Case-fatality rate of major bleeding events in patients on dual antiplatelet therapy after percutaneous coronary intervention: A systematic review and meta-analysis

Abstract

Background: Assessment of the case-fatality rate (CFR) of major bleeding on dual antiplatelet therapy (DAPT) may improve balancing risks and benefits of different durations of DAPT following percutaneous coronary intervention (PCI).

Objectives: To determine the CFR of major bleeding in patients on DAPT after PCI and to compare rates among different durations of DAPT.

Methods: Medline, Embase, and CENTRAL were searched from inception to August 2021 for randomized trials that reported fatal bleeding among patients who were randomized to ≥1 month of DAPT following PCI. Summary estimates for CFRs of major bleeding were calculated using the random-effects inverse-variance method. Statistical heterogeneity was evaluated using the I ² statistic.

Results: Of 2777 citations obtained by the search, 15 (48%) of 31 potentially eligible studies were excluded because fatal bleeding was not reported, leaving 16 studies that were included in the analysis. Overall, there were 823 major bleeding events including 91 fatal events in 48,884 patients who were assigned to receive DAPT during study follow-up. The CFR of major bleeding was 10.8% (95% confidence interval [CI], 7.1-16.2; I ² = 50%) in the entire study population, and 13.8% (95% CI, 6.5-27.1; I ² = 28%), 11.2% (95% CI, 6.7-18.0; I ² = 0%), and 5.8% (95% CI, 3.0-11.1; I ² = 0%) in those on short-term (≤6 months; n = 16,553), standard-term (12 months; n = 19,453), and long-term DAPT (>12 months; n = 10,238), respectively.

Conclusion: Fatal bleeding is not reported in many studies evaluating DAPT after PCI. The CFR of major bleeding on DAPT is substantial and may be higher in the first 12 months of DAPT than during long-term DAPT.

Keywords: bleeding; case‐fatality rate; drug‐eluting stent; dual antiplatelet therapy; meta‐analysis; percutaneous coronary intervention.

FIGURE 1

Study arms and follow‐up periods considered for the calculation of case‐fatality rates of major bleeding. The bifurcations indicate the time of randomization and start of follow‐up. We considered patients allocated to 18 months of DAPT in the NIPPON trial and 24 months of DAPT in the PRODIGY trial for the overall case‐fatality rate of major bleeding; neither treatment arm was considered for the calculation of the case‐fatality rate of major bleeding by treatment duration, because outcomes were not specifically reported according to our predefined groups by duration of DAPT. DAPT, dual antiplatelet therapy.

FIGURE 2

Case‐fatality rate of major bleeding in patients on DAPT after PCI with DES. Risk of bias legend: D1, bias arising from the randomization process; D2, bias because of deviation from the intended intervention; D3, bias because of missing outcome data; D4, bias in measurement of the outcome; D5, bias in selection of the reported result

FIGURE 3

Case‐fatality rate of major bleeding by duration of DAPT. CI, confidence interval

FIGURE 4

Case‐fatality rate of major bleeding by bleeding definition. CI, confidence interval