Sex differences in cardiovascular drug‐induced adverse reactions causing hospital admissions

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Cardiovascular disease, disease outcome, drug treatment and drug response differ between men and women. WHAT THIS STUDY ADDS• Adverse drug reactions attributed to cardiovascular drugs that require hospital admission show differences between men and women, even after taking into account age and the total number of drug prescriptions. AIMSCardiovascular disease in women is often underestimated. The effects of cardiovascular drugs differ between the sexes because of pharmacokinetic and pharmacodynamic differences. Adverse drug reactions (ADRs) within these drug classes may have serious consequences, leading to hospital admission. We aimed to study differences between men and women in hospital admissions for ADRs due to cardiovascular drugs. METHODSWe conducted a nationwide study of all hospital admissions between 2000 and 2005 with data from the Dutch National Medical Register. Relative risks were calculated of hospital admissions due to ADRs to the different cardiovascular drug groups for women compared with men. By an ecological design, risks were adjusted for the total number of Dutch inhabitants and the total number of prescriptions. RESULTSIn total, 14 207 of the hospital admissions (34% of all ADR-related admissions) were attributed to cardiovascular drugs [7690 in women (54%; 95% confidence interval 53-55%)].'Anticoagulants and salicylates' (n = 8988), 'high-and low-ceiling diuretics' (n = 2242) and 'cardiotonic glycosides' (n = 932) were responsible for the majority of the ADR-related hospital admissions. The most pronounced sex differences were seen in users of low-ceiling diuretics (relative risk 4.02; 95% confidence interval 3.12-5.19), cardiotonic glycosides (relative risk 2.38; 95% confidence interval 2.06-2.74), high-ceiling diuretics (relative risk 2.10; 95% confidence interval 1.91-2.32) and coronary vasodilators (relative risk 0.77; 95% confidence interval 0.65-0.91). CONCLUSIONSClear sex differences exist in ADRs requiring hospital admission for different cardiovascular drug groups. Sex differences should be taken into account in the prescription and evaluation of drugs.

A systematic review of hospitalization resulting from medicine‐related problems in adult patients

“…The reported median prevalence rates for MRPs were similar in retrospective ( n = 5) and prospective studies ( n = 13; Table ). The five retrospective studies showed a median prevalence rate of 12.6% (IQR, 10.8–13.3%).…”

“…Old age and polypharmacy were the main risk factors reported in most studies. Furthermore, some studies reported gender as a risk factor; females were more likely to develop MRPs . Fewer studies reported depression (three studies) , education (two studies) , cohabitation (two studies) and immobilization (one study) as risk factors.…”

Adverse drug reactions to anticoagulants in Spain: analysis of the Spanish National Hospital Discharge Data (2010–2013)

“…During the 4-year study period, we observed an increase in the incidence of anticoagulant-related hospitalisations, which was greater in men than in women for all age groups. These data are consistent with those reported by Rodenburg et al ,32 whose objective was to identify possible differences in ADRs to cardiovascular drugs between men and women over a 6-year period. The authors found that admissions for ADRs to anticoagulants and salicylates were more common in men (RR 0.94; 95% CI 0.90 to 0.98).…”

Metoprolol Dose Equivalence in Adult Men and Women Based on Gender Differences: Pharmacokinetic Modeling and Simulations

“…Further, the same increase in cardiac output increases renal artery blood flow, and the clearance of xenobiotics is also an influential factor. Overall, despite variables that account for gender differences in the pharmacokinetics of metoprolol, the findings in this article show a 50% dose reduction results in equivalent metoprolol exposure to men and may help to explain and remedy the findings from studies reporting women who experience greater adverse effects related to cardiovascular medications than men [6,15,16]. With the hopes of precision medicine, dose adjustments based on gender, genotype, or both will become increasingly sought after by clinicians in medical practice and patients being administered these medications.…”