Written by Peter Liu
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Even in patients who developed hypotension, sacubitril/valsartan likely conferred improvements to heart failure outcomes for patients in the PARADIGM trial.
Synopsis
This post-hoc analysis of the PARADIGM-HF trial investigated the impact of asymptomatic and symptomatic hypotension in heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan versus enalapril. Using time-updated Cox models, the study found both hypotension types were linked to increased cardiovascular events and mortality, with hazard ratios (HR) for sacubitril/valsartan vs. enalapril (ACEI) being 0.87 (asymptomatic) and 0.51 (symptomatic). However, sacubitril/valsartan maintained or enhanced its benefits even in hypotension cases. Key limitations include post-hoc design and reliance on trial-reported hypotension. Clinicians should cautiously manage hypotension with a goal of continuing sacubitril/valsartan as able, as its protective effects persist for these patients. (AI-generated)
Titrate sacubitril/valsartan to the maximum tolerated dose despite side effects
Hypotension is generally the most common reason why sacubitril/valsartan is not initiated or is stopped in patients with HFrEF. This post-hoc analysis clearly illustrates why: patients on sacubitril/valsartan have greater decreases in blood pressure than patients on an ACEI alone. However, this subgroup analysis of patients who developed symptomatic or asymptomatic hypotension on follow-up in the PARADIGM trial strongly suggests that the benefits of angiotensin receptor neprilysin inhibitor (ARNI) therapy remain despite the side effect of hypotension. Since it’s a post-hoc analysis, interpretation of the results is challenging. However, the results generally support the protocol of the PARADIGM trial, which was to reduce the study drug to the highest-tolerated dose when the pre-specified drug dosage could not be achieved.
Source
Asymptomatic vs Symptomatic Hypotension With Sacubitril/Valsartan in Heart Failure and Reduced Ejection Fraction in PARADIGM-HF. J Am Coll Cardiol. 2024 Oct 29;84(18):1685-1700. doi: 10.1016/j.jacc.2024.08.012. Epub 2024 Sep 25. PMID: 39320292
