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Background: The goal of antihypertensive therapy is to provide good blood pressure (BP) control without eliciting adverse effects.Objective: This study compared the risk-benefit profile of the angiotensin II receptor blocker valsartan with that of the angiotensin-converting enzyme inhibitor lisinopril in patients with mild to severe hypertension. The primary objective was to show that the equipotent BP-lowering effect of the valsartan-based treatment is accompanied by a better tolerability profile.Methods: This 16-week, randomized, double-blind, parallel-group study was conducted at 88 outpatient centers across Italy. After a 2-week placebo run-in period, patients aged ≥ 18 years with mild to severe hypertension (systolic BP [SBP], 160–220 mm Hg; diastolic BP [DBP], 95–110 mm Hg) were eligible. Patients were randomized to receive once-daily, oral, self-administered treatment with valsartan 160-mg capsules or lisinopril 20-mg capsules under double-blind conditions for 4 weeks. Responders continued monotherapy, whereas nonresponders had hydrochlorothiazide 12.5 mg added for the final 12 weeks of the study. The 2 primary variables used to assess the equivalence of therapeutic efficacy of the 2 regimens were sitting SBP and sitting DBP, which were measured at weeks 0 (baseline), 4, 8, and 16. The rate of drug-related adverse events (AEs) was used to assess whether 1 treatment had a better tolerability profile than the other. Tolerability was assessed by collecting information about AEs by means of questioning the patient or physical examination at each visit.Results: A total of 1213 patients were enrolled (635 men, 578 women; mean [SD] age, 54.5 [10.1] years [range, 28–78 years]). The study was completed by 1100 patients (553 receiving valsartan and 547 receiving lisinopril). Fifty-one patients (8.4%) treated with valsartan and 62 (1.2%) treated with lisinopril withdrew, mainly because of AEs (9 [1.5%] and 23 patients [3.8%], respectively). The valsartan- and lisinopril-based treatments were similarly effective in reducing sitting BP, with mean SBP/DBP reductions of 31.2/15.9 mm Hg and 31.4/15.9 mm Hg, respectively. At the end of the study, BP was controlled in 82.7% of the patients receiving valsartan and 81.6% of those receiving lisinopril. AEs were experienced by 5.1% of the patients treated with valsartan and 10.7% of those treated with lisinopril (P = 0.001), with dry cough observed in 1.0% and 7.2% of patients, respectively (P < 0.001).Conclusions: Valsartan and lisinopril were both highly effective in controlling BP in these patients with mild to severe hypertension, but valsartan was associated with a significantly reduced risk for AEs, especially cough. [Copyright &y& Elsevier]

The cost effectiveness of early treatment with lisinopril in acute myocardial infarction (MI) was estimated using survival and cost data gathered prospectively during the hospitalisation of the overall population of patients enrolled in the third study of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto (GISSI-3), which assessed the efficacy of early (within 24 hours) treatment with an angiotensin-converting enzyme (ACE) inhibitor (lisinopril) for 6 weeks in a group of 19,394 relatively unselected patients with acute MI. A statistically significant reduction in 6-week mortality was achieved among patients treated with lisinopril when compared with patients allocated to the control group (absolute reduction in mortality: 7.5 +/- 3.6 lives saved per 1000 treated patients). The comparative cost-effectiveness ratio for the use of lisinopril, expressed as cost per additional survivor among patients randomised to receive lisinopril, was $US2080 per life saved (1993 values). The sensitivity analysis conducted to examine the effects of varying the estimated absolute reduction in mortality throughout its 95% confidence interval, which ranged from 14.6 to 0.4 lives saved per 1000 treated patients, showed that the cost-effectiveness ratios consequently vary from $US1121 to $US40,910 per life saved. The cost effectiveness of early treatment with lisinopril of a relatively unselected population of patients with acute MI compares very favourably with that of other therapies judged to be worthwhile by the medical community. [ABSTRACT FROM AUTHOR]

The role of thrombolysis in the acute phase of myocardial infarction (AMI) has been definitely established in terms of mortality and ventricular function, as has the equivalence of different thrombolytic agents. The Second Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial showed that a large number of patients have either clinical heart failure or severe left ventricular damage on discharge from the hospital, with a large risk of death and poor prospects in terms of quality of life. Additional measures to limit ventricular damage are therefore essential to reducing morbidity. The GISSI-3 study protocol on the effects of lisinopril and nitrates, used alone or in combination, in patients with AMI is described in detail.

The efficacy and tolerability of a combination of lisinopril 20 mg and hydrochlorothiazide 12.5 mg once daily (L/HCTZ) was compared with a combination of captopril 50 mg and hydrochlorothiazide 25 mg once daily (C/HCTZ) in a multicentre, open, randomized, parallel-group study involving mild to moderate hypertensive patients. A total of 87 patients were randomized to lisinopril and 87 to captopril. Six weeks of treatment with lisinopril or captopril lowered supine BP by 13.3/8.8 mm Hg and 8.7/6.5 mm Hg, respectively. After 4 weeks of combination treatment, BP 24 hours post dose fell to 144.0 +/- 1.3/88.1 +/- 0.7 mm Hg in the L/HCTZ group vs 146.8 +/- 1.3/90.3 +/- 0.7 mm Hg in the C/HCTZ group (P less than 0.05 DBP; differences in SBP were not significant, ns). The proportion of patients normalized (DBP less than or equal to 90 mm Hg) was 79.5% vs 72% for L/HCTZ and C/HCTZ, respectively (ns). A total of 93.6% of patients on L/HCTZ achieved a fall in DBP of greater than or equal to 10 mm Hg, compared with 86.7% of patients on C/HCTZ (ns). One patient on lisinopril withdrew because of coughing. No statistically significant differences were observed between L/HCTZ and C/HCTZ with regard to adverse events. In conclusion, L/HCTZ was as well tolerated as C/HCTZ, but produced a greater fall in DBP.