ABSTRACT
BACKGROUND:Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina.RESULTS:During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P=0.98). There were no significant between-group differences in rates of acute pancreatitis (P=0.07) or pancreatic cancer (P=0.32).
Subject(s)
Diabetes Mellitus , Cardiovascular Diseases , Sitagliptin PhosphateABSTRACT
Objective: To define the changing incidence, risk, and therapy of acute myocardial infarction (A311). Data sources: Review of contemporary AMI data from the University of Alberta Hospitals, six other sites of the Clinical Quality Improvement Network (CQIN), and other Canadian and international centers. Data synthesis: Ischemic heart disease is age-related and the Canadian population is rapidly aging. At the University of Alberta Hospitals, the incidence of Q wave AMI (per 100,000 population) in 1985 was 113 and has remained unchanged (NS) since that time (129 in 1994). In contrast, the combined incidence of non.Q-wave AMI and unstable angina has increased markedly, from 74 in 1985 to 226 in 1994 (p < 0.05). The use of proven efficacious therapies for AMI has greatly increased in recent years, with thrombolytic drugs being given to approximately 35;percnt; of all patients by 1993; and beta-blockers and aspirin to 75;percnt; and 98;percnt; of patients, respectively. However, females and patients older than 70 years' despite their greater risk, received significantly less efficacious medication than males and younger AMI patients. The use of calcium antagonists decreased from a peak utilization rate of 60;percnt; for all AMI patients in 1989 to less than 10;percnt; by 1993. In-hospital AMI mortality risk has also decreased in the last several years, particularly among higher risk older patients (35;percnt;, 1987 vs. 19;percnt;,1993). In a population of 3896 consecutive AMI patients, recruited largely in 1992 and 1993 from seven CQIN sites, logistic regression analyses revealed aspirin was associated with the greatest relative risk reduction (61%); beta-blocker and thrombolytic therapy were related to risk reductions of 55;percnt; and 16;percnt;, respectively. Incremental age was the most important factor associated with increased relative risk in AMI, overall and in both sexes; sex was not an independent risk predictor. Qualitatively very similar AMI incidence, risk, and treatment data have also been recently observed in other centers in Canada, the United States, and elsewhere. Conclusions: Although widespread primary or secondary prevention is possibly contributory, the recent static incidence of Q-wave AMI and the marked increase in unstable angina and non-Q-wave AMI are more likely due to enhanced health awareness and diagnosis-seeking behavior in the population at risk. The decline in AMI mortality, at least for high-risk acute care patients, is compatible with a clinically relevant secondary prevention effect. There are still, however, windows of opportunity to further improve AMI outcomes by increasing the utilization of proven efficacious therapy, especially among women and older patients. Another particularly attractive epidemiologic benefit in the immediate future would accrue from the further development and effective use of efficacious therapies directed against unstable angina and n-Q-wave AMI.
