Cardiovascular safety of celecoxib in acute myocardial infarction patients: a nested case-control study

The objective was to measure the impact of exposure to coxibs and non-steroidal antiinflammatory drugs (NSAID) on morbidity and mortality in older patients with acute myocardial infarction (AMI). A nested case-control study was carried out using an exhaustive population-based cohort of patients aged 66 years and older living in Quebec (Canada) who survived a hospitalization for AMI (ICD-9 410) between 1999 and 2002. The main variables were all-cause and cardiovascular (CV) death, subsequent hospital admission for AMI, and a composite end-point including recurrent AMI or CV death. Conditional logistic regressions were used to estimate the risk of mortality and morbidity. A total of 19,823 patients aged 66 years and older survived hospitalization for AMI in the province of Quebec between 1999 and 2002. After controlling for covariables, the risk of subsequent AMI and the risk of composite end-point were increased by the use of rofecoxib. The risk of subsequent AMI was particularly high for new rofecoxib users (HR 2.47, 95% CI 1.57–3.89). No increased risk was observed for celecoxib users. No increased risk of CV death was observed for patients exposed to coxibs or NSAIDs. Patients newly exposed to NSAIDs were at an increased risk of death (HR 2.22, 95% CI 1.30–3.77) and of composite end-point (HR 2.28, 95% CI 1.35–3.84). Users of rofecoxib and NSAIDs, but not celecoxib, were at an increased risk of recurrent AMI and of composite end-point. Surprisingly, no increased risk of CV death was observed. Further studies are needed to better understand these apparently contradictory results

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)

The genetic and ecophysiological diversity of Microcystis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171576/1/emi15615.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171576/2/emi15615-sup-0002-FigureS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171576/3/emi15615_am.pd