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.

Benefits of Coronary Prevention: WOSCOPS

The preponderance of evidence supporting lipid modulation for reduction of coronary heart disease (CHD) springs from secondary prevention trials comprised largely of mid-life individuals with prior history of diabetes, stroke, or MI. Much less evidence is available to confirm the benefits of primary prevention through lowering of LDL. The West of Scotland Coronary Prevention Study (WOSCOPS) enrolled a population (n=6,595) of men with elevated cholesterol who had NOT sustained an MI, and randomized them to pravastatin 40 mg/d (PRAV) or placebo for 5 years. Inclusion criteria required LDL at baseline to be at least 174 mg/dL. At the conclusion of the trial the composite endpoint (CHD death plus nonfatal MI) was reduced by 30% in the PRAV group compared with the placebo group. Whether the 5-year PRAV intervention might result in continued benefit beyond the initial clinical trial period was the subject of this report by Ford, et al.

After the WOSCOPS trial completion, the two arms of the trial started to look fairly similar: almost equal percentages of each were receiving a statin (PRAV group=38.7%, placebo group= 35.2%).

Endpoint ascertainment 10 years after close of the clinical trial still showed a big advantage for study subjects originally assigned to PRAV (ie, the endpoint of fatal + nonfatal MI was still a 37% relative risk reduction seen in the PRAV group (p=0.001)). Considering the high number of persons in the placebo group on statins in the post-trial interval, these long-term benefits of PRAV treatment may actually be an underestimate.

Ford I, et al. N Engl J Med. 2007;357(15):1477-1486

Topiramate for Alcohol Dependence

Complex neurochemical mechanisms support the potential role of topiramate (TOP) for enhancing abstinence from alcohol (ABST). For instance, TOP has two different pathways by which it can reduce CNS dopamine release, thereby decreasing reinforcing aspects of alcohol ingestion. Indeed, favorable effects have already been seen in a short pilot trial.

The 14-week double-blind placebo controlled trial randomized 183 men to 300 mg/d TOP or placebo. Participants fulfilled DSM-IV criteria for alcohol dependence, and had at least 4 drinks/day (women) or 5 drinks/day (men). One drink was defined as 10 oz beer, 4 oz wine, or 1 oz of 100-proof liquor.

The primary efficacy endpoint was number of days of heavy drinking, defined as more than 5 drinks/d for men, or 4 drinks/d for women. Secondary outcomes included the percentage of days of successful total abstinence, and weekly average number of drinks.

At study endpoint, TOP was associated with a statistically significant reduction in the primary endpoint; the placebo group continued to engage in heavy drinking on 52% of days, vs 44% of days for TOP subjects. Similarly, the TOP group was over two times more likely to maintain at least 28 days of continuous abstinence than the placebo group. Differences between TOP and placebo were seen early (by 4 weeks), and were maintained throughout the trial. TOP seems a reasonable consideration to enhance alcohol abstinence.

Johnson BA, et al. JAMA 2007;98(14):1641-1651.

Job Strain and Recurrent CHD

Although the evidence is by no means incontrovertible, many clinicians concur with clinical trials which suggest job strain is a risk factor for and contributor to myocardial infarction (MI). Whether a second coronary event might also be related to job strain has been far less studied, and the trials addressing this question have been in very small populations.

Hospitals in Quebec, Canada, supplied study subjects for this large trial (n=1,191) of relatively young adults (age < 60) who had sustained an acute MI, and returned to work within 18 months after the index event. The primary outcome was incidence of new CHD events, including fatal and nonfatal MI, and angina. The Karasek Job Content Questionnaire, a validated metric for psychological demands of the work environment, was used.

After 2 years of followup, risk of a second cardiac event was more than twice as great amongst persons with the highest levels of job stress.

It is theorized that job strain induces sympathetic activation with subsequent enhanced thrombogenicity. Although less well supported, an additional theory about job stress is that persons under greater stress might be less adherent to medication and healthy lifestyle components. In any case, job strain does appear to exact a meaningful cardiovascular toll, which does not dissipate after the first event.

Aboa-Eboule C, et al. JAMA. 2007;298(14):1652-1660.