Sacubitril/Valsartan in heart failure. A critical review of the Paradigm-HF trial
The PARADIGM-HF trial was published in September 2014. The combination of sacubitril plus valsartan (SAC/VAL) at a fixed dose was demonstrated to be superior to enalapril in reducing the risk of death or admission for heart failure (HF).
Based on the results of this trial, SAC/VAL was approved for the treatment of chronic heart failure (CHF) in July 2015 (USA) and November 2015 (EU). This paper reviews the design of the PARADIGM-HF trial, the results obtained for efficacy and safety, and the trial’s most relevant limitations.
Should SAC/VAL replace standard treatment with angiotensin-converting-enzyme inhibitors (ACE inhibitor) or angiotensin-II-receptor blockers (ARB) as recommended by the PARADIGM-HF investigators? Overestimation of the benefits and underestimation of the harms associated with SAC/VAL limit the external validity of the efficacy and safety results of PARADIGM-HF. Limitations of the study include a stronger inhibition of the Renin-Angiotensin-Aldosterone System (RAAS) in the SAC/VAL arm, early trial stopping for benefit, and the use of multiple strict inclusion and exclusion criteria. Variables such as age, sex, functional class and comorbidities of patients in the double-blind trial do not match those of standard patients with CHF who receive ambulatory or hospital-based treatment in real life. SAC/VAL should only be used in patients with a very specific profile, similar to those for whom efficacy and safety have been demonstrated. SAC/ VAL cannot be considered a first-choice therapy for CHF.
- JUAN SIMÓ. Family Physician. Navarre Health Service, Spain