BACKGROUND Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications. METHODS This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS Between March 12, 2013, and May 10, 2016, we ; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043). INTERPRETATION Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding. FUNDING Bayer AG. Methods This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, i...

Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

Egészségügyi Informatikai Fejlesztő és Továbbképző Intézet, BudapestBevezetés: A heveny szívizominfraktust elszenvedett betegek halálozására vonatkozó hazai adatok hiányosak. Célki-tűzés: A szerzők a Magyar Infarctus Regiszterben szereplő 8582 infarktusos beteg (4981 ST-elevációval járó myocardialis infarctus) adatainak elemzésével a kórházi, a 30 napos és az egyéves halálozás vizsgálatát tűzték ki célul. Budapest öt kerületében rögzítették a prehospitális haláleseteket. Módszer: A halálozás kockázati tényezőinek vizsgálatára logisztikus regressziós analízist végeztek, majd ellenőrizték a modell illeszkedését. Eredmények: A kórházi, a 30 napos, illetve az egyéves halálozás az ST-elevációval járó infarktusos betegcsoportban 3,7%, 9,5%, illetve 16,5%, a nem ST-elevációs betegcsoportban 4%, 9,8% és 21,7% volt. A nem ST-elevációval járó infarktus miatt kezelt betegek egyéves halálozása szignifi kánsan magasabb volt. A halálozás kockázati tényezőit vizsgálva az életkor, a Killip-stá-dium, a kórelőzményben szereplő myocardialis infarctus, stroke, valamint a diabetes bizonyult prognosztikus jelentőségűnek. A percutan coronariaintervenció mindkét típusú infarktusban nagyon jelentősen javította a betegek rövid és hosszú távú életkilátásait. Következtetések: A prehospitális halálozás igen jelentős volt, a 30 napon belül bekövet-kező események 72,5%-a kórházon kívül történt. Orv. Hetil., 2013, 154, 1297 Short and long term prognosis of patients with myocardial infarction Hungarian Myocardial Infarction RegistryIntroduction: Mortality data of patients with acute myocardial infarction are incomplete in Hungary. Aim: The aim of the authors was to analyse the data of 8582 myocardial infarction patients (4981 with ST-elevation myocardial infarction) registered in the Hungarian Myocardial Infarction Register in order to defi ne the hospital, 30-day, and 1-year mortality. To evaluate the prehospital mortality of myocardial infarction, all myocardial infarction and sudden death were registered in fi ve districts of Budapest. Method: Multivariate logistic regression was performed to defi ne risk factors of mortality and the model were assessed using c statistics. Results: The hospital, 30-day and 1-year mortality of patients with ST elevation myocardial infarction were 3.7%, 9.5% and 16.5%, respectively. In patients without ST elevation myocardial infarction these fi gures were 4%, 9.8% and 21.7%, respectively. The 1-year mortality of patients without ST elevation was higher than those of with ST elevation and the difference was statistically signifi cant. Age, Killip class, diabetes mellitus, history of stroke and myocardial infarction were independent predictors of death. Coronary intervention improved the prognosis of patients with myocardial infarction signifi cantly. Conclusions: The rate of pre-hospital mortality was considerably high; 72.5% of 30 day mortality occurred before admission to hospital. Orv. Hetil., 2013, 154, 1297-1302

Background: Among patients with diabetes mellitus (diabetes) and chronic coronary disease (CCD), it is unclear if invasive management improves outcomes when added to medical therapy. Methods: The ISCHEMIA Trials (ISCHEMIA and ISCHEMIA CKD) randomized CCD patients to an invasive (medical therapy + angiography and revascularization if feasible) or a conservative approach (medical therapy alone with revascularization if medical therapy failed). Cohorts were combined after no trial-specific effects were observed. Diabetes was defined by history, HbA1c ≥6.5%, or use of glucose-lowering medication. The primary outcome was all-cause death or myocardial infarction (MI). Heterogeneity of effect of invasive management on death or MI was evaluated using a Bayesian approach to protect against random high or low estimates of treatment effect for patients with vs. without diabetes and for diabetes subgroups of clinical (female sex and insulin use) and anatomic features (coronary artery disease [CAD] severity or left ventricular function). Results: Of 5,900 participants with complete baseline data, the median age was 64 years interquartile range (IQR) [57-70], 24% were female, and the median estimated glomerular filtration was 80 ml/min/1.73 2 IQR [64-95]. Among the 2,553 (43%) of participants with diabetes, median percent hemoglobin A1c was 7% IQR [7-8%], and 30% were insulin treated. Participants with diabetes had a 49% increased hazard of death or MI (HR 1.49; 95% CI: 1.31-1.70, P<0.001). At median 3.1-year follow-up the adjusted event-free survival was 0.54 (95% bootstrapped CI: 0.48, 0.60) and 0.66 (95% bootstrapped CI: 0.61, 0.71) for patients with vs. without diabetes - a 12% (95% bootstrapped CI: 4%, 20%) absolute decrease in event-free survival among participants with diabetes. Female and male patients with insulin-treated diabetes had an adjusted event-free survival of 0.52 (95% bootstrapped CI: 0.42, 0.56) and 0.49 (95% bootstrapped CI: 0.42, 0.56), respectively. There was no difference in death or MI between strategies for patients with vs. without diabetes, or for clinical (female sex or insulin use) or anatomic features (CAD severity or left ventricular function) of patients with diabetes. Conclusions: Despite higher risk for death or MI, CCD patients with diabetes did not derive incremental benefit from routine invasive management compared with initial medical therapy alone. Clinical Trial Registration: URL: http://www.clinicaltrials.gov Unique identifier: NCT01471522