Relation of premature atrial complexes with stroke and death: Systematic review and meta-analysis.

Frequent premature atrial complexes (PACs) are universal in the general population; however, their clinical significance is unclear. We hypothesize that frequent PACs are associated with increased risk of stroke and death. The PubMed (from 1966 to April 2017) and Embase (from 1974 to April 2017) databases were searched for longitudinal studies that reported the relation of PACs with incidence of stroke and death with various etiologies. Study quality was evaluated, and the relative risks (RR) of unfavorable outcomes in subjects with frequent PACs vs those without were calculated. Eleven studies with overall high quality were eligible according to inclusion criteria. The meta-analysis demonstrated that frequent PACs were associated with an increased risk of stroke (unadjusted RR: 2.20, 95% confidence interval [CI]: 1.79-2.70; adjusted RR: 1.41, 95% CI: 1.25-1.60) and death from all causes (unadjusted RR: 2.17, 95% CI: 1.80-2.63; adjusted RR: 1.26, 95% CI: 1.13-1.41), cardiovascular diseases (unadjusted RR: 2.89, 95% CI: 2.20-3.79; adjusted RR: 1.38, 95% CI: 1.24-1.54), and coronary artery disease (unadjusted RR: 2.74, 95% CI: 1.64-4.58; adjusted RR: 1.74, 95% CI: 1.27-2.37). No significant publication bias was detected. The association was robust in sensitivity analysis, subgroup analysis, and pooled analysis of estimates adjusting for confounding factors. Frequent PACs are not benign phenomena; they are associated with higher risk of unfavorable outcomes. Further research on the optimal management of subjects with frequent PACs is urgently required.