Pharmacologic Treatment

Numerous new pharmacologic interventions are now available for PAD, which add to the tools in our toolbox to effectively treat PAD and reduce the risk for stroke and myocardial infarction.7 Some of the most important things that we do as clinicians are improving symptoms and modifying risk factors, and we need to do everything we can to reduce major adverse cardiovascular events and major adverse limb events. We should ensure that we use antiplatelet agents, usually aspirin or clopidogrel to start, for patients with symptomatic PAD.

We know that hypertension is prevalent in patients with PAD, so we can use angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors as these have been shown to improve vascular health. 


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Statins are beneficial for hyperlipidemia. I don’t look at statins as a lipid-lowering therapy per se; rather I view statins as plaque stabilization therapies.  We want to get patients on the highest dose that they can tolerate to stabilize plaques. There is some literature, especially with atorvastatin, that statins may cause plaque regression.8 So, these medications are extremely helpful in both mitigating the risk for hyperlipidemia while also addressing the underlying problem with atherosclerosis. 

Other medications that are available for PAD include cilostazol, which is a phosphodiesterase-3 inhibitor that makes red blood cells more pliable.  This medication won’t cure PAD, but it often helps patients walk farther without pain. 

The COMPASS trial (ClinicalTrials.gov Identifier: NCT01776424) looked at the effect of the combination of rivaroxaban 2.5 mg given twice daily and aspirin compared with aspirin alone in patients with lower extremity PAD.9  It found that the rivaroxaban and aspirin combination lowered the incidence of major adverse limb events and related complications. Therefore, this combination therapy is another good option in our toolbox for patients with lower extremity PAD.

Patients with diabetes should be on glucose-lowering therapy to reduce their risk of microvascular complications including renal disease and retinopathy. In addition, newer target-specific therapies have shown benefit in patients with cardiovascular disease. The glucagon-like peptide-1 receptor agonist liraglutide has been shown to reduce ischemic major adverse cardiovascular events in patients with diabetes.10 Inhibitors of sodium-glucose cotransporter 2 have been shown to reduce cardiovascular death and heart failure in patients with atherosclerosis, including PAD.11.12

These therapies should be considered as recommended by current guidelines. Partnering with a local diabetes specialist may be helpful in targeting intensive therapies for the complex and high-risk population with PAD and diabetes.

Vascular Team Approach

Lastly, I will touch upon promoting the vascular team approach to patients with PAD as I work closely with my colleagues in vascular surgery, interventional cardiology, and interventional radiology. Intervention certainly has a role in the treatment of PAD with lifestyle-limiting claudication. The open artery hypothesis has been proven over and over again in patients with critical limb ischemia.  In these patients, it is clear we want to open up arteries either with bypasses, stents, or angioplasties.

For patients with intermittent claudication, the question of surgical intervention is a different story.  Initial therapy for intermittent claudication is medical along with exercise therapy.  However, some patients with intermittent claudication, especially those who experience lifestyle limitations, should be considered for revascularization. The decision to opt for a surgical approach may be subjective and requires the clinician to sit down and have a heart-to-heart conversation with their patient about quality of life: are symptoms of claudication interfering with the patient’s ability to engage in activities of daily living?  Are symptoms interfering with activities that the patient enjoys doing, such as hobbies? 

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In my practice, I use the “Walmart test” with my patients.  Simply put, I ask them, “How far can you walk in Walmart before you have to stop to rest?” Their response allows us to quantify their impairment, and we can see how medical management and exercise therapies are working.  If a patient can walk farther after medical therapy and exercise, then we know that surgery isn’t indicated.  If a patient’s walking distance without pain becomes less and less, then we know that intervention therapy is something we should start to talk about.  We also want to quantify walking distance — how far a patient can walk without pain — and keep track of that. 

If a patient has lifestyle-limiting claudication, we have lots of different tools on the interventional side that can open up arteries and hopefully improve the claudication.  The usual interventional approach is to treat inflow first by addressing the lesion above where pain is occurring. Oftentimes the part of the leg that is involved in claudication gives us a clue as to where the lesion is located. For example, pain in the thigh is often aorta-iliac disease, pain in the calf is often femoral-popliteal disease, and pain in the foot is usually tibial-popliteal disease.  We also have many tests that can localize the disease including pulse volume recordings, segmental pressures, duplex ultrasounds, and computed tomographic angiograms. So, again, it’s really key to sit down with the patient and have a shared medical decision-making discussion on how his or her life is limited and whether surgical intervention is worth the risk. 

References

1. Shu J, Santulli G. Update on peripheral artery disease: epidemiology and evidence-based facts. Atherosclerosis. 2018;275:379-381.

2. Peripheral artery disease (PAD) fact sheet. Centers for Disease Control and Prevention website. https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_pad.htm. Reviewed June 16, 2016. Accessed December 5, 2019.

3. Rose GA. The diagnosis of ischaemic heart pain and intermittent claudication in field surveys. Bull World Health Organ. 1962;27:645-648.

4. Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. Centers for Disease Control and Prevention website. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html. Updated December 3, 2019.  Accessed December 9, 2019.

5. McDermott MM. Supervised treadmill exercise therapy for peripheral artery disease. American College of Cardiology website. Published July 12, 2017. Accessed December 9, 2019.

6. Decision memo for supervised exercise therapy (set) for symptomatic peripheral artery disease (PAD) (CAG-00449N). Centers for Medicare & Medicaid Services website. https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=287. May 25, 2017. Accessed December 5, 2019.

7. Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC guidelines on management of patients with lower extremity peripheral artery disease: executive summary. Vasc Med. 2017;22(3):NP1-NP43.

8. Hong YJ, Jeong MH, Hachinohe D, et al. Comparison of effects of rosuvastatin and atorvastatin on plaque regression in Korean patients with untreated coronary stenosis. Circ J. 2011;75(2):398-406.

9. Anand SS, Caron F, Eikelboom JW, et al. Major adverse limb events and mortality in patients with peripheral artery disease: The COMPASS trial. J Am Coll Cardiol. 2018;71(20):2306-2315.

10. Monami M, Dicembrini I, Nardini C, Fiordelli I, Mannucci E. Effects of glucagon-like peptide-1 receptor agonists on cardiovascular risk: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2014;16(1):38-47.

11. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.

12. Verma S, Mazer CD, Al-Omran M. Cardiovascular outcomes and safety of empagliflozin in patients with type 2 diabetes mellitus and peripheral artery disease. Circulation. 2018;137(4):405-407.