Efficacy and safety of aspirin combined with warfarin after acute coronary syndrome
Tóm tắt
A comprehensive meta-analysis was performed to investigate whether the combination of high-/low-dose of aspirin and various intensities of warfarin (W) offer greater benefit than aspirin (ASA) alone. A total of 14 randomized clinical trials (RCTs) having 26,916 patients with acute coronary syndrome (ACS) met inclusion criteria. The efficacy and safety of all outcomes which included myocardial infarction (MI), all-cause death, stroke, and bleeding were calculated. The overall outcomes analysis showed there was no significant difference in the risk of MI (relative ratio [RR] 0.959, 95 % confidence interval [CI] 0.78–1.04, P = 0.308), stroke (RR 0.789, 95 % CI 0.57–1.09, P = 0.145), and all-cause death (RR 1.007, 95 % CI 0.93–1.09, P = 0.87) between the combination group and ASA group. The subgroup analysis suggested that ASA (≤100 mg/day) plus W (mean international normalized ratio [INR] 2.0–3.0) decreased the risk rate of stroke (RR 0.660, 95 % CI 0.50–0.87, P = 0.003). There was a lower risk of MI (RR 0.605, 95 % CI 0.47–0.77, P < 0.0001) as well as stroke (RR 0.594, 95 % CI 0.45–0.79, P < 0.0001) between W (INR 2.0–3.0) combined with ASA (mean dose ≥100 mg/day) and ASA. However, the risk of major bleeding (RR 1.738, 95 % CI 1.45–2.08, P < 0.0001) and minor bleeding (RR 2.767, 95 % CI 2.12–3.61, P < 0.0001) was almost doubled in the combined groups. Compared with ASA, high-dose aspirin with moderate-intensity warfarin (INR 2.0–3.0) may better reduce the risk of MI and stroke but confer an increased risk of bleeding.
Tài liệu tham khảo
Bugiardini R (2004) Risk stratification in acute coronary syndrome: focus on unstable angina/non-ST segment elevation myocardial infarction. Heart 90:729–731
Lowy FD, Waldhausen JA, Miller M, Sopko G, Rosenberg Y, Skarlatos SI (2004) Report of the National Heart, Lung and Blood Institute-National Institute of Allergy and Infectious Diseases working group on antimicrobial strategies and cardiothoracic surgery. Am Heart J 147:575–581
Lopes RD, Li L, Granger CB, Wang TY, Foody JM, Funk M et al (2012) Atrial fibrillation and acute myocardial infarction: antithrombotic therapy and outcomes. Am J Med 125:897–905
Andreotti F, Testa L, Biondi-Zoccai GG, Crea F (2006) Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25,307 patients. Eur Heart J 27:519–526
Rothberg MB, Celestin C, Fiore LD, Lawler E, Cook JR (2005) Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit. Ann Intern Med 143:241–250
Haq SA, Heitner JF, Sacchi TJ, Brener SJ (2010) Long-term effect of chronic oral anticoagulation with warfarin after acute myocardial infarction. Am J Med 123:250–258
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558
Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634
Fiore LD, Ezekowitz MD, Brophy MT, Lu D, Sacco J, Peduzzi P (2002) Department of Veterans Affairs Cooperative Studies Program Clinical Trial comparing combined warfarin and aspirin with aspirin alone in survivors of acute myocardial infarction: primary results of the CHAMP study. Circulation 105:557–563
Huynh T, Theroux P, Bogaty P, Nasmith J, Solymoss S (2001) Aspirin, warfarin, or the combination for secondary prevention of coronary events in patients with acute coronary syndromes and prior coronary artery bypass surgery. Circulation 103:3069–3074
Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H (2002) Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 347:969–974
Cohen M, Adams PC, Parry G, Xiong J, Chamberlain D, Wieczorek I et al (1994) Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group. Circulation 89:81–88
Coumadin Aspirin Reinfarction Study (CARS) Investigators (1997) Randomised double-blind trial of fixed low-dose warfarin with aspirin after myocardial infarction. Lancet 350:389–396
Anand SS, Yusuf S, Pogue J, Weitz JI, Flather M (1998) Long-term oral anticoagulant therapy in patients with unstable angina or suspected non-Q-wave myocardial infarction: organization to assess strategies for ischemic syndromes (OASIS) pilot study results. Circulation 98:1064–1070
van Es RF, Jonker JJ, Verheugt FW, Deckers JW, Grobbee DE (2002) Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet 360:109–113
Brouwer MA, van den Bergh PJ, Aengevaeren WR, Veen G, Luijten HE, Hertzberger DP et al (2002) Aspirin plus coumarin versus aspirin alone in the prevention of reocclusion after fibrinolysis for acute myocardial infarction: results of the Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis (APRICOT)-2 Trial. Circulation 106:659–665
Herlitz J, Holm J, Peterson M, Karlson BW, Haglid Evander M, Erhardt L (2004) Effect of fixed low-dose warfarin added to aspirin in the long term after acute myocardial infarction; the LoWASA Study. Eur Heart J 25:232–239
The Organization to Assess Strategies for Ischemic Syndromes (OASIS) Investigators (2001) Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina. J Am Coll Cardiol 37:475–484
Williams MJ, Morison IM, Parker JH, Stewart RA (1997) Progression of the culprit lesion in unstable coronary artery disease with warfarin and aspirin versus aspirin alone: preliminary study. J Am Coll Cardiol 30:364–369
Cohen M, Adams PC, Hawkins L, Bach M, Fuster V (1990) Usefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group). Am J Cardiol 66:1287
Zibaeenezhad MJ, Mowla A, Sorbi MH (2004) Warfarin and aspirin versus aspirin alone in patients with acute myocardial infarction: a pilot study. Angiology 55:17–20
Smith P, Arnesen H, Holme I (1990) The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med 323:147–152
Walenga JM, Hoppensteadt D, Pifarre R, Cressman MD, Hunninghake DB, Fox NL et al (1999) Hemostatic effects of 1 mg daily warfarin on post CABG patients. Post CABG Studies Investigators. J Thromb Thrombolysis 7:313–318
Parashar S, Kella D, Reid KJ, Spertus JA, Tang F, Langberg J et al (2013) New-onset atrial fibrillation after acute myocardial infarction and its relation to admission biomarkers (from the TRIUMPH registry). Am J Cardiol 112:1390