Étude de la saxagliptine sur la survenue d'événements cardiovasculaires chez des patients diabétiques de type 2 (étude SAVOR-TIMI 53) : description de l'étude et des patients

The Saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus-thrombolysis in myocardial infarction (SAVOR-TIMI 53) trial was designed to test the effect of saxagliptin, a DPP-4 inhibitor, on the prevention of the occurrence of cardiovascular events in patients with type 2 diabetes (T2D). It is a 5-year, randomized, double-blind trial, conducted against placebo in 27 countries on 16,496 T2D patients. They received either a placebo or the saxagliptin 5 mg, or 2,5 mg in patients with renal failure (creatinine clearance <50 ml/minute). The treatment was given in addition to the usual treatment but gliptins or GLP-1 analogues were excluded. Patients were in secondary (80%) or primary cardiovascular prevention but with an additional risk factor (20%). The primary endpoint was a combined endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The trial was built to test a hypothesis from a non-inferiority to suggest the cardiovascular safety of the saxagliptin but also an assumption of superiority in cardiovascular prevention with a goal to reduce the relative risk of major cardiovascular events (primary endpoint) by 17%. The number of patients enrolled allowed testing these hypotheses with a good statistical power when 1040 events were observed. Patients were included in 27 countries with a large majority in North America and Western Europe. At inclusion the average age was 65.0 years with predominantly male (67%) patients. The average duration of diabetes was 11.9 years and mean HbA1c at baseline was 8.0+1.4%. Almost 12% of patients had retinopathy, 18% nephropathy and 2.5% amputation. Only 5% had no diabetes treatment and ~41% received insulin ± oral antidiabetics. The vast majority of patients (80%) received treatment with statins, antihypertensive and antiplatelet agents. Patients with cardiovascular history had more microvascular complications and were more often treated with insulin. The overall incidence of the primary endpoint was 2%/year. Investigators were asked to minimize the drop out of the patients less than 2,8%/year. The results of this study are expected in September 2013.