Anti‐arrhythmic medications increase non‐cardiac mortality – A meta‐analysis of randomized control trials

Abstract

IntroductionAnti-arrhythmic medications (AAMs) are known to increase cardiac mortality significantly due to their pro-arrhythmic effects. However, the effect of AAMs on non-cardiac mortality has not been evaluated.MethodsTrials published in English language journals from 1990 to 2015 were thoroughly retrieved by searching websites such as PubMed, Medline, Cochrane Library, and Google Scholar. Randomized controlled trials reporting non-cardiac deaths as primary or secondary outcomes were used to compare AAMs to non-arrhythmic therapy (AV nodal blocking agents, implantable cardiovascular defibrillation (ICD), or placebo). Information regarding the sample size, treatment type, baseline characteristics, and outcomes was obtained by using a standardized protocol. The fixed effect model was used to perform meta-analysis, and results were expressed in terms of odds ratio (OR) with confidence interval (CI) of 95%, inter study heterogeneity was assessed using I2. Intention to treat principle was applied to extract data.ResultsTotal of 18,728 patients were enrolled in 15 trials; 9359 patients received AAMs and 9369 received non-arrhythmic therapy. AAMs were associated with an increased risk of non-cardiac mortality (OR=1.30, [95% CI: 1.12, 1.50], p=0.0005, I2 index=24%) and all-cause mortality (OR=1.09, [95% CI: 1.01, 1.18], p=0.04, I2=54%) as compared to non-arrhythmic therapy. There was no difference in the cardiac mortality (OR=1.01, [95% CI: 0.92, 1.11], p=0.82, I2=53%) or arrhythmic mortality (OR=1.00, [95% CI: 0.89, 1.13], p=0.94, I2=64%) between the two groups.ConclusionAAMs are associated with an increased risk of non-cardiac and all-cause mortality. The effect of AAMs, especially amiodarone, on non-cardiac mortality requires further evaluation.

Mortality benefit of catheter ablation versus medical therapy in atrial fibrillation: An RCT only meta‐analysis

“…These benefits can be explained by a reduction in tachycardia‐mediated cardiomyopathy with the maintenance of sinus rhythm without the adverse effects associated with long‐term AAD use. 46,47 …”

Evaluating the benefits of home-based management of atrial fibrillation: current perspectives

“…According to the AFFIRM trial, routine rhythm control does not reduce the rate of death from CV causes, as compared to the rate control strategy 15,92. Amiodarone and dofetilide are commonly used AADs for rhythm control of AF in CHF and are associated with symptom and quality of life improvement93; however, studies have been conflicting regarding their overall benefits due to proposed higher risk of ACM 94. The AF-CHF trial on the other hand showed that individuals with both CHF and AF had no differences in mortality or worsening of CHF when comparing rate control to rhythm control strategies 95.…”

OCT2013, an ischaemia‐activated antiarrhythmic prodrug, devoid of the systemic side effects of lidocaine

“…Some drugs lacked efficacy because they increased mortality (CAST Investigators, 1989; Waldo et al, 1996), while the remainder lacked efficacy because doses were kept low to avoid adverse drug reactions (Køber et al, 2000; The Danish Study Group on Verapamil in Myocardial Infarction, 1990; The Multicenter Ditiazem Postinfarction Group, 1988). In a smaller cohort of acute myocardial infarction survivors, those at higher risk of VF and sudden cardiac death, amiodarone and mexiletine are sometimes administered but their risk/benefit ratio is poor (IMPACT Research Group, 1984; Julian et al, 1997; Pandya et al, 2016; Rutledge et al, 1985). It has been proposed that a drug with selectivity of action for the arrhythmogenic ischaemic myocardium may address the unmet therapeutic need to suppress ischaemia‐induced VF (Bain et al, 1997; Barrett et al, 1995; Barrett et al, 2000; Farkas et al, 1999; Walker & Guppy, 2003).…”