Chair of Internal Medicine, Almazov National Medical Research Centre, Akkuratova Str., 2, St Petersburg, Russian Federation.
Servier Medical Affairs, Suresnes, France.
Adv Ther. 2022 Sep;39(9):4189-4204. doi: 10.1007/s12325-022-02222-1. Epub 2022 Jul 17.
Beta-blockers are recommended by the European Society of Cardiology as first-line antianginal therapy for reducing heart rate (HR) and symptoms in patients with chronic coronary syndrome, despite a lack of data showing superiority to other antianginal agents. Most patients with angina pectoris require combination therapy to manage symptoms, with a second-line agent chosen to manage the predominant cardiovascular problem. Ivabradine, a selective sinus node I channel inhibitor shown to reduce HR and protect against anginal symptoms, has previously demonstrated noninferior anti-ischaemic and antianginal efficacy to beta-blockers.
This systematic review and meta-analysis assessed the efficacy and safety of ivabradine in patients with stable angina pectoris who remained symptomatic despite receiving beta-blockers. Keyword searches of PubMed, The Cochrane Central Library Register, ClinicalTrials.gov, The World Health Organization International Clinical Trials Registry Platform (ICTRP) and Google Scholar identified studies comparing ivabradine plus beta-blockers with placebo or other first- or second-line antianginal agents in patients with stable angina pectoris. No date limits or language restrictions were applied. Outcomes were evaluated after 1 and 4 months of treatment, including changes in HR, angina attacks, use of short-acting nitrates, quality of life and safety. Risk of bias was evaluated on the basis of recommendations of the Cochrane Handbook for Systematic Reviews of Interventions.
Seven relevant studies were identified (N = 6821). Ivabradine plus a beta-blocker consistently reduced HR, anginal symptoms and short-acting nitrate consumption within 1 month of initiating therapy, with continued reductions for up to 4 months. Furthermore, ivabradine plus beta-blocker therapy was well tolerated, with bradycardia rarely reported (0.1% of patients overall). This study is limited by the inclusion of only two randomised studies, which may lead to result interpretation bias.
Ivabradine may be valuable for tailoring early antianginal treatment when used in combination with beta-blockers for chronic stable angina inadequately controlled by beta-blockers.
欧洲心脏病学会建议将β受体阻滞剂作为治疗慢性冠状动脉综合征患者的一线抗心绞痛药物，以降低心率（HR）和症状，尽管缺乏数据表明其优于其他抗心绞痛药物。大多数心绞痛患者需要联合治疗来控制症状，选择二线药物来治疗主要的心血管问题。伊伐布雷定是一种选择性窦房结 I 通道抑制剂，已被证明可降低 HR 并预防心绞痛症状，先前已证明其在抗缺血和抗心绞痛方面与β受体阻滞剂具有非劣效性。
本系统评价和荟萃分析评估了伊伐布雷定在稳定型心绞痛患者中的疗效和安全性，这些患者在接受β受体阻滞剂治疗后仍有症状。通过对 PubMed、Cochrane 中央图书馆注册处、ClinicalTrials.gov、世界卫生组织国际临床试验注册平台（ICTRP）和 Google Scholar 进行关键字搜索，确定了比较伊伐布雷定加β受体阻滞剂与安慰剂或其他一线或二线抗心绞痛药物治疗稳定型心绞痛患者的研究。未设置日期限制或语言限制。评估了治疗 1 个月和 4 个月后的结局，包括心率变化、心绞痛发作、短效硝酸酯类药物的使用、生活质量和安全性。根据 Cochrane 干预系统评价手册的建议评估偏倚风险。
确定了 7 项相关研究（N=6821）。伊伐布雷定加β受体阻滞剂在开始治疗后 1 个月内持续降低 HR、心绞痛症状和短效硝酸酯类药物的使用，持续降低 4 个月。此外，伊伐布雷定加β受体阻滞剂治疗耐受性良好，很少有报道出现心动过缓（总体患者的 0.1%）。本研究受到仅纳入两项随机研究的限制，这可能导致结果解释偏倚。
伊伐布雷定与β受体阻滞剂联合用于治疗慢性稳定型心绞痛，当β受体阻滞剂不能充分控制时，可能有助于早期抗心绞痛治疗。
