Quality not quantity. Why not both? It is established that sacubitril/valsartan is superior to enalapril (or dose-equivalent ACE-I) when it comes to mortality and morbidity in HFrEF. But what about quality of life (QoL)? Patients enrolled in PARADIGM-HF had increased quality of life when randomized to sacubitril/valsartan.
In the 8399 HFrEF patients of the PARADIGM-HF study, 7623 patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) at multiple time points. This well-validated tool measures health related quality of life. The KCCQ assessment reflected improved in quality of life for patients on sacubitril/valsartan compared to dose-equivalent ACE-I. Worth mentioning, the first KCCQ was administered 5-10 weeks after randomization, following the “run-in” period after which patients were randomized in a blinded fashion to either enalapril BID or sacubitril/valsartan.
Changes in the clinical summary score (KCCQ-CS) and overall score (KCCQ-OS) were assessed between randomization and 8 months. In a multivariable model, randomization to sacubitril/valsartan remained an independent predictor of QoL improvement.
QoL scores were high in this study. The higher scores may reflect the unique study schedule of the PARADIGM-HF in that the first KCCQ survey was given following the run-in phase. Further, it is known that health related QoL perceptions can improve in the setting of a clinical trial.
In a heartbeat…
HFrEF patients treated with Sacubitril/Valsartan reported higher QoL score compared to patients randomized to enalapril.
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.
*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)
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.
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?