Hydrallazine and beta-blockade in refractory hypertension with characterization of acetylator phenotype

Abstract

In 30 refractory hypertensives a hydrallazine beta blocker combination was added to or substituted for previous antihypertensives. Over a mean period of 12 months a good or satisfactory blood pressure response resulted in 12 patients each, while six others had an unsatisfactory outcome. (Good = diastolic pressure (DP) less than 95 mmHg; Satisfactory = deltaDP greater than 15 mmHg or DP 95-105 mmHg; Unsatisfactory = DP greater than 105 mmHg or deltaDP less than 15mmHg.) Twelve of the patients had significant renal disease with serum creatinine greater than 2 mg/100 ml, but in these there was no evidence that renal hydrallazine retention potentiated an antihypertensive effect. Those with an unsatisfactory response were receiving slightly higher doses hydrallazine and propranol when compared with good responders. The average dose of hydrallazine was 258 mg/day and of propranolol 308 mg/day. Transient headache was not uncommon at the commencement of hydrallazine therapy. Angina and vertebro-basilar insufficiency were each aggravated in one patient, but resolved with dosage adjustment. A lupuslike rash developed in one patient, a slow acetylator on 300 mg hydrallazine/day who had received a total of 92 g over eleven months. The genetically determined acetylator phenotype was assessed in 75 subjects. A little over one third were found to be rapid acetylators. Those with slow acetylator phenotype did not show a more favourable phenotype did not show a more favourable blood-pressure response to equivalent doses of hydrallazine.