ISSUE-3

Third International Study on Syncope of Uncertain Etiology

Patient / Population Intervention / Exposure Comparison Outcome

In 77 patients aged 40 years or older with recurrent reflex syncope and asystole documented by an implantable loop recorder, an active dual-chamber pacemaker reduced recurrence of syncope at 2 years compared with the same pacemaker programmed to sensing only.

Design

Double-blind RCT (pacing on vs sensing only)

Endpoint

Time to first recurrence of syncope

Relevance

ResultTwo-year recurrence 25 % vs 57 % (log-rank p=0.039); relative risk reduction 57 % (95 % CI 4–81). Procedural complications in 5 patients.

Brignole M, Menozzi C, Moya A, et al. Circulation. 2012;125(21):2566-2571. 10.1161/CIRCULATIONAHA.111.082313

Discussion & critique

Only 77 of 511 screened patients were randomised, and the trial stopped at a p value that barely cleared its prespecified threshold, leaving a wide confidence interval. It is nevertheless the pivotal trial showing pacing works when asystole is objectively documented — the mechanism-guided selection strategy the guideline adopted.