Safety and efficacy of quinapril in hypertensive geriatric patients.

Abstract

To the Editor: To assess the safety and efficacy of ACE inhibitor therapy in older hypertensives, we performed a multicenter, open, uncontrolled study of a minimum of 3 months' duration of the effects of quinapril in male or female hypertensives aged 60 to 90 years. Patients were admitted to the study if they had a supine or sitting diastolic blood pressure (BP) between 90 and 120 mm Hg and/or a supine or sitting systolic BP of greater than 160 mm Hg but less than 200 mm Hg on or off antihypertensive therapy. Quinapril was substituted for other ACE inhibitors, and concomitant diuretic or calcium antagonist therapy could be continued, but beta-blocker therapy was stopped unless indicated for the treatment of ischemic heart disease. Quinapril was commenced at a dose of 10 mg once daily except in patients with impaired renal function (serum creatinine > 130 μmol/L) in whom the commencing dose was 2.5 mg daily. The dose of quinapril was increased to 20 mg once daily after 4 weeks and to 30 mg subsequently, and hydrochlorothiazide 25 mg daily was added if BP remained uncontrolled. Concomitant medications were kept constant. Serum creatinine and potassium levels were measured at the beginning of the study and after 1 and 3 months of therapy. Ethical approval for the study was obtained from the Southern Sydney Area Ethics Committee. A total of 179 patients were enrolled into the study. Twenty-one were excluded either because they were younger than 60 years of age or they did not have ages recorded. The mean age of the patients was 70.8 ± 7.49 years (SD) (range 60–90 years), and 46% were male. BP data was available for 141 patients after 1 month of therapy and for 123 patients after 3 months of therapy. The average dose of quinapril at the end of the study was to 12.3 mg per day (range 5–30 mg). Nine percent of patients received a diuretic, and 8% received a calcium antagonist. There was a highly significant reduction in blood pressure from baseline (Table 1). Ninety-two percent of patients achieved a diastolic blood pressure of less than 90 mm Hg after 3 months of therapy, and 70% achieved a systolic blood pressure of less than 150 mm Hg. Of 34 patients withdrawn from the study before the end of the 3-month treatment period, only nine were withdrawn because of adverse events (5.8%). The remainder were withdrawn for a variety of reasons, mainly unwillingness to continue in the study. Seven of the patients were withdrawn because of adverse events that were thought to be drug related. These events were cough (3 patients), rash (2 patients), dizziness, heavy-headedness, chest tightness, and angioedema (1 patient each). Adverse events were reported by 29 patients (18.9%), the most common being cough (6.5%) and dizziness (2.6%). Serum creatinine and potassium levels are presented in the Table 1. Creatinine levels were available for 129 patients at the beginning of the study and for 97 after either 3 months (68 patients) or 1 month (25 patients) of therapy. Serum potassium levels were available for 122 patients at the commencement of therapy and for 91 patients after either 3 months (65 patients) or 1 month (26 patients) of therapy. Creatinine levels increased by approximately 6% from baseline, mostly in patients with borderline creatinine levels (around 120 μmol/L). The greatest increase in creatinine was 66%, from 90 to 150 μmol/L. No patient was withdrawn because of worsening of renal impairment. Serum potassium levels increased by a statistically significant but clinically insignificant amount (Table 1). No patient was withdrawn or required specific treatment because of an increase in serum potassium level. The present study differs from previous studies of ACE inhibitors in older people, which found a similar incidence of adverse events,1,2 in that patients with abnormal creatinine levels were included and a more detailed evaluation of the effects on serum creatinine levels was performed. The increase in creatinine levels observed in the present study was slightly greater than that observed in a study of perindopril in older hypertensives, but the latter patients had significantly lower baseline creatinine levels (93 mmol/L, with an increase of 1.2% during perindopril therapy).2 In conclusion, the present study has provided data to support the safety and efficacy of therapy with the ACE inhibitor quinapril in an older, relatively unselected, geriatric population that included patients with abnormal baseline renal function.