Cocco Giuseppe, Chu David
Cardiology Office, Rheinfelden, Switzerland.
Cardiology. 2006;106(3):147-53. doi: 10.1159/000092769. Epub 2006 Apr 21.
Several gender-specific differences in cardiovascular diseases are known and pharmacokinetics of beta-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 beta-blocker.
心血管疾病存在一些性别特异性差异，β受体阻滞剂的药代动力学也显示出相关的性别特异性差异。例如，与男性相比，女性体内美托洛尔的血浆水平更高。然而，随机研究表明，心肌梗死后美托洛尔对女性死亡率的降低作用很小或没有更大的降低作用。我们检验了这样一个假设，即美托洛尔可能对慢性心绞痛患者有显著的性别特异性影响。女性的体重略低于男性（-9%），两组美托洛尔的每日剂量相似。因此，根据药代动力学，女性应该获得更高的该药物血浆水平，随之而来的美托洛尔药理作用应该更大。我们的结果并未证实这一假设。美托洛尔在降低男女心绞痛发作频率和硝酸甘油片消耗量方面程度相似。然而，治疗前的血流动力学特征证实了性别特异性差异的存在：女性在静息和运动时的心率和血压均显著更高。由于两组在年龄、合并症和用药方面具有可比性，现有的差异可能归因于性别特异性。在美托洛尔治疗期间，血流动力学差异依然存在：男性静息心率、血压和心率血压乘积降低的程度更大。在进行症状限制性运动试验时，ST段压低发作时间和心绞痛发作时间存在轻微差异，男性的这些时间略高，但可能由于病例数量有限，男女之间的差异未达到显著水平。另一方面，使用美托洛尔时，男性的运动持续时间以及相应的代谢当量显著高于女性。因此，尽管推测女性体内美托洛尔的血浆浓度更高，但我们发现抗缺血作用存在显著差异，男性更具优势。我们得出结论，美托洛尔对男性应激性心绞痛的治疗效果可能比对女性显著更大，在开具这种β受体阻滞剂处方时应考虑到这种差异。
