Cammarano Carolyn, Silva Matthew, Comee Morgan, Donovan Jennifer L, Malloy Michael J
Department of Pharmacy Practice, MCPHS University, Worcester, Massachusetts.
Department of Pharmacy Practice, MCPHS University, Worcester, Massachusetts.
Clin Ther. 2016 Feb;38(2):387-95. doi: 10.1016/j.clinthera.2015.12.018. Epub 2016 Feb 1.
Ivabradine is a novel If-channel antagonist that controls heart rate and may be helpful in treating patients with left ventricular dysfunction (LVD) who are unable to tolerate β-blockers or achieve a heart rate of 70 beats/min with standard therapy. Three landmark trials were used for the approval of ivabradine in the United States. These trials tested ivabradine in addition to a standard of care (including β-blockers) in patients with stable coronary artery disease (CAD) and found modest benefit in those with established LVD unable to tolerate β-blockers. The goal of this review was to pool data from ivabradine studies in all patients with stable CAD to compare cardiovascular and safety-related outcomes.
Three randomized, double-blind, placebo-controlled trials of ivabradine added to standard treatment (including β-blockers) in patients with stable CAD with and without LVD were reviewed for effects on mortality, cardiovascular outcomes, and adverse events. Data were independently abstracted by 2 reviewers; the Oxford quality scoring system was used to evaluate randomization, blinding, withdrawals, and dropouts; and a Mantel-Haenszel random effects pairwise meta-analysis was used to combine data into odds ratios.
The initial search identified 116 trials; 3 of these trials, representing 36,524 patients with stable CAD, met inclusion criteria. According to the pooled results, ivabradine did not consistently reduce all-cause mortality (odds ratio [OR], 1.00 [95% CI, 0.91-1.11]; P = 0.98], cardiovascular death (OR, 1.02 [95% CI, 0.91-1.15]; P = 0.74), or hospitalization for worsening or new onset heart-failure in patients with stable CAD (OR, 0.94 [95% CI, 0.71-1.25]; P = 0.69). Ivabradine did not increase serious adverse drug reactions (OR, 0.99 [95% CI, 0.88-1.13]; P = 0.93) or cardiac disorders (OR, 1.03 [95% CI, 0.87-1.22]; P = 0.74). However, it was associated with drug-specific effects, including new-onset atrial fibrillation (OR, 1.35 [95% CI, 1.19-1.53]; P < 0.001], bradycardia (OR, 6.54 [95% CI, 3.30-12.9]; P < 0.001), phosphenes (OR, 7.77 [95% CI, 4.12-14.63]; P < 0.001), and blurry vision (OR, 3.07 [95% CI, 2.18-4.32]; P < 0.001).
Unselective use of ivabradine in patients with stable CAD is not supported by evidence and can be associated with new-onset atrial fibrillation, bradycardia, and drug-related nuisance adverse events.
伊伐布雷定是一种新型的If通道拮抗剂，可控制心率，可能有助于治疗无法耐受β受体阻滞剂或采用标准治疗后心率仍无法达到70次/分钟的左心室功能不全（LVD）患者。在美国，三项具有里程碑意义的试验被用于批准伊伐布雷定。这些试验在稳定型冠状动脉疾病（CAD）患者中，除了采用包括β受体阻滞剂在内的标准治疗外，还对伊伐布雷定进行了测试，结果发现它对那些已确诊LVD且无法耐受β受体阻滞剂的患者有一定益处。本综述的目的是汇总伊伐布雷定在所有稳定型CAD患者研究中的数据，以比较心血管和安全性相关结局。
回顾了三项在有或无LVD的稳定型CAD患者中，将伊伐布雷定添加到标准治疗（包括β受体阻滞剂）中的随机、双盲、安慰剂对照试验，以评估其对死亡率、心血管结局和不良事件的影响。数据由两名审阅者独立提取；采用牛津质量评分系统评估随机化、盲法、撤药和失访情况；并使用Mantel-Haenszel随机效应成对荟萃分析将数据合并为比值比。
初步检索识别出116项试验；其中3项试验，代表36524例稳定型CAD患者，符合纳入标准。根据汇总结果，伊伐布雷定并不能持续降低全因死亡率（比值比[OR]，1.00[95%置信区间，0.91-1.11]；P = 0.98）、心血管死亡（OR，1.02[95%置信区间，0.91-1.15]；P = 0.74），或稳定型CAD患者因心力衰竭恶化或新发而住院的情况（OR，0.94[95%置信区间，0.71-1.25]；P = 0.69）。伊伐布雷定并未增加严重药物不良反应（OR，0.99[95%置信区间，0.88-1.13]；P = 0.93）或心脏疾病（OR，1.03[95%置信区间，0.87-1.22]；P = 0.74）。然而，它与特定药物效应相关，包括新发房颤（OR，1.35[95%置信区间，1.19-1.53]；P < 0.001）、心动过缓（OR，6.54[95%置信区间，3.30-12.9]；P < 0.001）、光幻视（OR，7.77[95%置信区间，4.12-14.63]；P < 0.001）和视物模糊（OR，3.07[95%置信区间，2.18-4.32]；P < 0.001）。
在稳定型CAD患者中无差别地使用伊伐布雷定缺乏证据支持，且可能与新发房颤、心动过缓及药物相关的烦扰性不良事件有关。
