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Efficacy and Safety of Ivabradine in Combination with Beta-Blockers in Patients with Stable Angina Pectoris: A
Alexander Nedoshivin1, Parvoleta T S Petrova2, Yuri Karpov3
1Chair of Internal Medicine, Almazov National Medical Research Centre, Akkuratova Str., 2, St Petersburg, Russian Federation. nedoshivin@almazovcentre.ru.
Insights
Ivabradine combined with beta-blockers effectively reduces heart rate and angina symptoms in patients with chronic stable angina. This combination therapy is well-tolerated, offering a valuable option for inadequately controlled symptoms.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Beta-blockers are first-line antianginal therapy but often require combination treatment for chronic coronary syndrome.
- Ivabradine, an If channel inhibitor, reduces heart rate and has shown comparable efficacy to beta-blockers.
Purpose of the Study:
- To assess the efficacy and safety of ivabradine as an add-on therapy for patients with stable angina pectoris who remain symptomatic despite beta-blocker treatment.
Main Methods:
- A systematic review and meta-analysis of studies comparing ivabradine plus beta-blockers with placebo or other antianginal agents.
- Searches included major databases without date or language restrictions.
- Outcomes evaluated included heart rate, angina attacks, nitrate use, quality of life, and safety over 1 and 4 months.
Main Results:
- Ivabradine plus beta-blocker therapy significantly reduced heart rate, angina symptoms, and nitrate use within 1 month, with sustained effects up to 4 months.
- The combination therapy was well-tolerated, with a very low incidence of bradycardia (0.1%).
Conclusions:
- Ivabradine in combination with beta-blockers is a valuable therapeutic option for managing chronic stable angina inadequately controlled by beta-blockers alone.
- This combination may help tailor early antianginal treatment strategies.
Introduction:
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 If channel inhibitor shown to reduce HR and protect against anginal symptoms, has previously demonstrated noninferior anti-ischaemic and antianginal efficacy to beta-blockers.
Methods:
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.
Results:
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.
Conclusions:
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.
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