Diuretics, potassium, and ventricular ectopy.

I tion alone accounted for this and whether the reduction would have been greater had the diuretics not caused a ‘‘backlash’’ of cardiotoxicty. Certainly, the introduction of orally available thiazide diuretics in 1957–8 revn November 1985, we reviewed the then current status of experimental and clinical evidence and opinion on diuretic-associated hypokalemia with particular attention to its potential for inducing ventricular ectopy. Nearly a decade later we had the olutionized the treatment of hypertension. Earlier oral drug regimens caused such significant deterioration of opportunity to revisit this topic in preparation for the Third Dahl Symposium; nearly 12 years later, we have the quality of life of patients with otherwise asymptomatic hypertension that convincing patients to be miserareviewed the current literature in preparation of this paper. What has changed? Not much in the way of ble in order to live longer was a difficult sales pitch. To paraphrase the late Herbert Langford, how can one solid data, but there does appear to be some alteration of the paradigm. This paper is a review of work by expect a patient to take medications that make them unable to cerebrate, defecate, or fornicate in the hope ourselves and others, but the reader must keep firmly in mind that, in the final analysis, it is an expression of living longer? Of course, one could add the visual of my personal opinion. and urinary sphincter changes plus orthostatic hypotension and depression to that short list. Oral diuretics WHAT ARE THE ISSUES? changed all of that by providing single-drug control for I see the issues as follows. First, there is the concern patients with milder hypertension and by permitting over why cardiovascular mortality has not been relower doses of other drugs when combined with them. duced by antihypertensive therapy over time to the In my opinion, none of the hypertension studies dedegree predicted when the reduction of cerebrovascusigned, completed, and published to date can be interlar mortality has met expectations. Second, there was preted to show true cardiotoxicity of diuretics. First, considerable concern over the promotion of potasthe patient population was middle-aged and patients sium supplements and potassium-sparing diuretics with cardiac risk factors were not excluded. Indeed, because they were expensive and thought to be unnecpatients with known coronary heart disease manifested essary. Third, there was considerable controversy by an old myocardial infarction or angina pectoris were about whether or not diuretics alone or associated specifically included. Second, very large doses of diwith hypokalemia could cause lethal or potentially uretics were generally used. A recent case-controlled lethal ventricular ectopy. Finally, the fact that there is study suggests that the use of 25 mg or less of hydroa current trend toward using non-diuretic antihyperchlorothiazide may actually be cardioprotective. Third, tensive drugs and using only low-dose diuretics, many trials were not really designed to test a specific could render most of the above discussion moot. hypothesis regarding cardiac mortality. Fourth, some of the diuretics used were combined with potassiumCardiovascular Mortality That the era of more insparing agents and some were not. The major clinical tense antihypertensive therapy has been accompanied trial, Antihypertensive and Lipid Lowering Treatment by a reduction in cardiovascular mortality is indisputto Prevent Heart Attack Trial (ALLHAT), is designed able. The questions are whether blood pressure reducto detect differences in cardiovascular mortality between different classes of drugs, including diuretics, but it will not be completed until after the turn of the From the Department of Medicine, University of Miami School of Medicine, Miami, Florida. century. In conclusion, I do not believe that anyone Address correspondence and reprint requests to Barry J. knows whether the use of diuretics limited the reMaterson, MD, MBA, University of Miami (M854) , 1150 NW 14th Street, Suite 105, Miami, FL 33136. duction of cardiovascular mortality. Furthermore, even