Statins Tied to Lower Mortality, Amputation Risks in PAD

Statin therapy, particularly with a high-intensity statin, is associated with lower risks of death and amputation in older patients with peripheral artery disease, a new analysis shows.

In a large, observational study of patients with PAD, treatment with a high-intensity statin was associated with a 33% lower risk of amputation and a 29% lower risk of death compared with no LDL cholesterol-lowering medication.

Treatment with a low-to-moderate-intensity statin also resulted in a significantly reduced the risk of clinical events, although the benefit was smaller. In these patients, risks of death and amputation each were 22% lower in treated patients.

“Anybody who has clinically obvious PAD should definitely be on a statin medication, particularly a high-dose statin,” said lead investigator Shipra Arya, MD (Emory University, Atlanta, GA). “It does appear to have a dose-dependent effect. The higher dose of a statin you’re on, the more protection you have in terms of mortality and limb loss.”  

The study—which was presented last week at the American Heart Association’s Arteriosclerosis, Thrombosis, and Vascular Biology | Peripheral Vascular Disease 2016 Scientific Sessions in Nashville, TN—included 208,275 patients (mean age 67 years) with PAD identified between 2003 and 2014 in the Veterans Affairs (VA) database. In the analysis, the researchers classified high-intensity statin therapy as rosuvastatin 20/40 mg and atorvastatin 40/80 mg; low-to-moderate intensity therapy included all other approved doses.

In the cohort, more than 27% were not taking a statin and 30.4% were taking simvastatin 80 mg, a dose no longer recommended given its high risk for muscle damage (individuals taking simvastatin were excluded from the analysis).  

During a median follow-up of 5.2 years, there were 17,643 amputations and 99,951 deaths. Overall, the risk of incident amputation and mortality was significantly lower at 1, 3, and 5 years among individuals treated with a low-to-moderate and high-dose statin compared with those not receiving lipid-lowering therapy. In a Cox model that adjusted for age, gender, race, comorbidities, cholesterol levels, and serum creatinine levels, treatment with a statin significantly lowered the risk of death and amputations.

To TCTMD, Arya said previous observational studies, as well as studies including PAD patients within larger cardiovascular trials, have shown statin therapy can reduce mortality and MI risks in this patient population. The VA analysis is one of the first to show a dose-dependent benefit on mortality and amputations, she said.  

Clinically speaking, Arya said her hospital routinely prescribes statins to patients with PAD, mainly to decrease the overall atherosclerotic risk burden, given that these patients tend to die from events such as MI and stroke. Statins can also play a role in stabilizing plaque in the periphery, which can prevent plaque rupture and downstream events such as acute and chronic limb ischemia.

In December, the American College of Cardiology/American Heart Association updated performance measures related to the use of statins in patients with PAD. The measures, which are based on the clinical guidelines, are a means to hold hospitals and hospital systems accountable for providing optimal medical care. For PAD, these hospitals will be measured on how many patients are offered moderate-to-high-intensity statins.

“Peripheral artery disease is essentially an atherosclerotic disease, just like coronary artery disease,” said Arya. “It’s the same plaque, the same risk factors, so the medical management . . . is pretty similar.” In addition to statins, she said patients are treated with antiplatelet therapy, as well as other drugs such as cilostazol to increase walking distance, and exercise.

Arya noted that PAD is often not diagnosed immediately, with leg pain frequently attributed to joint, muscle, or skeletal issues, and this can delay statin initiation. In the United States, PAD afflicts approximately 8% to 12% of the population, leading to approximately 100,000 amputations yearly. In the VA system, the prevalence of PAD is approximately 10% to 15%, she said.

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