valsartan and valsartan) enrolling a total 10,523 on RAAS antagonists and 6,259 controls. We did not identify any statistical difference in all-cause and cardiovascular mortality among RAAS antagonists and placebo. The combination of sacubitril-valsartan was associated with significantly decreased HF hospitalization risk compared with controls (odds ratio 0.73, 95% confidence interval 0.61 to 0.87) and angiotensin II receptor blockers (odds ratio 0.80, 95% confidence interval 0.71 to 0.91), without heterogeneity among studies (I2 = 0). Angiotensin receptor neprilysin inhibitor (ARNI) ranked better than other RAAS antagonists for HF hospitalizations (p value 0.9). In conclusion, RAAS antagonists do not affect mortality but the combination of sacubitril-valsartan is associated with lower HF hospitalizations in HFpEF patients.

Author/s:

Kuno, T, Ueyama, H, Fujisaki, T, Briasouli, A, Takagi, H, Briasoulis, A

Identifying optimal doses of heart failure medications in men compared with women: a prospective, observational, cohort study

Brian Desmarais — Sat, 24 Aug 2019 19:20:10 +0000

Date Added:

August 24, 2019

Journal/Publication:

The Lancet

Publication Date:

August 22, 2019

URL:

Type:

Clinical Research Results

Format:

Article

DOI (1):

https://doi.org/10.1016/S0140-6736(19)31792-1

Keywords

Cardiology

Vascular medicine

MeSH

ventricular dysfunction, left

Peptidyl-Dipeptidase A

Primary Prevention of Sudden Cardiac Death

It appears, from this analysis of a large clinical trial, that women with CHF need only half the doses of ACEs, ARBs, and beta blockers that men do to achieve the same benefits. James W. Mold, MD, MPH

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Summary

Background

Guideline-recommended doses of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), and β blockers are similar for men and women with heart failure with reduced ejection fraction (HFrEF), even though there are known sex differences in pharmacokinetics of these drugs. We hypothesised that there might be sex differences in the optimal dose of ACE inhibitors or ARBs and β blockers in patients with HFrEF.

Methods

We did a post-hoc analysis of BIOSTAT-CHF, a prospective study in 11 European countries of patients with heart failure in whom initiation and up-titration of ACE inhibitors or ARBs and β blockers was encouraged by protocol. We included only patients with left ventricular ejection fraction less than 40%, and excluded those who died within the first 3 months. Primary outcome was a composite of time to all-cause mortality or hospitalisation for heart failure. Findings were validated in ASIAN-HF, an independent cohort of 3539 men and 961 women with HFrEF.

Findings

Among 1308 men and 402 women with HFrEF from BIOSTAT-CHF, women were older (74 [12] years vs 70 [12] years, p<0·0001) and had lower bodyweights (72 [16] kg vs 85 [18] kg, p<0·0001) and heights (162 [7] cm vs 174 [8] cm, p<0·0001) than did men, although body-mass index did not differ significantly. A similar number of men and women reached guideline-recommended target doses of ACE inhibitors or ARBs (99 [25%] vs 304 [23%], p=0·61) and β blockers (57 [14%] vs 168 [13%], p=0·54). In men, the lowest hazards of death or hospitalisation for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and β blockers, but women showed approximately 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels. These sex differences were still present after adjusting for clinical covariates, including age and body surface area. In the ASIAN-HF registry, similar patterns were observed for both ACE inhibitors or ARBs and β blockers, with women having approximately 30% lower risk at 50% of the recommended doses, with no further benefit at higher dose levels.

Interpretation

This study suggests that women with HFrEF might need lower doses of ACE inhibitors or ARBs and β blockers than men, and brings into question what the true optimal medical therapy is for women versus men.

Funding

European Commission.

Author/s:

Santema, B.T., Ouwerkerk, W., Tromp, J., Sama, I.E., Ravera, A., Regitz-Zagrosek, V.

Primary Prevention of Sudden Cardiac Death

Brian Desmarais — Wed, 19 Jun 2019 00:11:44 +0000

Date Added:

June 18, 2019

Journal/Publication:

Journal of the American Medical Association

Publisher:

Journal of the American Medical Association

Publication Date:

June 13, 2019

URL:

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2019.7662

Keywords

MeSH

Mineralocorticoid Receptor Antagonists

myocardial infarction

Receptors, Angiotensin

Death, Sudden, Cardiac