1013-109 Effect of Picotamide in Preventing Cardiovascular Events in 438 Diabetic Patients: Results of a Multi-Centre, Placebo Controlled, 18-Month Study

Abstract

In the A.D.E.P (Atherosclerotic Disease Evolution by Picotamide) study 2,304 patients with peripheral obstructive arterial disease (POAD) were recruited for a double blind 18-month multi-centre trial comparing picotamide (300 mg t.i.d.), an antiplatelet drug which inhibits thromboxane A2 (TxA2) synthase and antagonizes TxA2 receptor, and placebo. In the study population as a whole, 151 events (13.1%) occurred on placebo and 122 (10.6%) on picotamide, with a relative risk reduction of 19%, (p = 0.056, Logrank test, intention to treat analysis). The effect of picotamide was assessed in the A.D.E.P subgroup of diabetic patients, in order to test if the drug was still effective in patients at higher risk of cardiovascular complications. Diabetic patients were 438 (230 on picotamide and 208 on placebo). Most of them were male (80%), with a mean age of 64 years (min 40, max 75). Six per cent were insulin-dependent. The main risk factors (smoking, hypertension, previous vascular surgery, ankle/arm pressure ratio, WBC count and fibrinogen) were similarly distributed in the two groups. Diabetic POAD patients on placebo suffered from a total of 33 cardiovascular events (12 major and 21 minor) (15.9%), whereas those on picotamide suffered from a total of 20 events (6 major and 14 minor) (8.7%) (relative reduction of risk: 45.2%, p = 0.022 at Logrank test, intention to treat analysis). Both major and minor events occurred more frequently in the placebo than in the picotamide group. The overall incidence of major events was 5.8% on placebo and 2.6% on picotamide (relative risk reduction of 59.8%). Death occurred in 6 patients on placebo (2.9%) and in 3 on picotamide (1.3%). Non fatal major events (stroke, myocardial infarction and amputation) were 6 on placebo and 3 on picotamide. Minor events were 10.1% on placebo and 6.1% on picotamide (relative risk reduction of 39.8%). Adverse reaction, mainly gastrointestinal, occurred in 16% of patients, regardless of the treatment. In conclusion, this analysis indicates that Picotamide significantly reduces cardiovascular events in diabetic POAD patients, suggesting its potential use in patients at high risk of atherosclerotic progression.