Dramatic effect of early clopidogrel administration in reducing mortality and MACE rates in ACS patients
BACKGROUND: Patients who have acute coronary syndromes with or without ST-segment elevation have high rates of major vascular events. We evaluated the efficacy of early clopidogrel administration (300 mg) (<24 hours) when given with aspirin in such patients.
METHODS: We included 30,243 patients who had an acute coronary syndrome with or without ST segment elevation. Data on early clopidogrel administration were available for 24,463 (81%). Some 15,525 (51%) of the total cohort were administrated clopidogrel within 24h of admission.
RESULTS: In-hospital death occurred in 2.9% of the patients in the early clopidogrel group treated with primary PCI and in 11.4% of the patients in the other group without primary percutaneous coronary intervention (PCI) and no early clopidogrel. The unadjusted clopidogrel odds ratio (OR) for mortality was 0.31 (95% confidence interval 0.27–0.34; p <0.001). Incidence of major adverse cardiac death (MACE) was 4.1% in the early clopidogrel group treated with 1°PCI and 13.5% in the other group without primary PCI and no early clopidogrel (OR 0.35, confidence interval 0.32–0.39, p <0.001). Early clopidogrel administration and PCI were the only treatment lowering mortality as shown by mutlivariate analysis.
CONCLUSIONS: The early administration of the anti-platelet agent clopidogrel in patients with acute coronary syndromes with or without ST-segment elevation has a beneficial effect on mortality and major adverse cardiac events. The lower mortality rate and incidence of MACE emerged with a combination of primary PCI and early clopidogrel administration.
- ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2011:32:2999–3054.
- Van de Werf F, Bax J, Betriu A, et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation. Eur Heart J. 2008; 29:2909–45.
- Husted S, Evidence-based prescribing and adherence to antiplatelet therapy – how much difference do they make to patients with atherothrombosis? Int J Cardiol. 2009; 134:150–9.
- Alexander D, Ou FS, Roe MT, et al. Use of and in hospital outcomes after early clopidogrel therapy in patients not undergoing an early invasive strategy for treatment of non-ST-segment elevation myocardial infarction: Results from Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines (CRUSADE). Am Heart J. 2008; 156:606–12.
- Silber S, Albertsson P, Avilés FF, et al. Guidelines for percutaneous coronary interventions. Eur Heart J. 2005; 26:804–47.
- Jackevicius CA, Tu JV, Demers V, et al. Cardiovascular outcomes after a change in prescription policy for clopidogrel. N Engl J Med. 2008; 359:1802–10.
- The CURE Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–500.
- Outcome of patients with acute coronary syndrome in hospitals of different sizes. A report from the AMIS Plus Registry. Radovanovic D, Urban P, Simon R, Schmidli M, Maggiorini M, Rickli H, Stauffer JC, Seifert B, Gutzwiller F, Erne P; AMIS Plus Investigators. Swiss Med Wkly. 2010;140(21-22):314–22.
- Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study Lancet. 2001;358:527–33.
- Sean C. Beinart, Paul Kolm, Emir Veledar, Zefeng Zhang, Elizabeth M. Mahoney, Olivier Bouin, et al. Long-term cost effectiveness of early and sustained dual oral antiplatelet therapy with clopidogrel given for up to one year after percutaneous coronary intervention: Results from the Clopidogrel for the Reduction of Events During Observation (CREDO) Trial. J Am Coll Cardiol. 2005;46:761–9.
- Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation N Engl J Med. 2001;345:494–502.
- Steinhubl SR, Berger PB, Mann 3rd JT, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;288:2411–20.
- Banihashemi B, Goodman SG, Yan RT, Welsh RC, Mehta SR, Montalescot G, et al.; Global Registry of Acute Coronary Events (GRACE/GRACE(2)) Investigators. Underutilization of clopidogrel and glycoprotein IIb/IIIa inhibitors in non-ST-elevation acute coronary syndrome patients: the Canadian global registry of acute coronary events (GRACE) experience. Am Heart J. 2009;158:917–24.
- Montalescot G, Dallongeville J, van Belle E, et al. STEMI and NSTEMI: are they so different? 1 year outcomes in acute myocardial infarction as defined by the ESC/ACC definition (the OPERA registry). Eur Heart J. 2007;28:1409–17.
- Dangas G, Mehran R, Guagliumi G, Caixeta A, Witzenbichler B, Aoki J, et al.; HORIZONS-AMI Trial Investigators. Role of clopidogrel loading dose in patients with ST-segment elevation myocardial infarction undergoing primary angioplasty: results from the HORIZONS-AMI (harmonizing outcomes with revascularization and stents in acute myocardial infarction) trial. J Am Coll Cardiol. 2009;54:1438–46.
- Bland JM and Altman DG. Statistics Notes: The odds ratio. BMJ. 2000;320:1468.