Abstract: From the 468 references identified after removing duplicates, we found two trials comprising 86 participants that met our inclusion criteria. Both trials included participants with Brugada syndrome who were randomized to ICD versus β-blocker therapy for secondary prevention for sudden cardiac death. Both studies were small, were performed by the same investigators, and exhibited a high risk of bias across multiple domains. In the group randomized to ICD therapy, there was a nine-fold lower risk of mortality compared with people randomized to medical therapy (0% with ICD versus 18% with medical therapy; RR 0.11, 95% CI 0.01 to 0.83; 2 trials, 86 participants). There was low quality evidence of a difference in the rates of combined fatal and non-fatal cardiovascular events, and the results were imprecise (26% with ICD versus 18% with medical therapy; RR 1.49, 95% CI 0.66 to 3.34; 2 trials, 86 participants). The rates of adverse events were higher in the ICD group, but these results were imprecise (28% with ICD versus 10% with medical therapy; RR 2.44, 95% CI 0.92 to 6.44; 2 trials, 86 participants). For secondary outcomes, the risk of non-fatal cardiovascular events was higher in the ICD group, but these results were imprecise and were driven entirely by appropriate ICD-termination of cardiac arrhythmias (26% with ICD versus 0% with medical therapy; RR 11.4, 95% CI 1.57 to 83.3; 2 trials, 86 participants). Approximately 25% of the ICD group experienced inappropriate ICD firing, all of which was corrected by device reprogramming. No data were available for quality of life or cost. We considered the quality of evidence low using the GRADE methodology, due to study limitations and imprecision of effects. Among people with Brugada syndrome who have survived a prior episode of sudden cardiac death, ICD therapy appeared to reduce mortality when compared to β-blocker therapy, but the true magnitude may be substantially different from the estimate of the effect because of study limitations and imprecision. Due to the large magnitude of effect, it is unlikely that there will be additional studies evaluating the role of ICDs for secondary prevention in this population. Further studies are necessary to determine the optimal treatment, if any, to prevent an initial episode of sudden cardiac death in people with cardiac ion channelopathies.

Plain-language summary: We searched scientific databases and found two randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) including 86 adults that met our inclusion criteria. Both trials compared implantable cardioverter defibrillators with medical therapy in people with Brugada syndrome who had already survived a sudden cardiac arrest event. We found no studies in people who had not experienced such an event or with other abnormalities. These two studies were small, were performed by the same investigators from Thailand, were funded by a device company, and had major methodological limitations, including being stopped early. Nearly all (98%) participants were men who had an average age of 44 years old. All-cause mortality (death from any cause) was lower in people who received the implantable cardioverter defibrillator. Rates of survived sudden cardiac arrest, heart attack, and stroke were higher, primarily due to differences in survived sudden cardiac arrest rates. Implantable cardioverter defibrillators had a higher rate of side effects compared with medical therapy, including receiving inappropriate shocks from their defibrillators, which required reprogramming of these devices. There was low quality evidence that implantable cardioverter defibrillators lower mortality in people with inherited heart rate abnormalities who have survived a sudden cardiac arrest event because of few, small, low quality studies. These devices carry a higher risk of side effects than medical therapy. Further research is very likely to have an important impact on our confidence in the results.