Recommended Heart Failure Medications and Adverse Drug Reactions in Women

omen treated with guideline-recommended cardiovascular medications experience more adverse drug reactions (ADRs) than men. 1 These women are not only at higher risk of hospitalization but may also discontinue their medications as a result of some of the adverse reactions, thus losing the potential benefit. 2 The safety of cardiovascular medications is evaluated both in clinical trials and through postmarketing surveillance.The latter is important because many ADRs rarely occur in clinical trial populations, which are generally younger and healthier than the target population.This is especially true for women, because their systematic underrepresentation in cardiovascular trials hinders the identification of gender differences in the efficacy and safety of cardiovascular medications.The underrepresentation of women is clearly illustrated in heart failure (HF) trials.Although approximately half of all HF patients are women and ≈60% of these women die from this syndrome, on average only 30% of HF trial populations are women, 3 possibly because of their older age at HF onset.The evaluation of medication safety in women is further hampered by poor inclusion of sex-specific data in trial reports. 3The increasing prevalence of the women-dominated HF subtype with preserved ejection fraction adds impetus to this issue, as the underlying mechanism of this syndrome appears to exhibit sex differences, and therapies are lacking. 4e performed a systematic review of the literature to quantify sex-specific reporting of ADRs of HF medications.HF medications recommended by the 2016 HF guidelines from the European Society of Cardiology 4 were grouped into 5 groups: angiotensin-converting enzyme inhibitors, β-blockers, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, and ivabradine. 4Digoxin was included because of its suggested harmful effects in women. 1 First, all clinical trials cited in the European Society of Cardiology 2016 HF guidelines were extracted.Second, a systematic search of the website clinicaltrials.govwas performed on November 11, 2017.The search strategy included "heart failure" and the intervention options "ACE inhibitor," "beta blocker," "mineralocorticoid receptor antagonists," "digoxin," "ivabradine," and "angiotensin II receptor blocker."Records were excluded in the following instances:1.The study was ongoing, had been withdrawn or terminated, or had no published report available.2. The intervention was not part of 1 of the 6 drug families mentioned above.3. The primary study population consisted of patients with comorbidities such as diabetes mellitus, chronic kidney disease, pulmonary hypertension, cancer, or Chagas disease.4. The outcome of interest was not (a) the incidence of cardiovascular disease, (b) hospitalization for cardiovascular disease, or (c) (cardiovascular) mortality.The European Society of Cardiology guidelines cited 15 trials and 2 trial substudies, adding up to 17 trials in total.The systematic search identified 6 additional