Generic placeholder image

Current Vascular Pharmacology


ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Research Article

Improved Lipid Target Level Attainment in Patients with Peripheral Artery Disease

Author(s): Jörn F. Dopheide*, Luise Adam, Sebastian Wiedmer, Mathias Kaspar, Günther Silbernagel, Iris Baumgartner* and Heinz Drexel*

Volume 19, Issue 6, 2021

Published on: 11 January, 2021

Page: [634 - 642] Pages: 9

DOI: 10.2174/1570161119666210111123621

Price: $65


Background: Patients with peripheral artery disease (PAD) fall under the category of a very high cardiovascular risk. Although consequent lipid-lowering therapy (LLT) is advised, only sparse data on attained target level in PAD exists.

Objectives: We aimed to analyse contemporary guideline recommendations for LLT in symptomatic PAD patients.

Methods: A monocentric, prospective, observational study involving 200 symptomatic PAD patients was conducted. Guideline target level attainment and LLT were analysed between 2017 and 2019.

Results: Overall, 78.5% of the patients were on statin therapy, mainly of high intensity, with atorvastatin in 50% and rosuvastatin in 33% of the cases. The average statin dosage adjusted for simvastatin was 55 mg/d. Low density lipoprotein-cholesterol (LDL-C) was <1.8 mmol/L in 53% and <1.4 mmol/L in 34% of the cases. Mean LDL-C levels were at 1.85 ± 0.88 mmol/L. We observed no difference in the treatment and the target level attainment of patients with a stable PAD (intermittent claudication) or chronic critical PAD. However, patients with ≥ 1 vascular region affected (i.e., coronary and/or cerebrovascular) were treated more intensively and had lower LDL-C levels than patients with PAD alone.

Conclusion: It appears that there are more awareness and improvement of previously documented undertreatment of LDL-C levels in symptomatic PAD patients. Although statin treatment is initiated in the majority of patients, our findings call for a continuously intensified LLT in symptomatic PAD patients.

Keywords: Peripheral artery disease, lipid-lowering therapy, statins, low-density lipoprotein-cholesterol, target attainment, cardiovascular risk.

Graphical Abstract
Aboyans V, Ricco J-B, Bartelink MEL, et al. ESC Scientific Document Group. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J 2018; 39(9): 763-816.
[] [PMID: 28886620]
Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J 2019; 14: 111-88.
[] [PMID: 31504418]
Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2017; 135(12): e686-725.
[] [PMID: 27840332]
Jacobson TA, Ito MK, Maki KC, et al. National lipid association recommendations for patient-centered management of dyslipidemia: part 1--full report. J Clin Lipidol 2015; 9(2): 129-69.
[] [PMID: 25911072]
Stone NJ, Robinson JG, Lichtenstein AH, et al. American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129(25)(Suppl. 2): S1-S45.
[] [PMID: 24222016]
Drozda JP Jr, Ferguson TB Jr, Jneid H, et al. 2015 ACC/AHA Focused Update of Secondary Prevention Lipid Performance Measures: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. J Am Coll Cardiol 2016; 67(5): 558-87.
[] [PMID: 26698405]
Collins R, Armitage J, Parish S, Sleight P, Peto R. Heart Protection Study Collaborative Group. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet 2004; 363(9411): 757-67.
[] [PMID: 15016485]
Heart Protection Study Collaborative Group. 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(4): 645-54.
[] [PMID: 17398372]
Cannon CP, Blazing MA, Giugliano RP, et al. IMPROVE-IT Investigators. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med 2015; 372(25): 2387-97.
[] [PMID: 26039521]
Sabatine MS, Giugliano RP, Keech AC, et al. FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med 2017; 376(18): 1713-22.
[] [PMID: 28304224]
Jukema JW, Szarek M, Zijlstra LE, et al. ODYSSEY OUTCOMES Committees and Investigators. Alirocumab in Patients With Polyvascular Disease and Recent Acute Coronary Syndrome: ODYSSEY OUTCOMES Trial. J Am Coll Cardiol 2019; 74(9): 1167-76.
[] [PMID: 30898609]
Bhatt DL, Steg PG, Miller M, et al. REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med 2019; 380(1): 11-22.
[] [PMID: 30415628]
Bonaca MP, Nault P, Giugliano RP, et al. Low-Density Lipoprotein Cholesterol Lowering With Evolocumab and Outcomes in Patients With Peripheral Artery Disease: Insights From the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). Circulation 2018; 137(4): 338-50.
[] [PMID: 29133605]
Vonbank A, Agewall S, Kjeldsen KP, et al. Comprehensive efforts to increase adherence to statin therapy. Eur Heart J 2017; 38(32): 2473-9.
[] [PMID: 28077470]
Dopheide JF, Papac L, Schindewolf M, Baumgartner I, Drexel H. Poor attainment of lipid targets in patients with symptomatic peripheral artery disease. J Clin Lipidol 2018; 12(3): 711-7.
[] [PMID: 29574071]
Second European Consensus Document on chronic critical leg ischemia. Eur J Vasc Surg 1992; 6Suppl A. : 1-32.
Diehm N, Pattynama PM, Jaff MR, et al. Clinical endpoints in peripheral endovascular revascularization trials: a case for standardized definitions. Eur J Vasc Endovasc Surg 2008; 36(4): 409-19.
[] [PMID: 18692415]
Catapano AL, Graham I, De Backer G, et al. ESC Scientific Document Group. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J 2016; 37(39): 2999-3058.
[] [PMID: 27567407]
Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019; 73(24): e285-350.
[] [PMID: 30423393]
Stroes ES, Thompson PD, Corsini A, et al. European Atherosclerosis Society Consensus Panel. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J 2015; 36(17): 1012-22.
[] [PMID: 25694464]
Defesche JC, Lansberg PJ, Umans-Eckenhausen MA, Kastelein JJ. Advanced method for the identification of patients with inherited hypercholesterolemia. Semin Vasc Med 2004; 4(1): 59-65.
[] [PMID: 15199434]
Dopheide JF, Ramadani H, Adam L, et al. Development of a 3-Dimensional Prognostic Score for Patients With Symptomatic Peripheral Artery Disease: PAD3D Score. Angiology 2020; 71(7): 658-65.
[] [PMID: 32342699]
Gitt AK, Lautsch D, Ferrieres J, et al. Low-density lipoprotein cholesterol in a global cohort of 57,885 statin-treated patients. Atherosclerosis 2016; 255(Suppl. C): 200-9.
[] [PMID: 27667299]
Kitkungvan D, Lynn Fillipon NM, Dani SS, Downey BC. Low-density lipoprotein cholesterol target achievement in patients at high risk for coronary heart disease. J Clin Lipidol 2010; 4(4): 293-7.
[] [PMID: 21122662]
Toth PP, Foody JM, Tomassini JE, et al. Therapeutic practice patterns related to statin potency and ezetimibe/simvastatin combination therapies in lowering LDL-C in patients with high-risk cardiovascular disease. J Clin Lipidol 2014; 8(1): 107-16.
[] [PMID: 24528691]
Al-Hashmi K, Al-Zakwani I, Al Mahmeed W, et al. Non-high-density lipoprotein cholesterol target achievement in patients on lipid-lowering drugs and stratified by triglyceride levels in the Arabian Gulf. J Clin Lipidol 2016; 10(2): 368-77.
[] [PMID: 27055968]
Teramoto T, Uno K, Miyoshi I, et al. Low-density lipoprotein cholesterol levels and lipid-modifying therapy prescription patterns in the real world: An analysis of more than 33,000 high cardiovascular risk patients in Japan. Atherosclerosis 2016; 251(Suppl. C): 248-54.
[] [PMID: 27419905]
Kuiper JG, Sanchez RJ, Houben E, et al. Use of Lipid-modifying Therapy and LDL-C Goal Attainment in a High-Cardiovascular-Risk Population in the Netherlands. Clin Ther 2017; 39(4): 819-827.e1.
[] [PMID: 28347514]
Ference BA, Robinson JG, Brook RD, et al. Variation in PCSK9 and HMGCR and Risk of Cardiovascular Disease and Diabetes. N Engl J Med 2016; 375(22): 2144-53.
[] [PMID: 27959767]
Landmesser U, Chapman MJ, Stock JK, et al. 2017 Update of ESC/EAS Task Force on practical clinical guidance for proprotein convertase subtilisin/kexin type 9 inhibition in patients with atherosclerotic cardiovascular disease or in familial hypercholesterolaemia. Eur Heart J 2018; 39(14): 1131-43.
[] [PMID: 29045644]
Dopheide JF, Veit J, Ramadani H, et al. Adherence to statin therapy favours survival of patients with symptomatic peripheral artery disease. Eur Heart J Cardiovasc Pharmacother 2019; 10: pvz081.
[] [PMID: 31886861]
Gislason GH, Rasmussen JN, Abildstrøm SZ, et al. Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction. Eur Heart J 2006; 27(10): 1153-8.
[] [PMID: 16399775]
Cacoub PP, Abola MTB, Baumgartner I, et al. REACH Registry Investigators. 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): e86-92.
[] [PMID: 19054514]
Subherwal S, Patel MR, Kober L, et al. Missed opportunities: despite improvement in use of cardioprotective medications among patients with lower-extremity peripheral artery disease, underuse remains. Circulation 2012; 126(11): 1345-54.
[] [PMID: 22874581]
Schwartz GG, Steg PG, Szarek M, et al. ODYSSEY OUTCOMES Committees and Investigators*. Peripheral Artery Disease and Venous Thromboembolic Events After Acute Coronary Syndrome: Role of Lipoprotein(a) and Modification by Alirocumab: Prespecified Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial. Circulation 2020; 141(20): 1608-17.
[] [PMID: 32223446]
Egashira K, Hirooka Y, Kai H, et al. Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. Circulation 1994; 89(6): 2519-24.
[] [PMID: 8205659]
Treasure CB, Klein JL, Weintraub WS, et al. Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med 1995; 332(8): 481-7.
[] [PMID: 7830728]
John S, Schlaich M, Langenfeld M, et al. Increased bioavailability of nitric oxide after lipid-lowering therapy in hypercholesterolemic patients: a randomized, placebo-controlled, double-blind study. Circulation 1998; 98(3): 211-6.
[] [PMID: 9697820]
Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 1998; 97(12): 1129-35.
[] [PMID: 9537338]
Fuhrman B, Koren L, Volkova N, Keidar S, Hayek T, Aviram M. Atorvastatin therapy in hypercholesterolemic patients suppresses cellular uptake of oxidized-LDL by differentiating monocytes. Atherosclerosis 2002; 164(1): 179-85.
[] [PMID: 12119208]
Gutierrez JA, Mulder H, Jones WS, et al. Polyvascular Disease and Risk of Major Adverse Cardiovascular Events in Peripheral Artery Disease: A Secondary Analysis of the EUCLID Trial. JAMA Netw Open 2018; 1(7): e185239.
[] [PMID: 30646395]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy