Acute Titration and Chronic Follow-up with Captopril in Hypertension. A One-Year Safety Profile on Combination Therapy with Captopril and a Diuretic

Mahapatra, Dipta; Mahapatra, Rajat K.; Yaden, Senka; Hunter, Kenneth W.
December 1986
Angiology;Dec1986 Part 1, Vol. 37 Issue 12, p865
Academic Journal
The present study examines acute titration with captopril and chronic follow-up data on captopril and a diuretic in patients with all forms of hypertension. Captopril was initiated in those patients in whom previous antihypertensive agents either failed to control high blood pressure or produced adverse reactions. Acute titration was done in 88 patients in whom avenge diastolic blood pressure was equal to or more than 95 mm Hg. Initial titration dosage was decided on the basis of initial blood pressure recordings. During initial titration, 5 patients received 12.5 mg, 51 received 25 mg, 28 received 50 mg, and the remaining 4 received 100 mg of captopril. Post-captopril blood pressure data were normalized by using pre-captopril data as 100% for each patient. The blood pressure-lowering effect of captopril on both systolic and diastolic blood pressure in all 88 patients was statistically significant (p < 0.05), within forty- five minutes of captopril administration irrespective of the doses. No adverse reactions were seen during the acute titration. After the Initial titration, in all 88 patients a diuretic was added to obtain a synergistic effect. Eleven patients were dropped from the study, for they could not follow the requirements of the protocol. In 77 patients the data for a one-year safety profile with captopril and diuretic were available. There were no overall significant statistical changes in serial white blood cell count, serum potassium, and serum creatinine values in those 77 patients. In 31 patients the initial and maintenance dosage of captopril and the diuretic remained unaltered for one year. Post-captopril blood pressure and heart rate data were nomalized, pre-captopril data being considered as 100% in those 31 patients. The blood pressure data following captopril and a diuretic therapy compared with the pre-captopril data were statistically significant (p < 0.05) throughout the study period. However, no significant changes in heart rates were observed during the study period. In all other patients, diuretic therapy was continued throughout the study period. In 6 severely hypertensive patients, an additional beta-blocker was needed for further control of high blood pressure. In 3 severe hypertensives with renal failure, besides a diuretic and a beta-blocker, minoxidil was needed to normalize their high blood pressure. In 4 of 77 patients, verapamil was used for treatment of either vasospastic angina or paroxsysmal supraventricular arrhythmia. The minor adverse reactions, such as skin rash (7), ageusla (4), hypogeusia (3), constipation (2), nausea (1), abdominal cramps (1), diarrhea (1), postural hypotension (7), and exacerbation of angina at rest (2), were managed with manipulation of the dosage of captopril and symptomatic therapy. In 2 patients with preexisting renal failure, azotemia deteriorated further, requiring discontinuation of captopril. One patient needed chronic hemodialysis and the other needed a cadaveric renal transplant. In both patients angiotensin converting enzyme (ACE) inhibitor combined with diuretic therapy might have predisposed to physiological reduction in renal function. It may be concluded that combined therapy with captopril and a diuretic was efficacious and safe in our patient population studied on a long-term basis. Side effects were generally mild and self-limiting despite the fact that all our patients had experienced tolerance and/or side effects with other previous antihypertensive agents.


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