Pharmacologic risk factor management in peripheral arterial disease: A vade mecum for vascular surgeons
2008; Elsevier BV; Volume: 47; Issue: 5 Linguagem: Inglês
10.1016/j.jvs.2007.12.033
ISSN1097-6809
AutoresThomas F. Rehring, Ryan S. Stolcpart, Harris W. Hollis,
Tópico(s)Lipoproteins and Cardiovascular Health
ResumoThere is broad and compelling evidence for risk factor reduction to limit cardiovascular morbidity and mortality in patients with peripheral arterial disease. Indeed, vascular surgeons have placed a call to arms to ensure this takes place. Despite this fact, some wariness exists on the part of many vascular surgeons to initiate these strategies, functionally abnegating their responsibilities in this regard. The purpose of this article is to provide a simple reference to guide effective therapies for overall cardiovascular risk reduction in patients with peripheral arterial disease. Specific recommendations are made for tobacco cessation, lipid-lowering therapy, antiplatelet therapy, blood pressure control, and maintenance of normoglycemia. There is broad and compelling evidence for risk factor reduction to limit cardiovascular morbidity and mortality in patients with peripheral arterial disease. Indeed, vascular surgeons have placed a call to arms to ensure this takes place. Despite this fact, some wariness exists on the part of many vascular surgeons to initiate these strategies, functionally abnegating their responsibilities in this regard. The purpose of this article is to provide a simple reference to guide effective therapies for overall cardiovascular risk reduction in patients with peripheral arterial disease. Specific recommendations are made for tobacco cessation, lipid-lowering therapy, antiplatelet therapy, blood pressure control, and maintenance of normoglycemia. The systemic ravages of atherosclerosis impact significantly on patients with peripheral arterial disease (PAD), who incurr an annual risk of a cardiovascular event of 5% to 7%.1Hirsch A.T. Haskal Z.J. Hertzer N.R. Bakal C.W. Creager M.A. Halperin J.L. et al.ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation.J Am Coll Cardiol. 2006; 47 (1239-12)Abstract Full Text Full Text PDF PubMed Scopus (938) Google Scholar The presence of PAD, even in the absence of a history of coronary artery disease (CAD), confers the same relative risk of a death from cardiovascular cause as in patients with a previous cardiovascular event.2Newman A.B. Shemanski L. Manolio T.A. Cushman M. Mittelmark M. 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Cleeman J.I. Merz C.N. Brewer Jr, H.B. Clark L.T. Hunninghake D.B. et al.Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines.Circulation. 2004; 110: 227-239Crossref PubMed Scopus (4846) Google Scholar, 6Smith Jr, S.C. Allen J. Blair S.N. Bonow R.O. Brass L.M. Fonarow G.C. et al.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.Circulation. 2006; 113: 2363-2372Crossref PubMed Scopus (1437) Google Scholar Risk factor modification includes therapeutic lifestyle changes, antiplatelet therapy, lipid modification, control of hypertension, smoking cessation, and glycemic control in diabetic patients. Although these tenets are understood well and even promoted7Bianchi C. Montalvo V. Ou H.W. Bishop V. Abou-Zamzam Jr, A.M. Pharmacologic risk factor treatment of peripheral arterial disease is lacking and requires vascular surgeon participation.Ann Vasc Surg. 2007; 21: 163-166Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 8Leon Jr, L.R. Labropoulos N. Lebda P. Kalman P.G. The vascular surgeon's role in risk factor modification: results of a survey.Perspect Vasc Surg Endovasc Ther. 2005; 17: 145-153Crossref PubMed Scopus (10) Google Scholar, 9Norgren L. Hiatt W.R. Dormandy J.A. Nehler M.R. Harris K.A. Fowkes F.G. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II).J Vasc Surg. 2007; 45: S5-S67Abstract Full Text Full Text PDF PubMed Scopus (3859) Google Scholar by vascular surgeons, there is significant unease in initiating specific medical therapies.10McDermott M.M. Hahn E.A. Greenland P. Cella D. Ockene J.K. Brogan D. et al.Atherosclerotic risk factor reduction in peripheral arterial disease: results of a national physician survey.J Gen Intern Med. 2002; 17: 895-904Crossref PubMed Scopus (118) Google Scholar, 11Kalman P.G. Irvine J. Ritvo P. How do vascular surgeons perceive atherosclerotic risk factor management?.Ann Vasc Surg. 2000; 14: 652-658Abstract Full Text PDF PubMed Scopus (6) Google Scholar The purpose of this article is to provide a simple reference to initiate treatment for overall cardiovascular risk reduction in patients with PAD. Specific recommendations are made for tobacco cessation, lipid-lowering therapy, antiplatelet therapy, blood pressure control, and maintenance of normoglycemia. All patients with PAD should undergo lifestyle modifications to limit their overall cardiovascular risk, as suggested by the AHA.12Lichtenstein A.H. Appel L.J. Brands M. Carnethon M. Daniels S. Franch H.A. et al.Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee.Circulation. 2006; 114: 82-96Crossref PubMed Scopus (2069) Google Scholar Such maneuvers include consumption of an overall healthy diet, weight loss to achieve a target body mass index <25, reductions in dietary total and saturated fat, and daily aerobic exercise. Weight loss provides decreases in low-density lipoprotein (LDL) cholesterol up to 40%, reduces serum triglycerides by 22%, and raises high-density lipoprotein (HDL) by as much as 9%.13Purnell J.Q. Kahn S.E. Albers J.J. Nevin D.N. Brunzell J.D. Schwartz R.S. Effect of weight loss with reduction of intra-abdominal fat on lipid metabolism in older men.J Clin Endocrinol Metab. 2000; 85: 977-982Crossref PubMed Scopus (132) Google Scholar Randomized data show that diet and exercise reduce lipid levels14Jenkins D.J. Kendall C.W. Marchie A. Faulkner D.A. Wong J.M. de Souza R. et al.Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein.JAMA. 2003; 290: 502-510Crossref PubMed Scopus (436) Google Scholar, 15Stefanick M.L. Mackey S. Sheehan M. Ellsworth N. Haskell W.L. Wood P.D. Effects of diet and exercise in men and postmenopausal women with low levels of HDL cholesterol and high levels of LDL cholesterol.N Engl J Med. 1998; 339: 12-20Crossref PubMed Scopus (445) Google Scholar and cardiovascular events16Sacks F.M. Katan M. Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease.Am J Med. 2002; 113: 13S-24SAbstract Full Text Full Text PDF PubMed Google Scholar; however, most patients will require additive pharmacotherapy to achieve goals for blood pressure17Chobanian A.V. Bakris G.L. Black H.R. Cushman W.C. Green L.A. Izzo Jr, J.L. et al.Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.Hypertension. 2003; 42: 1206-1252Crossref PubMed Scopus (9729) Google Scholar and lipids.4Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.Circulation. 2002; 106: 3143-3421Crossref PubMed Scopus (199) Google Scholar More than 80% of patients with PAD are current or former smokers.18Selvin E. Erlinger T.P. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000.Circulation. 2004; 110: 738-743Crossref PubMed Scopus (1385) Google Scholar Smoking cessation decreases the mortality rate by more than one-third in patients with CAD.19Critchley J. Capewell S. Smoking cessation for the secondary prevention of coronary heart disease.Cochrane Database. 2004; (CD003041)Google Scholar, 20Wilson K. Gibson N. Willan A. Cook D. Effect of smoking cessation on mortality after myocardial infarction: meta-analysis of cohort studies.Arch Intern Med. 2000; 160: 939-944Crossref PubMed Scopus (324) Google Scholar Indeed, the benefit of quitting smoking on mortality reduction is likely greater than the other risk management strategies that will be discussed. In contrast, smoking reduction does not appear to reduce all-cause mortality.21Godtfredsen N.S. Holst C. Prescott E. Vestbo J. Osler M. Smoking reduction, smoking cessation, and mortality: a 16-year follow-up of 19,732 men and women from The Copenhagen Centre for Prospective Population Studies.Am J Epidemiol. 2002; 156: 994-1001Crossref PubMed Scopus (167) Google Scholar In fact, smoking as few as 1 to 4 cigarettes a day substantially increases the risk of cardiovascular and all-cause mortality.22Bjartveit K. Tverdal A. Health consequences of smoking 1-4 cigarettes per day.Tobacco Control. 2005; 14: 315-320Crossref PubMed Scopus (322) Google Scholar Clearly, the goal for PAD patients who smoke is complete and lifelong cessation. Critical components of a successful tobacco cessation strategy include patient motivation, recurrent and timely physician advice (at each visit), behavioral therapy, and pharmacotherapy. Vascular surgeons have a unique opportunity to initiate cessation strategies. Patients often present to us in a vulnerable state, concerned over a life- or limb-threatening disorder. Reinforcement of the pernicious effects of smoking and its association with progression of disease, limb loss, and death may be particularly motivating under these conditions. Perhaps surprisingly to us as surgeons, tobacco dependence counseling is quite successful in helping patients quit smoking, whether administered in an individual, group, or telephone setting. Its effectiveness increases directly with duration of treatment time, but as little as 3 minutes of counseling helps patients quit.23Anderson J.E. Jorenby D.E. Scott W.J. Fiore M.C. Treating tobacco use and dependence: an evidence-based clinical practice guideline for tobacco cessation.Chest. 2002; 121: 932-941Crossref PubMed Scopus (163) Google Scholar, 24Fiore M.C. US public health service clinical practice guideline: treating tobacco use and dependence.Respir Care. 2000; 45: 1200-1262PubMed Google Scholar It is increasingly available at little or no cost through local communities, insurers, and managed care organizations. These sessions may include education, suggestions for tapering, and various coping mechanisms for assistance with relapse prevention. Quit rates at 1 year are approximately 20% for patients who complete a program25Lancaster T. Stead L.F. Individual behavioural counselling for smoking cessation.Cochrane Database Syst Rev. 2005; (CD001292)Google Scholar, 26Stead L.F. Lancaster T. Group behaviour therapy programmes for smoking cessation.Cochrane Database Syst Rev. 2005; (CD001007)Google Scholar, 27Stead L.F. Perera R. Lancaster T. Telephone counselling for smoking cessation.Cochrane Database Syst Rev. 2006; 3 (CD002850)PubMed Google Scholar; however, maximal quit rates are obtained when a multimodality approach is used. In addition to behavioral therapy, all smokers should be offered one of six medications with an established empiric record of efficacy in smoking cessation (Table I). BID, Twice daily; q, once daily. Nicotine is a potent psychoactive drug. After long-term use, its absence leads not only to the loss of the euphoric effects of the drug but also to symptoms of withdrawal. These may include dysphoria, depression, insomnia, anxiety, irritability, restlessness, and weight gain. Nicotine replacement therapy (NRT) helps curb some of these symptoms while the patient is undergoing concurrent behavioral therapy. Nicotine replacement therapy is safe28Greenland S. Satterfield M.H. Lanes S.F. A meta-analysis to assess the incidence of adverse effects associated with the transdermal nicotine patch.Drug Saf. 1998; 18: 297-308Crossref PubMed Scopus (121) Google Scholar and does not increase cardiac risk even in patients who continue to smoke while using the patch.29Joseph A.M. Norman S.M. Ferry L.H. Prochazka A.V. Westman E.C. Steele B.G. et al.The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease.N Engl J Med. 1996; 335: 1792-1798Crossref PubMed Scopus (419) Google Scholar Nicotine replacement therapy does not induce platelet aggregation, elevations in fibrinogen, coronary vasospasm, myocardial ischemia, or major changes in heart rate or blood pressure that are associated with smoking.30Ford C.L. Zlabek J.A. Nicotine replacement therapy and cardiovascular disease.Mayo Clinic Proc. 2005; 80: 652-656Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar Nicotine replacement is available in gum, lozenge, transdermal patch, nasal spray (Nicotrol NS; Pharmacia, Helsingborg, Sweden), and inhaler (Nicotrol Inhaler, Pharmacia). All have similar efficacy in the promotion of smoking cessation, increasing the odds of quitting 1.5- to 2-fold.31Silagy C. Lancaster T. Stead L. Mant D. Fowler G. Nicotine replacement therapy for smoking cessation.Cochrane Database Syst Rev. 2004; (CD000146)PubMed Google Scholar This benefit occurs even in the absence of supportive behavioral therapy. Slightly higher quit rates have been demonstrated with higher doses of the patch and gum, particularly in heavier smokers. For most patients, quit rates of 40% to 60% can be expected at the conclusion of a behavior therapy program combined with NRT therapy, decreasing to 25% to 30% at 1 year.24Fiore M.C. US public health service clinical practice guideline: treating tobacco use and dependence.Respir Care. 2000; 45: 1200-1262PubMed Google Scholar Bupropion is an atypical antidepressant with both dopaminergic and adrenergic actions. The sustained release form of the drug became available in 1998 specifically targeted at assisting with smoking cessation (Zyban; Glaxo SmithKline, Research Triangle Park, NC). It can be used in patients who have failed or are intolerant of NRT, unaccompanied as first-line therapy, or combined with NRT.32Jorenby D.E. Leischow S.J. Nides M.A. Rennard S.I. Johnston J.A. Hughes A.R. et al.A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.N Engl J Med. 1999; 340: 685-691Crossref PubMed Scopus (1323) Google Scholar Treatment with bupropion SR doubles quit rates at 1 year vs placebo.33Hughes J.R. Stead L.F. Lancaster T. Antidepressants for smoking cessation.Cochrane Database Syst Rev. 2007; (CD000031)Google Scholar Evidence suggests that monotherapy with bupropion is superior to NRT alone32Jorenby D.E. Leischow S.J. Nides M.A. Rennard S.I. Johnston J.A. Hughes A.R. et al.A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.N Engl J Med. 1999; 340: 685-691Crossref PubMed Scopus (1323) Google Scholar and that the addition of NRT to bupropion adds little to overall efficacy.34Simon J.A. Duncan C. Carmody T.P. Hudes E.S. Bupropion for smoking cessation: a randomized trial.Arch Intern Med. 2004; 164: 1797-1803Crossref PubMed Scopus (61) Google Scholar In general, bupropion is dosed twice daily (Table I); however, once-daily dosing may be equally effective and better tolerated.35Swan G.E. McAfee T. Curry S.J. Jack L.M. Javitz H. Dacey S. et al.Effectiveness of bupropion sustained release for smoking cessation in a health care setting: a randomized trial.Arch Intern Med. 2003; 163: 2337-2344Crossref PubMed Scopus (136) Google Scholar Bupropion lowers the threshold for seizures and thus is contraindicated in patients with a seizure disorder but is overall quite safe. The most common side effects are insomnia, dry mouth, and nausea. Varenicline (Chantix; Pfizer; Mission, KS) is a partial agonist of the α4β2 nicotinic acetylcholine receptor. It works by stimulating dopamine release in the brain, but to a lesser degree than nicotine, and blocks nicotine from binding to the nicotine receptor. This results in relief of nicotine withdrawal symptoms and cigarette cravings as well as decreases the reinforcement and reward associated with smoking. The United States Food and Drug Administration (FDA) approved it for assistance with smoking cessation in May 2006. It appears to increase the chance of successful quitting nearly threefold.36Cahill K. Stead L.F. Lancaster T. Nicotine receptor partial agonists for smoking cessation.Cochrane Database Syst Rev. 2007; (CD006103)Google Scholar In clinical studies, varenicline appears to have a slight advantage in continuous abstinence rates over bupropion SR at 3 and 6 months, but perhaps less so at later intervals.37Gonzales D. Rennard S.I. Nides M. Oncken C. Azoulay S. Billing C.B. et al.Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial.JAMA. 2006; 296: 47-55Crossref PubMed Scopus (1174) Google Scholar, 38Jorenby D.E. Hays J.T. Rigotti N.A. Azoulay S. Watsky E.J. Williams K.E. et al.Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.JAMA. 2006; 296: 56-63Crossref PubMed Scopus (1188) Google Scholar, 39Nides M. Oncken C. Gonzales D. Rennard S. Watsky E.J. Anziano R. et al.Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up.Arch Intern Med. 2006; 166: 1561-1568Crossref PubMed Scopus (325) Google Scholar In addition, 24 weeks of varenicline improves continuous abstinence rates at 6 months and 1 year compared with 12 weeks of therapy.40Tonstad S. Tonnesen P. Hajek P. Williams K.E. Billing C.B. Reeves K.R. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial.JAMA. 2006; 296: 64-71Crossref PubMed Scopus (548) Google Scholar These benefits come at some expense: varenicline costs nearly twice as much as bupropion SR and NRT. Serious side effects are rare, and no contraindications or drug–drug interactions have been identified for varenicline. Up to 30% of patients experience mild to moderate nausea that can be reduced by taking the medication after eating or with a full glass of water. In combination with targeted, personal physician advice and referral to behavioral therapy, we recommend bupropion SR at 150 mg/d for 3 days, then 150 mg twice daily for 7 weeks. The patient's intended quit date should be 1 week after the initiation of bupropion. Nicotine replacement therapy may be added to this regimen for the heaviest of smokers. Epidemiologic and prospective observational cohort studies have shown a graded correlation between serum cholesterol and the risk of coronary events.41Wallis E.J. Ramsay L.E. Ul Haq I. Ghahramani P. Jackson P.R. Rowland-Yeo K. et al.Coronary and cardiovascular risk estimation for primary prevention: validation of a new Sheffield table in the 1995 Scottish health survey population.BMJ. 2000; 320: 671-676Crossref PubMed Scopus (156) Google Scholar Several subsequent large, prospective randomized trials42Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).Lancet. 1994; 344: 1383-1389Abstract PubMed Scopus (4) Google Scholar, 43MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.Lancet. 2002; 360: 7-22Abstract Full Text Full Text PDF PubMed Scopus (7132) Google Scholar, 44Sacks F.M. Pfeffer M.A. Moye L.A. Rouleau J.L. Rutherford J.D. 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Cholesterol reduction yields clinical benefit: impact of statin trials.Circulation. 1998; 97: 946-952Crossref PubMed Scopus (412) Google Scholar Furthermore, statin pleiotropism in producing beneficial effects is nearly legendary, with known effects on atherosclerotic plaque stabilization and reduction in oxidative stress and vascular inflammation.48Liao J.K. Effects of statins on 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition beyond low-density lipoprotein cholesterol.Am J Cardiol. 2005; 96: 24F-33FAbstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar In general, recommendations for the treatment of hyperlipidemia are based upon the LDL cholesterol (LDL-C) fraction. The AHA/American College of Cardiology (ACC) guidelines published in 2006 recommend a LDL goal of <100 mg/dL for all patients with PAD.1Hirsch A.T. Haskal Z.J. Hertzer N.R. Bakal C.W. Creager M.A. Halperin J.L. et al.ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation.J Am Coll Cardiol. 2006; 47 (1239-12)Abstract Full Text Full Text PDF PubMed Scopus (938) Google Scholar The modified Third Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III or ATP III) guidelines, published in 2004, recommended an optional LDL goal of <70 mg/dL for “very-high-risk” patients.5Grundy S.M. Cleeman J.I. Merz C.N. Brewer Jr, H.B. Clark L.T. Hunninghake D.B. et al.Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines.Circulation. 2004; 110: 227-239Crossref PubMed Scopus (4846) Google Scholar The 2005 ACC/AHA guidelines define “very-high-risk” PAD patients as those with multiple risk factors (especially diabetes), severe or poorly controlled risk factors (especially smoking), and risk factors of the metabolic syndrome (especially elevated triglycerides in the face of an elevated non-HDL/HDL ratio).1Hirsch A.T. Haskal Z.J. Hertzer N.R. Bakal C.W. Creager M.A. Halperin J.L. et al.ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation.J Am Coll Cardiol. 2006; 47 (1239-12)Abstract Full Text Full Text PDF PubMed Scopus (938) Google Scholar Moreover, a recent prospective observational cohort study of nearly 1400 PAD patients showed that intensive therapy with statins targeting an LDL 135 mg/dL. Statins (3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitors) are the only class of lipid-lowering drugs shown to decrease overall mortality in primary and secondary prevention of coronary events. The PAD-specific, cholesterol-independent pleiotropic effects of statins are also well known and include improvements in leg functioning, ankle-brachial index, walking performance, symptoms of claudication, and perioperative and long-term mortality.50McDermott M.M. Guralnik J.M. Greenland P. Pearce W.H. Criqui M.H. Liu K. et al.Statin use and leg functioning in patients with and without lower-extremity peripheral arterial disease.Circulation. 2003; 107: 757-761Crossref PubMed Scopus (194) Google Scholar, 51Mohler 3rd, E.R. Hiatt W.R. Creager M.A. Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease.Circulation. 2003; 108: 1481-1486Crossref PubMed Scopus (391) Google Scholar, 52Mondillo S. Ballo P. Barbati R. Guerrini F. Ammaturo T. Agricola E. et al.Effects of simvastatin on walking performance and symptoms of intermittent claudication in hypercholesterolemic patients with peripheral vascular disease.Am J Med. 2003; 114: 359-364Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar Thus, statins serve as the primary foundation for effective lipid reduction in patients with PAD. Statins range in potency, reducing LDL between 20% and 55% (Table II).53Jones P.H. Davidson M.H. Stein E.A. Bays H.E. McKenney J.M. Miller E. et al.Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial).Am J Cardiol. 2003; 92: 152-160Abstract Full Text Full Text PDF PubMed Scopus (1214) Google Scholar, 54Bradford R.H. Shear C.L. Chremos A.N. Dujovne C.A. Franklin F.A. Grillo R.B. et al.Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: two-year efficacy and safety follow-up.Am J Cardiol. 1994; 74: 667-673Abstract Full Text PDF PubMed Scopus (101) Google Scholar The choice of which statin to initiate is determined by cost, availability within a formulary, potency, and effects on other triglyceride and HDL levels. Currently, three statins are available generically: lovastatin (Mevacor, Merck & Co Inc, Whitehouse Station, NJ), pravastatin (Pravachol, Bristol-Myers Squibb, New York, NY), and simvastatin (Zocor, Merck & Co, Inc). Atorvastatin (Lipitor, Pfizer Inc, New York, NY) retains a lead in overall United States sales and is slated to become available generically by 2011. Rosuvastatin (Crestor, AstraZeneca, London, United Kingdom) is the newest and most potent of the statins. LDL, Low-density lipoprotein; HDL, high-density lipoprotein. Considering potency, efficacy, and cost, we recommend simvastatin at 40 mg/d for the initiation of lipid-lowering therapy in PAD patients. A fasting lipid profile is obtained at baseline and 6 weeks. Although clear-cut data on routine monitoring do not exist, ATP III recommends follow-up every 6 weeks until LDL targets are achieved.4Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in
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