SHOULD EVERYONE OLDER THAN 50 TAKE ASPIRIN?

Thirty years have gone by since the first randomized trial evaluating the link between aspirin and myocardial infarction was published. Now, experts are debating whether all individuals older than 50 should take a daily dose of aspirin in an attempt to reduce the risk of heart attack or stroke. In the June 18 BMJ, Peter Elwood, MD, and his colleagues, of the Welsh Aspirin Group, argued for daily aspirin therapy, while Colin Baigent, MD, argued against it.

“The evidence now supports more widespread use of aspirin prophylaxis, and there needs to be a strategy to inform the public and enable older people to make their own decision,” stated Dr. Elwood’s group.

Currently, aspirin is given to people with vascular risk only if the five-year risk is 3% or more. According to findings from a 1984 study, among a cohort of men ages 45 to 49, half had a risk above 3% by age 45. Comparable data for women were derived from the Heart Beat Wales survey, which found that half of women have a risk above 3% by age 50. Despite this evidence, they noted that a survey conducted across Wales in 2003 found that of 1,300 patients known to be at high risk, only 53% were taking aspirin.

The Welsh Aspirin Group commented that with a low dose of aspirin, adverse effects are rare and seldom serious. They said people “are likely to accept a small increased risk of bleed or other side effect in exchange for a reduced risk of a heart attack or stroke.” The researchers estimated that 90% to 95% of the population could take low-dose aspirin without problems. “The advice that people without symptoms should consult a doctor before starting aspirin prophylaxis is unreasonable and places the doctor in an impossible position,” they maintained. “We insist that the general public should be well informed and the final decision should lie with each person.”

Dr. Baigent, meanwhile, argued that it would be unwise to adopt an age threshold approach to aspirin prophylaxis in people without known vascular disease until it is certain that older people will benefit from it. He stated that among people younger than 60, the expected benefit of aspirin on myocardial infarction (risk reduced from 7/1,000 population/year to 2/1,000 population/year) does not clearly exceed the expected risk of a major gastrointestinal bleed (1 to 2/1,000 population/year). However, raising the age threshold for daily aspirin to 65 or 70, as a response to the lack of benefit up to age 60, would be unwise, commented Dr. Baigent. Little is known about aspirin’s effects in older people, he explained. “We need decisive evidence of benefit in this age group before exposing large numbers of healthy people to potential harm.”

Baigent C. Aspirin for everyone older than 50? Against. BMJ. 2005;330:1442-1443.
Elwood P, Morgan G, Brown G, Pickering J. Aspirin for everyone older than 50? For. BMJ. 2005;330:1440-1441.

STATIN USE AND THE RISK OF DEMENTIA

Statin therapy is not associated with a reduced risk of dementia, according to Thomas D. Rea, MD, MPH, of the University of Washington, Seattle, and colleagues. “Although statin use is an important treatment for cardiovascular disease, additional investigation is needed to determine whether and for whom statin use may affect dementia risk,” they said. Results of their study were published in the July Archives of Neurology.

A total of 2,798 adults 65 and older who were free of dementia at baseline were analyzed to determine whether statin use is associated with a lower risk of dementia compared with never use of lipid-lowering agents.

During 15,030 person-years of follow-up, there were 480 incident cases of dementia; 245 were attributable to Alzheimer’s disease alone, 151 to a combination of Alzheimer’s disease and vascular dementia, 62 to vascular dementia alone, and 22 to other causes.

The researchers found that compared with never use of lipid-lowering agents, ever use of statins was not associated with the risk of all-cause dementia, Alzheimer’s disease alone, Alzheimer’s disease combined with vascular dementia, or vascular dementia alone. When ever use of statins was assessed by current use or former use, current use was not associated with the risk of dementia; however, former use was associated with an elevated risk of all-cause dementia and Alzheimer’s disease alone compared with never use. The researchers suggested that former use of statins might be a marker for declining health. No difference was observed between use of statins that were more or less lipophilic.

The researchers offered several reasons why statin use was not—as they had hypothesized—associated with a lower risk of dementia. They said statin exposure might need to occur earlier in adulthood or for longer periods to prevent dementia. Also, the potential benefit of statin use may depend on the particular type of statin used or the characteristics of the patient. “Alternatively,” they added, “statin use may not affect the development of dementia.”

According to Dr. Rea, two other recent studies—one conducted by Gail Li and Eric Larson and the other by Peter Zandi and John Breitner—found similar results, indicating that there is no protective association between statin use and risk of subsequent dementia. “Taken together, the trio of studies does give caution to the potential therapeutic role of statins in dementia and indicates a need for ongoing research,” said Dr. Rea.

Rea TD, Breitner JC, Psaty BM, et al. Statin use and the risk of incident dementia: the Cardiovascular Health Study. Arch Neurol. 2005;62:1047-1051.

AAN ISSUES PRACTICE PARAMETERS FOR TREATING ESSENTIAL TREMOR

After thoroughly reviewing 211 research articles, the Quality Standards Subcommittee of the American Academy of Neurology developed practice parameters for physicians and neurologists who treat patients with essential tremor. Theresa Zesiewicz, MD, and colleagues reviewed available literature regarding initiation of pharmacologic and surgical therapies, duration of their effect, their relative benefits and risks, and the strength of evidence supporting their use. Their findings were published in the June 28 Neurology.

“Though the tremors do not completely disappear with treatment, they can be managed, making a huge difference in the daily lives of people with essential tremor,” said Dr. Zesiewicz.

The panel strongly recommended the use of propranolol and primidone, which were found to significantly reduce limb tremor. Propranolol is also recommended for head tremor, although not as strongly as it is recommended for limb tremor. Alprazolam, atenolol, gabapentin, sotalol, and topiramate were also found to be effective in reducing limb tremor, whereas clonazepam, clozapine, nadolol, and nimodipine were found to “possibly” reduce limb tremor.

Modest evidence was available for the recommendation of botulinum toxin A for limb, head, and voice tremor. Dr. Zesiewicz noted that breathiness, hoarseness, and swallowing difficulties might occur in the use of botulinum toxin A for the treatment of voice tremor.

The panel found that chronic deep brain stimulation and thalamotomy are highly efficacious in reducing tremor; however, they noted that each procedure has a small risk of major complications. In addition, they found that insufficient evidence was available regarding the efficacy of gamma knife thalamotomy and surgical treatment. “The surgical option depends on each patient’s circumstances and the risk for complications during and after the procedure,” Dr. Zesiewicz commented.

The panel recommended that future research endeavors include an effort to:

• Standardize outcome measures to assess tremor and to correlate accelerometry with clinical rating scales.
• Determine clinical and pathologic heterogeneity of essential tremor and how these relate to profiles of pharmacologic responsiveness.
• Determine the cost/benefit profile for treatments of essential tremor.
• Assess the pharmacologic and surgical treatment of head and voice tremor.
• Better determine the efficacy and side effect profiles of pharmacologic and surgical therapies for essential tremor.

Suggested Reading
Zesiewicz TA, Elble R, Louis ED, et al. Practice parameter: therapies for essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2005;64:2008-2020.

NEW GUIDELINES FOR TRIALS OF BEHAVIORAL TREATMENTS FOR RECURRENT HEADACHE

In collaboration with the American Headache Society, Donald B. Penzien, PhD, and colleagues have developed guidelines for the design of clinical trials evaluating behavioral therapies for the management of primary headache disorders. “These guidelines are complementary to and modeled after guidelines for pharmacological trials published by the International Headache Society (IHS), but they address methodologic considerations unique to behavioral and other nonpharmacological treatments” and facilitate production of quality research, they said.

Below are just a few of the recommendations, which were reported in a supplement to the journal Headache.

• Patient selection: Investigators should clearly specify the eligibility criteria for patient entry into a trial, the sources of patients, methods for patient recruitment, all inducements for participation in the research, and the proportion of patients seeking versus not seeking treatment for their headaches. Patients in all age ranges and of both sexes should be included. Known psychiatric and medical comorbidities should be tracked and reported throughout a trial. Prophylactic headache medication is discouraged in behavioral trials. Patients who should be excluded from trials include, but are not limited to, those suspected of having medication overuse headache, women who are pregnant, are planning pregnancy, or are lactating, and patients with substantial medical or psychiatric comorbidities deemed likely to interfere with their ability to participate in the trial.

• Trial design: There is no single “gold standard” design for controlled trials. However, crossover designs are not possible when researching behavioral interventions; parallel group designs are strongly recommended. Furthermore, double-blinding behavioral treatment and control conditions is rarely practical or possible. Trials comparing the effectiveness of drug versus behavioral treatments require research designs that address the unique characteristics of both.

• Evaluation of results: Primary and secondary outcome measures should be clearly defined and reported. Outcomes should be assessed using multiple measures and across multiple domains. Consistency in assessment methodology across phases of trial is essential. Adverse events should be monitored and reported.

• Research ethics: Investigators evaluating headache therapies must consistently adhere to accepted ethical principles for research with human subjects, such as those outlined by the American Psychological Association Ethical Guidelines for Psychologists, the Belmont Report, and the Ethics Subcommittee of the IHS. Financial and other important support for the research should be disclosed to address concerns about conflict of interest.

The researchers emphasized that “none of these recommendations should be regarded as dogma, and that various solutions to specific problems can be equally appropriate.”

Penzien DB, Andrasik F, Freidenberg BM, et al. Guidelines for trials of behavioral treatments for recurrent headache, first edition: American Headache Society Behavioral Clinical Trials Workgroup. Headache. 2005;45[suppl 2]:S110-S132.

INCREASED RISK OF SCHIZOPHRENIA OR SCHIZOPHRENIA-LIKE PSYCHOSIS IN PATIENTS WITH EPILEPSY

Researchers have found a strong association between epilepsy and schizophrenia or schizophrenia-like psychosis, according to a report in the July 2 BMJ. Their findings suggest that the two conditions may share common genetic or environmental causes.

Ping Qin, MD, PhD, an Associate Professor at the University of Aarhus in Denmark, and colleagues examined a cohort of 2.27 million people to determine whether age at onset of epilepsy, type of epilepsy, family history of psychosis, or family history of epilepsy affected the risk of schizophrenia or schizophrenia-like psychosis among patients with epilepsy. The investigators reported that 34,494 people had a history of epilepsy, with a median age of 14.7 at first hospital admission.

During follow-up (up to 15 years), 276 patients were admitted for schizophrenia and 519 were admitted for schizophrenia-like psychosis. The median interval between first admission for epilepsy and first admission for schizophrenia or for schizophrenia-like psychosis was 8.2 and 8.0 years, respectively.

Dr. Qin’s group found that compared with the general population, people with epilepsy were 2.48 times more likely to have schizophrenia and 2.93 times more likely to have schizophrenia-like psychosis. This effect was the same in women as in men but differed by age. People ages 15 to 24, 25 to 34, and 35 and older were 2.03, 2.28, and 4.00 times more likely to have schizophrenia. Corresponding risks for schizophrenia-like psychosis were 2.38, 3.13, and 3.77.

The researchers also found that family history of both psychosis and epilepsy were risk factors for schizophrenia and schizophrenia-like psychosis after adjustment for personal history of epilepsy. Those with a family history of schizophrenia were 7.57 times more likely to have schizophrenia and 6.24 times more likely to have schizophrenia-like psychosis, and those with a family history of epilepsy were 1.11 times more likely to have schizophrenia and 1.20 times more likely to have schizophrenia-like psychosis. Furthermore, the investigators found that a personal history of epilepsy had a stronger effect on the risk of schizophrenia or schizophrenia-like psychosis in individuals without a family history of psychosis than in those with it.

According to Dr. Qin’s group, the increased risk of schizophrenia or schizophrenia-like psychosis was similar in patients with various types of epilepsy but was more pronounced in those with more hospital admissions for epilepsy. In particular, the researchers observed an even greater risk among people first admitted for epilepsy at later ages.

Qin P, Xu H, Laursen TM, et al. Risk for schizophrenia and schizophrenia-like psychosis among patients with epilepsy: population based cohort study. BMJ. 2005;331:23-28.

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