Burnier Michel, Pruijm Menno, Wuerzner Gregoire
Centre Hospitalier Universitaire Vaudois, Service of Nephrology and Hypertension, Rue du Bugnon 17, 1011 Lausanne, Switzerland.
Expert Opin Drug Metab Toxicol. 2009 Aug;5(8):981-7. doi: 10.1517/17425250903085135.
In all actual clinical guidelines, dihydropyridine calcium channel blockers (CCBs) belong to the recommended first line antihypertensive drugs to treat essential hypertension. Several recent large clinical trials have confirmed their efficacy not only in lowering blood pressure but also in reducing cardiovascular morbidity and mortality in hypertensive patients with a normal or high cardiovascular risk profile. In clinical trials such as ALLHAT, VALUE or ASCOT, an amlodipine-based therapy was at least as effective, when not slightly superior, in lowering blood pressure and sometimes more effective in preventing target organ damages than blood pressure lowering strategies based on the use of diuretics, beta-blockers and blockers of the renin-angiotensin system. One of the main clinical side effects of the first and second generation CCBs including amlodipine is the development of peripheral edema. The incidence of leg edema can be markedly reduced by combining the CCB with a blocker of the renin-angiotensin system. This strategy has now led to the development of several fixed-dose combinations of amlodipine and angiotensin II receptor antagonists. Another alternative to lower the incidence of edema is to use CCBs of the third generation such as lercanidipine. Indeed, although no major clinical trials have been conducted with this compound, clinical studies have shown that lercanidipine and amlodipine have a comparable antihypertensive efficacy but with significantly less peripheral edema in patients receiving lercanidipine. In some countries, lercanidipine is now available in a single-pill association with an ACE inhibitor thereby further improving its efficacy and tolerability profile.
在所有实际临床指南中,二氢吡啶类钙通道阻滞剂(CCB)属于治疗原发性高血压的推荐一线降压药物。最近的几项大型临床试验证实了它们不仅在降低血压方面有效,而且在降低心血管风险正常或较高的高血压患者的心血管发病率和死亡率方面也有效。在ALLHAT、VALUE或ASCOT等临床试验中,基于氨氯地平的治疗在降低血压方面至少同样有效(若不是略胜一筹的话),而且在预防靶器官损害方面有时比基于使用利尿剂、β受体阻滞剂和肾素-血管紧张素系统阻滞剂的降压策略更有效。包括氨氯地平在内的第一代和第二代CCB的主要临床副作用之一是外周水肿的发生。将CCB与肾素-血管紧张素系统阻滞剂联合使用可显著降低腿部水肿的发生率。这一策略现已促成了几种氨氯地平和血管紧张素II受体拮抗剂的固定剂量复方制剂的开发。另一种降低水肿发生率的方法是使用第三代CCB,如乐卡地平。事实上,虽然尚未对该化合物进行大型临床试验,但临床研究表明,乐卡地平和氨氯地平具有相当的降压效果,但接受乐卡地平治疗的患者外周水肿明显较少。在一些国家,乐卡地平现在有与ACE抑制剂的单片复方制剂,从而进一步改善了其疗效和耐受性。