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PAD prevalence was markedly high, considering the low mean age of the studied population (44+/-14.7 yrs). IC was detected in a minority of PAD subjects, indicating a considerable number of asymptomatic individuals. Diabetes, obesity, stroke and IHD were the stronger predictors of PAD. The authors concluded that ABI measurement should be considered in the evaluation of moderate to high cardiovascular risk patients.

Background: The VOYAGER PAD trial demonstrated superiority of rivaroxaban plus aspirin versus aspirin to reduce major cardiac and ischemic limb events following lower extremity revascularization (LER). Clopidogrel is commonly used as a short-term adjunct to aspirin after endovascular revascularization, whether clopidogrel modifies the efficacy and safety of rivaroxaban has not been described. Methods: VOYAGER PAD was a phase 3, international, double-blind, placebo-controlled trial in symptomatic PAD patients undergoing LER randomized to rivaroxaban 2.5 mg twice daily plus 100 mg aspirin daily or rivaroxaban placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke or cardiovascular death. The principal safety endpoint was TIMI major bleeding with ISTH major bleeding a secondary safety outcome. Clopidogrel use was allowed at the discretion of the investigator for up to six months following the qualifying revascularization. Results: 3313 (50.6%) of the randomized patients received clopidogrel, median duration of 29.0 days. Over 3-years the hazard ratio (HR) for the primary outcome of rivaroxaban versus placebo was 0.85 (95% CI 0.71-1.01) with clopidogrel and 0.86 (95% CI 0.73-1.01) without, without statistical heterogeneity (p-interaction =0.92). Rivaroxaban resulted in an early apparent reduction in acute limb ischemia (ALI) within 30 days, HR 0.45 (95%CI 0.14-1.46) with and HR 0.48 (95% CI 0.22-1.01) without clopidogrel (p-interaction = 0.93). Compared with aspirin, rivaroxaban increased TIMI major bleeding similarly regardless of clopidogrel use (p-interaction 0.71). With clopidogrel use >30 days, rivaroxaban was associated with more ISTH major bleeding within 365 days (HR 3.20, 95% CI 1.44-7.13) compared with shorter durations of clopidogrel (p-trend 0.06). Conclusions: In the VOYAGER PAD trial, rivaroxaban plus aspirin reduced the risk of adverse cardiovascular and limb events with an early benefit for ALI regardless of clopidogrel use. The safety of rivaroxaban was consistent regardless of clopidogrel use, but with a trend for more ISTH major bleeding with clopidogrel use > 30 days than a shorter duration. These data support the addition of rivaroxaban to aspirin after LER regardless of concomitant clopidogrel with a short (course ≤ 30 days) associated with less bleeding. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02504216

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In a report by Clarivate Analytics for the Brazilian Coordination for the Improvement of Higher-Level-Education Personnel (CAPES) about the Brazilian research productivity between 2013 and 2018, Brazil ranked 13th (250 680 publications) among countries with the highest research productivity, corresponding to 11% and 16% of the first ranked countries, United States and China, respectively. 1,2 In that period, the publications in Brazil increased by 30%, twice the global mean, 2 with over 50 000 articles published in 2018 only. A good example of that increase has been described in the study analyzing the number of papers published in Nature and Science from the

Background Vascular disease burden after lower extremity revascularization (LER) comprises more than the first event, more vascular beds than the local arteries, and more than one clinical event type. Objectives Assess total arterial and venous thrombotic burden after LER for symptomatic peripheral artery disease (PAD) and effect of low‐dose anticoagulation added to low‐dose antiplatelet therapy. Patients/Methods VOYAGER PAD randomized 6564 symptomatic PAD patients undergoing LER to rivaroxaban 2.5 mg twice‐daily or placebo on aspirin background. Marginal proportional‐hazards models used to generate treatment hazard ratios and associated 95% CIs for first and total events; non‐thrombotic deaths treated as competing terminal events. Incidence rates calculated as number of events per 100 patient‐years follow‐up. Results Over 2.5 years (median), first and total thrombotic event rates: 7.1 and 10.3 events/100 patient‐years, respectively, in placebo group. Two‐thirds (925/1372) of total thrombotic events (arterial 95%, venous 5%) were nonfatal first events. Nearly one‐third of patients with first event had a second arterial or venous thrombotic event. Rivaroxaban plus aspirin reduced first and total arterial and venous thrombotic events to 5.4 and 7.9 events/100 patient‐years, respectively, a reduction in total thrombotic events over aspirin of 23% (HR: 0.77, 95%CI: 0.67–0.89, p = .0005), preventing 6.1 total arterial and venous thrombotic events at 3 years. Conclusions Assessing total arterial and venous thrombotic events, not just first events, provides more complete information about disease burden and absolute on‐treatment impact. Following LER, judicious modulation of more than one coagulation pathway can provide broader benefit than intensifying inhibition of one hemostatic system component.

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