Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial

Jill J. F. Belch (Lead / Corresponding author), John Dormandy, CASPAR Writing Comm

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    156 Citations (Scopus)

    Abstract

    Objective: Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid (ASA) is superior to ASA alone in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. We sought to determine whether clopidogrel plus ASA conferred benefit on limb outcomes over ASA alone in patients undergoing below-knee bypass grafting.

    Methods: Patients undergoing unilateral, below-knee bypass graft for atherosclerotic peripheral arterial disease (PAD) were enrolled 2 to 4 days after surgery and were randomly assigned to clopidogrel 75 mg/day plus ASA 75 to 100 mg/day or placebo plus ASA 75 to 100 mg/day for 6 to 24 months. The primary efficacy endpoint was a composite of index-graft occlusion or revascularization, above-ankle amputation of the affected limb, or death. The primary safety endpoint was severe bleeding (Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries [GUSTO] classification).

    Results: In the overall population, the primary endpoint occurred in 149 of 425 patients in the clopidogrel group vs 151 of 426 patients in the placebo (plus ASA) group (hazard ratio [FIR], 0.98; 95% confidence interval [CI], 0.78-1.23). In a prespecified subgroup analysis, the primary endpoint was significantly reduced by clopidogrel in prosthetic graft patients (HR, 0.65; 95% CI, 0.45-0.95; P = .025) but not in venous graft patients (HR, 1.25; 95% CI, 0.94-1.67, not significant [NS]). A significant statistical interaction between treatment effect and graft type was observed (P-interaction =.008). Although total bleeds were more frequent with clopidogrel, there was no significant difference between the rates of severe bleeding in the clopidogrel and placebo (plus ASA) groups (2.1% vs 1.2%).

    Conclusion: The combination of clopidogrel plus ASA did not improve limb or systemic outcomes in the overall population of PAD patients requiring below-knee bypass grafting. Subgroup analysis suggests that clopidogrel plus ASA confers benefit in patients receiving prosthetic grafts without significantly increasing major bleeding risk. (J Vase Surg 2010;52:825-33.)

    Original languageEnglish
    Pages (from-to)825-833
    Number of pages9
    JournalJournal of Vascular Surgery
    Volume52
    Issue number4
    DOIs
    Publication statusPublished - Oct 2010

    Keywords

    • ACUTE MYOCARDIAL-INFARCTION
    • DRUG-ELUTING STENTS
    • ANTIPLATELET THERAPY
    • ORAL ANTICOAGULANTS
    • ISCHEMIC EVENTS
    • LOWER-EXTREMITY
    • ASPIRIN
    • PREVENTION
    • MANAGEMENT
    • RISK

    Cite this

    @article{fc3e824bb80740e38dbf8f35b6a0c567,
    title = "Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial",
    abstract = "Objective: Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid (ASA) is superior to ASA alone in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. We sought to determine whether clopidogrel plus ASA conferred benefit on limb outcomes over ASA alone in patients undergoing below-knee bypass grafting.Methods: Patients undergoing unilateral, below-knee bypass graft for atherosclerotic peripheral arterial disease (PAD) were enrolled 2 to 4 days after surgery and were randomly assigned to clopidogrel 75 mg/day plus ASA 75 to 100 mg/day or placebo plus ASA 75 to 100 mg/day for 6 to 24 months. The primary efficacy endpoint was a composite of index-graft occlusion or revascularization, above-ankle amputation of the affected limb, or death. The primary safety endpoint was severe bleeding (Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries [GUSTO] classification).Results: In the overall population, the primary endpoint occurred in 149 of 425 patients in the clopidogrel group vs 151 of 426 patients in the placebo (plus ASA) group (hazard ratio [FIR], 0.98; 95{\%} confidence interval [CI], 0.78-1.23). In a prespecified subgroup analysis, the primary endpoint was significantly reduced by clopidogrel in prosthetic graft patients (HR, 0.65; 95{\%} CI, 0.45-0.95; P = .025) but not in venous graft patients (HR, 1.25; 95{\%} CI, 0.94-1.67, not significant [NS]). A significant statistical interaction between treatment effect and graft type was observed (P-interaction =.008). Although total bleeds were more frequent with clopidogrel, there was no significant difference between the rates of severe bleeding in the clopidogrel and placebo (plus ASA) groups (2.1{\%} vs 1.2{\%}).Conclusion: The combination of clopidogrel plus ASA did not improve limb or systemic outcomes in the overall population of PAD patients requiring below-knee bypass grafting. Subgroup analysis suggests that clopidogrel plus ASA confers benefit in patients receiving prosthetic grafts without significantly increasing major bleeding risk. (J Vase Surg 2010;52:825-33.)",
    keywords = "ACUTE MYOCARDIAL-INFARCTION, DRUG-ELUTING STENTS, ANTIPLATELET THERAPY, ORAL ANTICOAGULANTS, ISCHEMIC EVENTS, LOWER-EXTREMITY, ASPIRIN, PREVENTION, MANAGEMENT, RISK",
    author = "Belch, {Jill J. F.} and John Dormandy and {CASPAR Writing Comm}",
    year = "2010",
    month = "10",
    doi = "10.1016/j.jvs.2010.04.027",
    language = "English",
    volume = "52",
    pages = "825--833",
    journal = "Journal of Vascular Surgery",
    issn = "0741-5214",
    publisher = "Elsevier",
    number = "4",

    }

    TY - JOUR

    T1 - Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial

    AU - Belch, Jill J. F.

    AU - Dormandy, John

    AU - CASPAR Writing Comm

    PY - 2010/10

    Y1 - 2010/10

    N2 - Objective: Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid (ASA) is superior to ASA alone in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. We sought to determine whether clopidogrel plus ASA conferred benefit on limb outcomes over ASA alone in patients undergoing below-knee bypass grafting.Methods: Patients undergoing unilateral, below-knee bypass graft for atherosclerotic peripheral arterial disease (PAD) were enrolled 2 to 4 days after surgery and were randomly assigned to clopidogrel 75 mg/day plus ASA 75 to 100 mg/day or placebo plus ASA 75 to 100 mg/day for 6 to 24 months. The primary efficacy endpoint was a composite of index-graft occlusion or revascularization, above-ankle amputation of the affected limb, or death. The primary safety endpoint was severe bleeding (Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries [GUSTO] classification).Results: In the overall population, the primary endpoint occurred in 149 of 425 patients in the clopidogrel group vs 151 of 426 patients in the placebo (plus ASA) group (hazard ratio [FIR], 0.98; 95% confidence interval [CI], 0.78-1.23). In a prespecified subgroup analysis, the primary endpoint was significantly reduced by clopidogrel in prosthetic graft patients (HR, 0.65; 95% CI, 0.45-0.95; P = .025) but not in venous graft patients (HR, 1.25; 95% CI, 0.94-1.67, not significant [NS]). A significant statistical interaction between treatment effect and graft type was observed (P-interaction =.008). Although total bleeds were more frequent with clopidogrel, there was no significant difference between the rates of severe bleeding in the clopidogrel and placebo (plus ASA) groups (2.1% vs 1.2%).Conclusion: The combination of clopidogrel plus ASA did not improve limb or systemic outcomes in the overall population of PAD patients requiring below-knee bypass grafting. Subgroup analysis suggests that clopidogrel plus ASA confers benefit in patients receiving prosthetic grafts without significantly increasing major bleeding risk. (J Vase Surg 2010;52:825-33.)

    AB - Objective: Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid (ASA) is superior to ASA alone in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. We sought to determine whether clopidogrel plus ASA conferred benefit on limb outcomes over ASA alone in patients undergoing below-knee bypass grafting.Methods: Patients undergoing unilateral, below-knee bypass graft for atherosclerotic peripheral arterial disease (PAD) were enrolled 2 to 4 days after surgery and were randomly assigned to clopidogrel 75 mg/day plus ASA 75 to 100 mg/day or placebo plus ASA 75 to 100 mg/day for 6 to 24 months. The primary efficacy endpoint was a composite of index-graft occlusion or revascularization, above-ankle amputation of the affected limb, or death. The primary safety endpoint was severe bleeding (Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries [GUSTO] classification).Results: In the overall population, the primary endpoint occurred in 149 of 425 patients in the clopidogrel group vs 151 of 426 patients in the placebo (plus ASA) group (hazard ratio [FIR], 0.98; 95% confidence interval [CI], 0.78-1.23). In a prespecified subgroup analysis, the primary endpoint was significantly reduced by clopidogrel in prosthetic graft patients (HR, 0.65; 95% CI, 0.45-0.95; P = .025) but not in venous graft patients (HR, 1.25; 95% CI, 0.94-1.67, not significant [NS]). A significant statistical interaction between treatment effect and graft type was observed (P-interaction =.008). Although total bleeds were more frequent with clopidogrel, there was no significant difference between the rates of severe bleeding in the clopidogrel and placebo (plus ASA) groups (2.1% vs 1.2%).Conclusion: The combination of clopidogrel plus ASA did not improve limb or systemic outcomes in the overall population of PAD patients requiring below-knee bypass grafting. Subgroup analysis suggests that clopidogrel plus ASA confers benefit in patients receiving prosthetic grafts without significantly increasing major bleeding risk. (J Vase Surg 2010;52:825-33.)

    KW - ACUTE MYOCARDIAL-INFARCTION

    KW - DRUG-ELUTING STENTS

    KW - ANTIPLATELET THERAPY

    KW - ORAL ANTICOAGULANTS

    KW - ISCHEMIC EVENTS

    KW - LOWER-EXTREMITY

    KW - ASPIRIN

    KW - PREVENTION

    KW - MANAGEMENT

    KW - RISK

    UR - http://www.scopus.com/inward/record.url?scp=77957660699&partnerID=8YFLogxK

    U2 - 10.1016/j.jvs.2010.04.027

    DO - 10.1016/j.jvs.2010.04.027

    M3 - Article

    VL - 52

    SP - 825

    EP - 833

    JO - Journal of Vascular Surgery

    JF - Journal of Vascular Surgery

    SN - 0741-5214

    IS - 4

    ER -