Picotamide reduced all cause mortality more than aspirin in type 2 diabetes mellitus and peripheral arterial disease

and commentary also appear in ACP Journal Club. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . For correspondence: Dr S Coccheri, University of Bologna, Bologna, Italy. coccheri@med.unibo.it Source of funding: Novartis S.p.a. Commentary P atients with type 2 diabetes have increased platelet adhesiveness. As a result, aggressive antiplatelet therapy would be expected to improve CV outcomes. However, 2 recent publications have shown that while aspirin improved CV outcomes in non-diabetic patients, this was not the case in patients with diabetes. 3 Aspirin inhibits platelet cyclooxygenase activity, leading to a decrease in thromboxane A2 (a potent platelet activator) while simultaneously decreasing the production of prostacyclin (a mediator known to decrease platelet aggregation and to produce vasodilation). The reduced benefit of aspirin in patients with diabetes is thought to occur because the loss of thromboxane A2 is minimised by the presence of numerous other platelet activators/aggregators present in the diabetic state. Thus, the platelet remains activated/aggregable while having lost the antiaggregating influence of prostacyclin. As a result, specific thromboxane A2 blockers have been developed to provide antithromboxane benefits without lowering prostacyclin concentrations. The 24 month DAVID study by Serneri et al compared picotamide with daily aspirin in patients with type 2 diabetes and PAD, and showed a decreased risk of all cause mortality. The only disappointing finding was the non-significant reduction of the composite endpoint of mortality and non-fatal CV events. This leaves the interpretation difficult and a need for further confirmatory trials. If proven equivalent to or better than aspirin in CV prevention, picotamide (which causes less bleeding requiring hospital admission and a lower frequency of gastrointestinal discomfort than aspirin) will be a welcome addition to calm the hyperactive platelets in diabetic patients. As wewait, the current recommendation by the American Diabetes Association of the use of daily aspirin (75–162 mg) in diabetic patients with vascular disease, age .40 years, or with additional CV risk factors, should be followed. Donald A Smith, MD, MPH Mount Sinai School of Medicine, New York, New York, USA 1 Colwell JA, Nesto RW. Diabetes Care 2003;26:2181–8. 2 Antithrombotic Trialists’ Collaboration. BMJ 2002;324:71–86. 3 Sacco M, Pellegrini F, Roncaglioni MC, et al. Diabetes Care 2003;26:3264–72. 4 Colwell JA. Diabetes Care 2004;27(Suppl 1):S72–3. Picotamide v aspirin for type 2 diabetes mellitus and peripheral arterial disease* Outcomes at 24 months Picotamide Aspirin RRR (95% CI) NNT (CI) All cause mortality 2.8% 5.1% 45% (2 to 69) 44 (22 to 1025) Composite endpoint 7.5% 9.0% 16% (–22 to 43) Not significant *Composite endpoint = death and non-fatal cardiovascular events. Other abbreviations defined in glossary; RRR, NNT, and CI calculated from data in article. THERAPEUTICS 79 EBM Volume 10 June 2005 www.evidence-basedmedicine.com