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The article presents a randomised controlled study that assessed the tolerability and safety of the oral platelet protease-activated receptor-1 antagonist SCH530348. The study was conducted in response to the need for an antithrombotic drug that safely reduces cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). Patients undergoing non-urgent PCI or coronary anigography with planned PCI were randomly assigned to SCH 530348 or matching placebo. The incidence of clinically significant major or minor bleeding according to the thrombolysis in myocardial infarction scale was the primary endpoint. Researchers found that SCH 530348 was well tolerated and did not cause increased thrombolysis in myocardial infarction (TIMI) bleeding.

SUMMARY BACKGROUND: Two placebo-controlled trials testing intravenous platelet glycoprotein IIb/IIIa antagonists in the setting of percutaneous coronary revascularisation with intracoronary stents have shown a durable reduction in ischaemic events to 6 months. These trials differed regarding their patient population, IIb/IIIa inhibitor, and reported extent of benefit. Whether a small-molecule agent affecting only the IIb/IIIa receptor would provide a similar outcome for ischaemic events and clinical restenosis at 6 months when directly compared with a monoclonal antibody known to affect several integrin receptors is unknown. METHODS: In 18 countries at 149 hospitals, 4809 patients undergoing elective or urgent stent implantation were randomly assigned a bolus and infusion of tirofiban or abciximab. Patients were followed for 6 months for the occurrence of death, myocardial infarction, and any target-vessel revascularisation. The results at 30 days have been reported previously. FINDINGS: At 6 months the composite endpoint of death, myocardial infarction, and target-vessel revascularisation occurred in 356 (14.8%) patients who received tirofiban and 345 (14.3%) patients who received abciximab (hazard ratio 1.04, 95% CI 0.90-1.21; p=0.591). The rates for the individual endpoints were 191 (8.0%) versus 159 (6.6%) for myocardial infarction (hazard ratio 1.21, 95% CI 0.98-1.50; p=0.074), 26 (1.1%) versus 25 (1.0%) for death (1.04, 0.60-1.80; p=0.893), and 194 (8.1%) versus 208 (8.6%) for target-vessel revascularisation (0.93, 0.77-1.14; p=0.495). INTERPRETATION: At 6 months, tirofiban provided a similar level of overall protection to abciximab against the composite of death, myocardial infarction, and any target-vessel revascularisation. [ABSTRACT FROM AUTHOR]

The authors discuss the effectiveness of percutaneous coronary intervention (PCI) for patients with non-acute coronary artery disease, referring to a study by Thomas Trikalinos and colleagues that examined PCI and medical therapy. They believe the results of the study should be unsurprising. They note that prevention of secondary vascular disease can be effective and that clinicians should treat the underlying artherosclerotic process with lifestyle modifications and drugs.

Summary: Background: Platelet glycoprotein IIb/IIIa inhibitors have been shown to reduce cardiac complications in patients undergoing percutaneous coronary intervention. The clinical efficacy of these drugs in acute coronary syndromes, however, is still unclear. We did a meta-analysis of all large randomised trials designed to study the clinical efficacy and safety of glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes who were not routinely scheduled to undergo early coronary revascularisation. Methods: Inclusion criteria were: randomisation of patients with acute coronary syndromes but without persistent ST elevation; comparison of a glycoprotein IIb/IIIa inhibitor with placebo or control therapy; non-recommendation of early coronary revascularisation during study-drug infusion; and enrolment of at least 1000 patients. Data on individual patients were obtained from all participants in these trials. Findings: Six trials, enrolling 31 402 patients, fulfilled the inclusion criteria. 30 days after randomisation, 3530 (11.2%) patients died or developed a myocardial infarction. At 30 days, a 9% reduction in the odds of death or myocardial infarction was seen with glycoprotein IIb/IIIa inhibitors compared with placebo or control (10.8% [1980/18 297] vs 11.8% [1550/13 105] events; odds ratio 0.91 [95% CI 0.84-0.98]; p=0.015). The relative treatment benefit was similar in subgroups of patients according to important clinical baseline characteristics; hence, the absolute treatment benefit was largest in high-risk patients. An unexpected and significant interaction was seen between sex and allocated treatment, with a treatment benefit in men (0.81 [0.75-0.89] but not in women (1.15 [1.01-1.30]). However, once patients were stratified according to troponin concentration, there was no evidence of a sex difference in treatment response, and a risk reduction was seen in men and women with raised troponin concentrations. Major bleeding complicatio... [ABSTRACT FROM AUTHOR]

Background: Two placebo-controlled trials testing intravenous platelet glycoprotein IIb/IIIa antagonists in the setting of percutaneous coronary revascularisation with intracoronary stents have shown a durable reduction in ischaemic events to 6 months. These trials differed regarding their patient population, IIb/IIIa inhibitor, and reported extent of benefit. Whether a small-molecule agent affecting only the IIb/IIIa receptor would provide a similar outcome for ischaemic events and clinical restenosis at 6 months when directly compared with a monoclonal antibody known to affect several integrin receptors is unknown.Methods: In 18 countries at 149 hospitals, 4809 patients undergoing elective or urgent stent implantation were randomly assigned a bolus and infusion of tirofiban or abciximab. Patients were followed for 6 months for the occurrence of death, myocardial infarction, and any target-vessel revascularisation. The results at 30 days have been reported previously.Findings: At 6 months the composite endpoint of death, myocardial infarction, and target-vessel revascularisation occurred in 356 (14.8%) patients who received tirofiban and 345 (14.3%) patients who received abciximab (hazard ratio 1.04, 95% CI 0.90-1.21; p=0.591). The rates for the individual endpoints were 191 (8.0%) versus 159 (6.6%) for myocardial infarction (hazard ratio 1.21, 95% CI 0.98-1.50; p=0.074), 26 (1.1%) versus 25 (1.0%) for death (1.04, 0.60-1.80; p=0.893), and 194 (8.1%) versus 208 (8.6%) for target-vessel revascularisation (0.93, 0.77-1.14; p=0.495).Interpretation: At 6 months, tirofiban provided a similar level of overall protection to abciximab against the composite of death, myocardial infarction, and any target-vessel revascularisation. [ABSTRACT FROM AUTHOR]