Higher statin doses tied to fewer deaths, amputations in PAD patients

High-intensity statin therapy for peripheral artery disease (PAD) patients reduces the risk of lower-extremity amputations by one-third and the risk of mortality by 26 percent, a new study found. However, the lipid-lowering drugs remain underutilized in the PAD population despite their guideline-recommended use.

“There are 148,000 major amputations done annually in the United States due to PAD,” lead author Shipra Arya, MD, with Emory University School of Medicine, and colleagues wrote in Circulation.

“Annual mortality (8.2 percent) is higher among patients with PAD than after a myocardial infarction (6.3 percent). Despite the significant limb and cardiovascular outcomes in PAD, there is poor risk factor modification relative to other atherosclerotic diseases like coronary artery disease (CAD) or stroke.”

To investigate the effect of statin intensity on PAD outcomes, the researchers studied 155,647 patients from the national Veterans Affairs database who were diagnosed with PAD from 2003 through 2014. The subjects were 97.9 percent men and aged 66.7 on average.

Twenty-eight percent of patients were not on a statin in the year surrounding their diagnosis (six months before and after). The researchers also found patients with PAD alone were less likely to receive statins (42 percent) versus those with concomitant carotid artery stenosis (34.9 percent), CAD (17.6 percent) or both (15.7 percent).

Compared to veterans on only antiplatelet therapy, those prescribed low or moderate intensity statins demonstrated a covariate-adjusted 19 percent decrease in amputation risk and a 17 percent decrease in mortality risk. The reductions ballooned to 33 percent and 26 percent, respectively, for high intensity therapy, which was defined according to 2013 American Heart Association/American College of Cardiology lipid guidelines and included atorvastatin between 40 and 80 milligrams and rosuvastatin 20-40 mg.

“Upon diagnosis of PAD, a patient should be started on the highest intensity of statin that can be tolerated much like coronary artery disease to reduce their lifetime risk of amputation and death,” Arya and coauthors wrote. “Emphasis needs to be laid on early diagnosis and treatment of PAD especially in the absence of CAD by all providers including primary care physicians, cardiologists, vascular specialists, etc.”

The authors called for consensus guidelines for medical management of PAD and further investigation into the mechanisms by which high-intensity statins reduce adverse events. They acknowledged they only assessed prescribed therapy over a finite period, so patients could have transitioned to another treatment group during follow-up.

“Further work is needed to quantify the risk benefit with patient medication adherence, the effect of statin intensity on disease severity of PAD as well as implementation of strategies to increase statin use in PAD patients,” Arya et al. wrote.