Association between proprotein convertase subtilisin/kexin type 9 targeted therapies and the risk of arrhythmias: a meta-analysis of randomized controlled trials

Proprotein convertase subtilisin/kexin type 9 (PCSK9) targeted therapies effectively lower low-density lipoprotein cholesterol (LDL-C) and circulating PCSK9 levels. However, their effect on the risk of arrhythmias remains uncertain, and this meta-analysis aims to investigate the association. We performed a systematic literature search on all electronic databases for relevant randomized controlled trials (RCTs) from inception until 16th August, 2024. Primary clinical endpoint was atrial fibrillation (AFib), while the secondary endpoints were atrial flutter (AFL), ventricular fibrillation (VF), ventricular tachycardia (VT), supraventricular tachycardia (SVT), sudden cardiac death (SCD), cardiac arrest and atrioventricular blocks. 28 RCTs with 95,520 patients were finally included in the analysis. The mean age of the group treated with PCSK9 inhibitors was similar to the control group (60.13 years vs. 60.06 years). At mean follow-up of 1.6 years the PCSK9i group had similar risk of AFib (OR, 0.88; 95%CI: 0.75-1.03, p =0.11), AFL (OR, 1.04; 95%CI: 0.70-1.54, p =0.84), VT (OR, 0.80; 95%CI: 0.58-1.11, p =0.18), VF (OR, 0.77;95%CI: 0.40-1.47, p =0.43) and SVT (OR, 0.94; 95%CI: 0.56-1.58, p =0.82) compared to control group. Similarly, the SCD (OR, 0.91; 95%CI: 0.62-1.32, p =0.61), and AV block (OR, 0.72; 95%CI: 0.34-1.52, p =0.39) did not differ between the groups. This meta-analysis did not find a significant association between PCSK9i and arrhythmias.