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Drug Evaluation in Atherosclerotic Vascular Disease in Diabetics - DAVID – (Picotamide vs. Aspirin)
Description:
The goal of the trial was to evaluate treatment with picotamide, a combined inhibitor of thromboxane A2 synthase and receptor, compared with aspirin among diabetic patients with peripheral arterial disease (PAD).
Hypothesis:
Treatment with picotamide will be associated with a reduction in cardiovascular morbidity and mortality compared with treatment with aspirin among diabetic patients with PAD.
Study Design
Study Design:
Patients Enrolled: 1,209
Mean Follow Up: Two years
Mean Patient Age: Mean age 64 years
Female: 27
Patient Populations:
Age 40-75 years, history of type 2 diabetes for five years or more, and PAD
Exclusions:
Myocardial infarction, stroke, or unstable angina in prior six months; severe neurological or mental deficits likely to make the patient noncompliant; severe comorbidity likely to limit life expectancy to <2 years; serum creatinine >2.0 mg/dl; high risk of endoocular bleeding; alanine aminotransferase or aspartate aminotransferase >3 times the upper limit of normal; platelets <100,000 per mm3; active peptic ulcer or gastroenteric bleeding in prior six months; pregnancy; severe, uncontrolled hypertension; total cholesterol level ≥300 mg/dl; picotamide or aspirin sensitivity; scheduled for major surgery; or requiring long-term anticoagulant
Primary Endpoints:
Overall mortality
Secondary Endpoints:
Combined incidence of death and nonfatal vascular events including myocardial infarction, ischemic stroke, and major amputation
Drug/Procedures Used:
Patients were randomized to picotamide (600 mg twice daily, n=603) or aspirin (320 mg once daily, n=606) treatment for two years.
Principal Findings:
Baseline characteristics were well matched between the study groups, with 70% using oral antidiabetic medications and 31% using insulin. Total mortality was lower in the picotamide group compared with aspirin (3.0% vs. 5.5%, relative risk 0.55, 95% confidence interval 0.31-0.98, p=0.047). The secondary endpoint of mortality plus nonfatal vascular events occurred in 7.1% of the picotamide group and 8.7% of the aspirin group (p=0.30). Bleeding events occurred in 1.3% of the picotamide group and 2.0% of the aspirin group.
The study drug was discontinued in 26.4% of patients in each group. Discontinuation due to an adverse event was similar in both treatment groups (11.9% picotamide group vs. 14.4% aspirin group).
Interpretation:
Among type 2 diabetic patients with PAD, treatment with picotamide, a combined inhibitor of thromboxane A2 synthase and receptor, was associated with a reduction in total mortality compared with aspirin.
The efficacy of prophylaxis antiplatelet therapy with aspirin in diabetic patients at high risk for vascular events has been uncertain, given the lack of randomized trials specifically focused on this population and the mainly subgroup analysis of other large trials to evaluate efficacy. The present study is the first large-scale randomized trial to compare these two antiplatelet agents in this study population. The mortality benefit associated with picotamide was promising, although the lack of efficacy in the secondary endpoint that combined morbidity along with mortality brings into question the mechanism for the survival advantage.
References:
Neri Serneri GG, Coccheri S, Marubini E, Violi F, for the Drug Evaluation in Atherosclerotic Vascular Disease in Diabetics (DAVID) Study Group. Picotamide, a combined inhibitor of thromboxane A2 synthase and receptor, reduces 2-year mortality in diabetics with peripheral arterial disease: the DAVID study. Eur Heart J 2004;25:1845-52.
Keywords: Risk, Insulin, Phthalic Acids, Platelet Aggregation Inhibitors, Thromboxane A2, Diabetes Mellitus, Type 2, Peripheral Arterial Disease, Hypoglycemic Agents, Confidence Intervals, Peripheral Vascular Diseases
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