ABSTRACT: Peripheral arterial disease (PAD) affects 202 million people worldwide, including 8.5 million people in the United States. It is caused by atherosclerosis that leads to limited blood flow in the legs and other parts of the body. There are several treatment options available, but awareness of the disease and how it can be prevented needs to be increased. Community pharmacists can have a significant impact on patients with PAD by encouraging a healthy lifestyle and smoking cessation for prevention and by assisting in medication adherence to improve outcomes.
US Pharm. 2019:44(2)25-31.
Peripheral arterial disease (PAD) describes a phenomenon in which circulation to the leg is diminished due to atherosclerosis, resulting in reduced blood flow and often causing pain that can be limiting to those who experience it. It is a common condition affecting 202 million people worldwide; in the United States there are approximately 8.5 million people affected.1,2 If left untreated, PAD can limit patients’ ability to walk, and in some cases it can lead to gangrene or amputation.1 Many diagnoses of PAD are missed because patients or physicians ignore the signs and symptoms, and it is estimated that only 25% of the U.S. population is even aware of what PAD is.2 Pharmacists in the community can intervene in several ways, not only to help make sure diagnosed patients are being treated to the highest standards of care but also to assist in encouraging preventive measures, increasing medication compliance, and even recommending that patients be examined for PAD.
Causes, Signs and Symptoms
Many patients with PAD present to the pharmacy complaining of leg cramps. This cramping as a result of PAD is referred to as intermittent claudication. PAD occurs when fatty deposits build up in the peripheral arteries of the body, restricting blood flow and oxygen to the legs and feet.1
The signs and symptoms of PAD vary among patients. Intermittent claudication sometimes occurs in the arms but is not as common as in the lower extremities, groin, and thighs.1 The most common sign is intermittent claudication in the calves, hips, or thighs when walking, exercising, climbing stairs, or performing physical activity. This cramping can vary in type and strength. It often occurs at night, and it generally affects older people. Other signs and symptoms may include leg pain that does not go away upon discontinuation of exercise or physical activity, wounds on the lower extremities that will not heal or heal very slowly, the presence of dead tissue or gangrene, shiny skin on the legs, a noticeable decrease in temperature of the leg or foot compared with the rest of the body, poor nail growth on the toes, poor hair growth on the lower leg or toes, and erectile dysfunction in men, especially those with diabetes.3
Diagnosis
PAD is often a part of the aging process; however, younger individuals who have diabetes or hypertension, who are smokers, or who have a family history of atherosclerosis have an increased risk of PAD.4 Men and women are affected equally; African Americans have a higher incidence than Hispanic and Caucasian patients.2
The initial diagnosis of PAD begins with a review of the patient’s history along with a physical examination and review of symptoms.5 Patients are at increased risk of PAD if they are age 65 years or older; ages 50 to 64 years with atherosclerotic risk factors or a family history of PAD; younger than age 50 years with diabetes mellitus and at least one other additional risk factor for atherosclerosis; or have a positive diagnosis of atherosclerotic disease.5 For these patients, a thorough examination, including palpation of lower extremity pulses, auscultation for femoral bruits, visual examination of the legs and feet, and bilateral measurement of blood pressure, should be conducted.5
A history of claudication, non–joint-related exertional symptoms of the lower extremities, trouble walking, or ischemic pain at rest may suggest PAD.5 These same patients may have evidence of vascular bruit, an abnormal lower extremity pulse, a slow or nonhealing extremity wound, gangrene on the lower extremity, or other abnormal vascular finding upon physical examination.5 Patients with suspicion of PAD upon physical examination or with an associated history should be referred for further diagnostic testing.5
For patients in whom lower PAD is suspected after physical examination, the resting ankle-brachial index (ABI) is the first-line diagnostic tool.5 This index compares the systolic blood pressure in the brachial artery and the ankle while the patient is lying down, using a doppler device.5 Results are reported as abnormal (ABI 0.90), borderline (ABI 0.91-0.99), normal (1.00-1.40), or noncompressible (ABI >1.40).5 The toe-brachial index is used for further diagnosis in patients with an ABI score in the noncompressible range, and exercise treadmill ABI testing may be done in patients with exertional, non–joint-related leg symptoms or a resting ABI in the normal or borderline range.5 To diagnose location and stenosis severity in patients with symptomatic PAD, duplex ultrasound, computed tomography angiography, or magnetic resonance angiography may be used if revascularization is being considered.5
Treatment
Treatment for patients with PAD may include options ranging from medication therapy and behavioral change to revascularization. For most patients, structured exercise and lifestyle modifications are at the core of treatment. For all patients, guideline-based therapy should be followed when determining the course of treatment. Structured exercise therapy may take place in a community-based or home-based program. Patients who continue to smoke should be urged to participate in smoking-cessation programs. For diabetic patients, glycemic control is imperative to reduce further complications. Diabetic patients should also be encouraged to continue to perform regular foot exams, and all patients with PAD should be encouraged to quickly seek treatment for signs of foot infection or nonhealing wounds to prevent further complications. All patients with PAD should receive an annual influenza vaccine.5 Compression stockings should not be worn for the treatment of PAD.6
Medication therapy for PAD is determined by patient risk factors, comorbidities, and type of PAD.5 Cilostazol and pentoxifylline are the most common drugs associated with management of PAD because they have indications for treatment of intermittent claudication. Cilostazol, a phosphodiesterase III inhibitor that increases cyclic adenosine monophosphate to cause vasodilation and inhibition of platelet aggregation, is effective for patients who have claudication to improve symptoms and increase their ability to walk greater distances.5,7 This therapy does not, however, appear to reduce the potential of other cardiovascular events.5 It should be used at a dose of 100 mg twice daily, and the patient should also be taking aspirin or clopidogrel.7 Main side effects include headache, diarrhea, abnormal stools, infection, and rhinitis.7
Pentoxifylline, a blood-viscosity reducer agent which increases the blood flow to the affected microcirculations through an unknown mechanism, should be given in a dose of 400 mg three times daily for intermittent claudication; the main side effects are gastrointestinal in nature, including nausea and vomiting.8 Although the American Heart Association/American College of Cardiology guidelines state that pentoxifylline has not been shown to have efficacy in the treatment of claudication and its use is discouraged by the American College of Chest Physicians, it is still sometimes used in treating patients with PAD.5,8
For patients who have symptomatic PAD, therapy should include aspirin (75-325 mg daily) alone or clopidogrel (75 mg daily) alone to reduce the risk of myocardial infarction, stroke, or vascular death.5 The most common side effect for these agents is bleeding. The use of dual antiplatelet therapy is not well established in patients with symptomatic PAD, unless the patient has undergone lower-extremity revascularization.5 The use of a statin is recommended for all patients with PAD. Antihypertensive medications are recommended for patients who have hypertension and PAD to reduce associated cardiovascular events.5
Patients who are eligible for revascularization treatment should also be treated with medication therapy, structured exercise programs, and plans to prevent further vascular damage.5 Candidates for revascularization therapy are chosen based on the severity of their PAD and the impact on their quality of life.5 The presence or absence of other comorbid conditions should also be a factor in assessing a candidate for revascularization therapy.5 Generally, candidates for revascularization therapy have claudication limiting their quality of life and have not responded adequately to other treatment measures.5 Whether a patient should undergo endovascular or surgical revascularization will depend on the severity of the condition and the desired outcome.5
Community Pharmacist Involvement
Pharmacists in the community can be involved with PAD prevention by promoting a healthy lifestyle, and they can also be key players in treatment of PAD by encouraging medication adherence. The main ways to prevent PAD are diet, weight loss if overweight, being physically active, and smoking cessation. Since atherosclerosis is one of the primary causes of PAD, eating a diet that reduces the amount of plaque buildup is key. The American Heart Association has a few tips for diet on its “The Skinny on Fats” web page that may aid in the prevention of PAD and other diseases (Table 1).9
Similar to the tips for diet, there are also simple recommendations and clinical pearls pharmacists can give patients to help with weight loss. Patients should be encouraged to set realistic goals.10 Setting goals starts with assessing the patient’s weight and body mass index, and educating them on what an ideal weight and body mass index should be. Once patients have the long-term goal in mind, they should then be encouraged to set short-term specific, measurable, achievable, realistic, timely (SMART) goals.11 An example of a short-term SMART goal would be losing 1 to 2 pounds per week for a total of 6 pounds in a month.
Patients should be encouraged to keep a food journal, watch portion sizes, and use simple substitutions in their diet to foster a lifestyle change.10 There are many templates that can be easily obtained for patients who prefer to manually write down foods, but patients should be encouraged to use a food-tracking app, many of which are free, as it will allow calorie and nutrient tracking, plus have nutritional information for many foods already loaded. This will help make patients aware of the amounts and types of foods they are consuming throughout the day, and it may allow them to notice trends in an effort to combat unhealthy eating habits. Patients can be given materials about the MyPlate method, which shows examples of correct portion sizes and meal compositions.12 Using the portion recommendations outlined in the MyPlate method can serve as a complement to the American Heart Association diet recommendations, and promoting healthful snacks, fruits, and vegetables as alternatives to unhealthful, processed foods can help patients achieve their weight-loss goals.
Pharmacists should also recommend that patients be physically active, reminding them that as long as they are getting their heart rate up, it counts as physical activity. Patients should aim for 150 minutes of physical activity weekly. For patients who are sedentary, it is fine for them to start with a lower amount of activity and gradually work their way up to more physical activity. Older adults should always be encouraged to consult with their physician to determine the best kinds of physical activity for them, as well as any limitations to consider when planning their activities.8
Smoking cessation is another way pharmacists can intervene. Pharmacists should be familiar with the 5 A’s of smoking cessation (ask, assess, advise, assist, arrange) and be ready to engage patients who are known smokers or who are interested in quitting.13 There are many materials and resources available for pharmacists and patients about smoking cessation, including calling the quit line (1-800-Quit Now [1-800-784-8669]). There are even some reimbursement opportunities in certain states for providing smoking-cessation services.
While a diagnosis cannot officially be made in the pharmacy, pharmacists may steer patients in the direction of seeing their physician to be evaluated for the disease. If a patient frequently complains of leg pain, he or she can be asked if there are other symptoms that resemble PAD. If so, the pharmacist should explain to the patient the possibility of PAD, and how important it is to be seen by a physician.
When patients have an official diagnosis of PAD, pharmacists may be influential in making sure their treatment is as effective as possible. Being prepared to assist patients with medication adherence is a key way pharmacists can intervene. In addition to helping patients brainstorm ideas like medication placement in their home to remind them to take it, or even using an alarm on their smartphone to remind them to take medications, many pharmacies have medication-synchronization programs and adherence packaging for patients with multiple medications. It is important to control diabetes, cholesterol, and hypertension in the treatment of PAD, as those conditions can impact the severity and progression of PAD. Reminding patients of the importance of overall health and making good choices will not only ensure they have the best quality of life possible but also increase their trust in the profession of pharmacy.
Conclusion
PAD is a disease that can negatively impact a patient’s quality of life if not diagnosed and treated properly. Pharmacists in the community setting can be advocates for prevention and education about the disease by encouraging healthy diet, weight loss, physical activity, and smoking cessation. They can also be helpful with patients remaining adherent to medications that treat PAD both directly and indirectly.
REFERENCES
1. Hellmich N. Peripheral artery disease skyrocketing worldwide. USA Today. www.usatoday.com/story/news/nation/2013/07/31/peripheral-artery-disease-worldwide/2603975/. Accessed October 29, 2018.
2. CDC. Peripheral arterial disease (PAD) fact sheet. www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_pad.htm. Accessed October 29, 2018.
3. American Heart Association. Peripheral artery disease: symptoms and diagnosis of PAD. www.heart.org/en/health-topics/peripheral-artery-disease/symptoms-and-diagnosis-of-pad. Accessed October 28, 2018.
4. Nowygrod R. Leg cramping: minor annoyance or a serious problem? http://columbiasurgery.org/news/2013/04/01/leg-cramping-minor-annoyance-or-serious-problem. Accessed November 2, 2018.
5. Gerhard-Herman MD, Gornick HL, Barrett C, et al. 2016 AHA/ACC Guideline on the management of patients with lower extremity peripheral artery disease. J Am Coll Cardiol. 2017; 69(11):1465-1508.
6. Lim CS, Davies AH. Graduated compression stockings. CMAJ. 2014;186(10):E391-E398.
7. Cilostazol. Lexi-Drugs. Lexicomp. http://online.lexi.com. Riverwoods, IL: Wolters Kluwer Health, Inc. Accessed January 10, 2019.
8. Pentoxifylline. Lexi-Drugs. Lexicomp. http://online.lexi.com. Riverwoods, IL: Wolters Kluwer Health, Inc. Accessed January 10, 2019.
9. American Heart Association. The skinny on fats. www.heart.org/en/health-topics/cholesterol/prevention-and-treatment-of-high-cholesterol-hyperlipidemia/the-skinny-on-fats. Accessed November 6, 2018.
10. American Heart Association. 5 steps to lose weight and keep it off. www.heart.org/en/healthy-living/healthy-eating/losing-weight/5-steps-to-lose-weight-and-keep-it-off. Accessed October 28, 2018.
11. S.M.A.R.T. weight loss and your fitness device. www.webmd.com/fitness-exercise/guide/smart-weight-loss-fitness-device. Accessed November 12, 2018.
12. United States Department of Agriculture. What is MyPlate? www.choosemyplate.gov/MyPlate. Accessed November 12, 2018.
13. Agency for Healthcare Research and Quality. Five major steps to intervention. www.ahrq.gov/professionals/clinicians-providers/guidelines-recommendations/tobacco/5steps.html. Accessed October 29, 2018.
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