Clinical Briefs

By Louis Kuritzky, MD

Polymorphisms in the Factor VII Gene and the Risk of MI

Myocardial infarction (mi) often results from the collusion of atherosclerotic coronary vascular disease and abnormal coagulation factors, including factor VII (F7). Elevated F7 levels have been reported in some (but not all) studies to be a predictor of mortality due to coronary heart disease, and are influenced by both environmental and genetic factors. Genetic polymorphisms result in variable levels of F7, and since some data suggest that F7 levels may either favorably, or unfavorably, affect the course of severe atherosclerosis, Girelli and colleagues selected a population (n = 444) of persons with angiographically proven severe multivessel coronary artery disease for evaluation of the relationship between F7 and vascular outcome.

Several different genetic polymorphisms were associated with statistically significantly different levels of F7. Similarly, some genotypes were found to be cardioprotective, in that they were associated with lesser frequency of MI than others. As anticipated, genotypes with the lowest mean activated F7 were also associated with reduced odds ratio for MI.

Girelli et al conclude that some of the difference in frequency of MI among persons with equally severe coronary artery stenosis may be secondary to differences in F7 levels, reflecting different underlying genetic polymorphisms.

Girelli D, et al. N Engl J Med 2000; 343:774-780.

Arthritis Drugs and GI Toxicity

The commonly quoted risk of significant gastrointestinal (GI) ulcer complications of NSAID treatment is 2-4% per year from the older, nonspecific NSAIDs. Newer COX-2 specific agents have been developed intending safer GI toxicity profiles, with equal therapeutic efficacy. The current trial compared patients with osteoarthritis or rheumatoid arthritis treated with six months therapy of celecoxib (Celebrex), ibuprofen (Motrin, and others), or diclofenac (Voltaren, and others).

Approximately 8000 patients were randomized. The dose of celecoxib used was substantially higher than typically used in practice in the United States: 400 mg twice daily. Doses of ibuprofen (800 t.i.d.) and diclofenac (75 mg b.i.d.) were more typical of standard use.

The annualized rate of GI ulcer complications in the celecoxib group was approximately half that of persons taking nonspecific NSAIDs (0.76% vs 1.45%). For GI adverse events of sufficient effect to cause drug withdrawal, celecoxib was associated with equal or lower rates than nonspecific NSAIDs, with the exception of rash, which was about twice as common on celecoxib, and pruritus, which was about 1.5 times more frequent with celecoxib. On the other hand, overall GI symptoms were significantly less frequent on celecoxib than comparators.

Silverstein and associates conclude that celecoxib, even in doses 2-4 times greater than typically used, provides a greater safety profile than traditional NSAIDs.

Silverstein FE, et al. JAMA 2000;284: 1247-1255.

Effect of Niacin in Patients with Diabetes and Peripheral Arterial Disease

Arteriosclerotic vascular disease remains the primary cause of death in diabetics, attributable to some degree to lipid aberrations often seen in this population. Although niacin treatment in nondiabetic populations demonstrates favorable effect on LDL, HDL, and triglycerides, concern about potential worsening of diabetic control as a result of niacin therapy has widely restricted its use. Conclusions that niacin is "relatively contraindicated" in diabetes stem from limited clinical data. Since lipid control and subsequent cardiovascular disease end points are of crucial importance, and expanding the therapeutic choices might enhance success in achieving normolipidemia, a trial in high-risk individuals with peripheral vascular disease (n = 468), of whom about 30% were diabetic, was performed to ascertain the potential role of niacin therapy. Patients received nicotinic acid at doses up to 3000 mg/d (or less, if not tolerated) for up to 60 weeks.

Niacin increased HDL (29%), and reduced LDL (8-9%) and triglycerides (23-28%) in diabetic and nondiabetic persons. There was no effect of niacin treatment from baseline on hemoglobin A1c, despite a small increase in glucose levels. Elam and colleagues conclude that niacin therapy may be safely and effectively prescribed in diabetics, and may serve as rational alternatives to patients who fail or do not tolerate statins or fibrates.

Elam MB, et al. JAMA 2000;284: 1263-1270.