Dual Antiplatelet Therapy vs. Single Antiplatelet Therapy After Transcatheter Aortic Valve Replacement: An Updated Systematic Review and Meta-Analysis

Abstract

Background: Although mainstream guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in patients following transcatheter aortic valve replacement (TAVR), it is not evidence-based. We aim to investigate the safety and efficacy of DAPT vs. single antiplatelet therapy (SAPT) after TAVR, and review updated evidence.Methods: We systematically searched PubMed, Embase, and Cochrane for studies comparing DAPT to SAPT after TAVR from inception to November 30, 2020. The primary outcome was major adverse cardiac and cerebrovascular events, including all-cause mortality, cardiovascular death, myocardial infarction (MI), stroke, and major or life-threatening bleeding (LTB). Subgroup analysis was performed according to study type (randomized control trials vs. observational studies) using a fixed-effects model. The quality of evidence was assessed by two scoring systems and GRADE (Grading of Recommendations Assessment, Development, and Evaluation).Results: Twelve studies of 20,766 patients were included in our meta-analysis. Compared with SAPT, DAPT was associated with an increased risk for combined life threatening and major bleeding [OR 1.73 (1.19–2.51), p = 0.004] after TAVR. Such a difference was largely driven by major bleeding [OR 2.29 (1.68–3.11), p < 0.001]. There were no significant differences on major adverse cardiovascular events (MACE) [OR 1.19 (0.99–1.44), p = 0.07], cardiovascular mortality [OR 1.46 (0.93–2.30), p = 0.10], and stroke [OR 0.97 (0.80–1.16), p = 0.71].Conclusions: Compared with SAPT, post-TAVR DAPT was associated with increased risks of major or life-threatening bleeding without additional benefits of reducing thrombotic events. Future guidelines for post-TAVR antiplatelet strategy are expected to be updated as new high-quality evidence emerges.Systematic Review Registration: PROSPERO, Identifier: CRD42021230075.

Optimal antiplatelet and antithrombotic regimen post‐transcatheter aortic valve replacement

“…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). Further examination revealed that DAPT was associated with higher CV mortality compared to SAPT in observational studies (OR 2.01, 95% CI 1.09–3.69, p = .03) but not in RCTs (OR 0.93, 95% CI 0.46–1.88, p = .84).…”

“…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 . Therefore, patients assigned to the DAPT arm may be at higher ischemic risk (e.g.…”

“…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.…”

Antithrombotic Therapy After Transcatheter Aortic Valve Replacement: An Overview

“…62 Other recent studies and updated meta-analyses largely agree with the findings that post-TAVR DAPT therapy increases the risk of bleeding events without reducing the rates of thromboembolism and mortality compared to SAPT. [63][64][65][66] Even though these results are in agreement, larger studies with a longer mean follow-up time are required to adequately assess these end points more effectively.…”

Evolving concepts in the management of antithrombotic therapy in patients undergoing transcatheter aortic valve implantation

“…Significantly lower rates of bleeding were observed in the aspirin alone group without an increase in thromboembolic events [10]. Meta-analyses have substantiated this finding [59][60][61]. Based on these studies (Table 1), clinical practice has shifted from DAPT in the first 3-6 months after TAVI to lifelong SAPT in patients without coexisting conditions necessitating OAC or DAPT [2,36].…”