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

Abstract

Background and Objectives Coronary artery disease (CAD) is the number one cause of death worldwide. The I f 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.

Saudi Heart Association Guidelines on Best Practices in the Management of Chronic Coronary Syndromes

“…Ivabradine reduces the frequency of hospitalization in CCS but does not seem to have a collective effect on cardiovascular mortality nor the frequency of CCS episodes [ 168 ]. In addition to its unreliable effect on mortality, the use of ivabradine in patients with CCS should be limited to HF patients and those with uncontrolled heart rate despite beta blockers therapy [ 169 , 170 ].…”

Ivabradine-Management of Heart Failure (Systematic Review)

“…Headache rash diplopia angioedema pruritus urticaria erythema vertigo not show any significant effect of ivabradine on cardiovascular mortality [19]. Beta-blockers in particular represent a rational intervention for HR modulation.…”

“…One reason for these negative outcomes of SIGNIFY might be the higher dosage of 10 mg BID in some patients, however, an audit of the data by the European Medicines Agency (EMA) did not agree with these findings. To reduce this risk of atrial fibrilation the EMA gives the following recommendations: a dosage of 5 to 7.5 mg BID, no combination with verapamil or diltiazem and sole use in angina patients in sinus rhythm with a heart rate ≥70 bpm who remain symptomatic despite anti-anginal therapy [19]. This data is in line with the recommendations by the EMA to use ivabradine only if the patient cannot be treated with beta-blockers, or in combination if beta-blockers alone are not sufficient.…”

Pre-operative continuation of ivabradine therapy for dilated cardiomyopathy – Skip it or not?

“…This can lead to myocardial ischemia due to supply demand mismatch. [ 3 ] Ivabradine is advocated as an add on drug to patients with increased baseline heart rate with diagnosis of chronic heart failure,[ 4 ] angina pectoris,[ 5 ] or/and dilated cardiomyopathy. [ 6 ] Ivabradine blocks HCN channel and results in inhibition of the inward funny current.…”