What is Optimal Medical Therapy for CLTI? Can We Move the Needle with Drugs Alone?

Quick Takes

  • Lifestyle modification is necessary for all patients with CLTI and should be addressed at each clinic visit.
  • Active management of diabetes, treatment of hypertension, and use of anti-thrombotic and lipid-lowering agents are evidence-based strategies supported by current guidelines to reduce cardiovascular and limb events in patients with CLTI.

Chronic limb-threatening ischemia (CLTI) represents the end stage of peripheral artery disease (PAD) and is associated with an impaired quality of life due to a high risk of major adverse limb events, including major amputation, adverse cardiovascular events, and mortality. This clinical syndrome is defined by the presence of objectively proven PAD in combination with rest pain, gangrene, or lower limb ulceration greater than 2 weeks duration, and is staged based on wound severity and presence of infection. CLTI often presents in tandem with atherosclerosis in other vascular beds, but can also occasionally manifest as thrombosis isolated to the lower extremities in the absence of significant atherosclerosis, a phenomenon rarely seen in coronary or carotid disease.1,2 Given the likelihood of systemic atherosclerosis in CLTI patients, optimal medical therapy is focused not only on reducing limb threat but also on improving overall cardiovascular health.1

Clinical Manifestations
Clinical presentation includes characteristic pain, tissue loss, or both usually at the level of the foot. Pain occurs at rest and is caused by a combination of ischemia, ischemic neuropathy, and tissue loss, if present. Foot wounds in diabetics are frequently painless due to concomitant peripheral neuropathy and can progress from minimal ulceration to extensive gangrene without significant change in symptoms to alert the patient. Loss of distal pulses, dependent rubor, shiny skin, and absence of hair are common on physical exam. Tissue loss (with or without infection) usually starts with the toes though pressure from poorly fitting footwear or minor trauma can present at the foot or even calf level.1 (Figure 1)

Figure 1

Treatment Strategies
The primary factors that contribute to the risk of limb threat are wound (W), ischemia (I) and foot infection (fI).3 The WIfI classification system should be used in the initial assessment of CLTI patients to determine the severity of ischemia and allow for risk stratification. Such scoring provides estimation of amputation risk and provides an objective method to determine further management regarding benefits of arterial imaging and/or revascularization.4 While timely revascularization is a cornerstone of treatment, the optimal revascularization strategy is uncertain and currently under investigation in two large, pragmatic, randomized controlled trials comparing surgical with endovascular revascularization.5,6 Goals of treating a patient with CLTI are not only to salvage a functional limb but also to improve cardiovascular outcomes through risk factor modification and best medical therapy.7

Lifestyle Modifications
A healthier lifestyle should be encouraged and stressed for patients with CLTI. Smoking cessation, adopting a healthy diet, and regular exercise are important for the preservation of both life and limb.7 The adverse impacts of tobacco use on cardiovascular health are well established and smokers have a significantly higher rate of PAD progression and major adverse cardiovascular events (MACE).8,9 Smoking cessation is associated with lower rates of adverse cardiovascular and limb events, bypass graft failure, amputation, and death in PAD patients.10,11 PAD patients who use any form of tobacco should be advised to quit at every visit and assisted in developing a plan for quitting.12,13 Numerous trials have demonstrated the benefits of supervised exercise therapy in intermittent claudication.14 While exercise therapy may be challenging for CLTI patients, it should be considered after successful revascularization.15,16

Medical Therapy for CLTI
In addition to lifestyle modification, ongoing counseling on preventive foot care should be offered to all patients.8,17-21 Principles of good wound care should be followed to promote healing and prevent infection.4,22 Active management of diabetes, treatment of hypertension, use of antiplatelet/antithrombotic and lipid-lowering agents are evidence-based strategies supported by current guidelines to reduce cardiovascular and limb events in patients with symptomatic PAD, including CLTI.4,23 (Table 1)

Table 1

Antiplatelets and Antithrombotics
Antiplatelet agents are strongly recommended for all patients with CLTI. While the largest body of evidence supports the use of low-dose aspirin, clopidogrel is approved as an alternative in symptomatic PAD based on a reduction in MACE compared with aspirin in the CAPRIE trial.4,7,23,24 Recent evidence shows support for the use of low-dose aspirin and rivaroxaban 2.5mg twice daily to reduce major cardiovascular and limb ischemic events in symptomatic PAD, particularly after lower extremity revascularization as seen in the VOYAGER trial.25,26 VOYAGER randomized 6,564 patients with symptomatic lower extremity PAD undergoing peripheral revascularization to aspirin with rivaroxaban 2.5mg twice daily or aspirin with placebo. The primary efficacy endpoint was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction (MI), ischemic stroke, or death from cardiovascular causes while the primary safety endpoint was the Thrombolysis in Myocardial Infarction (TIMI) major bleeding. The incidence of the primary composite endpoint at 3 years was 17.3% in the rivaroxaban group and 19.9% in the placebo group with a hazard ratio of 0.85 (95% CI 0.76-0.96; p=0.0009) and this was largely driven by a reduction in acute limb ischemia. This trial included 1,533 (23%) patients with critical limb ischemia (CLI) at baseline and there was no heterogeneity in the efficacy of rivaroxaban plus aspirin compared with aspirin alone based on the presence of CLI at index revascularization.26

Dual antiplatelet therapy (DAPT) is frequently employed for 1 to 6 months after peripheral revascularization though there is an absence of strong evidence supporting this practice.27-29 Treatment with DAPT is the standard in coronary artery disease following percutaneous coronary intervention and its use after peripheral revascularization is largely based on coronary literature.7,30 The CHARISMA trial in patients with stable atherosclerotic vascular disease or multiple atherothrombotic risk factors showed no significant reduction in MACE with clopidogrel plus aspirin (DAPT) compared with aspirin alone.31 A post hoc analysis of PAD patients (92% symptomatic PAD) also found no MACE benefit for DAPT.32 PEGASUS-TIMI 54 compared ticagrelor plus aspirin (DAPT) versus aspirin alone for the prevention of MACE in patients with prior MI. Ticagrelor DAPT significantly reduced MACE though increased the risk of major bleeding in the overall trial.33 In the PAD subgroup, the absolute risk reduction with ticagrelor DAPT for MACE was 4.1% and there was also a significant reduction in major adverse limb events (MALE) with an absolute excess of major bleeding of only 0.12%.34 The THEMIS trial also compared ticagrelor DAPT with aspirin alone for MACE prevention in patients with stable coronary artery disease and type 2 diabetes. While ticagrelor DAPT significantly reduced MACE compared with aspirin alone, there was a significant increase in TIMI major bleeding and intracranial hemorrhage. In the subgroup of patients with PAD, MALE had a significant risk reduction of 55% with ticagrelor DAPT compared with aspirin monotherapy. Despite the large reduction in MALE, the significant increase in major bleeding suggests that ticagrelor DAPT should be used with caution in the PAD population.35 Despite the similarities between percutaneous interventions in coronary and peripheral arteries, PAD patients have diminished responses to DAPT, and this practice is not supported by high quality evidence.36

Low density lipoprotein (LDL-C) reduction is proven to reduce MACE in patients with atherosclerotic disease.37,38 The overwhelming majority of CLTI patients qualify for maximally tolerated statin therapy with the goal of LDL-C reduction to <70mg/dL or ≥50% reduction if LDL-C is between 70 and 135mg/dL. If LDL-C levels remain elevated, the addition of non-statin agents should be considered.39 Ezetimibe plus simvastatin significantly reduced adverse cardiovascular outcomes compared with statins alone (HR 0.936, 95% CI 0.89-0.99, p=0.016) in the IMPROVE-IT trial.40 A pre-specified subgroup analysis of polyvascular patients, including those with PAD, showed a greater numerical absolute composite endpoint risk reduction with ezetimibe plus simvastatin.41 The FOURIER trial demonstrated the additional benefits of PCSK9 inhibitors when added to statins by a significant reduction in the composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (HR 0.80, 95% CI 0.73-0.88, p<0.001) in patients with atherosclerotic cardiovascular disease (ASCVD) and LDL-C ≥70 mg/dl.42 In the subgroup of patients with symptomatic PAD, evolocumab significantly reduced the primary composite endpoint (HR 0.79, 95% CI 0.66-0.94, p=0.0098), MACE (HR 0.73, 95% CI 0.59-0.91, p=0.0040), and MALE (HR 0.58, 95% CI 0.38-0.88, p=0.0093). There was a consistent relationship between lower achieved LDL-C and lower risk of MACE and MALE, and this effect continued to an LDL <10 mg/dL in a nearly linear fashion.42,43 Despite the greater reduction in cardiovascular risk with PCSK9 inhibitors, ezetimibe is favored as a second agent given the low cost-effectiveness of the former.39

Diabetes Management
Type 2 diabetes mellitus (DM) is present in the majority of CLTI patients and the extent of vascular disease appears related to the duration and severity of hyperglycemia.44,45 Metformin remains the first line agent for all DM patients with a goal hemoglobin A1c (HbA1c) of <7% for patients with CLTI.7,46,47 The addition of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) is preferred for patients with ASCVD independent of baseline or target HbA1c. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are reasonable alternatives to GLP-1 RA with beneficial effects on cardiovascular complications, renal disease, and mortality in DM.47 Despite the cardiovascular benefits of SGLT-2 inhibitors as a class, the CANVAS Program demonstrated a 2-fold increased risk of lower limb amputations (mainly minor) with the use of canagliflozin though no specific mechanism has been identified.48,49 While a black box warning was initially issued by the FDA for amputation risk with canagliflozin, recent safety information from real-world studies and a large clinical trial suggests that the risk of amputation is lower than previously described and the black box warning has subsequently been removed.50-53 If the HbA1c remains above target despite metformin and a GLP-1 RA or SGLT-2 inhibitor, an additional hypoglycemic agent, including a dipeptidyl peptidase 4 (DPP-4) inhibitor, thiazolidinedione, sulfonylurea, or basal insulin can be added with equal effectiveness.47,54

Management of hypertension is well accepted to reduce MACE in patients with PAD with a goal of maintaining systolic blood pressure (SBP) <130mmHg and diastolic blood pressure (DBP) <80mmHg. While certain classes may be preferred according to comorbidities, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium antagonists, beta-blockers, and diuretics are all suitable for antihypertensive treatment in CLTI, as monotherapy or in combinations.4,55 Additional evidence from two randomized trials favors ACEIs or ARBs as first-line agents in CLTI patients given a reduction in MACE and mortality with no adverse effect on limb outcomes in this subgroup.4,56

CLTI confers a high risk for lower extremity amputation, adverse cardiovascular events, and mortality. Lifestyle modification is necessary for all patients and should be addressed at each clinic visit. Timely revascularization is essential and can salvage a threatened limb. Significant progress has been made in the medical management of CLTI patients with numerous evidence-based strategies available that can decrease adverse cardiovascular and limb events and prolong life.


  1. Farber A. Chronic limb-threatening ischemia. N Engl J Med 2018;379:171-80.
  2. Narula N, Olin JW, Narula N. Pathologic disparities between peripheral artery disease and coronary artery disease. Arterioscler Thromb Vasc Biol 2020;40:1982-9.
  3. Mills JL Sr, Conte MS, Armstrong DG, et al. The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: risk stratification based on wound, ischemia, and foot infection (WIfI). J Vasc Surg 2014;59:220-34.e1-2.
  4. 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): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries Endorsed 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.
  5. Menard MT, Farber A, Assmann SF, et al. Design and Rationale of the Best Endovascular Versus Best Surgical Therapy for Patients With Critical Limb Ischemia (BEST-CLI) Trial. J Am Heart Assoc 2016;5:e003219.
  6. Popplewell MA, Davies H, Jarrett H, et al. Bypass versus angio plasty in severe ischaemia of the leg - 2 (BASIL-2) trial: study protocol for a randomised controlled trial. Trials 2016;17:11.
  7. Conte MS, Bradbury AW, Kolh P, et al. Global vascular guidelines on the management of chronic limb-threatening ischemia. J Vasc Surg 2019;69:3S-125S.e40.
  8. Blomster JI, Woodward M, Zoungas S, et al. The harms of smoking and benefits of smoking cessation in women compared with men with type 2 diabetes: an observational analysis of the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial. BMJ Open 2016;6:e009668.
  9. Willigendael EM, Teijink JAW, Bartelink ML, et al. Influence of smoking on incidence and prevalence of peripheral arterial disease. J Vasc Surg 2004;40:1158-65.
  10. Armstrong EJ, Wu J, Singh GD, et al. Smoking cessation is associated with decreased mortality and improved amputation-free survival among patients with symptomatic peripheral artery disease. J Vasc Surg 2014;60:1565-71.
  11. Selvarajah S, Black JH 3rd, Malas MB, Lum YW, Propper BW, Abularrage CJ. Preoperative smoking is associated with early graft failure after infrainguinal bypass surgery. J Vasc Surg 2014;59:1308-14.
  12. Hennrikus D, Joseph AM, Lando HA, et al. Effectiveness of a smoking cessation program for peripheral artery disease patients: a randomized controlled trial. J Am Coll Cardiol 2010;56:2105-12.
  13. Stead LF, Buitrago D, Preciado N, Sanchez G, Hartmann-Boyce J, Lancaster T. Physician advice for smoking cessation. Cochrane Database Syst Rev 2013;5:Cd000165.
  14. Lane R, Ellis B, Watson L, Leng GC. Exercise for intermittent claudication. Cochrane Database Syst Rev 2014;7:Cd000990.
  15. Jakubsevičienė E, Vasiliauskas D, Velička L, Kubilius R, Milinavičienė E, Venclovienė J. Effectiveness of a new exercise program after lower limb arterial blood flow surgery in patients with peripheral arterial disease: a randomized clinical trial. Int J Environ Res Public Health 2014;11:7961-76.
  16. Kruidenier LM, Nicolaï SP, Rouwet EV, Peters RJ, Prins MH, Teijink JAW. Additional supervised exercise therapy after a percutaneous vascular intervention for peripheral arterial disease: a randomized clinical trial. J Vasc Interv Radiol 2011;22:961-8.
  17. Athyros VG, Tziomalos K, Katsiki N, et al. The impact of smoking on cardiovascular outcomes and comorbidities in statin-treated patients with coronary artery disease: a post hoc analysis of the GREACE study. Curr Vasc Pharmacol 2013;11:779-84.
  18. Canavan RJ, Unwin NC, Kelly WF, Connolly VM. Diabetes- and nondiabetes-related lower extremity amputation incidence before and after the introduction of better organized diabetes foot care: continuous longitudinal monitoring using a standard method. Diabetes Care 2008;31:459-63.
  19. Dagenais GR, Yi Q, Lonn E, Sleight P, Ostergren J, Yusuf S. Impact of cigarette smoking in high-risk patients participating in a clinical trial. A substudy from the Heart Outcomes Prevention Evaluation (HOPE) trial. Eur J Cardiovasc Prev Rehabil 2005;12:75-81.
  20. Dehghan M, Mente A, Zhang X, et al. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study. Lancet 2017;390:2050-62.
  21. Williams DT, Powell-Chandler A, Qureshi Q, Zaidi A, Whitaker CJ. Improved limb salvage for patients with vascular disease and tissue loss associated with new model of provision targeted at the diabetic foot. Diabetes Res Clin Pract 2018;135:50-7.
  22. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg 2007;45 Suppl S:S5-67.
  23. Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation 2017;135:e686-e725.
  24. Committee CS. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996;348:1329-39.
  25. Anand SS, Bosch J, Eikelboom JW, et al. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet 2018;391:219-29.
  26. Bonaca MP, Bauersachs RM, Anand SS, et al. Rivaroxaban in peripheral artery disease after revascularization. N Engl J Med 2020;382:1994-2004.
  27. Cassar K, Ford I, Greaves M, Bachoo P, Brittenden J. Randomized clinical trial of the antiplatelet effects of aspirin-clopidogrel combination versus aspirin alone after lower limb angioplasty. Br J Surg 2005;92:159-65.
  28. Soden PA, Zettervall SL, Ultee KH, et al. Dual antiplatelet therapy is associated with prolonged survival after lower extremity revascularization. J Vasc Surg 2016;64:1633-44.e1.
  29. Tepe G, Bantleon R, Brechtel K, et al. Management of peripheral arterial interventions with mono or dual antiplatelet therapy--the MIRROR study: a randomised and double-blinded clinical trial. Eur Radiol 2012;22:1998-2006.
  30. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease. A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2016;134:e123-55.
  31. Bhatt DL, Fox KAA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006;354:1706-17.
  32. Cacoub PP, Bhatt DL, Steg PG, Topol EJ, Creager MA. Patients with peripheral arterial disease in the CHARISMA trial. Eur Heart J 2009;30:192-201.
  33. Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015;372:1791-800.
  34. Bonaca MP, Bhatt DL, Storey RF, et al. Ticagrelor for prevention of ischemic events after myocardial infarction in patients with peripheral artery disease. J Am Coll Cardiol 2016;67:2719-28.
  35. Steg PG, Bhatt DL, Simon T, et al. Ticagrelor in patients with stable coronary disease and diabetes. N Engl J Med 2019;381:1309-20.
  36. Gremmel T, Xhelili E, Steiner S, Koppensteiner R, Kopp CW, Panzer S. Response to antiplatelet therapy and platelet reactivity to thrombin receptor activating peptide-6 in cardiovascular interventions: differences between peripheral and coronary angioplasty. Atherosclerosis 2014;232:119-24.
  37. Group HPSC. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22.
  38. Ridker PM, Danielson E, Fonseca FAH, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195-207.
  39. 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: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol 2019;73:3168-3209.
  40. Murphy SA, Cannon CP, Blazing MA, et al. Reduction in total cardiovascular events with ezetimibe/simvastatin post-acute coronary syndrome: the IMPROVE-IT trial. J Am Coll Cardiol 2016;67:353-61.
  41. Bonaca MP, Gutierrez JA, Cannon C, et al. Polyvascular disease, type 2 diabetes, and long-term vascular risk: a secondary analysis of the IMPROVE-IT trial. Lancet Diabetes Endocrinol 2018;6:934-43.
  42. 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;137:338-50.
  43. Govsyeyev N, Nehler MR, Hiatt WR, Bonaca MP. Tackling elevated risk in PAD: focus on antithrombotic and lipid therapy for PAD. Curr Cardiol Rep 2020;22:13.
  44. Britton KA, Mukamal KJ, Ix JH, et al. Insulin resistance and incident peripheral artery disease in the Cardiovascular Health Study. Vasc Med 2012;17:85-93.
  45. Joosten MM, Pai JK, Bertoia ML, et al. Associations between conventional cardiovascular risk factors and risk of peripheral artery disease in men. JAMA 2012;308:1660-7.
  46. Association AD. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2020. Diabetes Care 2020;43:S66-s76.
  47. Association AD. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2020. Diabetes Care 2020;43:S98-s110.
  48. Matthews DR, Li Q, Perkovic V, et al. Effects of canagliflozin on amputation risk in type 2 diabetes: the CANVAS Program. Diabetologia 2019;62:926-38.
  49. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017;377:644-57.
  50. FDA removes Boxed Warning about risk of leg and foot amputations for the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR) (FDA.gov website). 2020. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-removes-boxed-warning-about-risk-leg-and-foot-amputations-diabetes-medicine-canagliflozin. Accessed 08/28/2020.
  51. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019;380:2295-306.
  52. Ryan PB, Buse JB, Schuemie MJ, et al. Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: a real-world meta-analysis of 4 observational databases (OBSERVE-4D). Diabetes Obes Metab 2018;20:2585-97.
  53. Yuan Z, DeFalco FJ, Ryan PB, et al. Risk of lower extremity amputations in people with type 2 diabetes mellitus treated with sodium-glucose co-transporter-2 inhibitors in the USA: aretrospective cohort study. Diabetes Obes Metab 2018;20:582-9.
  54. Palmer SC, Mavridis D, Nicolucci A, et al. Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes: a meta-analysis. JAMA 2016;316:313-24.
  55. Bavry AA, Anderson RD, Gong Y, et al. Outcomes among hypertensive patients with concomitant peripheral and coronary artery disease: findings from the INternational VErapamil-SR/Trandolapril STudy. Hypertension 2010;55:48-53.
  56. Armstrong EJ, Chen DC, Singh GD, Amsterdam EA, Laird JR. Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use is associated with reduced major adverse cardiovascular events among patients with critical limb ischemia. Vasc Med 2015;20:237-44.

Clinical Topics: Dyslipidemia, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Novel Agents

Keywords: Aneurysm, Peripheral Arterial Disease, Intermittent Claudication, Tobacco, Antihypertensive Agents, Fibrinolytic Agents, Gangrene, Quality of Life, Risk Factors, Smoking Cessation, Lower Extremity, Goals, Ischemia, Platelet Aggregation Inhibitors, Hemoglobin A, Coronary Artery Disease, Aspirin, Sodium-Glucose Transporter 2, Purinergic P2Y Receptor Antagonists, Antibodies, Monoclonal, Calcium, Cardiovascular Diseases, PCSK9 protein, human

< Back to Listings