Cardiovascular and cerebrovascular events in the randomized, controlled Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT) - PubMed (original) (raw)

Cardiovascular and cerebrovascular events in the randomized, controlled Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT)

ADAPT Research Group. PLoS Clin Trials. 2006.

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.

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Conflict of interest statement

Competing Interests: See section at end of manuscript.

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References

    1. Szekely CA, Thorne JE, Zandi PP, Ek M, Messias E, et al. Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer's disease: A systematic review. Neuroepidemiology. 2004;23:159–169. - PubMed
    1. Steering Committee of the Alzheimer's Disease Anti-inflammatory Prevention Trial. Statement from the Steering Committee of the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) for communication to the FDA Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee, 18 February 2005. 2005. Available at http://www.jhucct.com/adapt/pdf%20documents/FDA%20ADAPT%20STATEMENT_web%.... Accessed 22 December 2005.
    1. Martin BK, Meinert CL, Breitner JCS, for the ADAPT Research Group Double placebo design in a prevention trial for Alzheimer's disease. Control Clin Trials. 2002;23:93–99. - PubMed
    1. Shih JH. Sample size calculation for complex clinical trials with survival endpoints. Control Clin Trials. 1995;16:395–407. - PubMed
    1. Solomon SD, McMurray JV, Pfeffer MA, Wittes J, Fowler R, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005;352:1071–1080. - PubMed

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