A derivative of methoxy-isophthalic acid, picotamide not only inhibits the thromboxane A2 receptor but also inhibits thromboxane synthetase at equivalent concentrations.34 In contrast to aspirin, picotamide does not interfere with prostacyclin production. In a double-blind, placebo-controlled study in 2,304 patients with PAD, treatment with picotamide (300 mg bid) or placebo was administered for 18 months.35 End points of the study included major events (cardiovascular death, MI, stroke, or amputation) and minor events (unstable angina, transient ischemic attacks, hypertension, renal failure, or worsening of PAD symptoms). Although the intention-to-treat analysis revealed an 18.9% reduction in major plus minor events with picotamide, this difference was not statistically significant. However, the on-treatment analysis showed a 22.8% reduction in the same end points. Bleeding side effects were similar in the two groups. A post hoc subgroup analysis of the data from the 438 patients with diabetes included in the study revealed a 45.2% reduction in major and minor end points with picotamide compared with placebo.36 These findings prompted a randomized trial comparing picotamide (600 mg bid) with aspirin (320 mg/d) in 1,209 patients with diabetes with PAD.37 The primary efficacy end point was overall mortality, whereas the secondary end point was the composite of death and cardiovascular events. At 2 years, the overall mortality rates with picotamide and aspirin were 3.0% and 5.5%, respectively (relative risk [RR], 0.55; 95% CI, 0.31-0.98). Cardiovascular events occurred in 7.1% of patients given picotamide and 8.7% of those treated with aspirin. The difference in the combined end point of mortality plus cardiovascular events between the two groups did not reach statistical significance. Bleeding events were infrequent with both picotamide and aspirin (1.3% and 2.0%, respectively). Although these results are promising, additional studies are needed to establish the role of picotamide in patients with diabetes with PAD.