The Anti-Ischemic Effect of Metoprolol in Patients with Chronic Angina Pectoris Is Gender-Specific

Abstract

Several gender-specific differences in cardiovascular diseases are known and pharmacokinetics of β-blockers shows relevant sex-specific differences. The plasma levels of metoprolol, for example, are higher in women compared to men. However, randomized studies have shown that metoprolol has little or no greater reduction in the mortality of women following myocardial infarction. We tested the hypothesis that metoprolol might have significant gender-specific effects in patients with chronic angina pectoris. Body weight of women was slightly (–9%) less than that of men and the daily dose of metoprolol was similar in both groups. Thus, according to pharmacokinetics women should have obtained higher plasma levels of this drug and the ensuing pharmacologic effects of metoprolol should have been greater. Our results do not confirm this assumption. Metoprolol reduced the frequency of angina episodes and the consumption of nitroglycerin tablets to a similar extent in both sexes. However, the pretreatment hemodynamic profiles confirmed the existence of gender-specific differences: women had significantly higher heart rate and blood pressure both at rest and during exercise. Since both groups were comparable in age, comorbidities, and medications, the existing difference is likely to be due to gender-specificity. The hemodynamic differences persisted during therapy with metoprolol: resting heart rate, blood pressure and rate pressure product were reduced to a greater extent in men. During cycloergometry, there was a slight difference in the time of onset of ST depression and time of onset of angina, which were slightly higher in men, but probably because of the limited number of cases, the difference between men and women did not reach significance. On the other hand, with metoprolol the duration of exercise and, in parallel, the number of metabolic equivalents was significantly greater in males than in females. Thus in spite of a presumed greater plasma concentration of metoprolol in women, we found a significant difference in anti-ischemic effect in favor of men. We conclude that metoprolol might exert a significantly greater therapeutic effect on stress-induced angina pectoris in men than in women and this difference should be taken into account when prescribing this β-blocker.