Gastric Acid Secretion and the Absorption of Thyroxine

Pharmacology Watch

The absorption of thyroxine is strongly influenced by stomach acidity, according to new study. Researchers from Italy looked at 248 patients with multinodular goiter who were treated with thyroxine with a goal thyrotropin (TSH) level of 0.05 to 0.20 mU/L. Of these patients, 53 had Helicobacter pylori related gastritis and 60 had atrophic gastritis of the stomach. The reference group comprised 135 patients with multinodular goiter and no gastric disorders. The study also included 11 patients who were infected with H. pylori during the study and 10 patients who were treated with omeprazole and had no gastroesophageal reflux. Patients with H. pylori-related gastritis, atrophic gastritis, or both had a daily requirement of thyroxine that was 22-34% higher than the reference group. In the 11 patients who became infected with age by lower H. pylori during the study, thyrotropin levels increased significantly (P = 0 .002), an effect that was nearly reversed with eradication of H. pylori. Treatment with omeprazole also increased serum thyrotropin levels (median 1.70mU/L increase in thyrotropin; P = 0.002), requiring a 37% increase in thyroxine dose.

The authors conclude that normal gastric acid secretion is necessary for effective absorption of thyroxine, and factors that impair acid secretion including atrophic gastritis, H. pylori gastritis, and treatment with omeprazole require increased doses of thyroxine (N Engl J Med. 2006;354:1787-1795). This study has important implications, given millions of patients who take thyroxine, the frequency of H. pylori infections in this country, and frequency of use of OTC and prescription proton pump inhibitors.

Can Plavix Add to the Efficacy of Aspirin?

Does clopidogrel (Plavix) add to the efficacy of low aspirin in patients with vascular disease? No, according to new study published in the April 20th New England Journal of Medicine. CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) is a multinational study which randomized 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg/d) plus low-dose aspirin (75-162 mg/d) or placebo plus low-dose aspirin for median of 28 months. The efficacy primary end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes. The rate of this end point was 6.8% with the combined drug treatment versus 7.3% with aspirin plus placebo (P = 0.22) for the subgroup of patients with multiple risk factors, the rate of the primary end point was lower for aspirin plus placebo (5.5% aspirin plus placebo versus 6.6% aspirin plus clopidogrel; P = 0.20) and the rate of death from cardiovascular causes was also higher with clopidogrel plus aspirin vs aspirin plus placebo (3.9% versus 2.2%; P = 0.01). In the subgroup with clinically evident atherothrombosis, there was a slight benefit for aspirin plus clopidogrel (6.9% versus 7.9%, P = 0.46).

The authors conclude that overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular disease (N Engl J Med. 2006;354:1706-1717). An accompanying editorial acknowledges that there were many subgroups within CHARISMA that showed varying outcomes with clopidogrel plus aspirin, but cautions against differentiating patients along the lines used in the study. The editorialists find that "these data showed no significant benefit associated with long-term clopidogrel therapy in addition to aspirin." (N Engl J Med. 2006;354:1744-1746).

Prevention of Hypertension?

Prehypertension is defined as blood pressure in the range of 120 to 139 mm Hg systolic or 80 to 89 mm Hg diastolic. Since JNC-VII, there has been increased interest in prehypertension since it has been associated with excess morbidity and deaths from cardiovascular causes. A new study suggests that pharmacologic intervention in patients with prehypertension may help prevent progression to hypertension. The Trial of Preventing Hypertension (TROPHY) looked at 809 patients with prehypertension. A total of 409 patients were randomly assigned to candesartan or placebo for 2 years, followed by 2 years of placebo for both groups. When a study participant reached the study end point of stage I hypertension, they were treated with antihypertensive agents.

Both treatment and placebo groups were instructed in lifestyle changes to reduce blood pressure throughout the trial. During the first 2 years, hypertension developed in 154 participants in the placebo group and 53 in a candesartan group (P < 0.001). After 4 years, hypertension had developed in 240 participants in the placebo group and 208 in the candesartan group (relative risk reduction 15.6%; P < 0.007). Serious adverse events were slightly higher in the placebo group.

The authors conclude that treatment of prehypertension with candesartan was well-tolerated and reduced the risk of incident hypertension during the study period (N Engl J Med. 2006;354:1685-1697). In an accompanying editorial, it is pointed out the prehypertension is present in the about 70 million Americans, and is estimated to decrease average life expectancy by as much as 5 years. Despite this, the author urges caution in recommending wholesale treatment of all patients with prehypertension until more information is available on which drugs are most effective and the best duration of therapy. In the meantime, lifestyle changes, which benefit all risk factors, should be recommended for all patients with prehypertension (N Engl J Med. 2006;354:1742-1744).

Estrogen Alternatives

Since publication of the Women's Health Initiative (WHI), many postmenopausal women have discontinued estrogen, and most newly menopausal women are considering alternatives. A recently published paper systematically reviews clinical trials of nonhormonal treatments for hot flashes. More than 4000 studies were considered. Forty-three trials met inclusion criteria, including 10 trials of antidepressants, 10 trials of clonidine, 6 trials of other medications, and 17 trials of isoflavone extracts. In the antidepressant group, both selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) were effective in decreasing the daily number of hot flashes compared to placebo (mean difference -1.13; 95% CI, -1.70 to -0.57). Clonidine was also somewhat effective (-0.95; 95% CI, -1.44 to - 0.47), as was gabapentin (-2.05; 95% CI, -2.80 to -1.30). Red clover isoflavone extracts were not effective, and mixed soy isoflavones had mixed results. The authors conclude that SSRIs, SNRIs, clonidine, and gabapentin provide evidence for some efficacy; however, none are as effective as estrogen (JAMA. 2006;295:2057-2071).

FDA Actions

In April, the FDA issued a statement rejecting the medical use of marijuana, citing past evaluations by several US government agencies that showed that "no animal or human data supported the safety or efficacy of marijuana for general medical use." The statement supports the Drug Enforcement Agency's approach to treating all use of marijuana as a criminal act.

Zanamivir (Relenza), GlaxoSmithKline's inhaled anti-influenza drug has received a new indication for prophylaxis of influenza in patients age 5 years and older. The approval was based on 4 large-scale, placebo-controlled trials which showed that the drug was effective in reducing spread of influenza among household members and in community outbreaks.

This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: