Purpose: To investigate why so few women are eligible for treatment with sacubitril-valsartan.
Methods: We applied the PARADIGM-HF main inclusion and exclusion criteria to a community based heart failure population in northern Sweden and statistically compared the women and men cohort.
Results: Of the whole heart failure population of 1924 patients, 43% were women. However, in patients with ejection fraction (EF) = 35%, only 28% were women and after applying the PARADIGM-HF main inclusion and exclusion criteria, only 15 women would have been eligible for inclusion in the trial, corresponding to 16% of the eligible patients. The most common reason for not meeting the criteria was failure to reach target dose of ACE inhibitor or ARB. In patients with heart failure and reduced ejection fraction (HFrEF) women were older (81.1 ± 10.6 vs. 74.8 ± 11.5, p < 0.001) had lower body weight (69.4 ± 17.2 vs. 85.3 ± 17.5, p < 0.001), lower estimated glomerular filtration rate (48.5 ± 26.2 vs. 70.1 ± 34.5, p < 0.001), and higher systolic blood pressure (127.4 ± 19.0 vs. 122.5 ± 18.5, p = 0.018). Besides fewer women reached target dose of ACE inhibitor or ARB (26% vs. 43%, p = 0.001), heart failure therapy did not differ between the genders except that women were more often prescribed loop-diuretics and less likely to have an implantable cardioverter defibrillator or cardiac resynchronization therapy defibrillator.
Conclusions: Fewer women suffer from HFrEF and tolerate target doses of ACE inhibitor or ARB, and are consequently less eligible for sacubitril-valsartan compared to men. Women probably tolerate target doses to a lesser degree owing to being older, having lower body weight (less volume of distribution), and lower renal function. Though, we cannot exclude that women are treated differently because of gender bias. This study shows that target doses as entry criteria in clinical trials favors men, which is important to consider in future study design to gain better knowledge of how to offer women with heart failure the best available care. Since current guideline recommended target doses are mainly based on men, we suggest more individualized doses to women with heart failure.