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I have read with great interest the article by Rodrigues et al. and the editorial comment about the use of sacubitril/valsartan in patients with systolic heart failure, and I share the same concerns about the target population of this drug. In an epidemiological study in Lima, Peru, of 1075 patients with heart failure, 46% had normal ejection fraction and only 39% had heart failure with reduced ejection fraction (≤40%) (HFrEF). Overall, 30% of patients with heart failure also had chronic renal disease, leaving only 20-25% of patients eligible for treatment with sacubitril/valsartan. In a high-altitude population like Huancayo (3250 meters above sea level), the profile of heart failure patients is even more dissimilar, with 89.9% of patients having a normal ejection fraction, while around 25% of individuals have heart failure and chronic lung disease, leaving only 2.2% of patients eligible for this drug. Another concern is about how many patients will tolerate the target dose of 97/103 mg, because as Antol et al. pointed out, only 17.4% of patients in their retrospective study could achieve this goal. Despite this result, the hospitalization rate, symptoms and weight gain decreased in those who were treated with sacubitril/valsartan. In search of an answer about the profile of patients who will benefit from sacubitril/valsartan, the PARAGON-HF trial is currently under way and will try to determine if the drug is useful for patients with preserved ejection fraction (HFpEF). Caution must be exercised because drugs used for HFrEF that showed promise for HFpEF did not improve prognosis for this condition when tested in large clinical trials. As Ricardo Fontes-Carvalho pointed out in his editorial comment, we must recognize that sacubitril/valsartan is an important advance for heart failure therapy, even though its benefits have not been proved in a broader, real-world heart failure population. Taking this into account, new drugs are needed for patients with heart failure who have chronic renal or pulmonary conditions or have normal or intermediate ejection fraction.

The PARADIGM-HF population may be very different from real-world heart failure patients