Temporal Changes in Secondary Prevention and Cardiovascular Outcomes after Revascularization for Peripheral Arterial Disease in Denmark: A Nationwide Cohort Study

Background: Patients with peripheral arterial disease (PAD) are at increased risk of cardiovascular morbidity and mortality. Medical prevention with antithrombotic and statin therapies is a mainstay of treatment to prevent adverse outcomes; nevertheless, patients with PAD are often undertreated. This study described the temporal changes in medical prevention and adverse outcomes in a national cohort of patients with symptomatic PAD after revascularization. Methods: We identified all patients with a first open surgical or endovascular revascularization procedure in the lower extremities or abdomen in Denmark, from 2000 to 2016. We examined temporal changes in the use of aspirin, clopidogrel, and statins and one-year cause-specific hazard ratios (HR) for adverse clinical outcomes, after adjusting for procedure type, treatment indication, age, sex and cardiovascular risk factors. The analyses were performed overall, and within strata of index procedure (endovascular vs. surgical), treatment indication, age, sex, and high-risk comorbidities. Results: Between 2000 and 2016, we identified 32,911 patients that underwent revascularization for symptomatic PAD. The mean age was 69 years and increased over time as did the burden of comorbidity. The cumulative incidence of medication use increased between 2000-2004 and 2013-2016, respectively, from 57.3% to 64.3% for aspirin, 3.6% to 24.8% for clopidogrel, and from 36.2% to 77.1% for statins. Concurrently, the one-year outcome rates declined. Compared with 2000-2004, the adjusted HRs in 2013-2016 were 0.73 (95% CI 0.62-0.84) for major adverse cardiovascular events, 0.92 (95% CI 0.85-1.00) for major adverse limb events, 0.60 (95% CI 0.48-0.74) for myocardial infarction, 0.94 (95% CI 0.75-1.18) for ischemic stroke, 0.92 (95% CI 0.75-1.12) for major bleeding, 0.54 (95% CI 0.39-0.76) for cardiovascular death, and 0.80 (95% CI 0.72-0.88) for all cause death. These improvements in prognosis were most prominent from 2000-2004 to 2005-2008, and occurred in all strata of index procedure, treatment indication, sex, age and comorbidity. In contrast, the adjusted HR for major amputations was 1.00 (95% CI 0.90-1.11), when comparing 2013-2016 to 2000-2004. Conclusions: Medical prevention of adverse events has increased considerably over time in patients that underwent revascularization for symptomatic PAD. This increase was accompanied by reductions in all adverse outcomes, except major amputations.