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      Cost‐Effectiveness of Clopidogrel‐Aspirin Versus Aspirin Alone for Acute Transient Ischemic Attack and Minor Stroke

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          Abstract

          Background

          Treatment with the combination of clopidogrel and aspirin taken soon after a transient ischemic attack (TIA) or minor stroke was shown to reduce the 90‐day risk of stroke in a large trial in China, but the cost‐effectiveness is unknown. This study sought to estimate the cost‐effectiveness of the clopidogrel‐aspirin regimen for acute TIA or minor stroke.

          Methods and Results

          A Markov model was created to determine the cost‐effectiveness of treatment of acute TIA or minor stroke patients with clopidogrel‐aspirin compared with aspirin alone. Inputs for the model were obtained from clinical trial data, claims databases, and the published literature. The main outcome measure was cost per quality‐adjusted life‐years (QALYs) gained. One‐way and multivariable probabilistic sensitivity analyses were performed to test the robustness of the findings. Compared with aspirin alone, clopidogrel‐aspirin resulted in a lifetime gain of 0.037 QALYs at an additional cost of CNY 1250 (US$ 192), yielding an incremental cost‐effectiveness ratio of CNY 33 800 (US$ 5200) per QALY gained. Probabilistic sensitivity analysis showed that clopidogrel‐aspirin therapy was more cost‐effective in 95.7% of the simulations at a willingness‐to‐pay threshold recommended by the World Health Organization of CNY 105 000 (US$ 16 200) per QALY.

          Conclusions

          Early 90‐day clopidogrel‐aspirin regimen for acute TIA or minor stroke is highly cost‐effective in China. Although clopidogrel is generic, Plavix is brand in China. If Plavix were generic, treatment with clopidogrel‐aspirin would have been cost saving.

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          Most cited references24

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          Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association.

          The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches to the implementation of guidelines and their use in high-risk populations.
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            A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee.

            (1996)
            Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of clinical thrombotic events. Aspirin and ticlopidine have been shown to be effective, but both have potentially serious adverse effects. Clopidogrel, a new thienopyridine derivative similar to ticlopidine, is an inhibitor of platelet aggregation induced by adenosine diphosphate. CAPRIE was a randomised, blinded, international trial designed to assess the relative efficacy of clopidogrel (75 mg once daily) and aspirin (325 mg once daily) in reducing the risk of a composite outcome cluster of ischaemic stroke, myocardial infarction, or vascular death; their relative safety was also assessed. The population studied comprised subgroups of patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease. Patients were followed for 1 to 3 years. 19,185 patients, with more than 6300 in each of the clinical subgroups, were recruited over 3 years, with a mean follow-up of 1.91 years. There were 1960 first events included in the outcome cluster on which an intention-to-treat analysis showed that patients treated with clopidogrel had an annual 5.32% risk of ischaemic stroke, myocardial infarction, or vascular death compared with 5.83% with aspirin. These rates reflect a statistically significant (p = 0.043) relative-risk reduction of 8.7% in favour of clopidogrel (95% Cl 0.3-16.5). Corresponding on-treatment analysis yielded a relative-risk reduction of 9.4%. There were no major differences in terms of safety. Reported adverse experiences in the clopidogrel and aspirin groups judged to be severe included rash (0.26% vs 0.10%), diarrhoea (0.23% vs 0.11%), upper gastrointestinal discomfort (0.97% vs 1.22%), intracranial haemorrhage (0.33% vs 0.47%), and gastrointestinal haemorrhage (0.52% vs 0.72%), respectively. There were ten (0.10%) patients in the clopidogrel group with significant reductions in neutrophils (< 1.2 x 10(9)/L) and 16 (0.17%) in the aspirin group. Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction, or vascular death. The overall safety profile of clopidogrel is at least as good as that of medium-dose aspirin.
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              Recommendations of the Panel on Cost-effectiveness in Health and Medicine.

              To develop consensus-based recommendations for the conduct of cost-effectiveness analysis (CEA). This article, the second in a 3-part series, describes the basis for recommendations constituting the reference case analysis, the set of practices developed to guide CEAs that inform societal resource allocation decisions, and the content of these recommendations. The Panel on Cost-Effectiveness in Health and Medicine, a nonfederal panel with expertise in CEA, clinical medicine, ethics, and health outcomes measurement, was convened by the US Public Health Service (PHS). The panel reviewed the theoretical foundations of CEA, current practices, and alternative methods used in analyses. Recommendations were developed on the basis of theory where possible, but tempered by ethical and pragmatic considerations, as well as the needs of users. The panel developed recommendations through 2 1/2 years of discussions. Comments on preliminary drafts prepared by panel working groups were solicited from federal government methodologists, health agency officials, and academic methodologists. The panel's methodological recommendations address (1) components belonging in the numerator and denominator of a cost-effectiveness (C/E) ratio; (2) measuring resource use in the numerator of a C/E ratio; (3) valuing health consequences in the denominator of a C/E ratio; (4) estimating effectiveness of interventions; (5) incorporating time preference and discounting; and (6) handling uncertainty. Recommendations are subject to the ¿rule of reason,¿ balancing the burden engendered by a practice with its importance to a study. If researchers follow a standard set of methods in CEA, the quality and comparability of studies, and their ultimate utility, can be much improved.
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                Author and article information

                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                ahaoa
                jah3
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                Blackwell Publishing Ltd
                2047-9980
                June 2014
                5 June 2014
                : 3
                : 3
                : e000912
                Affiliations
                [1 ]Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (Y.P., A.W., G.L., X.Z., X.M., L.L., C.W., Y.W., Y.W.)
                [2 ]China National Health Development Research Center, Beijing, China (K.Z.)
                [3 ]Departments of Neurology and Epidemiology, University of California, San Francisco, CA (C.J.)
                Author notes
                Correspondence to: Yongjun Wang, MD, or Yilong Wang, MD, No. 6 Tiantanxili, Dongcheng District, Beijing, China, 100050. E‐mail: yongjunwang1962@ 123456gmail.com , yilong528@ 123456gmail.com

                Dr Pan and Dr Wang contributed equally to the manuscript.

                A list of the CHANCE Investigators is provided in the Appendix.

                Article
                jah3560
                10.1161/JAHA.114.000912
                4309076
                24904018
                00b85de9-7f45-4eae-ae6c-7bfdde61085d
                © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 16 March 2014
                : 29 April 2014
                Categories
                Original Research
                Stroke

                Cardiovascular Medicine
                clopidogrel,cost‐effectiveness,quality‐adjusted life‐year,stroke
                Cardiovascular Medicine
                clopidogrel, cost‐effectiveness, quality‐adjusted life‐year, stroke

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