Almaraz Policontundido

PLoS CLINICAL TRIALS

Cardiovascular and Cerebrovascular Events in the Randomized, Controlled Alzheimer’s Disease Anti-Inflammatory Prevention Trial (ADAPT)
ADAPT Research Group * . . .
Trial Registration: ClinicalTrials.gov: NCT00007189 Funding: This work was supported by the National Institute on Aging (NIA), grant U01 AG15477. NIA collaborators participated in the design and conduct of thestudy and in the interpretation and review of the study results. Celecoxib and the matching placebo were provided by Pfizer, and naproxen sodium and the matching placebo were provided by Bayer Healthcare; Pfizer and Bayer did not participate in the design, conduct, or analysis of the study, but did provide comments on the manuscript. Competing Interests: See section at end of manuscript.Citation: ADAPT Research Group (2006) Cardiovascular and cerebrovascular events in the randomized, controlled Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT). PLoS Clin Trials 1(7): e33. doi:10.1371/ journal.pctr.0010033 Received: June 26, 2006 Accepted: September 29, 2006 Published: November 17, 2006 Copyright: Ó 2006 ADAPT Research Group. This is an open-access article distributed underthe terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abbreviations: AD, Alzheimer’s dementia; ADAPT, Alzheimer’s Disease Anti-inflammatory Prevention Trial; APC, Adenoma Prevention with Celecoxib trial; APPROVe, Adenomatous Polyp Prevention on Vioxx trial; b.i.d.,bis in die (twice daily); CHF, congestive heart failure; CI, confidence interval; CLASS, Celecoxib Long-term Arthritis Safety Study; COX-2, cyclooxygenase-2; CV, cardiovascular; CVD, cardiovascular disease; FDA, Food and Drug Administration; MI, myocardial infarction; NIA, National Institute on Aging; NSAID, nonsteroidal antiinflammatory drug; PreSAP, Prevention of Sporadic Adenomatous Polyps trial;TIA, transient ischemic attack; VIGOR, Vioxx Gastrointestinal Outcomes Research trial * To whom correspondence should be addressed. E-mail: bmartin@ jhsph.edu (Barbara K. Martin)

. . . . ABSTRACT . ............................................................................................................................................. . . . . . . Objectives: The Alzheimer’s DiseaseAnti-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 suspendedtreatment 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, alongwith 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)...