Lisinopril dose-response relationship in essential hypertension.

1. This was a multicentre, double-blind, parallel study in 216 patients with mild to moderate (supine diastolic blood pressure = 95-115 mm Hg) essential hypertension. 2. After a 4-week placebo washout, patients were randomized to placebo or lisinopril 1.25, 5.20 or 80 mg once daily for 6 consecutive weeks. Supine and erect blood pressure was measured 24 h postdose at the end of weeks -2, 0, 2, 4, and 6. 3. There was a linear dose-response relationship for both supine and erect blood pressure. Diastolic blood pressure reductions in the lisinopril 20 and 80 mg day-1 groups were significantly greater than in the placebo or lisinopril 1.25 and 5 mg day-1 groups. 4. Lisinopril, at doses up to 80 mg day-1, was well tolerated.

Enalapril in hypertension and congestive heart failure. Overall review of efficacy and safety.

Multiclinic controlled studies have shown that enalapril alone 10 to 40 mg/day orally is effective in lowering blood pressure in patients with essential hypertension. Enalapril has been compared with thiazides and beta-blockers (propranolol, metoprolol and atenolol). The effect on systolic blood pressure has been greater with enalapril than with beta-blockers. The proportion of patients who respond to enalapril alone with a decrease in diastolic blood pressure (greater than or equal to 10mm Hg) is around 70%. When a thiazide is added to the treatment, the proportion is above 90%. Enalapril improves the signs and symptoms associated with congestive heart failure. Patients increased their exercise tolerance by an average of 148 sec and improved in their NYHA cardiac status and prognosis classification. The overall incidence of side effects is similar to that seen in the placebo control groups. Side effects such as agranulocytosis, taste loss, rash, proteinuria were not characteristic of enalapril. This supports the hypothesis that the improved safety profile of enalapril is the result of being a nonsulphydryl angiotensin-converting enzyme (ACE) inhibitor. The most common side effects reported were dizziness, headache and asthenia. Abnormalities in electrolytes, uric acid, glucose or in lipids have generally not been associated with enalapril.

Long-term enalapril--a new converting enzyme inhibitor--in the treatment of mild to moderate essential hypertension, results of a worldwide multiclinic study. Comparing two ways of analyzing data.

The antihypertensive effect of enalapril maleate, a new converting enzyme inhibitor, was evaluated in a multiclinic, double-blind, randomized study in patients with mild to moderate essential hypertension. The analyses were done in two ways, with patients who violated the entry criteria of the protocol excluded, and according to the intention to treat principle. Enalapril in dosages of 10 to 40 mg daily administered alone or concomitantly with hydrochlorothiazide was compared to propranolol (80 to 240 mg daily) alone or concomitantly with the diuretic. The study showed that enalapril significantly lowered both systolic and diastolic blood pressure. At each timepoint measured in the course of 26 weeks of therapy, the patients in the enalapril group consistently had greater decreases in blood pressure than patients in the propranolol group although not always significantly. The enalapril treatment group had a decrease in the mean arterial blood pressure of 22.2 mmHg compared to the propranolol group of 17.9 mmHg at the end of the study. These results were similarly independent of the way the data were analyzed. Fewer patients in the enalapril group required the addition of hydrochlorothiazide to maintain optimal control of blood pressure. Enalapril was found to be safe and well tolerated over the long-term of 48 weeks. Side effects such as leukopenia and taste perversions believed to be sulfhydryl-related were not encountered. The occurrence of rash and proteinuria was rare. Thiazide-induced hypokalemia, hyperuricemia and hyperglycemia appeared to be attenuated by enalapril. The favorable efficacy and side-effect profile provide the basis for enalapril to be a drug of choice when initiating antihypertensive therapy.

'Osmosin': a multi-centre evaluation of a technological advance in the treatment of osteoarthritis.

A multi-centre, double-blind trial was carried out in 272 out-patients with osteoarthritis of the knee(s) to compare the efficacy and tolerability of 'Osmosin', the osmotic release system for indomethacin (7 mg per hour for approximately 10 hours), with that of conventional indomethacin capsules (25 mg 3-times daily) over a period of 12 weeks. The results, as assessed by the subjective and objective clinical variables and laboratory parameters studied, showed that 'Osmosin' provided not only comparable overall therapeutic response but also a preferable tolerability profile to the indomethacin capsule regimen. At completion of the study, 89% of patients treated with 'Osmosin' were being maintained on one dose daily, and 80% of these patients were rated as having a good or excellent response. The results indicate that 'Osmosin' given once daily is a well-tolerated and efficacious therapy for patients with osteoarthritis.

'Osmosin' (sodium indomethacin trihydrate) in the treatment of elderly patients with osteoarthritis.

A 12-week, double-blind, multi-centre trial was carried out in 402 out-patients with osteoarthritis to compare the efficacy and tolerability of the osmotic-release formulation of indomethacin ('Osmosin') with that of indomethacin capsules. Data from a sub-set of 178 patients aged 60 years or over were analyzed separately. The results indicated that 'Osmosin', releasing the equivalent of 7 mg indomethacin per hour over approximately 10 hours, provided efficacy comparable to or better than that of indomethacin capsules (25 mg 3-times daily) and had a better tolerance profile. Fewer patients treated with 'Osmosin' developed adverse experiences (p less than 0.05), especially central nervous system symptoms (p less than 0.05), and fewer were withdrawn from treatment because of adverse experiences (p less than 0.05). A reduction in the number of patients having gastro-intestinal symptoms was also identified. The majority of the patients maintained on one daily dose of 'Osmosin' had a good or excellent therapeutic response.