Achieving Very Low LDL-C in Peripheral Artery Disease Beneficial, Regardless of Prior Myocardial Infarction or Stroke: Presented at AHA

By Walter Alexander

ANAHEIM, California -- November 15, 2017 -- Among patients with peripheral artery disease (PAD), physicians should consider reducing low-density lipoprotein cholesterol (LDL-C) to very low levels to decrease the risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), according to results of the FOURIER trial presented here at the 2017 Annual Scientific Sessions of the American Heart Association (AHA).

Patients with lower extremity PAD are at high risk of MACE, stated FOURIER lead investigator Marc P. Bonaca, MD, MPH, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, speaking here on November 13.

The overall FOURIER trial, conducted among 27,564 high-risk, stable patients with established cardiovascular disease revealed a 59% reduction in LDL-C with subcutaneous evolocumab (140 mg every 2 weeks or 420 mg each month) compared with placebo, to a median of 30 mg/dL over a median follow-up of 2.2 years. The trial also demonstrated a 20% reduction in combined cardiovascular death, myocardial infarction, and stroke.

The PAD analysis of the FOURIER trial included 3,642 patients (mean age 64 years, 72% female) with symptomatic lower extremity PAD, 1,505 of them with no prior myocardial infarction or stroke. PAD was defined as intermittent claudication and ankle brachial index (ABI) <0.85 or prior peripheral revascularisation or amputation for ischaemia.

Among patients receiving placebo, the rate of combined cardiovascular death, myocardial infarction, and stroke was 13.0% in patients with PAD and 7.6% in those with no PAD and prior myocardial infarction and stroke (adjusted hazard ratio 1.81, P< .001). For those with prior myocardial infarction/stroke and PAD, it was 14.9%.

Treatment with evolocumab reduced the combined endpoint in patients with PAD to 9.5%, a 27% relative risk reduction (P = .0040), with a number needed to treat (NNT) for 2.5 years of 29. In those with no PAD, the combined endpoint rate was reduced to 6.2% (NNT = 72).

The MALE event (acute limb ischaemia, major amputation, or urgent revascularisation) rate in all patients was reduced by 42% from 0.45% with placebo to 0.27% with evolocumab (hazard ratio 0.58, P = .0093).

Dr. Bonaca noted that the benefits of evolocumab extended to patients with PAD who did not have prior myocardial infarction or stroke, with an absolute risk reduction for MACE or MALE of 6.3% (NNT = 16) at 2.5 years.

“LDL-C reduction to very low levels should be considered in patients with PAD, regardless of their history of myocardial infarction or stroke,” he concluded.

[Presentation title: Evolocumab and Outcomes in Patients With Peripheral Artery Disease.]

To read more Conference Dispatch articles, click here.