Abstract and Introduction
Abstract
Background: Clinical trials have helped clarify the efficacy of clopidogrel for the treatment and prevention of vascular disease. Costs for its use exceeded $5.9 billion in 2005, making it the second greatest source of drug expenditure in the world. However, little is known about the appropriateness of that use. Overuse of clopidogrel could have important implications for health care quality and drug expenditures.
Methods: We conducted a retrospective cohort study linking all filled prescriptions to all clinical encounter data for Medicare beneficiaries enrolled in a large state-wide pharmacy assistance program. We identified all patients newly prescribed clopidogrel during a recent 2-year period and determined the proportion who had indications for clopidogrel, the mean number of tablets filled by patients with and without apparent indications in the year after starting therapy, and the costs associated with the observed patterns of clopidogrel use.
Results: We identified 4977 patients who were newly prescribed clopidogrel. Of these patients, only 47% had ≥1 documented indications for clopidogrel according to clinical trial findings. Using looser criteria, the number of patients with appropriate indications was 56%. During the first year of therapy, 43% ($2.05 million) of total clopidogrel expenditures for the patients studied was spent on patients without an indication that this agent was required, using the extended criteria for evidence-based use.
Conclusions: More than 40% of the clopidogrel used in this population appears to have been prescribed to patients for whom the drug had no documented advantage over aspirin or no antiplatelet therapy. If the same proportion applies nationally, in 2005, it would represent almost $1.5 billion of potentially unnecessary health care expenditure.
Introduction
Numerous large-scale randomized trials have clarified the role of clopidogrel (Plavix, Bristol-Myers Squibb, New York, NY) for the treatment and prevention of vascular disease. The combination of clopidogrel and aspirin has been shown to be superior to aspirin alone for patients who have had an acute coronary syndrome (ACS) or who have undergone percutaneous coronary intervention. Similarly, clopidogrel monotherapy is more effective than aspirin alone for patients with peripheral arterial disease, recent stroke, or recent myocardial infarction (MI). This study also found that clopidogrel caused less gastrointestinal toxicity than aspirin, although it was compared with 325 mg daily of aspirin rather than the 81 to 162 mg daily more commonly used at present for cardioprotection. In contrast, a combined regimen of clopidogrel plus aspirin in patients with less acute vascular disease or those without known vascular disease but with multiple atherothrombotic risk factors was not found to provide any incremental benefit over aspirin alone and increased the risk of bleeding.
The use of clopidogrel has risen sharply since its introduction in 1997 (see Figure 1), spurred in part by a very active program of promotion to both physicians and patients, with an estimated $110 million spent in 2005 for print and broadcast advertising to patients alone. Despite this, the underuse of clopidogrel is common, occurs to an extent that is similar to that observed for other cardiovascular drugs, and may have important effects on patient outcomes.
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Figure 1.
Increasing use of Plavix in the United States. Figures represent Plavix sales by Bristol-Myers Squibb since its introduction in 1997. Data obtained from Securities and Exchange Commission filings by Bristol-Myers Squibb (available at www.sec.gov). Annual 2006 figures extrapolated from first quarter sales (assuming a 12% growth rate compared with 2005).
In contrast, it is likely that some proportion of clopidogrel prescribing occurs in the absence of published literature supporting its use. Because a daily dose of Plavix in 2006 cost approximately $4, whereas the daily cost of aspirin is just 3 cents, the overuse of clopidogrel may have significant clinical and economic implications when used in patients for whom aspirin has been shown to been equally effective. Accordingly, clopidogrel represents an increasingly common problem in pharmacotherapy: a newer, costly branded product that is equivalent to an older, far less expensive agent for many patients but more effective for a well-defined subset of patients. With the advent of Medicare drug coverage and the availability and much wider use of costly medications supported by public funding, this problem has gained added importance.
We sought to determine what proportion of patients newly prescribed clopidogrel had evidence-based indications for this therapy and to evaluate the economic implications of the observed patterns of clopidogrel use.