Abstract
Objectives:The Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) was designed to evaluate the conventional NSAID naproxen sodium and the selective COX-2 inhibitor celecoxib for primary prevention of Alzheimer's dementia (AD). On 17 December 2004, after the Adenoma Prevention with Celecoxib (APC) trial reported increased cardiovascular risks with celecoxib, the ADAPT Steering Committee suspended treatment and enrollment. This paper reports on cardiovascular and cerebrovascular events in ADAPT.Design:ADAPT is a randomized, placebo-controlled, parallel chemoprevention trial with 1–46 mo of follow-up.Setting:The trial was conducted at six field sites in the United States: Baltimore, Maryland; Boston, Massachusetts; Rochester, New York; Seattle, Washington; Sun City, Arizona; and Tampa, Florida.Participants:The 2,528 participants were aged 70 y and older with a family history of AD.Interventions:Study treatments were celecoxib (200 mg b.i.d.), naproxen sodium (220 mg b.i.d.), and placebo.Outcome measures:Outcome measures were deaths, along with nonfatal myocardial infarction (MI), stroke, congestive heart failure (CHF), transient ischemic attack (TIA), and antihypertensive treatment recorded from structured interviews at scheduled intervals. Cox proportional hazards regression was used to analyze these events individually and in several composites.Results:Counts (with 3-y incidence) of participants who experienced cardiovascular or cerebrovascular death, MI, stroke, CHF, or TIA in the celecoxib-, naproxen-, and placebo-treated groups were 28/717 (5.54%), 40/713 (8.25%), and 37/1070 (5.68%), respectively. This yielded a hazard ratio (95% confidence interval [CI]) for celecoxib of 1.10 (0.67–1.79) and for naproxen of 1.63 (1.04–2.55). Antihypertensive treatment was initiated in 160/440 (47.43%), 147/427 (45.00%), and 164/644 (34.08%). This yielded hazard ratios (CIs) of 1.56 for celecoxib (1.26–1.94) and 1.40 for naproxen (1.12–1.75).Conclusions:For celecoxib, ADAPT data do not show the same level of risk as those of the APC trial. The data for naproxen, although not definitive, are suggestive of increased cardiovascular and cerebrovascular risk.
Highlights
Epidemiological studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) may delay or prevent the onset of Alzheimer’s dementia (AD)
We believe we are obligated to make these results available to the scientific community and the public at large, and we present them as a contribution to the larger body of evidence about the potential cardiovascular and cerebrovascular risks of COX-2 inhibitors and conventional NSAIDs
The outcomes we report here are adverse events, including occurrences of death, myocardial infarction (MI), stroke, congestive heart failure (CHF), and transient ischemic attack (TIA)
Summary
Epidemiological studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) may delay or prevent the onset of Alzheimer’s dementia (AD). In order to reliably find out whether NSAIDs reduce the risk of Alzheimer’s, it is important to perform a properly designed randomized trial Such a trial, ADAPT, was sponsored by the United States National Institute on Aging, and the study started recruitment in 2001. It was planned that 2,625 participants would be recruited and that the primary outcome of interest was incidence of Alzheimer’s disease in the three treatment arms; the trial would run for 7 y This trial was terminated early, a decision based in part on information from other studies that demonstrated an increased risk of certain harms, such as heart attacks and strokes, in people taking celecoxib and other types of COX-2 inhibitors. Data about the chance of these harms are available from the ADAPT results, and these results are presented here
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