Sex and gender differences in cardiovascular drug therapy

This chapter outlines sex differences in pharmacokinetics and pharmacodynamics of the most frequently used drugs in cardiovascular diseases, e.g., coronary artery disease, hypertension, heart failure. Retrospective analysis of previously published drug trials revealed marked sex differences in efficacy and adverse effects in a number of cardiovascular drugs. This includes a higher mortality among women taking digoxin for heart failure, more torsade de pointes arrhythmia in QT prolonging drugs and more cough with ACE inhibitors. Trends towards a greater benefit for women and/or female animals have been observed in some studies for endothelin receptor antagonists, the calcium channel blocker amlodipine, the ACE-inhibitor ramipril and the aldosterone antagonist eplerenone. However, reproduction of these results in independent studies and solid statistical evidence is still lacking. Some drugs require a particularly careful dose adaptation in women: the beta-blocker metoprolol, the calcium channel blocker verapamil, loop-, and thiazide diuretics. In conclusion, sex differences in pharmacokinetics and pharmacodynamics have to be taken into account for cardiovascular drug therapy in women.