Ken Fukunaga, Christian

Abstract Aims Routine aspirin use for primary prevention yields modest cardiovascular benefit but increases bleeding risk in average-risk adults. Whether individuals with elevated lipoprotein(a) [Lp(a)] levels or high-risk LPA variants derive greater benefit remains uncertain. Methods and results Following Cochrane and PRISMA guidelines, we systematically searched PubMed/MEDLINE, Embase, and Cochrane Central for studies of adults without ASCVD, elevated Lp(a) (≥50 mg/dL), high-risk LPA genotypes, or elevated genetic risk scores, comparing aspirin vs. no aspirin use. Random-effects meta-analyses using restricted maximum-likelihood (REML) estimation with Hartung–Knapp–Sidik–Jonkman (HKSJ) adjustment were used to pool hazard ratios (HR) and 95% confidence intervals (CI). In six studies, 6628 participants were included. Pooled random effects showed no significant reduction in major adverse cardiovascular events (MACE) with aspirin (HR = 0.60; 95% CI 0.31–1.17; P = 0.1) or clinical bleeding events (HR = 1.24; 95% CI 0.83–1.87; P = 0.18). Subgroup analyses showed a nonsignificant reduction MACE among elevated Lp(a) (HR = 0.63; 95% CI 0.16 to 2.49; P = 0.284) and statistically significant reduction among LPA rs3798220 carriers (HR = 0.37; 95% CI 0.19 to 0.71; P = 0.003), though this finding was not consistent in the sensitivity analyses. Conclusion Among adults without ASCVD but with elevated Lp(a) or high-risk LPA genotypes, aspirin use did not confer a statistically significant cardiovascular benefit and was associated with numerically higher bleeding risk. The apparent reduction seen in rs3798220 carriers was inconsistent and likely reflects small-sample bias.

ABSTRACT Patients undergoing transcatheter aortic valve implantation (TAVI) often require long‐term oral anticoagulation (OAC), but it is unclear whether to continue or interrupt OAC during the procedure. This meta‐analysis compares clinical outcomes of continuing versus interrupting OAC during TAVI. PubMed, Embase, and Cochrane Central databases were searched from inception to September 2024 for studies comparing continuation versus interruption of OAC in patients undergoing TAVI with an indication for OAC, including vitamin K antagonists and direct oral anticoagulants. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a random‐effects model. Sensitivity analysis was performed using the Hartung‐Knapp‐Sidik‐Jonkman method. Three studies were included, one randomized controlled trial and two cohort studies, with 2773 patients, of whom 1314 (47.4%) continued OAC during TAVI. At a 30‐day follow‐up after TAVI, there were no significant differences between groups in all‐cause mortality (RR 0.74; 95% CI 0.45–1.20; p = 0.22), any bleeding (RR 1.08; 95% CI 0.81–1.43; p = 0.60), and major bleeding (RR 0.90; 95% CI 0.67–1.21; p = 0.48). However, the continued OAC group was associated with a lower stroke rate (RR 0.65; 95% CI 0.42–1.01; p = 0.053), also attested after a sensitivity analysis (RR 0.65; 95% CI 0.47–0.90; p < 0.03). In patients with an indication for OAC undergoing TAVI, uninterrupted anticoagulation is associated with similar thrombotic and hemorrhagic outcomes compared to interrupted OAC. Stroke risk was lower in the continued OAC group, with a significant reduction, as demonstrated in sensitivity analysis.