title: The Risk of Atrial Fibrillation With Ivabradine Treatment: A Meta-analysis With Trial Sequential Analysis of More Than 40000 Patients.
abstract: Recent trials reported that risk of atrial fibrillation (AF) is increased in patients using ivabradine compared with controls. We performed this meta-analysis to investigate the risk of AF association with ivabradine treatment on the basis of data obtained from randomized controlled trials (RCTs). We searched PubMed, EMBASE, Scopus, and the Cochrane Library for RCTs that comprised >100 patients. The incidence of AF was assessed. We obtained data from European Medicines Agency (EMA) scientific reports for the RCTs in which the incidence of AF was not reported. We used trial sequential analysis (TSA) to provide information on when we had reached firm evidence of new AF based on a 15% relative risk increase (RRI) in ivabradine treatment. Three RCTs and 1 EMA overall oral safety set (OOSS) pooled analysis (included 5 RCTs) were included in the meta-analysis (N = 40 437). The incidence of AF was 5.34% in patients using ivabradine and 4.56% in placebo. There was significantly higher incidence of AF (24% RRI) in the ivabradine group when compared with placebo before (RR: 1.24, 95% confidence interval: 1.08-1.42, P = 0.003, I 1980 = 53%) and after excluding OOSS (RR: 1.24, 95% confidence interval: 1.06-1.44, P = 0.008). In the TSA, the cumulative z-curve crossed both the traditional boundary (P = 0.05) and the trial sequential monitoring boundary, indicating firm evidence for ≥15% increase in ivabradine treatment when compared with placebo. Study results indicate that AF is more common in the ivabradine group (24% RRI) than in controls.
authors: Department of Cardiology, Medical School, Atatürk University, Erzurum, Turkey. haliltanboga@yahoo.com.|Department of Biostatistics, Medical School, Atatürk University, Erzurum, Turkey. haliltanboga@yahoo.com.
authors: İbrahim Halil
authors: İH
authors: Tanboğa
authors: Department of Cardiology, Medical School, Atatürk University, Erzurum, Turkey.|Department of Biostatistics, Medical School, Atatürk University, Erzurum, Turkey.
authors: Selim
authors: S
authors: Topçu
authors: Department of Cardiology, Medical School, Atatürk University, Erzurum, Turkey.
authors: Enbiya
authors: E
authors: Aksakal
authors: Department of Cardiology, Medical School, Atatürk University, Erzurum, Turkey.
authors: Oktay
authors: O
authors: Gulcu
authors: Department of Cardiology, Medical School, Atatürk University, Erzurum, Turkey.
authors: Emrah
authors: E
authors: Aksakal
authors: Department of Cardiology, Medical School, Atatürk University, Erzurum, Turkey.
authors: Uğur
authors: U
authors: Aksu
authors: Department of Cardiology, Medical School, Bahçeşehir University, Istanbul, Turkey.
authors: Vecih
authors: V
authors: Oduncu
authors: Department of Cardiology, Yalova State Hospital, Yalova, Turkey.
authors: Fatih Rıfat
authors: FR
authors: Ulusoy
authors: Department of Cardiology, Medical School, Atatürk University, Erzurum, Turkey.
authors: Serdar
authors: S
authors: Sevimli
authors: Department of Cardiology, Kosuyolu Heart Hospital, Istanbul, Turkey.
authors: Cihangir
authors: C
authors: Kaymaz
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D001552:Benzazepines / Q000009:adverse effects*; D002317:Cardiovascular Agents / Q000009:adverse effects*; D016009:Chi-Square Distribution; D003327:Coronary Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D001552:Benzazepines; D002317:Cardiovascular Agents; D000077550:Ivabradine
keywords: Ivabradine; atrial fibrillation; meta-analysis