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IIIa inhibitors reduce mortality in diabetic patients with non–ST-segment elevation acute coronary syndromes
General Cardiology
an approach would increase the bleeding risk beyond those seen in this trial. Currently bivalirudin should be considered primarily when patients develop heparin-induced thrombocytopenia. RM
Abstracts
Thrombin-Specific Anticoagulation With Bivalirudin vs. Heparin in Patients Receiving Fibrinolytic Therapy for Acute Myocardial Infarction: The HERO-2 Randomised Trial
Platelet Glycoprotein IIb/IIIa Inhibitors Reduce Mortality in Diabetic Patients With Non–ST-Segment Elevation Acute Coronary Syndromes
The Hirulog and Early Reperfusion or Occlusion (HERO)-2 Trial Investigators. Lancet 2001;358:1855– 63.
Roffi M, Chew DP, Mukherjee D, et al. Circulation 2001;104: 2767–71.
Study Question: Is bivalirudin (formerly hirulog, a thrombinspecific anticoagulant) more effective than heparin when combined with streptokinase for the treatment of patients with acute ST elevation myocardial infarction (STEMI)? Methods: Patients with STEMI were randomized in an openlabel trial to an intravenous bolus and 48-hour infusion of either bivalirudin (0.25 mg/kg bolus followed by 0.5 mg/ kg/hour over first 12 hours and 0.25 mg/kg/hour over the next 36 hours; n⫽8516) or heparin (5000 units bolus followed by an infusion of 1000 units/hour if body weight ⱖ80 kg or 800 units/hour if body weight ⬍80 kg; n⫽8557), together with 1.5 million units of streptokinase over 60 minutes. Results: The primary end point (30-day mortality) was similar in the bivalirudin and heparin groups (10.8% vs. 10.9%, odds ratio [OR] 0.99, 95% confidence interval [CI] 0.90 –1.09; p⫽0.85). The adjusted mortality (for baseline risk factors) was also similar in the two groups (10.5% for bivalirudin and 10.9% for heparin [OR 0.96, 95% CI 0.86 – 1.07; p⫽0.46]). There were significantly fewer reinfarctions within 96 h (secondary end point) in the bivalirudin group than in the heparin group (1.6% vs. 2.3%, OR 0.70, 95% CI 0.56 – 0.87, p⫽0.001). Severe bleeding occurred in 0.7% in the bivalirudin group vs. 0.5% in the heparin group (p⫽0.07), while intracerebral bleeding occurred in 0.6% vs. 0.4%, respectively (p⫽0.09). The rates of moderate and mild bleeding were significantly higher in the bivalirudin group than the heparin group (OR 1.32, 95% CI 1.00 – 1.74, p⫽0.05; and OR 1.47, 95% CI 1.34 –1.62, p⬍0.0001; respectively). Transfusions were given in similar proportions in the two groups (1.4% vs. 1.1%, p⫽0.11). Conclusions: Bivalirudin compared with unfractionated heparin reduced the rate of adjudicated reinfarction within 96 h by 30% with similar 30-day mortality in patients with STEMI receiving streptokinase. This occurred at the risk of a small absolute increase in mild and moderate bleeding in patients given bivalirudin. Perspective: While the trial suggests that bivalirudin is a reasonable anticoagulation option in patients receiving streptokinase for STEMI, this trial’s results should be interpreted with caution for patients with STEMI who receive TPA or other newer thrombolytic agents then and undergo an aggressive invasive strategy with revascularization. Such
Study Question: Is platelet glycoprotein (GP) IIb/IIIa receptor inhibition particularly beneficial in diabetic patients with acute coronary syndromes (ACS)? Methods: A meta-analysis of the diabetic populations (n⫽6458) enrolled in the six large-scale platelet GP IIb/IIIa inhibitor randomized ACS trials was performed. These trials included PRISM, PRISM-PLUS, PARAGON A, PARAGON B, PURSUIT and GUSTO IV. Results: Platelet GP IIb/IIIa inhibition was associated with a significantly lower mortality at 30 days as compared to placebo (6.2% vs. 4.6%, odds ratio [OR] 0.74; 95% confidence interval [CI] 0.59 to 0.92; p⫽0.007). No survival benefit was observed among the 23,072 nondiabetic patients (mortality 3.0% for patients who did and those who did not receive GP IIb/IIIa receptor antagonist). Thirty-day mortality was significantly higher among ACS patients with diabetes compared to those without it (adjusted OR 2.05, p⬍0.0001), similar for all ACS patients treated with or without GP IIb/IIIa receptor antagonists (OR 1.01, p⫽0.85) but substantially lower for diabetic patients treated with GP II/IIIa receptor blockers (adjusted OR 0.75, p⫽0.036). Diabetic patients undergoing percutaneous coronary intervention (PCI) during index hospitalization (n⫽1279) benefited the most from the use of these agents with a striking 70% mortality reduction at 30 days (4.0% vs. 1.2%, OR 0.30; 95% CI 0.14 to 0.69; p⫽0.002). Conclusions: This meta-analysis shows that GP IIb/IIIa receptor antagonists significantly decreases mortality at 30 days in ACS patients with diabetes. This survival benefit appears to be more pronounced in patients undergoing PCI. Therefore, platelet GP IIb/IIIa inhibitors should be strongly considered in all diabetic patients with ACS. Perspective: The intense platelet activation and aggregation that occurs among diabetic patients with ACS may explain the much greater benefit observed with intravenous GP IIb/IIIa in these patients. Therefore, ACS patients with diabetes should be considered for GP IIa/IIIb inhibition along with other subgroups likely to derive the most benefit from such therapy (ACS patients with ST-segment deviations, elevated troponin and those undergoing PCI). RM
ACC CURRENT JOURNAL REVIEW May/Jun 2002
11
an approach would increase the bleeding risk beyond those seen in this trial. Currently bivalirudin should be considered primarily when patients develop heparin-induced thrombocytopenia. RM
Abstracts
Thrombin-Specific Anticoagulation With Bivalirudin vs. Heparin in Patients Receiving Fibrinolytic Therapy for Acute Myocardial Infarction: The HERO-2 Randomised Trial
Platelet Glycoprotein IIb/IIIa Inhibitors Reduce Mortality in Diabetic Patients With Non–ST-Segment Elevation Acute Coronary Syndromes
The Hirulog and Early Reperfusion or Occlusion (HERO)-2 Trial Investigators. Lancet 2001;358:1855– 63.
Roffi M, Chew DP, Mukherjee D, et al. Circulation 2001;104: 2767–71.
Study Question: Is bivalirudin (formerly hirulog, a thrombinspecific anticoagulant) more effective than heparin when combined with streptokinase for the treatment of patients with acute ST elevation myocardial infarction (STEMI)? Methods: Patients with STEMI were randomized in an openlabel trial to an intravenous bolus and 48-hour infusion of either bivalirudin (0.25 mg/kg bolus followed by 0.5 mg/ kg/hour over first 12 hours and 0.25 mg/kg/hour over the next 36 hours; n⫽8516) or heparin (5000 units bolus followed by an infusion of 1000 units/hour if body weight ⱖ80 kg or 800 units/hour if body weight ⬍80 kg; n⫽8557), together with 1.5 million units of streptokinase over 60 minutes. Results: The primary end point (30-day mortality) was similar in the bivalirudin and heparin groups (10.8% vs. 10.9%, odds ratio [OR] 0.99, 95% confidence interval [CI] 0.90 –1.09; p⫽0.85). The adjusted mortality (for baseline risk factors) was also similar in the two groups (10.5% for bivalirudin and 10.9% for heparin [OR 0.96, 95% CI 0.86 – 1.07; p⫽0.46]). There were significantly fewer reinfarctions within 96 h (secondary end point) in the bivalirudin group than in the heparin group (1.6% vs. 2.3%, OR 0.70, 95% CI 0.56 – 0.87, p⫽0.001). Severe bleeding occurred in 0.7% in the bivalirudin group vs. 0.5% in the heparin group (p⫽0.07), while intracerebral bleeding occurred in 0.6% vs. 0.4%, respectively (p⫽0.09). The rates of moderate and mild bleeding were significantly higher in the bivalirudin group than the heparin group (OR 1.32, 95% CI 1.00 – 1.74, p⫽0.05; and OR 1.47, 95% CI 1.34 –1.62, p⬍0.0001; respectively). Transfusions were given in similar proportions in the two groups (1.4% vs. 1.1%, p⫽0.11). Conclusions: Bivalirudin compared with unfractionated heparin reduced the rate of adjudicated reinfarction within 96 h by 30% with similar 30-day mortality in patients with STEMI receiving streptokinase. This occurred at the risk of a small absolute increase in mild and moderate bleeding in patients given bivalirudin. Perspective: While the trial suggests that bivalirudin is a reasonable anticoagulation option in patients receiving streptokinase for STEMI, this trial’s results should be interpreted with caution for patients with STEMI who receive TPA or other newer thrombolytic agents then and undergo an aggressive invasive strategy with revascularization. Such
Study Question: Is platelet glycoprotein (GP) IIb/IIIa receptor inhibition particularly beneficial in diabetic patients with acute coronary syndromes (ACS)? Methods: A meta-analysis of the diabetic populations (n⫽6458) enrolled in the six large-scale platelet GP IIb/IIIa inhibitor randomized ACS trials was performed. These trials included PRISM, PRISM-PLUS, PARAGON A, PARAGON B, PURSUIT and GUSTO IV. Results: Platelet GP IIb/IIIa inhibition was associated with a significantly lower mortality at 30 days as compared to placebo (6.2% vs. 4.6%, odds ratio [OR] 0.74; 95% confidence interval [CI] 0.59 to 0.92; p⫽0.007). No survival benefit was observed among the 23,072 nondiabetic patients (mortality 3.0% for patients who did and those who did not receive GP IIb/IIIa receptor antagonist). Thirty-day mortality was significantly higher among ACS patients with diabetes compared to those without it (adjusted OR 2.05, p⬍0.0001), similar for all ACS patients treated with or without GP IIb/IIIa receptor antagonists (OR 1.01, p⫽0.85) but substantially lower for diabetic patients treated with GP II/IIIa receptor blockers (adjusted OR 0.75, p⫽0.036). Diabetic patients undergoing percutaneous coronary intervention (PCI) during index hospitalization (n⫽1279) benefited the most from the use of these agents with a striking 70% mortality reduction at 30 days (4.0% vs. 1.2%, OR 0.30; 95% CI 0.14 to 0.69; p⫽0.002). Conclusions: This meta-analysis shows that GP IIb/IIIa receptor antagonists significantly decreases mortality at 30 days in ACS patients with diabetes. This survival benefit appears to be more pronounced in patients undergoing PCI. Therefore, platelet GP IIb/IIIa inhibitors should be strongly considered in all diabetic patients with ACS. Perspective: The intense platelet activation and aggregation that occurs among diabetic patients with ACS may explain the much greater benefit observed with intravenous GP IIb/IIIa in these patients. Therefore, ACS patients with diabetes should be considered for GP IIa/IIIb inhibition along with other subgroups likely to derive the most benefit from such therapy (ACS patients with ST-segment deviations, elevated troponin and those undergoing PCI). RM
ACC CURRENT JOURNAL REVIEW May/Jun 2002
11