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Ivabradine for the Therapy of Chronic Stable Angina Pectoris: a Systematic Review and Meta-Analysis
Christina Kalvelage1, Christian Stoppe1,2, Nikolaus Marx3
1Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany.
Insights
Ivabradine, an If channel inhibitor, did not significantly reduce cardiovascular mortality or angina episodes in patients with coronary artery disease. However, it showed a significant effect on reducing hospitalizations in a small subgroup. This systematic review adds evidence to current guidelines.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Coronary artery disease (CAD) is a leading global cause of mortality.
- Angina pectoris is a primary symptom of CAD.
- Ivabradine is an If channel inhibitor used as a second-line treatment for angina.
Purpose of the Study:
- To systematically review and meta-analyze the evidence for ivabradine's efficacy in treating angina pectoris.
- To assess the impact of ivabradine on cardiovascular mortality, hospitalizations, and angina episodes.
Main Methods:
- Systematic search of multiple databases (MEDLINE, Embase, CENTRAL, Web of Science) for randomized controlled trials (RCTs).
- Inclusion of 11 RCTs with 16,039 participants comparing ivabradine to placebo or standard therapy.
- Meta-analysis using random-effects models to calculate hazard ratios and mean differences, with risk of bias and GRADE assessments.
Main Results:
- Ivabradine did not demonstrate a significant effect on cardiovascular mortality (HR, 1.10; 95% CI, 0.94-1.28).
- No significant reduction in angina pectoris episodes was observed (weighted MD, -1.06; 95% CI, -2.74 to -0.61).
- A significant reduction in hospitalizations was found in a small cohort (HR, 0.19; 95% CI, 0.04-0.92).
Conclusions:
- This meta-analysis provides evidence to complement existing European Society of Cardiology guidelines for angina management.
- While not impacting mortality or angina frequency, ivabradine may reduce hospitalizations in certain patient groups.
- Further research may refine the role of ivabradine in CAD patient care.
Background And Objectives:
Coronary artery disease (CAD) is the number one cause of death worldwide. The If channel inhibitor ivabradine serves as second line medication for the CAD leading symptom angina pectoris. This systematic review and meta-analysis assess the existing evidence of ivabradine in angina pectoris.
Methods:
We systematically searched MEDLINE, Embase, CENTRAL, and Web of Science (September 2019) for randomized controlled trials (RCTs) that compared ivabradine versus placebo, standard therapy (ST) or other anti-anginal drugs. Two review authors independently assessed trials for inclusion and performed data extraction. We completed a 'risk of bias' assessment for all studies and assessed quality of the trial evidence using the Grading of Recommendations Assessment, Development and Evaluation methodology. We meta-analysed data were applicable and calculated mean differences (MDs) and risk ratios using a random-effects model.
Results:
A total of 11 RCTs (n=16,039) were included. Compared to placebo/ST, we found significant effects on the frequency of hospitalisation in a small cohort (n=90; hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.04, -0.92; p=0.04), but no effects on cardiovascular mortality (n=19,102; HR, 1.10; 95% CI, 0.94, 1.28; p=0.25) or the frequency of angina pectoris episodes (n=167; weighted MD, -1.06; 95% CI, -2.74, -0.61; p=0.21).
Conclusions:
The present work makes an important contribution to optimal patient care in angina pectoris by complementing the current European Society of Cardiology guideline-recommending class IIa with evidence level B-decisively with 8 further studies.
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