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

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.

Pharmacologic Management of Newly Detected Atrial Fibrillation

Tracy Ashby — Fri, 30 Nov 2018 06:00:00 +0000

Date Added:

November 30, 2018

Publisher:

American Academy of Family Physicians

Publication Date:

April 1, 2017

Type:

Meta-analyses, Reviews, and Guidelines, Meta-analyses, Reviews, and Guidelines

Format:

Article

Keywords

atrial fibrillation

pharmacologic management

MeSH

atrial fibrillation

retrospective studies

prospective studies

This is an evidence-based set of recommendations from the AAFP for pharmacologic management of patients with atrial fibnrillation.

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Purpose
To review the evidence and provide clinical recommendations for the pharmacologic management of atrial fibrillation.

Methods
This guideline is based on two systematic reviews of published randomized controlled trials (RCTs) and prospective and retrospective observational studies from 2000 to 2012. An updated literature search was performed to identify new studies from 2012 to December 31, 2015. The target audience for the guideline includes all primary care clinicians, and the target patient population includes adults who have nonvalvular atrial fibrillation that is not due to a reversible cause. This guideline was developed using a modified version of GRADE to evaluate the quality of the evidence and make recommendations based on the balance of benefits and harms.

Author/s:

Frost, Jennifer L., Campos-Outcalt, Doug, Hoelting, David, LeFevre, Michael, Lin, Kenneth W., Vaughan, William, Bird, Melanie D.