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PARADIGM-HF established sacubitril/valsartan as a major evidence-based option for patients with heart failure with reduced ejection fraction (HFrEF). In this randomized double-blind trial, sacubitril/valsartan was compared with enalapril in more than 8,000 patients with symptomatic HFrEF. The trial was stopped early because the primary composite endpoint of cardiovascular death or hospitalization for heart failure was significantly lower with sacubitril/valsartan. All-cause mortality was also reduced. For internists, the practical lesson is that neurohormonal modulation in HFrEF should be viewed as a coordinated disease-modifying strategy rather than simply symptom treatment. The study helped shift routine practice toward angiotensin receptor–neprilysin inhibition in eligible patients. Clinicians still need to assess blood pressure, renal function, potassium, prior ACE-inhibitor exposure and the risk of angioedema when selecting therapy. The broader implication for APICON-style guideline-versus-reality discussions is that proven therapies may underperform in practice when initiation is delayed or doses are not optimized. Early, structured implementation of guideline-directed therapy therefore remains a central opportunity for improving outcomes.
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PARADIGM-HF established sacubitril/valsartan as a major evidence-based option for patients with heart failure with reduced ejection fraction (HFrEF). In this randomized double-blind trial, sacubitril/valsartan was compared with enalapril in more than 8,000 patients with symptomatic HFrEF. The trial was stopped early because the primary composite endpoint of cardiovascular death or hospitalization for heart failure was significantly lower with sacubitril/valsartan. All-cause mortality was also reduced. For internists, the practical lesson is that neurohormonal modulation in HFrEF should be viewed as a coordinated disease-modifying strategy rather than simply symptom treatment. The study helped shift routine practice toward angiotensin receptor–neprilysin inhibition in eligible patients. Clinicians still need to assess blood pressure, renal function, potassium, prior ACE-inhibitor exposure and the risk of angioedema when selecting therapy. The broader implication for APICON-style guideline-versus-reality discussions is that proven therapies may underperform in practice when initiation is delayed or doses are not optimized. Early, structured implementation of guideline-directed therapy therefore remains a central opportunity for improving outcomes.
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