Low-dose of oral factor Xa inhibitors in patients with a recent acute coronary syndrome: A systematic review and meta-analysis of randomized trials

BACKGROUND: Recently, randomized controlled trials (RCTs) have shown that therapy with new oral activated factor X (Xa) inhibitors in acute coronary syndrome (ACS) yielded a reduction of ischemic events. However, this therapy was associated with a dose-related increase in major bleeding complications. We aimed to perform a systematic review and meta-analysis to appraise the clinical efficacy and safety of the lowest doses of oral factor Xa inhibitors compared with placebo in patients after a recent ACS. METHODS: The primary endpoint was cardiovascular mortality. The rate of new myocardial infarction (MI) was the secondary efficacy endpoint, whereas major bleeding complications were recorded as a safety endpoint. Five RCTs were included in the meta-analysis enrolling a total of 25,643 patients. RESULTS: There was no significant difference in mortality between patients treated with new antithrombotics compared with those receiving the standard therapy: odds ratio (OR), [95% confidence interval (CI)] = 0.97 [0.72-1.31], p = 0.86. Recurrent MI rates were decreased in the anti-Xa group: OR [95%CI] = 0.86 [0.76-0.98], p = 0.02, number needed to treat (NNT) = 189. The administration of new oral anticoagulants was associated with a strongly increased risk of major bleedings compared with the standard treatment: OR [95%CI] = 3.24 [2.29-4.59], p < 0.001, number needed to harm (NNH) = 104; similarly, intracranial bleeding rates were significantly higher in the anti-Xa arm. CONCLUSIONS: The addition of the new oral anticoagulants on top of standard therapy in the setting of ACS results in an excessive risk of major bleedings without any clear evidence of outweighing clinical benefits

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

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, 120.29 percentage points; 95% confidence interval [CI], 120.32 to 120.27). 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). CONCLUSIONS Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events. (Funded by Merck Sharp & Dohme; TECOS ClinicalTrials.gov number, NCT00790205.