Clinical Briefs By Louis Kuritzky, MD
Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.
Risk of Death in Elderly Users of Conventional vs Atypical Antipsychotic Medications
Atypical antipsychotic medications (AAM) such as aripiprazole (Abilify), clozapine (Clozaril), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal) and ziprasidone (Geodon) are commonly prescribed for elders suffering dementia, delirium, psychosis, and affective disorders. Very recently (April 2005), clinicians have been advised that numerous placebo-controlled trials (n = 17) of AAM in elders indicate an increased risk—almost a doubling—of death. Additionally, despite common popular usage, AAM have never been indicated for treatment of dementia, and this ‘non-approved' status has also been highlighted by inclusion in the ‘black box' warning appended to all AAM.
This recent warning message might have led one to assume that the earlier ‘conventional' antipsychotic medications (CAM) are not fraught with such risk. Instead, the issue has not been well studied. CAM include such medications as chlorpromazine (Thorazine), fluphenazine (Prolixin), mesoridazine (Serentil), perphenazine (Trilafon), thioridazine (Mellaril), trifluoperazine (Stelazine), and haloperidol (Haldol).
A retrospective cohort study (n = 22,890) of adults older than age 65 in Pennsylvania who had received a new antipsychotic prescription (AAM or CAM) was undertaken. Results were adjusted for confounding variables such as coexisting illness (eg, diabetes, arrhythmias, cardiovascular disease, cancer). The primary study end point was the relative risk of death for persons receiving a CAM versus an AAM.
Treatment with a CAM was associated with an overall unadjusted hazard ratio for death within 180 days of 1.51. These data suggest that CAM are associated with even greater mortality risk than AAM.
Wang PS, et al. N Engl J Med. 2005; 353:2335-2341.
Beta-Blockers to Prevent Gastroesophageal Varices in Cirrhosis Patients
In patients with established esophageal varices (ESV), non-selective beta-blockers (BB) are effective in reducing risk of hemorrhage. This may be a result of decreased portal pressure through a combination of decreased cardiac output—a beta-1 effect, and reduced splanchnic blood flow—a beta-2 effect. Hence, selective BB (which are beta-1 selective) may or may not provide similar benefit.
Theoretically, BB might be useful to prevent the development of ESV, not just reduce bleeding from them. Groszmann et al studied a population (n = 213) of high-risk individuals for development of ESV: cirrhotics with portal hypertension as demonstrated by an elevated hepatic venous pressure gradient. This placebo-controlled trial involved administration of timolol (Blocadren) titrated to up to 80 mg/d with followup every 3 months for 54.9 months (mean). Study subjects underwent, in addition to hematology monitoring, endoscopy and measurement of hepatic venous pressure gradient on an annual basis.
The primary end point, development of ESV or ESV bleeding, was no different in the timolol group than placebo. Disturbingly, there were more serious adverse events in the timolol group than in the placebo group. Nonselective beta blockers are not effective for preventing the development of ESV in high-risk patients.
Groszmann RJ, et al. N Engl J Med. 2005;353:2254-2261.
Effects of Protein, Monounsaturated Fat, and Carbohydrate Intake on Blood Pressure and Serum Lipids
Identification of the ‘best diet' remains an elusive target. Cardiovascular disease (CVD) remains the #1 cause of death in the United States, and reduction in saturated fat (SAT) is commonly suggested as a tool for CVD prevention. If one is to reduce the amount of SAT, unless the total number of calories are also reduced, some other nutrient category must be correspondingly increased. Whether substituting carbohydrate, protein, or unsaturated fat for the omitted SAT provides better impact upon blood pressure (BP) and lipids is the object of this study.
Adults (n = 164) with either prehypertension or stage 1 hypertension were randomized to 3 periods of dietary management, in each of which SAT was substituted: protein-enriched, carbohydrate enriched, and unsaturated fat-enriched. Weight was maintained constant throughout each 6-week feeding.
Using the carbohydrate-enriched diet for comparison, both protein-enriched and monounsaturated fat-enriched diets resulted in favorable, very similar changes in lipids and blood pressure. Although the impact of dietary change upon BP and lipids was small, it was sufficient to reduce estimated 10-year CHD risk (Framingham scoring).
Appel LJ, et al. JAMA. 2005;294: 2455-2464.
Risk of Death in Elderly Users of Conventional vs Atypical Antipsychotic Medications; Beta-Blockers to Prevent Gastroesophageal Varices in Cirrhosis Patients; Effects of Protein, Monounsaturated Fat, and Carbohydrate Intake on Blood Pressure and Serum LipidsSubscribe Now for Access
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