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Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial.

Abstract

CONTEXT

Laboratory evidence that inflammatory mechanisms contribute to neuronal injury in Alzheimer disease (AD), along with epidemiological evidence, suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) may favorably influence the course of the disease.

OBJECTIVE

To determine whether treatment with a selective cyclooxygenase (COX) -2 inhibitor (rofecoxib) or a traditional nonselective NSAID (naproxen) slows cognitive decline in patients with mild-to-moderate AD.

DESIGN

Multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to study medications.

SETTING

Forty ambulatory treatment centers affiliated with the Alzheimer's Disease Cooperative Study consortium.

PARTICIPANTS

Participants with mild-to-moderate AD (Mini-Mental State Examination score of 13-26) were recruited from December 1999 to November 2000 using clinic populations, referrals from community physicians, and local advertising. Stable use of cholinesterase inhibitors, estrogen, low-dose aspirin, and vitamin E was allowed. Participants with inflammatory diseases that might respond to the study medications were excluded. Of 474 participants screened, 351 were enrolled.

INTERVENTIONS

Once-daily rofecoxib, 25 mg, or twice-daily naproxen sodium, 220 mg, or placebo.

MAIN OUTCOME MEASURES

The primary outcome measure was the 1-year change in the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) subscale score. Secondary outcome measures included the Clinical Dementia Rating scale sum-of-boxes, the Neuropsychiatric Inventory, the Quality of Life-AD, and the time to attainment of significant end points (4-point decline from baseline ADAS-Cog score, 1-step worsening on the global Clinical Dementia Rating scale, 15-point decline on the ADCS activities of daily living inventory, institutionalization, or death).

RESULTS

The 1-year mean (SD) change in ADAS-Cog scores in participants treated with naproxen (5.8 [8.0]) or rofecoxib (7.6 [7.7]) was not significantly different from the change in participants treated with placebo (5.7 [8.2]). Results of secondary analyses showed no consistent benefit of either treatment. Fatigue, dizziness, and hypertension were more commonly reported in the active drug groups, and more serious adverse events were found in the active treatment group than in the placebo group.

CONCLUSION

The results of this study indicate that rofecoxib or low-dose naproxen does not slow cognitive decline in patients with mild-to-moderate AD.

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  • Authors+Show Affiliations

    ,

    Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA. psa@georgetown.edu

    , , , , , , , , ,

    Source

    JAMA 289:21 2003 Jun 04 pg 2819-26

    MeSH

    Activities of Daily Living
    Aged
    Alzheimer Disease
    Anti-Inflammatory Agents, Non-Steroidal
    Cyclooxygenase 2
    Cyclooxygenase 2 Inhibitors
    Cyclooxygenase Inhibitors
    Disease Progression
    Double-Blind Method
    Female
    Humans
    Isoenzymes
    Lactones
    Male
    Membrane Proteins
    Naproxen
    Neuropsychological Tests
    Proportional Hazards Models
    Prostaglandin-Endoperoxide Synthases
    Regression Analysis
    Sulfones
    Treatment Outcome

    Pub Type(s)

    Clinical Trial
    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    12783912

    Citation

    Aisen, Paul S., et al. "Effects of Rofecoxib or Naproxen Vs Placebo On Alzheimer Disease Progression: a Randomized Controlled Trial." JAMA, vol. 289, no. 21, 2003, pp. 2819-26.
    Aisen PS, Schafer KA, Grundman M, et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA. 2003;289(21):2819-26.
    Aisen, P. S., Schafer, K. A., Grundman, M., Pfeiffer, E., Sano, M., Davis, K. L., ... Thal, L. J. (2003). Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA, 289(21), pp. 2819-26.
    Aisen PS, et al. Effects of Rofecoxib or Naproxen Vs Placebo On Alzheimer Disease Progression: a Randomized Controlled Trial. JAMA. 2003 Jun 4;289(21):2819-26. PubMed PMID: 12783912.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. AU - Aisen,Paul S, AU - Schafer,Kimberly A, AU - Grundman,Michael, AU - Pfeiffer,Eric, AU - Sano,Mary, AU - Davis,Kenneth L, AU - Farlow,Martin R, AU - Jin,Shelia, AU - Thomas,Ronald G, AU - Thal,Leon J, AU - ,, PY - 2003/6/5/pubmed PY - 2003/6/13/medline PY - 2003/6/5/entrez SP - 2819 EP - 26 JF - JAMA JO - JAMA VL - 289 IS - 21 N2 - CONTEXT: Laboratory evidence that inflammatory mechanisms contribute to neuronal injury in Alzheimer disease (AD), along with epidemiological evidence, suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) may favorably influence the course of the disease. OBJECTIVE: To determine whether treatment with a selective cyclooxygenase (COX) -2 inhibitor (rofecoxib) or a traditional nonselective NSAID (naproxen) slows cognitive decline in patients with mild-to-moderate AD. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to study medications. SETTING: Forty ambulatory treatment centers affiliated with the Alzheimer's Disease Cooperative Study consortium. PARTICIPANTS: Participants with mild-to-moderate AD (Mini-Mental State Examination score of 13-26) were recruited from December 1999 to November 2000 using clinic populations, referrals from community physicians, and local advertising. Stable use of cholinesterase inhibitors, estrogen, low-dose aspirin, and vitamin E was allowed. Participants with inflammatory diseases that might respond to the study medications were excluded. Of 474 participants screened, 351 were enrolled. INTERVENTIONS: Once-daily rofecoxib, 25 mg, or twice-daily naproxen sodium, 220 mg, or placebo. MAIN OUTCOME MEASURES: The primary outcome measure was the 1-year change in the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) subscale score. Secondary outcome measures included the Clinical Dementia Rating scale sum-of-boxes, the Neuropsychiatric Inventory, the Quality of Life-AD, and the time to attainment of significant end points (4-point decline from baseline ADAS-Cog score, 1-step worsening on the global Clinical Dementia Rating scale, 15-point decline on the ADCS activities of daily living inventory, institutionalization, or death). RESULTS: The 1-year mean (SD) change in ADAS-Cog scores in participants treated with naproxen (5.8 [8.0]) or rofecoxib (7.6 [7.7]) was not significantly different from the change in participants treated with placebo (5.7 [8.2]). Results of secondary analyses showed no consistent benefit of either treatment. Fatigue, dizziness, and hypertension were more commonly reported in the active drug groups, and more serious adverse events were found in the active treatment group than in the placebo group. CONCLUSION: The results of this study indicate that rofecoxib or low-dose naproxen does not slow cognitive decline in patients with mild-to-moderate AD. SN - 0098-7484 UR - https://www.unboundmedicine.com/medline/citation/12783912/Effects_of_rofecoxib_or_naproxen_vs_placebo_on_Alzheimer_disease_progression:_a_randomized_controlled_trial_ L2 - https://jamanetwork.com/journals/jama/fullarticle/vol/289/pg/2819 DB - PRIME DP - Unbound Medicine ER -