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.

Smoking: If at First You Don't Succeed…

Current tools to assist in smoking cessation are successful in only a minority of persons. Clinical trials are generally based upon a single cessation attempt, usually measured over 6-12 months to assess long-term abstinence. Given the fact that most smokers (70%) indicate that they would like to quit, it is surprising that so little evidence has been assembled about 'next step management:' what to do when the patient fails an initial cessation attempt or relapses.

Fu et al collected data on almost 1,000 smokers at a VA Hospital who had recently attempted smoking cessation. Subjects received a phone call 6 months after their prescription for a smoking cessation intervention. As predicted from previous trials, approximately two thirds of respondents had already relapsed.

One might intuitively conclude that a recently relapsed smoker would have little interest in trying again, but au contraire, 65% stated that they wished to make another attempt within the next 30 days. The majority of relapsed smokers wanted to have a combination of behavioral and pharmacologic treatments, but only a tiny fraction (2%) were interested solely in behavioral treatment.

On average, those who ultimately permanently quit smoking over the long term require about 4 attempts at cessation before they are successful. These data suggest that relapsed subjects feel positive about attempting cessation again promptly. Perhaps a rapid cycling approach by clinicians, by encouraging relapsed patients who are wiling to try again quickly to do so, will facilitate a greater degree of success.

Fu SS, et al. Am J Manag Care. 2006;12:235-243.

Can Hypertension be Prevented by Pharmacotherapy?

Prehypertension (pHTN), defined as either a systolic blood pressure of 135-139, a diastolic BP of 85-89, or both, evolves into frank hypertension (HTN) in most individuals. Although treatment tools for established HTN are well defined, whether treatment of pHTN is both feasible and tolerable has only been the subject of limited study.

Subjects with pHTN (n = 809) were randomly assigned to the angiotensin receptor blocker (ARB) candesartan 16 mg/d or placebo, and followed for four years. For the first 2 years of the trial, subjects received either candesartan or placebo; for the next 2 years, both groups received placebo.

At 2 years, 40.4% of placebo recipients developed HTN, as compared with 13.6% in the candesartan group. At the 4-year measurement (remember that the candesartan group had been off medication for 2 years at this point), those who had received ARB treatment for the first 2 years still enjoyed a 16% relative risk reduction for HTN compared to placebo-only treated patients. Adverse effects were LESS frequent in the treatment group than placebo.

Even though this study confirms that treatment of pHTN prevents HTN, the authors close their discussion with a note of caution that until further confirmatory research of the benefits of pHTN treatment are at hand, the time is not yet right to advocate for universal treatment of pHTN patients.

Julius S, et al N Eng J Med. 2006;354:1685-1697.

Does an Impaired Gastric Acid Environment Reduce Absorption of Thyroxine?

The treatment of hypothyroidism with levothyroxine is generally straightforward. Nonetheless, simple missteps in treatment can compromise success. For instance, co-administration of calcium salts or iron interferes with thyroxine absorption. Maintenance of gastric acid pH may also play a role.

Centanni et al studied patients receiving levothyroxine (n = 248) who had one of several possible etiologies for a less acidic gastric environment: Helicobacter gastritis, atrophic gastritis, or treatment with a proton pump inhibitor (omeprazole). Thyroxine doses necessary to maintain a therapeutic TSH were compared in subjects with one of these three reasons for an increased gastric pH, compared with a group of matched controls.

On average, the amount of levothyroxine needed to appropriately suppress TSH was 22-34% higher in subjects with elevated gastric pH than in controls. Supportive of the fact that gastric acidity was the critical element, thyroxine doses after cessation of PPI treatment reverted to the levels required prior to PPI treatment. The authors conclude that gastric acidity ultimately affects the effectiveness of levothyroxine absorption.

Centanni M, et al. N Engl J Med. 2006;354:1787-1795.