Negative effects of diuretic drugs on metabolic risk factors for coronary heart disease: possible alternative drug therapies.

The results of 8 major hypertension treatment trials, all using diuretics as first-line therapy, show a clear-cut reduction in stroke and congestive heart failure, but coronary heart disease (CHD) is not consistently benefited. It is unclear why CHD is not controlled, but diuretics can subtly upset metabolic risk factors for CHD, among which are lipid and glucose concentrations. Although these metabolic disturbances appear clinically unimpressive, risk table analysis reveals that they can offset or even reverse the benefits of reducing blood pressure. A link between glucose intolerance and increased serum lipid concentrations during diuretic-based therapy is suggested by multiple correlations between them. Replacement of diuretics as first-line therapy for mild and moderate hypertension should therefore be considered. Spironolactone seems to counter the adverse metabolic effects, but its effect on lipoproteins needs more study. A drug that does not disturb glucose and lipid metabolism would seem preferable. Thus prazosin is a promising candidate.