BACKGROUND Inflammation is causally related to atherothrombosis. Treatment with canakinumab, a monoclonal antibody that inhibits inflammation by neutralizing interleukin-1β, resulted in a lower rate of cardiovascular events than placebo in a previous randomized trial. We sought to determine whether an alternative approach to inflammation inhibition with low-dose methotrexate might provide similar benefit. METHODS We conducted a randomized, double-blind trial of low-dose methotrexate (at a target dose of 15 to 20 mg weekly) or matching placebo in 4786 patients with previous myocardial infarction or multivessel coronary disease who additionally had either type 2 diabetes or the metabolic syndrome. All participants received 1 mg of folate daily. The primary end point at the onset of the trial was a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Near the conclusion of the trial, but before unblinding, hospitalization for unstable angina that led to urgent revascularization was added to the primary end point. RESULTS The trial was stopped after a median follow-up of 2.3 years. Methotrexate did not result in lower interleukin-1β, interleukin-6, or C-reactive protein levels than placebo. The final primary end point occurred in 201 patients in the methotrexate group and in 207 in the placebo group (incidence rate, 4.13 vs. 4.31 per 100 person-years; hazard ratio, 0.96; 95% confidence interval [CI], 0.79 to 1.16). The original primary end point occurred in 170 patients in the methotrexate group and in 167 in the placebo group (incidence rate, 3.46 vs. 3.43 per 100 person-years; hazard ratio, 1.01; 95% CI, 0.82 to 1.25). Methotrexate was associated with elevations in liver-enzyme levels, reductions in leukocyte counts and hematocrit levels, and a higher incidence of non–basal-cell skin cancers than placebo. CONCLUSIONS Among patients with stable atherosclerosis, low-dose methotrexate did not reduce levels of interleukin-1β, interleukin-6, or C-reactive protein and did not result in fewer cardiovascular events than placebo. (Funded by the National Heart, Lung, and Blood Institute; CIRT ClinicalTrials.gov number, .)

Background 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are widely prescribed for hyperlipidemia, yet their effect on the evolution of coronary atherosclerosis has not been defined.Methods and Results To address this issue, 331 patients with diffuse but not necessarily severe coronary atherosclerosis documented on a recent arteriogram and with fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a randomized, double-blind, placebo-controlled trial. All patients received intensive dietary counseling. Lovastatin or placebo was begun at 20 mg/d and was titrated to 40 and 80 mg during the first 16 weeks to attain a fasting low-density lipoprotein (LDL) cholesterol .130 mg/dL. The mean lova-

Rapid reperfusion of the infarct-related artery is the cornerstone of therapy for the management of acute ST-elevation myocardial infarction (STEMI). Canada's geography presents unique challenges for timely delivery of reperfusion therapy for STEMI patients. The Canadian R ESUM ELa reperfusion rapide de l'artère responsable de l'infarctus est la pierre angulaire th erapeutique de la prise en charge de l'infarctus aigu du myocarde avec el evation du segment ST (STEMI). Les caract eristiques g eographiques du Canada posent des d efis particuliers pour prodiguer aux

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Out of hospital cardiac arrest (OHCA) is associated with a low rate of survival to hospital discharge and high rates of neurological morbidity among survivors. Programmatic efforts to institute and integrate OHCA best care practices from the bystander response through to the in-hospital phase have been associated with improved patient outcomes. This Canadian Cardiovascular Society position statement was developed to provide comprehensive yet practical recommendations to guide the in-hospital care of OHCA patients. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system recommendations have been generated. Recommendations on initial care delivery on the basis of presenting rhythm, appropriate use of targeted temperature management, postarrest angiography, and revascularization in the initial phase of care of the OHCA patient are detailed within this statement. In addition, further description of best practices on sedation, use of neuromuscular blockade, oxygenation targets, hemodynamic monitoring, and blood product transfusion triggers in the critical care environment are contained in this document. Last, discussion of optimal care systems for the OHCA patient is provided. These guidelines aim to serve as a practical guide to optimize the in-hospital care of survivors of cardiac arrest and encourage the adoption of "best practice" protocols and treatment pathways. Emphasis is placed on integrating these aspects of in-hospital care as part of a postarrest "care bundle." It is hoped that this position statement can assist all medical professionals who treat survivors of cardiac arrest.