Gender-Specific Implications for Cardiovascular Medication Use in the Elderly

Abstract

Sex should be considered during the selection of cardiovascular medications and dosages of cardiovascular medications. There is mounting evidence that clinically important differences between the sexes exist in the pharmacokinetic processes that determine drug concentrations and in the pharmacodynamic processes that determine physiologic responses to pharmacologic agents. Although aging also affects these processes, aging does not eliminate the sex-related differences. The major pharmacokinetic differences between the sexes, on average, are lower weight and distribution volumes in women compared with men and lower renal drug clearance in women compared with men. Sex-related differences in hepatic drug clearance are less predictable. Pharmacodynamic responses that differ between the sexes include increased adverse cardiovascular drug effects in women compared with men (torsade de pointes arrhythmias, increased risk of hemorrhagic consequences of anticoagulation or thrombolytic therapy, electrolyte abnormalities with diuretics, myopathy with HMG Co-A reductase inhibitors, cough with ACE inhibitors, and increased incidence of thrombosis). Recommendations for optimizing cardiovascular drug therapy for the older women include individualization of drug selection to minimize the number of medications and side effects; dosage adjustment based on age, size, and sex; close monitoring for side effects; and consideration of cost and access to medications. Optimal care for the older woman with cardiovascular disease will also require investigation of cardiovascular medications in older women and of therapies for cardiovascular diseases that are more common in women than men.A lthough there is increasing evidence to support invasive and acute cardiac interventions in the elderly, most of therapeutic cardiac interventions for the elderly are pharmacologic. It is therefore important to periodically review evolving clinical concepts for drug selection and modifications for patient subgroups. Despite the underrepresentation of women in clinical investigations and cardiovascular clinical trials, 1-3 it is becoming clear that the response to medications may differ between the sexes. One striking example of the impact of sex differences in drug responses is highlighted by drug withdrawals from the US market during the period from 1997 until early 2001. Of the 10 drugs removed from marketing during that period, 4 were prescribed more frequently to women (for weight loss [dexfenfluramine as Redux and dexfenfluramine as Pondimin], for diabetes [troglitazone as Rezulin], and for inflammatory disease (Lotronex)] and 4 had higher rates of toxicity in women but were prescribed in equal rates to men and women (for hypertension [Mibefradil as Posicor] antihistamines [terfenadine as Seldane or Hismanal], heartburn [cisapride as Propulsid]. Two were prescribed in equal rates and had equal toxicity in men and women (grepafloxacin, an oral fluroquinolone antibiotic, as Raxar; and for pain relief, bromfenac as Duract). In later 2001, cerivastatin...

Antihypertensive Medication Prescribing in 27,822 Elderly Canadians With Diabetes Over the Past Decade

“…Although the teratogenic risks with ACE inhibitors are well known, this is clearly not a concern in this cohort of elderly patients. However, some authors have raised concerns about the safety of ACE inhibitors in elderly women (17). Indeed, we did find that although women were more likely to continue treatment with other antihypertensive drugs than men, they were significantly more likely to discontinue ACE inhibitor therapy than men (49 vs. 41%), a finding consistent with that in other studies (18 -23).…”

ACCF/AHA 2011 Health Policy Statement on Therapeutic Interchange and Substitution

“…Pharmacodynamic differences exist for women related to lower weight, lower volume of distribution, and lower renal drug clearance in women. 84 In addition, sex-based prolongation of the QT interval warrants caution in the prescription of cardiovascular and noncardiovascular drugs that may potentially prolong the QT interval and lead to serious arrhythmias. Other cardiovascular drug-related adverse effects more common in women include hemorrhagic complications of anticoagulants and antiplatelet drugs, electrolyte abnormalities with diuretics, myopathy with statins, and cough with ACE inhibitors.…”

“…Other cardiovascular drug-related adverse effects more common in women include hemorrhagic complications of anticoagulants and antiplatelet drugs, electrolyte abnormalities with diuretics, myopathy with statins, and cough with ACE inhibitors. 84 A specific example relates to the use of digoxin. In a post hoc analysis of the Digitalis Investigation Group (DIG) trial, there was a suggestion that digoxin use was associated with an increased risk of mortality in women with heart failure and a left ventricular ejection fraction Յ45% compared with men.…”

The Significance of the Furosemide Test for Predicting Ascites Control by Diuretics in Cirrhotics: A Comparison with Volume Expansion and Octreotide Infusion

“…Approximately 85% of patients in the study by Spahr et al were men, but three of the four women included belonged to the ascites-responsive group [3]; thus, the conclusions that can be drawn from this study basically apply to male patients. Electrolyte abnormalities following diuretic use occur more commonly in women [15], likely because of males' greater body water (which means a greater volume of distribution). Therefore, the original FIN test protocol may be modified by either administering furosemide at a dose adjusted for body weight, while maintaining a single cutoff value to analyze the results, or using two different cutoff values for males and females.…”