Contributor: Steven Stroud

It is reported that more is more for HFrEF patients and angiotensin converting enzyme inhibitor (ACE-I) and angiotensin receptor blocker (ARB) therapy. In a recent meta-analysis of six randomized trials*, higher doses of ACE-I/ARBs were associated with a reduction in all-cause mortality. Of note, when the ARB trial (HEAAL) was taken out of the analysis, higher dose ACE-I alone did not reach statistical significance.

What about hospitalizations? Four out of the 6 trials found no difference between high dose and low dose ACE-I/ARB and all-cause or HF hospitalizations. When HF hospitalizations and all-cause mortality outcomes were combined in 3 trials, higher doses had a significant hospitalization reduction.

No surprise, potassium was elevated – higher doses of ACE-I/ARB were associated with 2x the risk of hyperkalemia. No differences in drug discontinuation, hypotension, or kidney failure were seen between high and low dose regimens, however.

In a heartbeat… Higher doses of ACE-I/ARBs when compared to lower doses are associated with a reduction in all-cause mortality in HFrEF.

*High dose vs low dose ACE-I or ARB were defined as:

Lisinopril 32.5-35 vs 2.5-5mg (ATLAS),
Enalapril 2.5-5 vs 10mg BID (NETWORK),
Enalapril 20 vs 60mg (Nanas et al),
Enalapril 5 BID vs 20mg BID (Pacher et al),
Captopril 25 BID vs 50mg BID (CHIPS).
Losartan 50 vs 150mg (HEAAL)
Study Link: Dose of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Outcomes in Heart Failure: A Meta-Analysis
Commentary and thoughts on titrating ACEI/ARB in clinical practice: Goldilocks Dilemma of Dose Titration in Heart Failure With Reduced Ejection Fraction: Too Little, Too Much, or Just Right?