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不同剂量阿司匹林治疗心血管疾病的效果比较
Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease


W. Schuyler Jones ... 心脑血管疾病 • 2021.05.27
相关阅读
• 阿司匹林用于二级预防:81 mg vs. 325 mg • 急性冠脉综合征后抗血栓治疗的管理 • 在后他汀时代是否应将阿司匹林用于一级预防

创新、廉价、实效试验设计让阿司匹林研究再次登顶NEJM

 

魏盟*,刘蓉

上海嘉会国际医院心血管内科

*通讯作者

 

在美国,动脉粥样硬化性心血管疾病(ASCVD)仍然是致病和致死的主要原因。阿司匹林被推荐用于已确诊ASCVD的患者,以降低不良健康事件。然而,对于ASCVD患者服用阿司匹林的首选剂量,目前的观察性研究和随机对照试验的事后分析结论仍不一致。一些研究表明,使用不同剂量阿司匹林的风险及获益均不同。

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摘要


背景

动脉粥样硬化性心血管疾病确诊患者通过服用适当剂量阿司匹林来降低死亡、心肌梗死和卒中风险并最大限度地减少大出血是一个存在争议的问题。

 

方法

我们应用开放标签、实效性设计,将动脉粥样硬化性心血管疾病确诊患者随机分组,两组分别采用每日81 mg或325 mg阿司匹林的治疗策略。主要效果结局是在至事件发生的时间分析中评估由全因死亡、心肌梗死住院或卒中住院构成的复合结局。主要安全性结局是在至事件发生的时间分析中评估大出血住院。

 

结果

共计15,076例患者接受了中位26.2个月随访(四分位距[IQR],19.0~34.9)。随机分组之前,13,537例患者(在获得阿司匹林用药史信息的患者中占96.0%)已在服用阿司匹林,其中85.3%每日服用81 mg阿司匹林。81 mg组590例患者(估计百分比,7.28%)和325 mg组569例患者(估计百分比,7.51%)发生了死亡、心肌梗死住院或卒中住院(风险比,1.02;95%置信区间[CI],0.91~1.14)。81 mg组53例患者(估计百分比,0.63%)和325 mg组44例患者(估计百分比,0.60%)发生了大出血住院(风险比,1.18;95% CI,0.79~1.77)。325 mg组患者变更剂量的发生率高于81 mg组患者(41.6% vs. 7.1%),并且前者接受所分配剂量的中位天数较少(434日[IQR,139~737] vs. 650日[IQR,415~922])。

 

结论

在此项纳入心血管疾病确诊患者的实效性试验中,有大量患者将剂量变更为每日81 mg阿司匹林,并且每日81 mg阿司匹林组患者和每日325 mg阿司匹林组患者在心血管事件或大出血方面无显著差异(由以患者为中心的结局研究会[Patient-Centered Outcomes Research Institute]资助,ADAPTABLE在ClinicalTrials.gov注册号为NCT02697916)。





作者信息

W. Schuyler Jones, M.D., Hillary Mulder, M.S., Lisa M. Wruck, Ph.D., Michael J. Pencina, Ph.D., Sunil Kripalani, M.D., Daniel Muñoz, 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 N. 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. for the ADAPTABLE Team*
From Duke Clinical Research Institute, Duke University, Durham (W.S.J., H.M., L.M.W., M.J.P., M.T.R., H.R.R., L.H.C., A.G.S., L.G.B., B.G.H., D.F.H., L.G.Q., G.M.-G., A.F.H.), University of North Carolina at Chapel Hill, Chapel Hill (D.A.D.), and Wake Forest University School of Medicine, Winston-Salem (L.Z.) — all in North Carolina; Vanderbilt University Medical Center, Nashville (S.K., D.M., D.L.C., R.L.R.); Ochsner Health (M.B.E., R.N.R.) and Louisiana Public Health Institute (T.W.C., E.N.) — both in New Orleans; University of Kansas Medical Center, Kansas City (K.G.); University of Florida, Gainesville (R.D.A., C.J.P., E.M.H., B.R.M., E.A.S.); University of Pittsburgh Medical Center, Pittsburgh (S.K.J., K.M.M.), Penn State College of Medicine, Hershey (J.L.K.), and Temple University, Philadelphia (A.P.) — all in Pennsylvania; University of Iowa, Iowa City (S.G., D.R.); Medical College of Wisconsin, Milwaukee (J.W.), and Marshfield Clinic Research Institute, Marshfield (J.J.V.) — both in Wisconsin; Albert Einstein College of Medicine, Bronx (Y.H.G.), and Weill Cornell Medicine and New York–Presbyterian Hospital, New York (R.K.) — both in New York; Mayo Clinic, Rochester (V.L.R.), Essentia Health Heart and Vascular Center, Duluth (C.P.B.), and Allina Health and Minneapolis Heart Institute, Minneapolis (S.M.B.) — all in Minnesota; University of Utah School of Medicine (R.H.) and Intermountain Medical Center Heart Institute (K.U.K.) — both in Salt Lake City; University of Michigan, Ann Arbor (P.F.); Johns Hopkins University School of Medicine, Baltimore (D.E.F.); HealthCore, Wilmington, DE (K.H.); University of Chicago Medicine (T.S.P.) and Northwestern University Feinberg School of Medicine (D.J.F., F.S.A., A.N.K.) — both in Chicago; University of Nebraska Medical Center, Omaha (J.C.M., J.R.C.); University of California, Los Angeles, Los Angeles (D.S.B., G.C.F.), University of California, San Francisco, San Francisco (M.F.M., G.M.M.), and Stanford University School of Medicine, Stanford (R.A.H.) — all in California; University of Missouri School of Medicine, Columbia (L.R.W.); University of Colorado School of Medicine, Anschutz Medical Campus, Aurora (F.A.M.); Brigham and Women’s Hospital, Harvard Medical School, Boston (E.M.A.); Chicago (D.R.D.); St. Joseph, MO (K.E.); Brighton, MI (J.G.M.); Columbia, TN (L.S.B.); Alachua, FL (D.N.Z.); Columbia, MD (T.E.M.); North Hills, CA (J.D.A.); and Metairie, LA (K.C.G.). Address reprint requests to Dr. Jones at the Division of Cardiology, Duke University Health System, DUMC 3330, Durham, NC 27710, or at schuyler.jones@duke.edu. *A complete list of the ADAPTABLE investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Virani SS, Alonso A, Benjamin EJ, et al. Heart disease and stroke statistics — 2020 update: a report from the American Heart Association. Circulation 2020;141(9):e139-e596.

2. The ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 2018;379:1529-1539.

3. Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet 2018;392:1036-1046.

4. McNeil JJ, Wolfe R, Woods RL, et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med 2018;379:1509-1518.

5. Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373:1849-1860.

6. Xian Y, Wang TY, McCoy LA, et al. Association of discharge aspirin dose with outcomes after acute myocardial infarction: insights from the Treatment with ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) Study. Circulation 2015;132:174-181.

7. The CURRENT–OASIS 7 Investigators. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med 2010;363:930-942.

8. Kohli P, Udell JA, Murphy SA, et al. Discharge aspirin dose and clinical outcomes in patients with acute coronary syndromes treated with prasugrel versus clopidogrel: an analysis from the TRITON-TIMI 38 study (trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-thrombolysis in myocardial infarction 38). J Am Coll Cardiol 2014;63:225-232.

9. Mahaffey KW, Huang Z, Wallentin L, et al. Association of aspirin dose and vorapaxar safety and efficacy in patients with non-ST-segment elevation acute coronary syndrome (from the TRACER Trial). Am J Cardiol 2014;113:936-944.

10. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;130:2354-2394.

11. Smith SC Jr, Benjamin EJ, Bonow RO, et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation 2011;124:2458-2473.

12. Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the Management of Stable Coronary Artery Disease of the European Society of Cardiology. Eur Heart J 2013;34:2949-3003.

13. Hall HM, de Lemos JA, Enriquez JR, et al. Contemporary patterns of discharge aspirin dosing after acute myocardial infarction in the United States: results from the National Cardiovascular Data Registry (NCDR). Circ Cardiovasc Qual Outcomes 2014;7:701-707.

14. Marquis-Gravel G, Roe MT, Robertson HR, et al. Rationale and design of the Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) Trial. JAMA Cardiol 2020;5:598-607.

15. Ford I, Norrie J. Pragmatic trials. N Engl J Med 2016;375:454-463.

16. Loudon K, Treweek S, Sullivan F, Donnan P, Thorpe KE, Zwarenstein M. The PRECIS-2 tool: designing trials that are fit for purpose. BMJ 2015;350:h2147-h2147.

17. Hernandez AF, Fleurence RL, Rothman RL. The ADAPTABLE Trial and PCORnet: shining light on a new research paradigm. Ann Intern Med 2015;163:635-636.

18. Ahmad FS, Ricket IM, Hammill BG, et al. Computable phenotype implementation for a national, multicenter pragmatic clinical trial: lessons learned from ADAPTABLE. Circ Cardiovasc Qual Outcomes 2020;13(6):e006292-e006292.

19. Fishman E, Barron J, Dinh J, et al. Validation of a claims-based algorithm identifying eligible study subjects in the ADAPTABLE pragmatic clinical trial. Contemp Clin Trials Commun 2018;12:154-160.

20. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2016;68:1082-1115.

21. Marquis-Gravel G, Roe MT, Harrington RA, Muñoz D, Hernandez AF, Jones WS. Revisiting the role of aspirin for the primary prevention of cardiovascular disease. Circulation 2019;140:1115-1124.

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