Comparison of efficacy of antiplatelet treatments for patients with claudication

Stefania Basili; Valeria Raparelli; Annarita Vestri; Gian Luca Di Tanna; Francesco Violi

doi:10.1160/TH09-09-0635

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 103(04): 766-773
DOI: 10.1160/TH09-09-0635

Platelets and Blood Cells

Schattauer GmbH

Comparison of efficacy of antiplatelet treatments for patients with claudication

A meta-analysis

Stefania Basili

¹Internal Medicine Division – Atherothrombosis Centre and BioMedical Statistics and Clinical Epidemiology Centre, Department of Experimental Medicine, “La Sapienza” University of Rome, Italy

,

Valeria Raparelli

¹Internal Medicine Division – Atherothrombosis Centre and BioMedical Statistics and Clinical Epidemiology Centre, Department of Experimental Medicine, “La Sapienza” University of Rome, Italy

,

Annarita Vestri

¹Internal Medicine Division – Atherothrombosis Centre and BioMedical Statistics and Clinical Epidemiology Centre, Department of Experimental Medicine, “La Sapienza” University of Rome, Italy

,

Gian Luca Di Tanna

¹Internal Medicine Division – Atherothrombosis Centre and BioMedical Statistics and Clinical Epidemiology Centre, Department of Experimental Medicine, “La Sapienza” University of Rome, Italy

,

Francesco Violi

¹Internal Medicine Division – Atherothrombosis Centre and BioMedical Statistics and Clinical Epidemiology Centre, Department of Experimental Medicine, “La Sapienza” University of Rome, Italy

› Author Affiliations

Abstract

Summary

It was the aim of the present study to investigate if antiplatelet treatment reduced cardiovascular events in patients with claudication and/ or an ankle/brachial index (ABI) ≤0.99 and to analyse if specific antiplatelet treatment had a different impact on clinical outcome. We performed a meta-analysis of 29 clinical randomized trials on antiplatelet therapy for prevention of vascular death, myocardial infarction, and stroke in 10,735 peripheral artery disease patients. The primary end-point utilizing in the meta-analysis construction was Cardiovascular Adverse Event. We found 1,900 (17.70%) patients in trials with aspirin, 5,326 (49.61%) in those with thienopyridines, 2,324 (21.65%) in those with picotamide and 1,185 (11.04 %) in those with others antiplatelet drugs. A statistically significant effect of antiplatelet treatment [odds ratio (OR) 0.839; 95% confidence interval (CI) 0.729–0.965; p=0.014] was observed. There was a statistically significant reduction of clinical outcome [OR 0.779; 95% CI 0.639–0.950; p=0.014] in the thienopyridine-treated group vs. control. Patients treated with picotamide [OR 0.785; 95% CI 0.495–1.243; p=0.302] or aspirin [OR 0.847; 95%CI 0.653–1.097; p=0.084] showed reduced cardiovascular outcomes, that, however, did not reach significance. The study confirms that anti-platelet treatment reduces vascular outcome in claudicants. Significant reduction was observed with thienopyridines while data regarding aspirin and picotamide were inconclusive.

Keywords

Antiplatelet agents - atherosclerosis - atherothrombosis - clinical trials - antiplatelet drugs - vasculopathies

Full Text

References

References
1 Selvin E, Erlinger TP. 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: 738-743.
2 US Census Bureau, Population Division, Population Projections Branch.. National Population Projections. http://www.census.gov/population/www/projections/natproj.html (8 July 2004).
3 Leng GC, Lee AJ, Fowkes FG. et al. Incidence, natural history and cardiovascular events in symptomatic and asymptomatic peripheral arterial disease in the general population. Int J Epidemiol 1996; 25: 1172-1181.
4 Criqui MH, Langer RD, Fronek A. et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992; 326: 381-386.
5 Steg PG, Bhatt DL, Wilson PW. et al. REACH Registry Investigators. One-year cardiovascular event rates in outpatients with atherothrombosis. J Am Med Assoc 2007; 297: 1197-1206.
6 Davì G, Gresele P, Violi F. et al. Diabetes mellitus, hypercholesterolemia, and hypertension but not vascular disease per se are associated with persistent platelet activation in vivo. Evidence derived from the study of peripheral arterial disease. Circulation 1997; 96: 69-75.
7 Blann AD, Tan KT, Tayebjee MH. et al. Soluble CD40L in peripheral artery disease. Relationship with disease severity, platelet markers and the effects of angioplasty. Thromb Haemost 2005; 93: 578-583.
8 Bennett PC, Silverman SH, Gill PS, Lip GY. Peripheral arterial disease and Virchow’s triad. Thromb Haemost 2009; 101: 1032-1040.
9 Antithrombotic Trialists’ Collaboration.. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Br Med J 2002; 324: 71-86.
10 Meru AV, Mittra S, Thyagarajan B. et al. Intermittent claudication: an overview. Atherosclerosis 2006; 187: 221-237.
11 Landry GJ. Functional outcome of critical limb ischemia. J Vasc Surg 2007; 45: A141-148.
12 Schmieder FA, Comerota AJ. Intermittent claudication: magnitude of the problem, patient evaluation, and therapeutic strategies. Am J Cardiol 2001; 87: 3D-13D.
13 Antiplatelet Trialists’ Collaboration.. Secondary prevention of vascular disease by prolonged antiplatelet treatment. Br Med J (Clin Res Ed) 1988; 296: 320-331.
14 Antiplatelet Trialists’ Collaboration.. Collaborative overview of randomised trials of antiplatelet therapy--I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists’ Collaboration. BMJ 1994; 308: 81-106.
15 Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 22: 719-748.
16 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 07: 177-188.
17 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558.
18 Critical Leg Ischaemia Prevention Study (CLIPS) Group. Catalano M, Born G, Peto R. Prevention of serious vascular events by aspirin amongst patients with peripheral arterial disease: randomized, double-blind trial. J Intern Med 2007; 261: 276-284.
19 Belch J, MacCuish A, Campbell I. et al. Prevention of Progression of Arterial Disease and Diabetes Study Group; Diabetes Registry Group; Royal College of Physicians Edinburgh. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. Br Med J 2008; 337: a1840.
20 Bhatt DL, Flather MD, Hacke W. et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol 2007; 49: 1982-1988.
21 Balsano F, Violi F. Effect of picotamide on the clinical progression of peripheral vascular disease. A double-blind placebo-controlled study. The ADEP Group. Circulation 1993; 87: 1563-1569.
22 Berger JS, Krantz MJ, Kittelson JM. et al. Aspirin for the prevention of cardiovascular events in patients with peripheral artery disease: a meta-analysis of randomized trials. J Am Med Assoc 2009; 301: 1909-1919.
23 Fowkes G. AAA: Randomised controlled trial of low dose aspirin in the prevention of cardiovascular events and death in subjects with asymptomatic atherosclerosis. Congress Reports 2009 – Hot Lines & Clinical Trial Updates. Session number: 175–176. ESC Congress 2009, Barcelona, Spain.
24 McDermott MM, Criqui MH. Aspirin and secondary prevention in peripheral artery disease: a perspective for the early 21st century. J Am Med Assoc 2009; 301: 1927-1928.
25 Antithrombotic Trialists’ (ATT) Collaboration. Baigent C, Blackwell L, Collins R. et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373: 1849-1860.
26 Hirsch AT, Haskal ZJ, Hertzer NR. et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): 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. Circulation 2006; 113: e463-654.
27 Patrono C, Bachmann F, Baigent C. et al. Expert consensus document on the use of antiplatelet agents. The task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the European society of cardiology. Eur Heart J 2004; 25: 166-181.
28 Sobel M, Verhaeghe R. American College of Chest Physicians.. Antithrombotic therapy for peripheral artery occlusive disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133: 815S-843S.
29 Neri Serneri GG, Coccheri S, Marubini E. et al. Drug Evaluation in Atherosclerotic Vascular Disease in Diabetics (DAVID) Study Group. Picotamide, a combined inhibitor of thromboxane A2 synthase and receptor, reduces 2-year mortality in diabetics with peripheral arterial disease: the DAVID study. Eur Heart J 2004; 25: 1845-1852.
30 CAPRIE Steering Committee.. A randomised, blinded,trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348: 1329-1339.