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Current oasis 7

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Current oasis 7

  1. 1. CURRENT-OASIS 7: Clopidogrel and aspirin optimal dose Usage in individuals undergoing percutaneous coronary intervention to Reduce RecurrENT events – seventh Organization to Assess Strategies in Ischemic Symptoms <ul><li>Purpose </li></ul><ul><li>To assess whether doubling of the loading and maintenance dose of clopidogrel for 7 days was better than the standard dose, and whether high-dose aspirin was better than low-dose aspirin in patients undergoing percutaneous coronary intervention (PCI). </li></ul><ul><li>Reference </li></ul><ul><li>Mehta SR, Tanguay JF, Eikelboom JW, et al. for the CURRENT-OASIS 7 Investigators. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet 2010; 376 :1233–1243. </li></ul>
  2. 2. CURRENT-OASIS 7: Clopidogrel and aspirin optimal dose Usage in individuals undergoing percutaneous coronary intervention to Reduce Recurrent evENTs – seventh Organization to Assess Strategies in Ischemic Symptoms - TRIAL DESIGN - <ul><li>Design </li></ul><ul><li>Randomized trial with a 2x2 factorial design. </li></ul><ul><li>Patients </li></ul><ul><li>25,086 patients with acute coronary syndromes (ACS) with or without ST-segment elevation and electrocardiographic evidence of ischemia or raised biomarkers. Exclusion criteria included an increased risk of, or active, bleeding. </li></ul><ul><li>Follow-up, primary and secondary endpoints </li></ul><ul><li>The primary outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI) or stroke by 30 days. Secondary outcomes were the primary outcome plus recurrent ischemia, individual outcome components and stent thrombosis. </li></ul><ul><li>Treatment </li></ul><ul><li>Clopidogrel 600 mg on day 1 and 150 mg once daily (od) on days 2–7, or 300 mg on day 1 and 75 mg od on days 2–7, plus aspirin ≥300 mg on day 1 and 300–325 mg or 75–100 mg daily on days 2–30. Other therapies were left to the discretion of the attending physician. </li></ul>
  3. 3. CURRENT-OASIS 7: Clopidogrel and aspirin optimal dose Usage in individuals undergoing percutaneous coronary intervention to Reduce Recurrent evENTs – seventh Organization to Assess Strategies in Ischemic Symptoms - TRIAL DESIGN continued - Baseline characteristics Clopidogrel double-dose (n=8560) Clopidogrel standard-dose (n=8703) Aspirin double-dose (n=8624) Aspirin standard-dose (n=8639) Mean age (years) 61.2 61.2 61.1 61.3 Female sex (%) 24.0% 25.1% 24.9% 24.1% Admission diagnosis Unstable angina or NSTEMI Time from randomization to PCI (h) STEMI Time from randomization to PCI (h) 62.8% 3.1 37.1% 0.5 63.4% 3.3 36.6% 0.5 63.4% 3.2 36.6% 0.5 62.9% 3.2 37.1% 0.5 Previous history Current smoker Hypertension Dyslipidemia Diabetes mellitus MI PCI CABG 37.5% 59.4% 40.3% 22.3% 17.2% 14.6% 5.7% 36.6% 58.8% 40.3% 22.2% 16.8% 14.5% 5.7% 36.8% 59.0% 40.4% 22.9% 17.1% 14.8% 5.6% 37.3% 59.2% 40.2% 21.6% 16.9% 14.3% 5.8% Abbreviations: CABG, coronary artery bypass graft; NSTEMI, non-ST-segment elevation myocardial infarction; STEMI, ST-segment elevation. Mehta et al. Lancet 2010; 376 :1233–1243.
  4. 4. CURRENT-OASIS 7: Clopidogrel and aspirin optimal dose Usage in individuals undergoing percutaneous coronary intervention to Reduce Recurrent evENTs – seventh Organization to Assess Strategies in Ischemic Symptoms - RESULTS - <ul><li>Primary and secondary endpoints </li></ul><ul><li>In the clopidogrel dose comparison, the primary outcome occurred in 3.9% of patients receiving a </li></ul><ul><li>double dose. It also occurred in 4.5% of patients receiving standard dose (adjusted hazard ratio [HR], </li></ul><ul><li>0.86; p =0.039). </li></ul><ul><li>Rates of the secondary combined outcome were also significantly lower in the double-dose group, at </li></ul><ul><li>4.2% versus 5.0% in the standard-dose group (adjusted HR, 0.85; p =0.025). </li></ul><ul><li>There was no significant difference in the rate of the primary outcome or the combined secondary </li></ul><ul><li>outcome between the high- and low-dose aspirin groups, at 4.1% versus 4.2% (adjusted HR, 0.98; </li></ul><ul><li>p =0.76) and 4.4% versus 4.8% (adjusted HR, 0.92; p =0.92), respectively. </li></ul><ul><li>No significant differences in the rate of definite or probable stent thrombosis were observed </li></ul><ul><li>between high- and low-dose aspirin groups (adjusted HR, 0.90; p =0.36). </li></ul><ul><li>Differences between aspirin and clopidogrel dose comparisons </li></ul><ul><li>There was nominally significant heterogeneity between the aspirin and clopidogrel dose groups for the </li></ul><ul><li>primary outcome ( p =0.026). There was no significant heterogeneity for major bleeding ( p =0.42). </li></ul>
  5. 5. CURRENT-OASIS 7: Clopidogrel and aspirin optimal dose Usage in individuals undergoing percutaneous coronary intervention to Reduce Recurrent evENTs – seventh Organization to Assess Strategies in Ischemic Symptoms - RESULTS continued - Major efficacy and safety endpoints Clopidogrel double-dose (n=8560) Clopidogrel standard-dose (n=8703) Hazard ratio (95% CI) p value CV death, MI or stroke CV death, MI, stroke, or recurrent ischemia CV death MI stroke Recurrent ischemia Total mortality CURRENT-defined major bleed CURRENT-defined severe bleed TIMI-defined major bleed Fatal bleed Intracranial bleed 330 (3.9%) 363 (4.2%) 160 (1.9%) 172 (2.0%) 30 (0.4%) 39 (0.5%) 166 (1.9%) 139 (1.6%) 96 (1.1%) 81 (1.0%) 6 (0.07%) 3 (0.04%) 392 (4.5%) 435 (5.0%) 169 (1.9%) 226 (2.6%) 36 (0.4%) 48 (0.6%) 179 (2.1%) 99 (1.1%) 72 (0.8%) 60 (0.7%) 13 (0.2%) 4 (0.05%) 0.86 (0.74–0.99) 0.85 (0.74–0.98) 0.96 (0.77–1.19) 0.79 (0.64–0.96) 0.87 (0.53–1.41) 0.85 (0.56–1.31) 0.94 (0.76–1.16) 1.41 (1.09–1.83) 1.34 (0.99–1.82) 1.36 (0.97–1.90) 0.46 (0.18–1.22) 0.77 (0.17–3.43) 0.039 0.025 0.71 0.018 0.56 0.47 0.57 0.009 0.060 0.074 0.12 0.73 Aspirin high-dose (n=8624) Aspirin low-dose (n=8639) Hazard ratio (95% CI) p value CV death, MI or stroke CV death, MI, stroke, or recurrent ischemia CV death MI stroke Recurrent ischemia Total mortality CURRENT-defined major bleed CURRENT-defined severe bleed TIMI-defined major bleed Fatal bleed Intracranial bleed 356 (41.%) 381 (4.4%) 156 (1.8%) 196 (2.3%) 37 (0.4%) 31 (0.4% 160 (1.9%) 128 (1.5%) 92 (1.1%) 79 (0.9%) 10 (0.1%) 4 (0.05%) 366 (4.2%) 417 (4.8%) 173 (2.0%) 202 (2.4%) 29 (0.3%) 56 (0.7%) 185 (2.1%) 110 (1.3%) 76 (0.9%) 62 (0.7%) 9 (0.1%) 3 (0.03%) 0.98 (0.84–1.13) 0.92 (0.80–1.06) 0.90 (0.72–1.12) 0.97 (0.80–1.19) 1.26 (0.77–2.05) 0.56 (0.36–0.88) 0.86 (0.70–1.07) 1.18 (0.92–1.53) 1.22 (0.90–1.66) 1.29 (0.93–1.80) 1.12 (0.90–1.66) 1.34 (0.30–5.98) 0.76 0.23 0.35 0.80 0.36 0.011 0.18 0.20 0.20 0.13 0.80 0.70 Abbreviations: TIMI, thrombosis in myocardial infarction. Mehta et al. Lancet 2010; 376 :1233–1243.
  6. 6. CURRENT-OASIS 7: Clopidogrel and aspirin optimal dose Usage in individuals undergoing percutaneous coronary intervention to Reduce Recurrent evENTs – seventh Organization to Assess Strategies in Ischemic Symptoms - RESULTS continued - Days Clopidogrel standard-dose Clopidogrel double-dose Cumulative hazard Abbreviations: CI, confidence interval. Primary outcome: clopidogrel dose comparison Mehta et al. Lancet 2010; 376 :1233–1243. 0.0 0.01 0.02 0.04 0.03 0.05 0 3 6 9 12 15 18 21 27 24 30 Adjusted HR, 0.86; 95% CI, 0.74–0.99; p =0.039.
  7. 7. CURRENT-OASIS 7: Clopidogrel and aspirin optimal dose Usage in individuals undergoing percutaneous coronary intervention to Reduce Recurrent evENTs – seventh Organization to Assess Strategies in Ischemic Symptoms - RESULTS continued - Cumulative hazard Days Mehta et al. Lancet 2010; 376 :1233–1243 . Aspirin low-dose Primary outcome: aspirin dose comparison 0.0 0.01 0.02 0.04 0.03 0.05 0 3 6 9 12 15 18 21 27 24 30 Aspirin high-dose Adjusted HR, 0.98; 95 % CI, 0.84–1.13; p =0.76.
  8. 8. CURRENT-OASIS 7: Clopidogrel and aspirin optimal dose Usage in individuals undergoing percutaneous coronary intervention to Reduce Recurrent evENTs – seventh Organization to Assess Strategies in Ischemic Symptoms - SUMMARY - <ul><li>A 7-day double dose of clopidogrel was more effective than the standard-dose regimen in the prevention of the primary outcome of CV death, MI, or stroke, and stent thrombosis for patients who underwent PCI. </li></ul><ul><li>In contrast, high-dose aspirin did not differ significantly from low-dose aspirin in prevention of these outcomes. </li></ul><ul><li>Double-dose clopidogrel increased the risk of major bleeding, but the risk of bleeding that was intracranial or fatal did not increase. Major bleeding did not differ between high-dose and low-dose aspirin groups. </li></ul><ul><li>A double-dose clopidogrel regimen can be considered for all patients with ACS treated with an early invasive strategy and intended PCI. </li></ul>

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