Antithrombotic Therapy in Peripheral Artery Disease

Jones WS, Patel MR.
Antithrombotic Therapy in Peripheral Artery Disease: Generating and Translating Evidence Into Practice. J Am Coll Cardiol 2018;71:352-362.

The following are key points to remember from this review article about antithrombotic therapy in peripheral artery disease (PAD):

  1. Atherosclerotic cardiovascular disease affects more than 200 million adults worldwide. Lower extremity PAD is associated with significant morbidity and mortality; 5-10% of PAD patients will have recurrent events each year.
  2. Most patients with PAD are asymptomatic. PAD-associated symptoms include atypical leg pain, intermittent claudication, ischemic rest pain, ulceration, and gangrene.
  3. Patients with PAD have an elevated risk of cardiovascular death, myocardial infarction (MI), and stroke. The annual risk of cardiovascular death, MI, or hospitalization is 21%. The annual risk of major adverse limb events varies from 2-10% based on age, symptom classification, concomitant medical therapy, and prior revascularization procedures.
  4. In the United States, medical treatment of PAD has traditionally involved antiplatelet monotherapy (either aspirin or clopidogrel), which is associated with an estimated 25% risk reduction in major vascular events (American Heart Association/American College of Cardiology lower extremity PAD guideline Class I, Level of Evidence A recommendation).
  5. Despite being considered a “coronary artery disease (CAD) risk equivalent,” the use of antiplatelet and statin medications is significantly lower among PAD patients as compared to patients with CAD. Clinicians and health centers are encouraged to improve medical therapy rates, using techniques such as population health queries, audit and feedback, and other quality improvement or learning health system methods.
  6. In patients with symptoms despite background medical therapy, cilostazole and supervised exercise training have been associated with improvements in walking distance and quality of life. There are few proven medical therapies for patients with critical limb ischemia, where the mortality rate is nearly 50% at 1 year.
  7. Vorapaxar is a protease-activated receptor-1 (PAR-1) inhibitor that has been shown to reduce cardiovascular death, MI, or stroke by 1.2% (11.3% vs. 11.9% with placebo, hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.78-1.14). Despite lower risk of hospitalization, there was an increase in moderate and severe bleeding associated with vorapaxar use.
  8. In the recently published COMPASS trial, patients with stable atherosclerotic vascular disease (including PAD) were randomized to one of three arms: aspirin 100 mg daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg daily plus rivaroxaban 2.5 mg twice daily. After 2 years of follow-up, use of rivaroxaban 2.5 mg plus aspirin 100 mg was associated with lower rates of MI, ischemic stroke, and cardiovascular death (4.1% vs. 5.4%, HR, 0.76; 95% CI, 0.66-0.86). There was higher major bleeding with the combination therapy (3.1% vs. 1.9%, HR, 1.70; 95% CI, 1.40-2.15).
  9. For patients with PAD in the COMPASS trial, the use of rivaroxaban 2.5 mg plus aspirin 100 mg was associated with lower rates of MI, ischemic stroke, and cardiovascular death (5.1% vs. 6.9%, HR, 0.72; 95% CI, 0.57-0.90). The risk of major bleeding was higher with combination therapy (3.1% vs. 1.9%, HR, 1.61; 95% CI, 1.12-2.31).
  10. In the ongoing VOYAGER PAD study, patients with PAD are randomized to rivaroxaban 2.5 mg twice daily or placebo in addition to aspirin 100 mg after peripheral or endovascular PAD revascularization.
  11. In the ongoing BEST-CLI study, patients with critical limb ischemia are randomized (open-label) to surgical or endovascular revascularization in addition to best medical therapy.

Clinical Topics: Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Nonstatins, Novel Agents, Statins, Acute Heart Failure, Interventions and Coronary Artery Disease, Interventions and Vascular Medicine, Exercise

Keywords: Aspirin, Atherosclerosis, Coronary Artery Disease, Intermittent Claudication, Endovascular Procedures, Exercise, Exercise Therapy, Fibrinolytic Agents, Gangrene, Geriatrics, Heart Failure, Hemorrhage, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Ischemia, Myocardial Infarction, Myocardial Revascularization, Peripheral Arterial Disease, Platelet Aggregation Inhibitors, Primary Prevention, Quality Improvement, Quality of Life, Risk Reduction Behavior, Stroke, Thrombosis, Vascular Diseases

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