The Efficacy of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Men and Women with Heart Failure with Reduced Ejection Fraction
[Thesis]
Wali, Muhammad Ahmer
Pilote, Louise
McGill University (Canada)
2020
79
M.Sc.
McGill University (Canada)
2020
Background. Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are essential to the treatment of heart failure with reduced ejection fraction (HFrEF). However, little data are available to determine whether their efficacy in reducing hospitalizations and mortality may differ between men and women with HFrEF. Purpose. To explore whether differences exist in the efficacy of ACEi/ARBs in HFrEF by sex. Methods. We conducted a pooled analysis of individual data from 4 randomized clinical trials: The Study of Left Ventricular Dysfunction (SOLVD) Treatment, SOLVD Prevention, Candesartan in Heart Failure: Assessment of Morbidity and Mortality (CHARM) Alternative and Added trials. The primary outcome was a composite of death or hospitalization for heart failure. Multivariable analyses were conducted using Cox proportional hazards models, adjusting for confounders, to obtain sex specific hazard ratios (HRs) and the interaction was tested by a sexby- randomized treatment term. Results. Among the 11,373 participants (19% women; mean age 61.5), women were older, with a higher prevalence of type 2 diabetes and hypertension, and a lower prevalence of ischemic heart disease than men regardless of treatment group. The ACEi/ARBs group had a lower incidence of the primary outcome compared to placebo [13.3 vs 16.6 per 100 person-year], with a similar efficacy in both men and women [adjusted-HR men 0.76 vs women 0.88, p-sex-by-drug interaction = 0.12]. However, women were more likely than men to be hospitalized for HF despite treatment [adjusted-HR men 0.65 95%CI 0.54-0.79 vs women 0.82 95%CI 0.74-0.90, p-sex-by-drug interaction = 0.09]. Conclusions. The association between ACEi/ARB and the primary outcome of death or HF hospitalization did not differ between men and women. However, women were more likely than men to have HF hospitalizations despite ACEi/ARB treatment. Future trials should include a larger enough sample size of women and men to enable sex-specific recommendations about HF drug efficacy.