Patient acceptance of guanethidine as therapy for mild to moderate hypertension. A comparison with reserpine

R K Ferguson, R J Rothenberg, A S Nies
1976 Circulation  
The relative benefits and risks of reserpine and guanethidine were compared in patients with thiazide-treated mild to moderate hypertension (diastolic pressure 95-115 mm Hg). Fortynine ambulant patients (30 men, 19 women) were treated throughout the study with hydrochlorothiazide, 50 mg/day. In this double blind crossover study each drug was added in graded increments until a predetermined therapeutic response was obtained, blood pressure measurements and side effect scores were evaluated
more » ... ly. Major conclusions of the study were: 1) guanethidine, as well as reserpine, will reduce mild to moderate blood pressures to normal; 2) in most CONTINUOUSLY EFFECTIVE ANTIHYPERTEN-SIVE THERAPY requires drugs that are not only effective but also well-tolerated. Lack of patient compliance is the major problem in drug therapy of mild-moderate hypertension since the disease is usually asymptomatic. An ideal drug should be free of serious or annoying side effects and should have kinetic properties that allow simple dosage regimens. In spite of these considerations, the choice of therapy for hypertension is hampered by a lack of studies comparing the relative clinical efficacy of drugs available. For years reserpine has been considered by authorities to be the antihypertensive drug of choice for treatment of mild to moderate hypertensives who have an inadequate response to thiazide diuretics. In addition to its demonstrated efficacy, reserpine can be given in a single daily dose. However, reserpine can cause several troublesome or serious side effects. These not only limit patient acceptability of the drug but restrict the useful dosage range, so that alternative therapies may be required. Although many other antihypertensive drugs are available, all except guanethidine must be given more than once daily, and many share with reserpine side effects related to the central nervous system. Guanethidine is not distributed to the brain as readily and has a long half-life allowing once daily dosage.2 However, guanethidine has traditionally been reserved for use in severely hypertensive patients who have failed to respond to less effective agents.3 In these patients with very high blood pressure, guanethidine in large doses often produces a number of side effects related to essentially complete sympathetic blockade. Data do not exist to indicate whether guanethidine is as From the cases, side effects which did occur while taking guanethidine or reserpine were well tolerated and neither drug was clearly superior. Side effects associated with larger doses of guanethidine employed in severe hypertension were absent or only slightly bothersome. Thus, guanethidine appears to have a good benefit-to-risk ratio in the therapy of mild to moderate hypertension and offers a number of advantages over drugs commonly used in this syndrome. This study refutes the common belief that guanethidine must be reserved only for the treatment of more severe degrees of hypertension. effective and well tolerated as other commonly used drugs in patients with less severe hypertension. This study was designed to compare reserpine with guanethidine in patients who have persistent mild to moderate hypertension during treatment with hydrochlorothiazide alone. Criteria for efficacy were defined prospectively and each drug was given in the dose necessary to achieve this goal. Particular attention was paid to undesirable effects with each drug, which were evaluated in a standard fashion after the blood pressure had been lowered to the predefined level. This method allowed comparison of acceptance of the two drugs at equi-effective doses. We found that guanethidine is an acceptable alternative to reserpine for patients with mild-moderate hypertension. Methods Patients Fifty-four patients with a sustained standing diastolic blood pressure of 95-115 mm Hg on hydrochlorothiazide, 50 mg/day, participated in this study. Patients were studied by a common protocol at Vanderbilt University, Nashville, Tennessee, and at Michigan State University, East Lansing, Michigan. With one exception, all patients were classified as having essential hypertension on the basis of compatible history and normal physical examination, and normal results for urinalysis, serum sodium, serum potassium, serum creatinine, VMA, rapid-sequence pyelogram and in some cases renal arteriograms. One man had stable chronic renal disease as evidenced by history, elevated blood urea nitrogen (50 mg%), and granular casts in the urine. The average age of the patients was 43 years (range 26-66). There were 19 white and 13 black men, 11 white and 11 black women in the study. Informed, written consent was obtained from each individual following a careful explanation of the nature and purposes of the study. All antihypertensive drugs were discontinued; other drugs were either discontinued or kept constant for the duration of the study. All patients were instructed to follow a no-added salt diet (2-3 g sodium daily) during the study, but no 32 by guest on
doi:10.1161/01.cir.54.1.32 pmid:776441 fatcat:ww5pgeqw6fahvi6ec3yerdssvq