IOWA CITY, IOWA — Nearly 30% of veterans with peripheral artery disease (PAD) die within four years of diagnosis, while others experience limb amputation or critical limb ischemia. New research pointed out that failure to provide guideline-recommended treatment might contribute to the high rates of poor outcomes.

The study conducted by researchers at the Iowa City, IA, VAMC and the University of Iowa Carver College of Medicine noted that, despite statins’ strong association with lower mortality rates and reduced complications in the disease, 40% of veterans with PAD did not receive a prescription for the drugs.1

Atherosclerosis causes most cases of peripheral artery disease, although blood clots, limb injury and unusual anatomy can also trigger the condition. Smoking, diabetes, obesity, hypertension, hypercholesterolemia and age increase the risk of PAD. Nearly one-quarter of veterans have diabetes, and an equal percentage smoke; about one-third have diagnosed hypertension, and 41% are obese.

“Even though risk factors for PAD are heavily entrenched among veterans, PAD is likely underdiagnosed and undertreated,” explained Saket Girotra, MBBS, MS, an investigator with VA’s Health Services Research & Development Service and corresponding author of the study, which was published in the Journal of Vascular Surgery.

The researchers identified 175,865 veterans newly diagnosed with PAD between 2009 and 2011 who received care through the VA. That number may be significantly understated, as about half of those with PAD have no symptoms. Nonspecific symptoms also may contribute to underdiagnosis or delayed diagnoses of PAD, Girotra told U.S. Medicine, while more pressing comorbidities may shift focus away from limb and vascular care.

The researchers discovered that veterans with PAD had very high rates of comorbid conditions: 77.2% had hypertension, 46.5% had diabetes, 23% had chronic obstructive pulmonary disease, 13.6% had cerebrovascular disease, 12.9% had chronic renal failure, 11.8% had congestive heart failure and, 11.6% had cancer.

A high rate of comorbidities and the need to change behaviors to improve or stop the progression of PAD can be challenging for patients and physicians. “Managing PAD requires lifestyle changes such as exercise, smoking cessation, blood pressure and glucose control, along with using appropriate medications, and when necessary surgical intervention,” said Maen Aboul Hosn, MD, staff vascular surgeon at the Iowa City VAMC and the University of Iowa Hospitals and Clinics. “Many patients are not compliant, failing to follow clinical recommendations.”

In addition, patients with PAD and multiple other conditions often see a number of physicians from a variety of specialties, including “cardiologists, interventional radiologists, neurointerventionalists and others, all with their own guidelines,” Hosn told U.S. Medicine.

The American Heart Association/American College of Cardiology guidelines for management of patients with lower extremity PAD strongly recommend pharmacotherapy to reduce cardiovascular ischemic events and events that affect the limbs.2 Medications should include antiplatelet therapy with aspirin or clopidogrel and statin therapy for all patients and antihypertensives for those with hypertension. The guidelines also recommend angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, but not anticoagulants, to reduce cardiovascular ischemic events. Cilostazol may improve PAD symptoms and increase the distance patients who experience claudication or cramping leg pain can walk.

Among veterans in the study, however, prescription rates for the recommended medications was quite low. Just 60.8% of veterans with PAD filled a statin prescription within three months of diagnosis, and 17.1% took a nonaspirin antiplatelet medication. About 4% took any anti-claudication drug, even though cramping leg pain with activity is the most common presenting symptom of the disease.

Patients also did not receive much pharmacological support for the most important lifestyle change, smoking cessation, according to the report. The AHA/ACC guidelines encourage physicians to discuss quitting in every visit with a smoker with PAD and to help patients develop a plan to quit that includes pharmacological assistance such as varenicline, bupropion or nicotine replacement therapy and/or referral to a smoking cessation program. Smoking cessation therapies were used by 7.2% of veterans in the study.

The researchers also found a lower-than-expected rate of revascularization. Less than 3% had revascularization surgery during the first year after diagnosis. Knowing the “right” rate of revascularization remains a tricky matter; recent studies show a sharp rise nationally that might indicate overuse of the procedure, according to the authors.

“Current guidelines recommend patients with critical limb ischemia (i.e., advanced PAD that is causing rest pain, ulceration or gangrene) benefit from revascularization and may avoid amputation. On the other extreme are asymptomatic patients who are unlikely to benefit from revascularization,” Girotra explained.

Hosn estimated that 8% to 10% of PAD patients would be eligible for and benefit from revascularization. Both recommended risk factor modification first, along with structure exercise and aggressive medical therapy.

“Endovascular interventions are attractive because they are minimally invasive, but we know all stents/angioplasty interventions will ultimately fail due to the natural progression of the disease (atherosclerosis and PAD),” said Hosn. “Moreover, it is very easy to burn bridges with aggressive endovascular procedures and turn an otherwise stable PAD patient with claudication into one with critical ischemia, if the stents/interventions fail.”

During the 3.8 years of follow-up, 28.6% of patients died, and 3.7% experienced amputation or critical limb ischemia requiring hospitalization. Older age, comorbidities such as congestive heart failure, chronic obstructive pulmonary disease, renal disease and liver disease and critical limb ischemia or amputation at diagnosis predicted mortality.

Use of low- or moderate-intensity statins reduced the mortality risk 13%, and the use of high-intensity statins lowered it by 18%. Non-white race reduced the risk of death by a similar amount. Older age reduced the risk of amputation or critical limb ischemia.

Girotra encouraged clinicians to use the recommended medications and work together to mitigate the high risk of mortality and limb loss facing patients with PAD. Veterans have multiple risk factors such as hypertension, diabetes and smoking that “are hard to tackle in isolation, and their collective convergence in PAD patients makes care of these patients uniquely challenging. We need to work together to redesign care delivery models that ensure high quality preventive care for PAD patients.”

1Willey J, Mentias A, Vaughan-Sarrazin M, McCoy K, Rosenthal G, Girotra S. Epidemiology of lower extremity peripheral artery disease in veterans. J Vasc Surg. 2018 March:1-9.

2Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017 March; 135(12):3726-e779.