Heavy NSAID Use Linked to Dementia in Elderly

Study differs from previous studies; possibly due to delayed onset

24 april 2009- Contrary to earlier studies suggesting that users of nonsteroidal anti-inflammatory drugs (NSAIDs) have a reduced risk of developing dementia, heavy NSAID use in the elderly is associated with a higher risk of developing dementia, according to a study published online April 22 in Neurology.

John C. S. Breitner, M.D., from the Department of Veterans Affairs Medical Center in Seattle, and colleagues examined the association between the use of NSAIDs and dementia in 2,736 elderly (65 years and older) dementia-free individuals.

Based on computerized pharmacy records, the researchers found that 351 individuals (12.8 percent) were heavy NSAID users (more than 500 standard daily doses) at baseline, while an additional 107 became heavy users during the follow-up period. After up to 12 years of follow up, 476 individuals developed dementia, of which 356 was Alzheimer dementia. Heavy NSAID use was associated with a higher risk of developing dementia (adjusted hazard ratios of 1.66 for dementia and 1.57 for Alzheimer dementia).

"These findings differ from those of other studies with younger cohorts," Breitner and colleagues conclude. "The results observed elsewhere may reflect delayed onset of Alzheimer dementia in NSAID users."

Abstract
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More evidence that NSAIDs are harmful to heart-failure patients

30 mar 2009- Further evidence that even commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) are harmful to heart-failure patients has come from a new study [1].

The study, published in the January 26, 2009 issue of the Archives of Internal Medicine, shows dose-related increases in risk of death and rehospitalization for heart failure or MI with all COX-2 inhibitors or other NSAIDs.

Lead author Dr Gunnar Gislason (Gentofte University Hospital, Hellerup, Denmark), commented to heartwire: "Although our study is observational, and you can never exclude all confounding factors, we have very consistent results estimated using two different statistical methods. And these results are similar to many other previous studies. In addition, we see a strong dose-related response. I think the data are very convincing."

And it is not just the COX-2 inhibitors that are the problem, as diclofenac showed a similar risk. "This is very disturbing, as this drug is so widely used and is available off prescription in many countries," Gislason noted.

He described the effect as "quite considerable." For example, for rofecoxib (Vioxx, Merck), the number of patients needed to treat for one year to cause one death was just nine, and the corresponding number for celecoxib (Celebrex, Pfizer) was 14 and diclofenac 11. "These numbers are very low," Gislason said, noting that for antihypertensive drugs, the number needed to treat for one year to save one life is in the range of 50 to 100. "Everyone agrees that it is worth treating hypertension. So the harmful effect of some NSAIDs is much greater than the beneficial effect of antihypertensive treatment."

Even naproxen risky at high dose

"Our results suggest that all NSAIDs have harmful effects in heart-failure patients, even naproxen at high doses. Naproxen is probably the best of the bunch, but it still increases fluid retention, which is bad news for heart-failure patients," Gislason added.

But he points out that these drugs are still being used in this population. "I don't think doctors are aware of this problem. We need to raise awareness. I think the main culprits are primary-care doctors, as these drugs are so widely prescribed in general practice," he commented. "The fact that some of these drugs are available over the counter makes the situation much worse, as anyone can buy them without advice from a doctor. All NSAIDs should be prescription-only drugs. Making them available in petrol stations and supermarkets gives the impression that they are not harmful. Many heart-disease patients will not be aware that they shouldn't take them."

In the current study, Gislason and colleagues used Danish national records of hospitalizations and pharmacy drug dispensing to identify 107 092 patients surviving their first hospitalization due to heart failure between 1995 and 2004 and their subsequent use of NSAIDs.

They found that 36 354 patients (33.9%) claimed at least one prescription of an NSAID after discharge; 60 974 patients (56.9%) died, and 8970 (8.4%) and 39 984 (37.5%) were rehospitalized with MI or heart failure.

After adjustment for age, sex, calendar year, comorbidity, medical treatment, and severity of disease, the authors found a clear dose-related increase in risk with the drugs.

Using coxibs and NSAIDs to treat osteoarthritis

Outcomes of the OARSI international COX-2 workshop 2007
Mt Laurel, NJ – 13 August 2007 - In an Editorial, to be published in the international journal Osteoarthritis and Cartilage (http://intl.elsevierhealth.com/journals/joca/), published by Elsevier, a panel of arthritis research experts has recommended that coxibs and nonsteroidal anti-inflammatory drugs (NSAIDs) must remain a significant part of the tool kit used in treating osteoarthritis (OA). The Editorial summarizes the outcomes of an international workshop organized by the Osteoarthritis Research Society International (OARSI) and the International COX-2 Study Group, held 24–25 March 2007. The authors urge that an evidence-based approach must be taken when making recommendations to patients.
OA, the most common form of arthritis, is a major medical problem. It has been estimated that over 20 million Americans are afflicted with OA, and that number will rise to 40 million by the year 2020. Controversy now exists as to the safest and most efficacious way of treating the disease, particularly with respect to use of NSAIDs, both non-selective and selective (so-called COX-2 selective agents or coxibs). Adverse reactions related to the gastrointestinal tract, particularly with the non-selective NSAIDs, have been described; more recently, concerns have been expressed related to the cardiovascular system with both groups of agents.
A recent scientific statement from the American Heart Association (AHA) made recommendations with regard to the treatment of OA.1 A number of these recommendations are challenged in the Editorial2 in Osteoarthritis and Cartilage, with particular concern about their impact on appropriate use of these agents.
The Editorial questions the recommendation made in the AHA statement which described a stepped care approach to pharmacologic therapy for musculoskeletal diseases. The Editorial strongly recommends that several aspects of the AHA statement be reconsidered. For example, it urges that the AHA withdraw their non-evidence-based recommendations that high-dose aspirin be administered alone as a first line therapy for patients with chronic pain and arthritis.
Dr Roland W. Moskowitz, Professor of Medicine at Case Western Reserve University/University Hospitals of Cleveland, lead author of the Editorial comments, "Careful review of the pros and cons of using these agents, and the situations in which they are most safely and effectively used, is required to help us understand how best to take advantage of their availability".
The input by the OARSI/COX-2 International Study Group provides evidence-based background and guidance that will be of help to physicians, and to patients, in the use of these important commonly used agents.
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Editor’s Note: Please see the article for additional information including author affiliations, financial disclosures, funding and support etc.
References:- 1. E.M. Antman, J.S. Bennett, A. Daugherty, C. Furberg, H. Roberts, K.A. Taubert, Use of nonsteroidal antiinflammatory drugs. An update for clinicians: a scientific statement from the American Heart Association, Circulation. 2007;113:2906–2913.
2. R.W. Moskowitz, S. Abramson, F Berenbaum, L.S.Simon, M. Hochberg, Coxibs and NSAIDS — Is the air any clearer? Perspectives from the OARSI international COX-2 workshop 2007, Osteoarthritis and Cartilage. 2007;15:849–856.