Van Bortel Luc M, Fici Francesco, Mascagni Flavio
Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
Am J Cardiovasc Drugs. 2008;8(1):35-44. doi: 10.2165/00129784-200808010-00005.
Lowering BP to normal levels without quality of life deterioration is the most important means of reducing cardiovascular risk. Recent studies have challenged the position of beta-adrenoceptor antagonists (beta-blockers) as first-line antihypertensive drugs. Nebivolol is a third-generation, highly selective beta(1)-blocker that causes vasodilation through nitric oxide (NO) release. This meta-analysis investigates the efficacy and tolerability of nebivolol compared with other antihypertensive drugs and placebo in patients with hypertension.
Twelve randomized controlled studies were included in which nebivolol 5 mg once daily was compared with the recommended clinical doses of other antihypertensive drugs (n = 9), placebo (n = 2), and both (n = 1). The clinical studies were selected after a MEDLINE search up to 2007 using the key words 'nebivolol' and 'hypertension.'
Antihypertensive response rates (the percentage of patients achieving target BP levels or a defined DBP reduction) were higher with nebivolol than with ACE inhibitors (odds ratio [OR] 1.92; p = 0.001) and all antihypertensive drugs combined (OR 1.41; p = 0.001) and similar to beta-blockers, calcium channel antagonists (CCAs) and the angiotensin receptor antagonist (ARA) losartan. Moreover, a higher percentage of patients receiving nebivolol achieved target BP levels compared with patients treated with losartan (OR 1.98; p = 0.004), CCAs (OR 1.44; p = 0.024), and all antihypertensive drugs combined (OR 1.35; p = 0.012). The percentage of patients experiencing adverse events did not differ between nebivolol and placebo; adverse event rates were significantly lower with nebivolol than losartan (OR 0.52; p = 0.016), other beta-blockers (OR 0.56; p = 0.007), nifedipine (OR 0.49; p < 0.001), and all antihypertensive drugs combined (OR 0.59; p < 0.001).
Results of previous pharmacokinetic studies suggest that nebivolol 5 mg may not conform completely to the definition of a classic beta-blocker demonstrating additional antihypertensive effect due to endothelial NO release-mediated vasodilation. This meta-analysis showed that nebivolol 5 mg achieved similar or better rates of treatment response and BP normalization than other drug classes and other antihypertensive drugs combined, with similar tolerability to placebo and significantly better tolerability than losartan, CCAs, other beta-blockers, and all antihypertensive drugs combined. Although not definitive, this meta-analysis suggests that nebivolol 5 mg is likely to have advantages over existing antihypertensives and may have a role in the first-line treatment of hypertension.
在不降低生活质量的前提下将血压降至正常水平是降低心血管风险的最重要手段。近期研究对β-肾上腺素能受体拮抗剂(β受体阻滞剂)作为一线降压药物的地位提出了挑战。奈必洛尔是第三代高选择性β1受体阻滞剂,可通过释放一氧化氮(NO)引起血管舒张。本荟萃分析旨在研究奈必洛尔与其他降压药物及安慰剂相比,在高血压患者中的疗效和耐受性。
纳入12项随机对照研究,其中将每日一次服用5mg奈必洛尔与其他降压药物的推荐临床剂量(n = 9)、安慰剂(n = 2)以及两者联合使用(n = 1)进行比较。通过检索截至2007年的MEDLINE数据库,使用关键词“奈必洛尔”和“高血压”筛选出这些临床研究。
奈必洛尔的降压有效率(达到目标血压水平或舒张压明确降低的患者百分比)高于ACE抑制剂(优势比[OR] 1.92;p = 0.001)以及所有降压药物联合使用时(OR 1.41;p = 0.001),与β受体阻滞剂、钙通道拮抗剂(CCAs)和血管紧张素受体拮抗剂(ARA)氯沙坦相似。此外,与接受氯沙坦治疗的患者相比,接受奈必洛尔治疗的患者达到目标血压水平的百分比更高(OR 1.98;p = 0.004),与CCAs相比(OR 1.44;p = 0.024),与所有降压药物联合使用时相比(OR 1.35;p = 0.012)。奈必洛尔组和安慰剂组患者发生不良事件的百分比无差异;奈必洛尔的不良事件发生率显著低于氯沙坦(OR 0.52;p = 0.016)、其他β受体阻滞剂(OR 0.56;p = 0. 007)、硝苯地平(OR 0.49;p < 0.001)以及所有降压药物联合使用时(OR 0.59;p < 0.001)。
既往药代动力学研究结果表明,5mg奈必洛尔可能不完全符合经典β受体阻滞剂的定义,因其可通过内皮NO释放介导的血管舒张发挥额外的降压作用。本荟萃分析表明,5mg奈必洛尔的治疗反应率和血压正常化率与其他药物类别及所有降压药物联合使用时相似或更佳,其耐受性与安慰剂相似,且显著优于氯沙坦、CCAs、其他β受体阻滞剂以及所有降压药物联合使用时。尽管并非定论,但本荟萃分析表明,5mg奈必洛尔可能优于现有降压药物,在高血压一线治疗中可能发挥作用。