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...

The known Sex differences in the management and outcomes of patients with acute coronary syndromes have been reported, but many reported analyses were not adjusted for confounding covariates.The new Despite broader awareness of STEMI protocols, revascularisation rates for women with STEMI are lower than for men. In hospital, rates of major adverse cardiovascular events and mortality were similar, but at 6 months were significantly higher for women. Women were less frequently referred for cardiac rehabilitation or prescribed preventive medications on discharge.The implications Clinicians should consider potential barriers to equity for women in the management of STEMI. C ardiovascular disease is the leading cause of morbidity and mortality in both sexes, but an extensive literature has described differences between men and women in clinical presentation and pathophysiology that may influence management and outcomes.1,2 Observational studies have found that women with acute coronary syndromes (ACS) more frequently present with atypical symptoms, 3 with more comorbidities, 4 and at an older age, and that plaque rupture 5 and high risk features 3,6,7 are less likely to be identified during angiography than in men.Large hospital registry studies have found that women with ACS are less likely to receive evidence-based management, including coronary angiography and appropriate medications in hospital and at discharge. 4,6,[8][9][10] Australian data similarly indicate that women with ACS are underinvestigated and that evidence-based therapies are less often prescribed than for male patients. [10][11][12] Some studies have found that the higher mortality rates for women than for men with ACS in hospital, 4,6,9,10,13 at 30 days, 7,14 and at 6 months 3,13 are attenuated after adjusting for age and comorbid conditions, but others have found that differences persist despite adjustment. 8 In our investigation, we wanted to avoid confounding by the significant interactions between sex and type of ACS identified in earlier studies. 7,14 We therefore focused on patients with STEMI, as the clinical presentation and diagnosis of this condition is relatively consistent and the patients receive a largely standardised management plan. We hypothesised that management and outcomes for men and women with STEMI should be similar after adjusting for risk level.Our specific aims were to identify sex differences in the characteristics and outcomes of patients presenting with STEMI; to examine associations between sex and outcomes (morbidity and mortality) after adjusting for relevant covariates; and to explore whether there with differences in the prescribing of preventive medications for men and women after STEMI. MethodsWe analysed data from the CONCORDANCE (Cooperative National Registry of Acute Coronary care, Guideline Adherence and Clinical Events) registry, an ongoing prospective ACS registry Main outcome measures: Rates of revascularisation (percutaneous coronary intervention [PCI], thrombolysis, coronary artery bypass grafting [CAB...

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Background: Inflammation plays a crucial role in clinical manifestations and complications of acute coronary syndromes (ACS). Colchicine, a commonly used treatment for gout, has recently emerged as a novel therapeutic option in cardiovascular medicine owing to its anti-inflammatory properties. We sought to determine the potential usefulness of colchicine treatment in patients with ACS. Methods: This was a multicenter, randomized, double-blind, placebo-controlled trial involving 17 hospitals in Australia that provide acute cardiac care service. Eligible participants were adults (18–85 years) who presented with ACS and had evidence of coronary artery disease on coronary angiography managed with either percutaneous coronary intervention or medical therapy. Patients were assigned to receive either colchicine (0.5 mg twice daily for the first month, then 0.5 mg daily for 11 months) or placebo, in addition to standard secondary prevention pharmacotherapy, and were followed up for a minimum of 12 months. The primary outcome was a composite of all-cause mortality, ACS, ischemia-driven (unplanned) urgent revascularization, and noncardioembolic ischemic stroke in a time to event analysis. Results: A total of 795 patients were recruited between December 2015 and September 2018 (mean age, 59.8±10.3 years; 21% female), with 396 assigned to the colchicine group and 399 to the placebo group. Over the 12-month follow-up, there were 24 events in the colchicine group compared with 38 events in the placebo group ( P =0.09, log-rank). There was a higher rate of total death (8 versus 1; P =0.017, log-rank) and, in particular, noncardiovascular death in the colchicine group (5 versus 0; P =0.024, log-rank). The rates of reported adverse effects were not different (colchicine 23.0% versus placebo 24.3%), and they were predominantly gastrointestinal symptoms (colchicine, 23.0% versus placebo, 20.8%). Conclusions: The addition of colchicine to standard medical therapy did not significantly affect cardiovascular outcomes at 12 months in patients with ACS and was associated with a higher rate of mortality. Registration: URL: https://www.anzctr.org.au ; Unique identifier: ACTRN12615000861550.