美国杜克大学健康系统W. Schuyler Jones团队比较了不同剂量阿司匹林治疗心血管疾病的疗效。2021年5月15日，《新英格兰医学杂志》发表了该成果。

在已确诊的动脉粥样硬化性心血管疾病患者中，适当剂量的阿司匹林可降低死亡、心肌梗死和中风的风险，但如何减少大出血是一个有争议的话题。

研究组采用开放标签、务实的设计，招募患有动脉粥样硬化性心血管疾病的患者，将其随机分组，每天服用81 mg或325 mg的阿司匹林。主要疗效结局是全因死亡、因心肌梗死住院或因中风住院的综合结果，通过事件时间分析进行评估。主要安全性结局是因大出血而住院治疗。

共有15076名患者接受了平均26.2个月的随访。随机分组前，13537名患者已经服用阿司匹林，85.3%的患者以前每天服用81 mg阿司匹林。81 mg组中有590例（7.28%）患者发生主要疗效结局，325 mg组中有569例（7.51%），风险比为1.02。81 mg组中有53例（0.63%）患者发生大出血，325 mg组中有44例（0.60%），风险比为1.18。81 mg组的剂量转换率为7.1%，325 mg组为41.6%；325 mg组分配剂量的中位暴露时间为434天，显著短于81 mg组（650天）。

研究结果表明，动脉粥样硬化性心血管疾病患者每天服用81 mg或325 mg阿司匹林在心血管事件或大出血方面没有显著差异。

附：英文原文

Title: Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease | NEJM

Author: W. Schuyler Jones, M.D.,, Hillary Mulder, M.S.,, Lisa M. Wruck, Ph.D.,, Michael J. Pencina, Ph.D.,, Sunil Kripalani, M.D.,, Daniel Muoz, M.D.,, David L. Crenshaw, L.M.S.W.,, Mark B. Effron, M.D.,, Richard N. Re, M.D.,, Kamal Gupta, M.D.,, R. David Anderson, M.D.,, Carl J. Pepine, M.D.,, Eileen M. Handberg, Ph.D.,, Brittney R. Manning, M.P.H.,, Sandeep K. Jain, M.D.,, Saket Girotra, M.D.,, Danielle Riley, M.S.,, Darren A. DeWalt, M.D.,, Jeff Whittle, M.D.,, Ythan H. Goldberg, M.D.,, Veronique L. Roger, M.D.,, Rachel Hess, M.D.,, Catherine P. Benziger, M.D.,, Peter Farrehi, M.D.,, Li Zhou, M.D.,, Daniel E. Ford, M.D.,, Kevin Haynes, Pharm.D.,, Jeffrey J. VanWormer, Ph.D.,, Kirk U. Knowlton, M.D.,, Jennifer L. Kraschnewski, M.D.,, Tamar S. Polonsky, M.D.,, Dan J. Fintel, M.D.,, Faraz S. Ahmad, M.D.,, James C. McClay, M.D.,, James R. Campbell, M.D.,, Douglas S. Bell, M.D.,, Gregg C. Fonarow, M.D.,, Steven M. Bradley, M.D.,, Anuradha Paranjape, M.D.,, Matthew T. Roe, M.D.,, Holly R. Robertson, Ph.D.,, Lesley H. Curtis, Ph.D.,, Amber G. Sharlow, M.B.A.,, Lisa G. Berdan, M.H.S.,, Bradley G. Hammill, Dr.P.H.,, Debra F. Harris, B.A.,, Laura G. Qualls, M.S.,, Guillaume Marquis-Gravel, M.D.,, Madelaine F. Modrow, M.P.H.,, Gregory M. Marcus, M.D.,, Thomas W. Carton, Ph.D.,, Elizabeth Nauman, Ph.D.,, Lemuel R. Waitman, Ph.D.,, Abel M. Kho, M.D.,, Elizabeth A. Shenkman, Ph.D.,, Kathleen M. McTigue, M.D.,, Rainu Kaushal, M.D.,, Frederick A. Masoudi, M.D.,, Elliott M. Antman, M.D.,, Desiree R. Davidson, A.A.,, Kevin Edgley, M.B.A.,, James G. Merritt, Ph.D.,, Linda S. Brown,, Doris N. Zemon, R.N.,, Thomas E. McCormick, III, M.S.,, Jacqueline D. Alikhaani, B.A.,, Kenneth C. Gregoire,, Russell L. Rothman, M.D.,, Robert A. Harrington, M.D.,, and Adrian F. Hernandez, M.D.

Issue&Volume: 2021-05-15

Abstract:

Background

The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy.

Methods

Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis.

Results

A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]).

Conclusions

In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily.

DOI: 10.1056/NEJMoa2102137

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2102137