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 enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; 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.

• MeSH
• amputace statistika a číselné údaje   MeSH
• Aspirin aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• cévní mozková příhoda epidemiologie   etiologie   prevence a kontrola   MeSH
• dolní končetina krevní zásobení   chirurgie   MeSH
• dvojitá slepá metoda MeSH
• incidence MeSH
• infarkt myokardu epidemiologie   etiologie   prevence a kontrola   MeSH
• inhibitory agregace trombocytů aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• inhibitory faktoru Xa aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• kardiovaskulární nemoci mortalita   prevence a kontrola   MeSH
• kombinovaná farmakoterapie MeSH
• krvácení chemicky indukované   MeSH
• lidé středního věku MeSH
• lidé MeSH
• morbidita MeSH
• nemoci arterie carotis komplikace   farmakoterapie   epidemiologie   MeSH
• onemocnění periferních arterií komplikace   farmakoterapie   epidemiologie   MeSH
• rivaroxaban aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• Aspirin MeSH
• inhibitory agregace trombocytů MeSH
• inhibitory faktoru Xa MeSH
• rivaroxaban MeSH

OBJECTIVES: To evaluate the association of masked hypertension (MH) in treated type 2 diabetic patients without history of cardiovascular disease with carotid artery target organ damage. METHODS: Sixty-four type 2 diabetic patients treated for hypertension with office BP below 140/90 mm Hg were examined by 24-h BP monitoring and carotid sonography. MH was diagnosed if daily mean ambulatory BP was >or=135/85 mm Hg. The association of MH with carotid artery parameters was evaluated. RESULTS: The average age of patients was 62+/-5 years. Twenty-four patients had MH (37.5%). Carotid artery IMT was 0.74+/-0.08 mm in patients with MH and 0.69+/-0.06 mm without MH (p=0.03). The distensibility of common carotid artery was 0.24+/-0.07 mmHg(-1) in patients with MH and 0.29+/-0.1mm Hg(-1) without MH (p=0.14). After adjustment for age, gender, smoking, duration of diabetes, BMI and clinic blood pressure (BP) values the association of MH with carotid artery IMT was sustained. CONCLUSION: Masked hypertension in treated type 2 diabetic patients is associated with carotid artery IMT.

• MeSH
• antihypertenziva terapeutické užití   MeSH
• diabetes mellitus 2. typu komplikace   farmakoterapie   patologie   MeSH
• hypertenze diagnóza   farmakoterapie   etiologie   MeSH
• krevní tlak účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci arterie carotis komplikace   farmakoterapie   patologie   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antihypertenziva MeSH