After an 8-week placebo period, 73 patients whose diastolic blood pressures were between 90 and 110 mmHg were randomly assigned to receive 125μg (low dose) or 500μg of cyclopenthiazide (standard dose) for a period of one year. Blood pressure was measured in the patient's home by the same observer at two-weekly intervals during an 8-week placebo run-in period, every 4 weeks for a further 12 weeks and at 24, 36 and 52 weeks thereafter. Serum potassium, urate, glucose, glycosylated haemoglobin, total and HDL cholesterol, and apolipoproteins were measured at the end of the placebo period and at 4, 8, 24 and 52 weeks of active treatment.Twelve of the 73 patients had an inadequate antihypertensive response—five on the higher dose and seven on the lower dose. One patient receiving 500μg was withdrawn because of adverse effects. In the remaining 60 patients, systolic and diastolic blood pressures were significantly reduced when compared with pretreatment values in both treatment groups throughout the one year period. The decreases in blood pressure were not significantly different from each other (p>0.65). Three patients on 500μg required potassium supplements. Maximum decreases in the serum potassium of 0.52 mmol/l(500μg dose) and 0.14 mmol/l(125μg dose) were observed at 24 weeks of treatment in the remaining 57 patients. The differences between the two doses at this time were statistically significant (p<0·05), as were the increases in serum urate observed at 4, 8 and 24 weeks (p<0.05). Five hundred micrograms of cyclopenthiazide increased total serum cholesterol at eight and 24 weeks (0.35, 0.36 mmol/l respectively) when compared with pretreatment values (p<0.01) and almost achieved statistical significance when compared with the corresponding low dose value (p=0.066). This study confirms that 125μg of cyclopenthiazide is a useful antihypertensive agent with a favourable metabolic profile which is maintained in the
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