Volume 21, Issue 2 , Pages 175-177, February 2010
Statin Prescription is Essential in Peripheral Vascular Disease
Article Outline
Hypercholesterolemia is an important and easily modifiable risk factor for peripheral arterial disease (PAD), but is frequently not adequately addressed by vascular interventionists. Patients with PAD often have extensive atherosclerotic disease elsewhere and have a 1-year mortality rate as high as 20%, mainly from cardiovascular events. This case discussion briefly addresses the evidence for treating hypercholesterolemia in this subgroup of patients. Statins not only lower cholesterol, but also are antiinflammatory, antiproliferative, and antithrombogenic, and improve endothelial function. Current guidelines are reviewed and an approach to initiation of statins and their management is discussed.
Abbreviations: HDL, high-density lipoprotein, LDL, low-density lipoprotein, PAD, peripheral arterial disease, TGL, triglyceride
Clinical Presentation
A 62-year-old man was referred by his primary care physician with symptoms of severe disabling right leg claudication, which had progressed during the preceding 5 years. The patient was a 40–pack-year smoker. There had been no previous diagnosis of hypertension or ischemic heart disease, cerebrovascular disease, dyslipidemia, or diabetes mellitus. The patient was not taking any regular medication before presentation and he rarely sought medical attention. Physical examination revealed a very weak femoral pulse on the right side and nonpalpable arterial pulses further distally in the right leg. Blood pressure was recorded as 134/86 mm Hg in the left arm in supine position. The right ankle brachial pressure index was calculated as 0.40. A fasting lipid profile revealed total cholesterol level of 309 mg/dL, low-density lipoprotein cholesterol (LDL-C) level of 206 mg/dL, triglyceride (TGL) level of 254 mg/dL, high-density lipoprotein cholesterol (HDL-C) level of 40 mg/dL, and cholesterol:HDL-C ratio of 7.5. The patient went on to have catheter angiography, which confirmed right common iliac artery occlusion (Fig 1), for which the patient underwent balloon angioplasty and stent placement with excellent angiographic results (Fig 2).
Figure 1.
Angiographic image pre-stenting.
Figure 2.
Angiographic image post-stenting.
In summary, the patient is a 62-year-old man with diagnosis of peripheral arterial disease (PAD) and dyslipidemia.
Discussion
As interventional radiologists are increasingly conducting vascular clinics, it is of utmost importance that we adequately address vascular risk factors, particularly hypercholesterolemia. Patients with critical limb ischemia have been shown to have 1- and 10-year all-cause mortality rates of approximately 20% and 75%, respectively, with mortality at 1 year predominantly cardiovascular (1). We briefly discuss the management of hypercholesterolemia in this setting.
Statins (ie, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) form a class of hypolipidemic drugs used to improve lipid profile in people with or at risk of cardiovascular atherosclerotic disease. Statins are antiinflammatory, antiproliferative, antithrombogenic, and antiproteolytic and improve endothelial dysfunction. They are known to inhibit atherogenesis and to improve plaque stability, which in turn reduces the likelihood of plaque rupture (2).
The evidence for statins in preventing cardiac and cerebrovascular ischemic events is well known. However, the evidence relating to the role of statins in peripheral vascular disease is comparatively limited. The Scandinavian Simvastatin Survival Study (2, 3) demonstrated a statistically significant reduction in new or worsening intermittent claudication, with a reduction from 3.6% to 2.3% for the simvastatin group compared with placebo. The Heart Protection Study (4) demonstrated the benefits of cholesterol-lowering statin therapy in patients with PAD, regardless of their presenting cholesterol levels and other presenting features. That study (4) showed that daily administration of 40 mg simvastatin reduced the rate of first major vascular events by approximately one fourth, and that of peripheral vascular events by approximately one sixth, with large absolute benefits seen in participants with PAD because of their high cardiovascular risk. The numbers needed to treat from the study to prevent a first major vascular event were 16 in the PAD subgroup and 20 in those without PAD (4).
In 2009, Momsen et al (5) conducted a systematic review and metaanalysis of 43 robust randomized controlled studies of drug therapy for improving walking distance in intermittent claudication. They concluded that statins were the most efficient drug in improving maximum walking distance on a treadmill, with a mean increase of more than 160 m for lipid-lowering agents compared with 50 m for other agents. In a review on managing risk factors for atherosclerosis in PAD, Gottsäter (1) concluded that statins may be particularly beneficial in patients with increased inflammatory markers, with a favorable influence on walking ability, graft patency, and complication rates after revascularization.
In the Justification for the Use of Statins in Prevention study (6), a randomized trial of apparently healthy men and women (N = 17,802) who had LDL-C levels of less than 130 mg/dL but also had elevated levels of high-sensitivity C-reactive protein, the rates of a first major cardiovascular event and death from any cause were significantly reduced among the participants who received rosuvastatin compared with those who received placebo. The number needed to treat to prevent the occurrence of a first major cardiovascular event, defined as nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, arterial revascularization procedure, or confirmed death from cardiovascular causes, was calculated as 25. The study highlighted the possible antiinflammatory role of rosuvastatin in addition to the lipid-lowering effect, as rosuvastatin was highly effective at reducing levels of cholesterol and high-sensitivity C-reactive protein by 50% and 37%, respectively (6).
The Institute of Clinical Systems Improvement guideline for lipid management in adults (7), published in June 2007, recommends an LDL-C goal less than 70 mg/dL for patients with established coronary artery disease, noncardiac atherosclerosis, or coronary artery disease equivalent. The National Cholesterol Education Programme Adult Treatment Panel III Guidelines on cholesterol management issued in 2001 (8) recommend aiming for an LDL-C level of 70 mg/dL in patients at very high risk as well as considering combining a fibrate or nicotinic acid with an LDL-C–lowering drug when a patient at high risk has high TGL level or low HDL-C level. The American Heart Association/American College of Cardiology guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease issued in 2006 (9) advocated a goal for LDL-C of less than 70 mg/dL. The key points from the current American Heart Association/American College of Cardiology lipid management guideline are summarized in the Table.
Key Points from the American Heart Association/American College of Cardiology Lipid Management Secondary Prevention Guidelines (9)
•Assess fasting lipid profile in all patients, and within 24 h of hospitalization for those with an acute cardiovascular event. •Start dietary therapy. Promote daily physical activity and weight management. •Adding plant stanol/sterols and viscous fiber will further lower LDL-C. Encourage increased consumption of omega-3 fatty acids. •LDL-C should be <100 mg/dL and a further reduction of LDL-C to <70 mg/dL is reasonable. •If on-treatment LDL-C is ≥100 mg/dL, intensify LDL-lowering drug therapy (may require combination of standard dose of statin with ezetimibe, bile acid sequestrant, or niacin). •If TGLs are 200–499 mg/dL, non–HDL-C should be <130 mg/dL, a further reduction of non-HDL-C to <100 mg/dL is reasonable. (Non–HDL-C = total cholesterol minus HDL-C.) Therapeutic options are more intense LDL-C–lowering therapy/niacin/fibrate therapy. •If TGLs are ≥500 mg/dL, therapeutic options to prevent pancreatitis are fibrate or niacin before LDL-lowering therapy; treat LDL-C to goal after TGL-lowering therapy. Achieve non–HDL-C <130 mg/dL if possible. •The combination of high-dose statin and fibrate can increase risk for severe myopathy. Patients with very high TGLs should not consume alcohol. The use of bile acid sequestrant is relatively contraindicated when TGLs are >200 mg/dL. |
Statins should be used with caution in those with a history of liver disease or with a high alcohol intake. Liver enzymes should be measured before treatment, and measurements should be repeated within 3 months and at 12 months of starting treatment unless indicated at other times by signs or symptoms suggestive of hepatotoxicity. Those with serum aminotransferase levels of more than three times the upper limit of the reference range should discontinue statin therapy. Statins should be used with caution in those with risk factors for myopathy or rhabdomyolysis and have been reported to cause myalgia, myositis, and myopathy, which may lead to rhabdomyolysis. Muscular effects of statins are rare but often significant. Patients should be advised to promptly report any unexplained muscle pain, tenderness, or weakness. If myopathy is suspected and the serum creatine phosphokinase level is more than five times the upper limit of normal, or if muscular symptoms are severe, statins should be discontinued. As serum creatine phosphokinase can sometimes be normal in statin-induced myopathy, patients should proceed to undergoing a muscle biopsy if deemed necessary on clinical grounds. Contraindications to statin therapy include active liver disease, persistent unexplained increases in serum aminotransferase levels to more than three times the upper limit of normal, pregnancy, lactation, and hypersensitivity to a statin. The authors strongly recommended that practitioners should take efforts to familiarize themselves with their respective formularies on statin therapy before any prescription is issued.
Clinical Management
For the management of our patient's lipid profile, we initiated simvastatin 40 mg orally every night as the first-line therapy. A repeat lipid panel will be obtained after 8 weeks of treatment and again after any adjustments in dose. If total cholesterol remains higher than 154 mg/dL and/or LDL-C remains higher than 70 mg/dL, simvastatin will be increased to 80 mg/d in increments of 20 mg. For persistent elevation, rosuvastatin or ezetimibe will be considered. When the target range has been met, annual checks should suffice.
Key Points
PAD is treated as a coronary artery disease equivalent in most current guidelines. Given the high risk of cardiovascular mortality and morbidity in patients with PAD and the vast evidence for statin therapy, initiation of a statin is essential upon recognition of PAD in the absence of contraindications.
References
- . Managing risk factors for atherosclerosis in critical limb ischaemia. Eur J Vasc Endovasc Surg. 2006;32:478–483
- . The role of statins in vascular disease. Eur J Vasc Endovasc Surg. 2004;27:6–16
- Effect of simvastatin on ischemic signs and symptoms in the Scandinavian Simvastatin Survival Study (4S). Am J Cardiol. 1998;81:333–335
- . Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditions. J Vasc Surg. 2007;45:645–654
- . Drug therapy for improving walking distance in intermittent claudication: a systematic review and meta-analysis of robust randomised controlled studies. Eur J Vasc Endovasc Surg. 2009;38:463–474
- Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–2207
- . ICSI Health Care Guideline: Lipid Management in Adults. Bloomington, MN: ICSI; 2009;http://www.icsi.org/guidelines_and_more/gl_os_prot/cardiovascular/lipid_management_3/lipid_management_in_adults__4.htmlAccessed November 9, 2009
- Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation. 2004;110:227–239
- AHA/ACC Guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update endorsed by the National Heart, Lung, and Blood Institute. J Am Coll Cardiol. 2006;47:2130–2139
None of the authors have identified a conflict of interest.
PII: S1051-0443(09)01542-5
doi:10.1016/j.jvir.2009.12.381
© 2010 SIR. Published by Elsevier Inc. All rights reserved.
Refers to article:
- Introduction to New Series of Clinical Practice Articles
Volume 21, Issue 2 , Pages 175-177, February 2010