Korean Circ J.  2020 Sep;50(9):773-786. 10.4070/kcj.2020.0031.

Ivabradine for the Therapy of Chronic Stable Angina Pectoris: a Systematic Review and Meta-Analysis

• Kalvelage C
• Stoppe C
• Marx N
• Marx G
• Benstoem C

• KMID: 2505732
• DOI: http://doi.org/10.4070/kcj.2020.0031

Abstract

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.

Keyword

Ivabradine; Angina pectoris; Cardiovascular diseases; Systematic review; Meta-analysis

Figure

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  Figure 1 Study flow diagram. The study flow diagram shows the number of included studies over the entire process of screening.

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  Figure 2 Risk of bias. The risk of bias graph shows the different risk of bias types (I–VII) for each included study. The risk is categorized by colours (green, yellow, red) depending on the risk level.

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  Figure 3 Forest plot analyses. (A) The frequency of angina pectoris episodes after one month comparing ivabradine vs. standard therapy; (B) The exercise capacity measured by the decrease of the maximum heart rate after 3 to 4 months comparing ivabradine vs. atenolol; (C) Exercise capacity measured by the decrease of the RPP after 3 to 4 months comparing ivabradine vs. atenolol.CI = confidence interval; MD = mean difference; RPP = rate pressure product; SD = standard deviation.

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