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- Harrington, Robert A., et al.
(författare)
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The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA.CER) trial : study design and rationale
- 2009
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 158:3, s. 327-334
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Tidskriftsartikel (refereegranskat)abstract
- Background The protease-activated receptor 1 (PAR-1), the main platelet receptor for thrombin, represents a novel target for treatment of arterial thrombosis, and SCH 530348 is an orally active, selective, competitive PAR-1 antagonist. We designed TRA.CER to evaluate the efficacy and safety of SCH 530348 compared with placebo in addition to standard of care in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and high-risk features. Trial design TRA.CER is a prospective, randomized, double-blind, multicenter, phase III trial with an original estimated sample size of 10,000 subjects. Our primary objective is to demonstrate that SCH 530348 in addition to standard of care will reduce the incidence of the composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization compared with standard of care alone. Our key secondary objective is to determine whether SCH 530348 will reduce the composite of cardiovascular death, MI, or stroke compared with standard of care alone. Secondary objectives related to safety are the composite of moderate and severe GUSTO bleeding and clinically significant TIMI bleeding. The trial will continue until a predetermined minimum number of centrally adjudicated primary and key secondary end point events have occurred and all subjects have participated in the study for at least I year. The TRA.CER trial is part of the large phase III SCH 530348 development program that includes a concomitant evaluation in secondary prevention. Conclusion TRA.CER will define efficacy and safety of the novel platelet PAR-1 inhibitor SCH 530348 in the treatment of high-risk patients with NSTE ACS in the setting of current treatment strategies.
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| 2. |
- Koshizaka, Masaya, et al.
(författare)
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Obesity, Diabetes, and Acute Coronary Syndrome : Differences Between Asians and Whites
- 2017
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Ingår i: American Journal of Medicine. - : Elsevier BV. - 0002-9343 .- 1555-7162. ; 130:10, s. 1170-1176
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Most diabetes and cardiovascular studies have been conducted in white patients, with data being extrapolated to other population groups.METHODS:For this analysis, patient-level data were extracted from 5 randomized clinical trials in patients with acute coronary syndrome; we compared obesity levels between Asian and white populations, stratified by diabetes status. By using an adjusted Cox proportional hazards model, hazard ratios (HRs) for cardiovascular outcomes after an acute coronary syndrome were determined.RESULTS:We identified 49,224 patient records from the 5 trials, with 3176 Asians and 46,048 whites. Whites with diabetes had higher body mass index values than those without diabetes (median 29.3 vs 27.2 kg/m(2); P <.0001), whereas Asians with diabetes and without diabetes had similar body mass index (24.7 vs 24.2 kg/m2). Asians with diabetes (HR, 1.63; 95% confidence interval [CI], 1.32-2.02), whites with diabetes (HR, 1.15; 95% CI, 1.06-1.25), and Asians without diabetes (HR, 1.36; 95% CI, 1.14-1.64) had higher rates of the composite of death, myocardial infarction, or stroke at 30 days than whites without diabetes. Asians with diabetes (HR, 1.84; 95% CI, 1.47-2.31), whites with diabetes (HR, 1.47; 95% CI, 1.33-1.62), and Asians without diabetes (HR, 1.38; 95% CI, 1.11-1.73) had higher rates of death at 1 year compared with whites without diabetes. There were no significant interactions between race and diabetes for ischemic outcomes.CONCLUSIONS:Although Asians with diabetes and acute coronary syndrome are less likely to be obese than their white counterparts, their risk for death or recurrent ischemic events was not lower.
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| 3. |
- Tricoci, Pierluigi, et al.
(författare)
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Thrombin-receptor antagonist vorapaxar in acute coronary syndromes
- 2012
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 366:1, s. 20-33
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation.METHODS:In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization.RESULTS:Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups.CONCLUSIONS:In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).
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