Single Versus Dual Antiplatelet Therapy After Transcatheter Aortic Valve Replacement: A Meta-Analysis of Randomized Clinical Trials

Abstract

Background Guidelines recommend dual antiplatelet therapy (DAPT) after transcatheter aortic valve replacement (TAVR) but guidelines predate the publication of the largest randomized trial. There have been few trials in the field to date, and with a small number of total patients; pooling their results may therefore be helpful. Methods We systematically identified all randomized trials comparing SAPT to DAPT after TAVR. The primary endpoint was the risk of major bleeding. Secondary endpoints included all bleeding, life-threatening bleeding, stroke, myocardial infarction, death and cardiac death. Results Four trials, randomizing 1086 participants, were eligible (541 randomized to SAPT and 545 randomized to DAPT). The weighted mean follow-up was 9.1 months. The risk of major bleeding was significantly increased after DAPT (relative risk (RR) 2.36, 95% confidence interval (CI) 1.27 to 4.40, P = 0.007). There was a similar increased risk for all bleeding (RR 1.65, 95% CI 1.24 to 2.19, P < 0.001), although not for life-threatening bleeding (RR 1.44, 95% CI 0.74 to 2.77, P = 0.282). There were no significant differences in the risk of stroke, myocardial infarction (MI), death or cardiac death. There was no heterogeneity observed for any endpoint (I 2 = 0.0%). Conclusions DAPT after TAVR is associated with an increased risk of major bleeding and all bleeding. There is no evidence of a significant difference between DAPT or SAPT for the risks of stroke, MI, death or cardiac death. However, the total number of patients randomized is small and the duration of follow-up is short. Larger scale randomized trials with longer follow-up are required to assess for any potential differences in ischemic endpoints or mortality.

Optimal antiplatelet and antithrombotic regimen post‐transcatheter aortic valve replacement

“…advanced age, frailty and history of major bleeding). This ‘observational bias’ may, in part, account for the higher incidence of CV events with DAPT vs. SAPT and no overall difference in major bleeding between the two groups as seen in our study, which are contrary to prior RCT findings showing no difference in ischemic events and higher bleeding with DAPT vs. SAPT 27,30 . However, partial adjustment of ischemic risk (subgroup analysis in those with and without CAD) showed significantly higher CV events with DAPT vs. SAPT post‐TAVR in those without CAD, which is a finding that cannot be explained by ‘observational bias’ alone, and merits further consideration.…”

“…Prior patterns of higher CV events with DAPT vs. SAPT post‐TAVR in observational studies not seen in RCTs 22,30 suggest that this finding may be due to inherent bias associated with observational studies. In observational studies, patients are empirically assigned to DAPT vs. SAPT based on the physician's clinical assessment of bleeding and ischemic risk 22 .…”

“…DAPT was associated with a higher rate of major or life‐threatening bleeding events compared to SAPT (10.8% vs. 3.6%, p = .038). Larger RCTs 27,28 and meta‐analyses 22,29,30 subsequently demonstrated no advantage of DAPT over SAPT with an increased risk of major or life‐threatening bleeding post‐TAVR.…”

“…31,32 Recent metaanalysis showed that compared to SAPT, rates of major or life-bleeding were higher with both 3-month (relative risk [RR] 2.13, p = .016] and 6-month (RR 2.54, p = .007) DAPT with no difference between 3-month and 6-month DAPT groups. 32 Another meta-analysis including four RCTs randomizing 1086 patients 30 similarly demonstrated higher major bleeding with DAPT vs. SAPT post-TAVR (RR 2.36, 95% CI 1.27-4.40, p = .007) without any difference in the risk of stroke, MI, death or cardiac death. In comparison, recent meta-analysis by Zhang et al 22 which included both RCTs and observational studies showed higher bleeding risk with DAPT compared to SAPT post-TAVR (pooled odds ratio [OR] 2.75, 95% CI 1.45-521, p = .002) as well as a trend towards higher major adverse CV events (MACE) with DAPT vs. SAPT (OR 1.19, 95% CI 0.99-1.44, p = .07).…”

“…3.6%, p = .038). Larger RCTs 27,28 and meta-analyses 22,29,30 subsequently demonstrated no advantage of DAPT over SAPT with an increased risk of major or life-threatening bleeding post-TAVR. In the antiplatelet therapy group, SAPT was considered referent and the value listed is the adjusted HR of DAPT vs. SAPT.…”