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Background: An antithrombotic drug is needed that safely reduces cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). We therefore assessed the tolerability and safety of SCH 530348-an oral platelet protease-activated receptor-1 antagonist., Methods: We randomly assigned patients aged 45 years or older and undergoing non-urgent PCI or coronary angiography with planned PCI to an oral loading dose of SCH 530348 (10 mg, 20 mg, or 40 mg) or matching placebo in a 3:1 ratio in a multicentre international study. Those in the SCH 530348 group who subsequently underwent PCI (primary PCI cohort) continued taking an oral maintenance dose (0.5 mg, 1.0 mg, or 2.5 mg per day), and patients in the placebo group continued placebo for 60 days. The primary endpoint was the incidence of clinically significant major or minor bleeding according to the thrombolysis in myocardial infarction (TIMI) scale. Both investigators and patients were unaware of treatment allocation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00132912., Findings: 257 patients were assigned to placebo and 773 to SCH 530348. The primary endpoint occurred in 2 (2%) of 129, 3 (3%) of 120, and 7 (4%) of 173 patients, respectively, in the SCH 530348 10 mg, 20 mg, and 40 mg groups compared with 5 (3%) of 151 patients in the placebo group (p=0.5786). TIMI major plus minor bleeding occurred in 3 (2%) of 136, 5 (4%) of 139, and 4 (3%) of 138 patients given SCH 530348 0.5 mg, 1.0 mg, and 2.5 mg once per day, respectively (p=0.7561)., Interpretation: Oral SCH 530348 was generally well tolerated and did not cause increased TIMI bleeding, even when administered concomitantly with aspirin and clopidogrel. Further testing in phase III trials to accurately define the safety and efficacy of SCH 530348 is warranted.

Background: Listing status for heart transplantation (Tx) patients was changed in 1999 from Status 1 and 2 to Status 1A, 1B and 2. Because the selection process was modified in favor of seriously ill patients, it was not clear whether this change would affect survival or other aspects of transplant management., Methods: We examined outcomes in 551 patients transplanted at our institution between 1986 and 2002 (pre-1999: n = 419; post-1999: n = 132) to determine the effects of change in listing protocol on transplant outcome., Results: Using Cox proportional hazard analysis, survival was not different between pre-1999 (pre) and post-1999 (post). Overall waiting-list times were longer post-1999 (pre: 134 +/- 10.5 days, post: 172 +/- 15.6 days; p = 0.044), and were longer post-1999 for blood groups A (177 vs 123 days), B (96 vs 84 days) and O (229 vs 172 days), but were shorter post for blood group AB (42 vs 68 days). Survival was not affected by age (pre: 53.7 +/- 0.52 years, post: 53.1 +/- 1.04 years; hazard ratio [HR] 1.00; 95% confidence interval [CI] 0.996 to 1.023; p = 0.181), male gender (HR 1.132; 95% CI 0.822 to 1.56; p = 0.447) or waiting-list time. Serum creatinine was similar between the 2 groups (pre: 1.25 +/- 0.02, post: 1.26 +/- 0.04; p = 0.794), whereas pulmonary artery (PA) diastolic pressure was increased post-1999 (pre: 24.9 +/- 0.46, post: 27.0 +/- 0.74; p = 0.023). Survival was not affected by PA pressure (HR 1.00; 95% CI 0.986 to 1.014; p = 0.976), but an elevated pre-transplant creatinine reduced survival (HR 1.484; 95% CI 1.139 to 1.933; p = 0.003)., Conclusions: The change in listing status implemented in 1999 caused an increase in wait times for patients with blood types A, B and O, and shortened wait time for type AB; however, no differences occurred in overall post-transplant survival after the change in listing protocol. Age, gender and PA pressure had no effect on survival in either time period, whereas pre-transplant serum creatinine decreased survival in both patient groups.