How Can We Improve Outcomes in CLI and PAD?

Hello, and welcome to the March edition of Vascular Disease Management.  I have chosen to comment on the overall medical evaluation and medical therapy of patients presenting with critical limb ischemia (CLI) and peripheral arterial disease (PAD) in general.

I have chosen to comment on this subject because although CLI interventional and surgical treatments have resulted in improved limb salvage, mortality rates have remained high, with reported mortality rates of 20% within 6 months of diagnosis and greater than 50% at 5 years.^1-3  In fact, PAD in general is associated with markedly increased mortality. The majority of these deaths are related to cardiovascular events with myocardial infarction being the most common culprit.

Although there have been published medical therapy guidelines,^4,5 many patients are not treated within those guidelines of smoking cessation, lipid control, hypertension and diabetic treatment, use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and use of antiplatelet agents.^6,7 Many patients do not adhere to their physician’s recommendations. Even when guidelines are strictly followed, mortality rates remain high. We must question if outcomes can be improved by other means or if the high mortality rates are simply a function of very sick patients with an inevitable poor prognosis.

PAD and CLI are closely related to advanced age, diabetes, and cigarette smoking. Other typical modifiable cardiovascular risk factors such as hyperlipidemia and hypertension are associated to a lesser degree with the development of PAD.

Patients presenting with CLI are typically older and less mobile than other patients with PAD. These patients may have impaired angina warning related to diabetes or the inability to chronotropically stress the heart with exertion.

As myocardial infarction remains the leading cause of death in CLI and PAD patients, one must wonder if routine provocative testing such as cardiac positron emission tomography or Lexiscan perfusion studies should be part of the routine workup with recommended coronary revascularization when appropriate.

One must question if utilization of less iodinated contrast in diagnostic angiography and interventions (utilizing external duplex or CO₂ guidance) would affect short- and long-term prognosis. One must question if more comprehensive long-term follow-up would impact outcomes.   

I have often stated at medical conferences that “Sick legs are rarely attached to healthy individuals.” PAD in general and CLI specifically must be recognized as systemic disorders with the presenting symptoms arising from the legs. We must do more than restore blood flow to the legs and heal wounds. We must strive to improve overall health outcomes, including lowering the mortality rate.

I believe that we must reconsider the diagnostic and treatment strategies utilized in CLI evaluations and in patients with any form of PAD. Studies are needed to determine if more aggressive risk factor modification and prophylactic treatment strategies such as myocardial revascularization have the potential to improve outcomes. We must ultimately determine if these strategies save lives and if they are cost-effective.

REFERENCES

1. Murabito JM, Evans JC, Nieto K, Larson MG, Levy D, Wilson PW. Prevalence and clinical correlates of peripheral arterial disease in the Framingham Offspring Study. Am Heart J. 2002;143(6):961-965.

2. McKenna M, Wolfson S, Kuller L. The ratio of ankle and arm arterial pressure as an independent predictor of mortality. Atherosclerosis. 1991;87(2-3):119-128.

3. Criqui M, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med. 1992;326(6):381-386.

4. Stoyioglou A, Jaff MR. Medical treatment of peripheral arterial disease: a comprehensive review. J Vasc Interv Radiol. 2004;15(11):1197-1207.

5. Norgen L, et al. Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg. 2007;45 (suppl S): S5-S67.

6. Cacoub P, Abola MT, Baumgartner I, et al. Cardiovascular risk factor control and outcomes in peripheral artery disease patients in the Reduction of Atherothrombosis for Continued Health (REACH) Registry. Atherosclerosis. 2009;204(2):e86-e92.

7. Ajello FA, Khan AA, Meltzer AJ, Gallagher KA, McKinsey JF, Schneider DB. Statin therapy is associated with superior clinical outcomes after endovascular treatment of critical limb ischemia. J Vasc. Surg. 2012;55(2):371-379.