MACE and All-Cause Mortality Reduced With Statin Therapy in Asymptomatic Peripheral Artery Disease

Major cardiovascular adverse events and all-cause mortality were significantly reduced in patients without clinical CVD but with asymptomatic peripheral artery disease.

In patients without clinical cardiovascular disease (CVD) but with asymptomatic peripheral arterial disease (PAD), statin therapy appears effective at reducing major adverse cardiovascular events (MACE) and all-cause mortality.1

As described by the authors, CVD prevention using statins is typically considered a “high-risk” strategy, reserved for patients with a high likelihood of developing disease. Using the ankle-brachial index (ABI) to screen for asymptomatic PAD may be a useful tool for identifying candidates for “intensive risk factor management” because low ABI values are associated with an increased risk of CVD, independent of risk calculated by the Framingham function.

However, as the authors pointed out, ABI screening may not be the ideal screening tool. Guidelines from the American College of Cardiology (ACC), American Heart Association (AHA), and Inter-Society Consensus for the management of patients with PAD recommend ABI screening, whereas the US Preventive Services Task Force advises against routine ABI screening in asymptomatic adults. “One fundamental reason for this uncertainty,” the authors wrote, “is the lack of evidence about the effectiveness of risk reduction interventions when asymptomatic PAD is detected.”

In light of this lack of evidence, researchers set out to test whether statin use could reduce CVD incidence and mortality in patients with asymptomatic PAD as detected by ABI.

Data from a total of 5480 patients (mean age: 67 years; 44% women) treated (n=2740) or not treated with statins (n=2740) were included in the study. Patients had an ABI of ≤0.95, and none had clinically recognized CVD. While “borderline” cardiovascular risk exists with an ABI between 0.91 and 0.95, researchers chose a value of ≤0.95 instead of 0.90, as used in a previous trial with aspirin, to identify those individuals with asymptomatic PAD.2

MACE incidence was 19.7 events per 1000 person-years in statin new users and 24.7 events per 1000 person-years in nonusers (95% confidence interval [CI]: 17.2-22.5 and 21.8-27.8, respectively). Mortality rates were 24.8 per 1000 person-years in new users and 30.3 per 1000 person-years in nonusers, respectively (95% CI: 22.0-27.8 and 27.2-33.6, respectively).

Hazard ratios (HR) for MACE were 0.80 and 0.81 for overall mortality. HRs adjusted for hypertension, hypercholesterolemia, aspirin use, nonstatin lipid-lowering drug use, ABI, and 10-year coronary heart disease risk did not significantly differ from propensity score matching model.

“In the absence of clinically recognized CVD, asymptomatic ABI ≤0.95 might be sufficient to indicate statin use independently of the risk estimated by risk functions,” the authors wrote.

They added that their results support the recent blood cholesterol treatment guidelines from the ACC/AHA, suggesting that ABI can be used as an additional factor to encourage statin therapy in patients with low 10-year coronary heart disease risk with moderate LDL cholesterol blood levels.

Future studies should address the utility of systematic screening for PAD and initiation of statin therapy on the basis of ABI measurement alone as a population-based strategy for fatal and nonfatal CV event prevention.


  1. Ramos R, Garcia-Gil M, Comas-Cufi M, et al. Statins for prevention of cardiovascular events in a low-risk population with low ankle brachial index. J Am Coll Cardiol. 2016;67(6):630-640. doi: 10.1016/j.jacc.2015.11.052.
  2. Fowkes FG, Price JF, Stewart MC, et al; for the Aspirin for Asymptomatic Atherosclerosis trialists. Aspirin for the prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized control trial. JAMA. 2010;303(9):841-848. doi: 10.1001/jama.2010.221.