Efficacy of high- versus moderate-dose statin therapy on lower extremity artery disease after revascularization

Aim: Statins are one of the most important agents in the treatment of atherosclerotic peripheral arterial disease. We aim to compare high- and moderate-dose statin therapy in patients with lower extremity artery disease (LEAD) who have undergone percutaneous transluminal angioplasty (PTA). Patients and Methods: Ninety-four patients treated with PTA were selected consecutively and retrospectively and were divided into two groups according to the high- or moderate-dose statin treatments they were given. Groups were compared for the absence of restenosis and occlusion as primary patency and the need for reintervention in the treated arterial segment as secondary patency. All patients underwent computed tomography (CT) angiography or duplex scan one year after receiving PTA. Results: Coronary revascularization (p<0.001) and prior statin usage (p:0.02) were more common in the high-dose statin group when compared to the moderate-dose statin group. Lesion characteristics did not differ between the two groups. Primary patency rate was significantly higher (36.1% vs. 27.6%, p 0.01) in the high-dose statin group. Major amputation (4.2% vs. 10.6%, p:0.03) and minor amputation (12.7% vs. 19.1%, p:0.03) rates were significantly lower in the high-dose statin group. Regression analysis revealed that the usage of high-dose statin therapy was an independent predictor of higher primary patency in patients who were treated with prior PTA(Odds ratio:2.208, p<0.001) Conclusion: High-dose long-term statin treatment might have better outcomes on primary patency in patients who underwent prior PTA for infrapopliteal lesions as a subgroup of peripheral artery disease. The administration of the high-dose long-term statin therapy might be important in the prognosis of peripheral arterial disease, especially for those with infrapopliteal lesions.

___

  • Istvan ES, Deisenhofer J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science 2001;292:1160-4. doi: 10.1126/science.1059344.
  • Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. EurHeart J 2016; 37:2999. doi: 10.1093/eurheartj/ehw272.
  • Mach F, Baigent C, Catapano AL, et al. ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020 Jan 1; 41:111-88. doi: 10.1093/eurheartj/ehz455.
  • Aung PP, Maxwell HG, Jepson RG, et al. Lipid-lowering for peripheral arterial disease of the lower limb. Cochrane Database Syst Rev 2007; 4; CD000123. doi:10.1002/14651858. CD000123.pub2.
  • Antoniou GA, Fisher RK, Georgiadis GS, et al. Statin therapy in lower limb peripheral arterial disease: systematic review and meta-analysis.Vascul Pharmacol 2014;63:79-87. doi: 10.1016/j.vph.2014.09.001.
  • 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 highrisk conditions. J Vasc Surg 2007; 45:645-54. doi: 10.1016/j. jvs.2006.12.054.
  • Kumbhani DJ, Steg PG, Cannon CP, et al. Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry. EurHeart J 2014; 35:2864-72. doi: 10.1093/eurheartj/ehu080.
  • Rand T, Uberoi R. Current status of interventional radiology treatment of infrapopliteal arterial disease. Cardiovasc Intervent Radiol 2013; 36: 588-98. doi: 10.1007/s00270.012.0524-8.
  • Aboyans V, Ricco JB, Bartelink MEL, et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS). Rev Esp Cardiol (EnglEd) 2018 ; 71:111. doi: 10.1016/j.rec.2017.12.014.
  • Aboyans V, Ricco JB, 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 ; 39:763-816. doi: 10.1093/eurheartj/ehx095.
  • Elsayed S, Clavijo LC. Critical limb ischemia. Cardiol Clin 2015; 33:37-47. doi: 10.1016/j.ccl.2014.09.008.
  • Fowkes FG, Housley E, Riemersma RA, et al. Smoking, lipids, glucose intolerance, and blood pressure as risk factors for peripheral atherosclerosis compared with ischemic heart disease in the Edinburgh Artery Study. Am J Epidemiol 1992; 135:331-40. doi: 10.1093/oxfordjournals.aje.a116294
  • Schmidt A, Ulrich M, Winkler B, et al. Angiographic patency and clinical outcome after balloon‑angioplasty for extensive infrapopliteal arterial disease. Catheter Cardiovasc Interv 2010;76:1047-54. doi: 10.1002/ccd.22658.
  • Cannon CP, Steinberg BA, Murphy SA, et al. Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J Am Coll Cardiol 2006;48:438-45. doi: 10.1016/j.jacc.2006.04.070.
  • Pedersen TR, Faergeman O, Kastelein JJ, et al. Highdose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 2005;294:2437-45. doi: 10.1001/jama.294.19.2437.
  • Arya S, Khakharia A, Binney ZO, et al. Association of statin dose with amputation and survival in patients with peripheral artery disease. Circulation 2018;137:1435-46. doi: 10.1161/ CIRCULATIONAHA.117.032361.
  • Foley TR, Singh GD, Kokkinidis DG, et al. High-intensity statin therapy is associated with improved survival in patients with peripheral artery disease. J Am Heart Assoc 2017 ;6:e005699. doi: 10.1161/JAHA.117.005699.
  • Stoekenbroek RM, Boekholdt SM, Fayyad R, et al. Incremental decrease in end points through aggressive lipid lowering study group. High-dose atorvastatin is superior to moderate-dose simvastatin in preventing peripheral arterial disease. Heart 2015;101:356-62. doi: 10.1136/heartjnl-2014-306906.
  • Spring S, Simon R, van der Loo B, et al. High-dose atorvastatin in peripheral arterial disease (PAD): effect on endothelial function, intima-media-thickness and local progression of PAD. An open randomized controlled pilot trial. Thromb Haemost 2008 ;99:182-9.
  • Fowkes FG, Rudan D, Rudan I, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet 2013;382:1329-40. doi: 10.1160/TH07-04-0265.
  • Romiti M, Albers M, Brochado-Neto FC, et al. Meta-analysis of infrapopliteal angioplasty for chronic critical limb ischemia. J Vasc Surg 2008:47:975-81. doi: 10.1016/j.jvs.2008.01.005.
  • Fernandez N, McEnaney R, Marone LK, et al. Predictors of failure and success of tibial interventions for critical limb ischemia. J Vasc Surg 2010 ;52:834-42. doi: 10.1016/j. jvs.2010.04.070.
  • Sadowitz B, Maier KG, Gahtan V. Basic science review: Statin therapy—Part I: The pleiotropic effects of statins in cardiovascular disease. Vasc Endovascular Surg 2010 ;44:241- 51. doi: 10.1177/153.857.4410362922. .
  • Silva VS, Martin LC, Franco RJ, et al. Pleiotropic effects of statins may improve outcomes in atherosclerotic renovascular disease. Am J Hypertens2008 ;21:1163-8. doi: 10.1038/ ajh.2008.249.
  • Subramanian S, Emami H, Vucic E, et al. High-dose atorvastatin reduces periodontal inflammation: a novel pleiotropic effect of statins. J Am Coll Cardiol 2013 ;62:2382- 91. doi: 10.1016/j.jacc.2013.08.1627.