Epstein Benjamin J, Vogel Katherine, Palmer Biff F
Department of Pharmacy Practice and Division of Internal Medicine, Colleges of Pharmacy and Medicine, University of Florida, Gainesville, FL 32610-0486, USA.
Drugs. 2007;67(9):1309-27. doi: 10.2165/00003495-200767090-00005.
Dihydropyridine calcium channel antagonists have been maligned in recent years because of concerns regarding their cardiovascular and overall safety profile. Specifically, it was widely publicised in the mid-1990s that these agents might increase the risk of myocardial infarction, gastrointestinal bleeding and cancer. Data linking these agents with increased cardiovascular risk were based on nonrandomised studies and implicated short-acting, immediate-release agents. These results were inappropriately extrapolated to longer-acting compounds, extended-release products, and to the non-dihydropyridine class. Fortunately, recent studies have vindicated the class from safety allegations. These studies are reviewed herein. Compared with both diuretics and contemporary agents, amlodipine decreases cardiovascular events to a similar or greater extent without evidence for increased coronary heart disease, gastrointestinal bleeding or cancer. Despite these data, initial concerns have had lasting repercussions, as the use of dihydropyridine calcium channel antagonists appears to lag behind what emerging data would support. Dihydropyridine calcium channel antagonists have several noteworthy attributes that merit consideration in the management of hypertension. The blood pressure response to this class of drugs is less contingent on patient factors such as age and race compared with other antihypertensive agents (e.g. ACE inhibitors). Dihydropyridine calcium channel antagonists may exert effects that protect against stroke that are independent of their blood pressure-lowering mechanism. Unlike diuretics and beta-adrenoceptor anatagonists (beta-blockers), dihydropyridine calcium channel antagonists are lipid neutral and do not disturb glucose homeostasis. Dihydropyridine calcium channel antagonists demonstrate a highly desirable profile when administered as part of combination therapy. Combinations of dihydropyridine calcium channel antagonists and ACE inhibitors or angiotensin receptor antagonists display additive efficacy and an enviable adverse-effect profile. Collectively, the cardiovascular benefit, metabolic neutrality and homogeneous blood pressure response illuminated in recent studies, and reviewed here, represent a reaffirmation of the benefit of long-acting dihydropyridine calcium channel antagonists and should serve to help reinforce the critical importance of these agents in the therapeutic armamentarium against cardiovascular disease.
近年来，二氢吡啶类钙通道拮抗剂一直备受诋毁，原因是人们对其心血管安全性及整体安全性存在担忧。具体而言，在20世纪90年代中期广泛宣传称，这些药物可能会增加心肌梗死、胃肠道出血和癌症的风险。将这些药物与心血管风险增加联系起来的数据基于非随机研究，且涉及短效、速释制剂。这些结果被不恰当地外推至长效化合物、缓释产品以及非二氢吡啶类药物。幸运的是，近期研究已为该类药物洗刷了安全方面的指控。本文对这些研究进行综述。与利尿剂和当代药物相比，氨氯地平在降低心血管事件方面的程度相似或更大，且没有证据表明会增加冠心病、胃肠道出血或癌症的风险。尽管有这些数据，但最初的担忧仍产生了持久影响，因为二氢吡啶类钙通道拮抗剂的使用似乎落后于新出现数据所支持的情况。二氢吡啶类钙通道拮抗剂具有几个值得关注的特性，在高血压管理中值得考虑。与其他抗高血压药物（如血管紧张素转换酶抑制剂）相比，这类药物对血压的反应较少依赖于年龄和种族等患者因素。二氢吡啶类钙通道拮抗剂可能发挥独立于其降压机制的预防中风的作用。与利尿剂和β-肾上腺素能受体拮抗剂（β受体阻滞剂）不同，二氢吡啶类钙通道拮抗剂对脂质无影响，也不会干扰葡萄糖稳态。当作为联合治疗的一部分给药时，二氢吡啶类钙通道拮抗剂显示出非常理想的特性。二氢吡啶类钙通道拮抗剂与血管紧张素转换酶抑制剂或血管紧张素受体拮抗剂的联合使用具有相加疗效，且不良反应谱令人满意。总体而言，近期研究中阐明并在此综述的心血管益处、代谢中性以及均匀的血压反应，再次证实了长效二氢吡啶类钙通道拮抗剂的益处，并应有助于强化这些药物在对抗心血管疾病治疗手段中的关键重要性。
