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Vanderbilt University Medical Center—
Prescribing NSAIDs for Cardioprotection: A Red Herring?
The Vanderbilt CERTs focuses on observational studies of medication effects, evaluation of the effects of policy changes, and improving medication use.
Key projects:
- Retrospective study to assess outcomes of medical vs. surgical treatment of gastroesophageal reflux disease
- Evaluation and documentation of effectiveness of risk-awareness campaigns on coxib use in various communities and clinical settings
- Measurement of the comparative safety and efficacy for two major classes of non-aspirin, non-steroidal anti-inflammatory drugs in patients with heart disease
The safe use of anti-inflammatory drugs is a central concern of the Vanderbilt University CERTs as well. Principal investigator Dr. Wayne Ray and his colleagues concentrate on observational studies of existing medications and apply the results to changing the clinical use of these drugs and the policies surrounding them. This year they turned to the use of non-aspirin, non-steroidal anti-inflammatory drugs (NANSAIDs) and their effects on heart disease.
Controversial findings from a previous study suggested that the NANSAID naproxen, a commonly prescribed and popular over-the-counter pain reliever, could protect against heart attack and other cardiovascular complications. But the data were far from conclusive and physicians were unsure if naproxen could be given to their patients most at risk for heart disease to prevent heart attacks.
One of the actions of NANSAIDs is platelet inhibition. NANSAIDs help keep platelets, the blood cells that produce clotting, from binding together and so potentially blocking blood vessels. Specifically, they can block the production of an enzyme called thromboxane, which helps make platelets “sticky.”
Of course, the primary function of NANSAIDs is to reduce inflammation. As recent study findings highlighted in the news have shown, inflammation may be a prime culprit in the development of coronary artery disease and other cardiovascular ills, perhaps even more important than cholesterol. The anti-inflammatory effect of naproxen could hold the potential to reduce the damage done to arteries and decrease the likelihood of a heart attack.
However, NANSAIDs are complex medicines. They have a wide range of effects on the body that vary greatly depending on dosage. At high doses, NANSAIDs inhibit the production of a compound called prostacyclin. Prostacyclin is one of the body's natural platelet blockers and so the clot-preventing effects of NANSAIDs may be reversed at sufficient doses. At these high doses, NANSAIDs may also contribute to high blood pressure, another risk factor for heart disease.
The intricacies of NANSAIDs' physiological effects leave doctors and patients at an impasse. Do NANSAIDs protect against heart disease and should they be prescribed just for this effect? If a patient needs a NANSAID for arthritis pain, is there a need to prescribe aspirin also? As a new class of pain relievers called coxibs increases in popularity and NANSAIDs perhaps become less commonly prescribed, this is an issue much on physicians' minds.
While few doctors were prescribing NANSAIDS for prevention of heart disease, consideration of discontinuing aspirin if a NANSAID was required for arthritis pain was an issue for millions of Americans.
Answering this kind of question on the best and safest use of a medication is the heart of the CERTs mission. Dr. Ray and his team set out to do so with a challenging and far-reaching study of 11 years' worth of records from the Tennessee Medicaid program.
The investigators combed the records of over 180,000 new NANSAIDs users and an equal number of non-users as a control group, all over the age of 50 and at risk for heart disease. They looked for hospitalizations for heart attack or death from heart disease. The records were from 1987 to 1998, before coxibs came to market, so these latest anti-inflammatories were not included in the study.
Dr. Ray's team performed several complex analyses to adjust for various baseline risk factors for heart disease. One excluded those patients who had existing heart failure, a condition that some research suggests is worsened by NANSAIDs. Another analysis focused on those patients most likely to benefit from any cardioprotective effect of NANSAIDs, including those taking the drugs at doses sufficient to reach the anti-platelet effect.
No matter how the data were approached and filtered, no protective benefit from NANSAIDs was found. The two groups of patients suffered heart attacks at roughly equal rates. Without randomized trials providing evidence to the contrary, Dr. Ray concluded that naproxen and other NANSAIDs should not be prescribed to protect against heart disease. Most importantly, we can now tell doctors that patients who must be treated with NANSAIDS must also be treated with aspirin if they meet the usual criteria for primary or secondary prevention of vascular disease with aspirin.
Dr. Ray's study demonstrates an important function of CERTs. Not only can CERTs research identify how existing medications are being used, as in the UAB CERTs coxib study, it can also penetrate the clouds of conflicting data and insufficient study to answer important questions about common therapies and provide sound evidence on their safe use.
Dr. Ray and his team published their findings in the January 12, 2002 issue of The Lancet.