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.
Should Beta-Blockers Remain First Choice in the Treatment of Primary Hypertension?
With all the cardiovascular science that has flowed through our journals in the past decade, one would think that all of the basic questions about hypertension (HTN) would have been answered by now. Were you to ask most clinicians whether beta-blockers (BETA) are appropriate first-line hypertensive agents, most would surely reply affirmatively. Remember that the ALLHAT trial, our largest-ever antihypertensive trial, did not contain a BETA treatment arm, hence the only available comparisons from that trial are between diuretic, ACE inhibitor, calcium channel blocker, and alpha blocker.
Although the merit of BETA in either the post-MI setting or heart failure is not disputed, recent analysis of BETA treatment for HTN—atenolol, specifically—has suggested much less sanguine efficacy than clinician utilization would imply. Lindholm et al performed a meta-analysis to evaluate the efficacy of a various BETA treatment for HTN.
The data analysis by Cochrane review included subjects (n = 105,951) from randomized, controlled trials (RCT). Studies involved either BETA versus placebo, or BETA compared with other classes of treatment.
Stroke reduction is one of the hallmarks of HTN treatment success. Disappointingly, this meta-analysis indicates that stroke reductions afforded by BETA treatment of HTN were only about 19%, or about half the degree of stroke reduction seen in RCT of other antihypertensive drug classes. Based upon these findings, the authors suggest that BETA no longer be considered as first-line treatment and that BETA are not appropriate as comparator treatment in controlled trials, since other treatments (eg, diuretic, calcium blocker, ACE) are superior.
Lindholm LH, et al. Lancet. 2005;366:1545-1553.
Obstructive Sleep Apnea as a Risk Factor for Stroke and Death
The reductions in stroke achieved through treatment of hypertension and atrial fibrillation notwithstanding, stroke remains the #2 cause of death worldwide. Obstructive sleep apnea (OSA) has been associated with increased risk of cardiovascular morbidity and mortality. OSA has a 4% prevalence amongst the general population, compared with 60% in the stroke population. OSA has also been associated with hypertension (HTN), but whether OSA is independently associated with stroke (ie, separate from the fact that OSA leads to increased BP which leads to stroke) has not yet been ascertained.
An observational cohort study population (n = 1022) of persons referred to the Yale Center for Sleep Medicine underwent polysomnography. A diagnosis of OSA was based upon an apnea-hypopnea index (AHI) of 5 or greater (ie, at least 5 events/hour of sleep); the mean AHI of the study group was 35, compared with the control group AHI of 2 . Study subjects were followed for 4 years.
There was a statistically significant association between OSA and stroke or death. This relationship remained significant even after adjustment for sex, race, smoking, alcohol, BMI, diabetes, lipids, atrial fibrillation, and hypertension. The worse the degree of OSA was, the greater the risk. Overall, OSA was associated with approximately a doubling of risk for stroke or death. Whether treatment of OSA will reduce this heightened CV risk remains to be clarified.
Yaggi H, et al. N Engl J Med. 2005;353:2034-2041.
Cholinesterase Inhibitors for Alzheimer’s Disease
Clinicians and caregivers alike hope for useful pharmacotherapeutic tools to forestall decline in cognitive function in persons with Alzheimer’s disease (ALZ). Cholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) are often prescribed for ALZ, predicated on the belief that raising CNS acetylcholine levels will compensate for the recognized deficit in CNS acetylcholine, and provide either improved cognitive function, or at least a slowing of cognitive function decline. The authors inform us that they were prompted to do a systematic review of these medications based upon the observation that only 10% of dementia pharmacotherapy in Germany is comprised of cholinesterase inhibitors, calling into question the perceived efficacy of this choice.
A review of 22 published, double- blind, randomized, controlled trials of a cholinesterase inhibitor vs placebo was performed. Unfortunately, based upon their review the authors conclude that the combination of flaws in study design plus small increments in clinical benefit places the scientific foundation for recommendation of cholinesterase inhibitors into the category of "questionable."
Kaduszkiewicz H, et al. 2005;331:321-327.
Should Beta-Blockers Remain First Choice in the Treatment of Primary Hypertension?; Obstructive Sleep Apnea as a Risk Factor for Stroke and Death; Cholinesterase Inhibitors for Alzheimers DiseaseSubscribe Now for Access
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