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Purporse: Many hypertensive patients have other, usually long-term diseases. Antihypertensive therapy may interfere with these diseases and their therapies. in the present study, the possible interactions of the ACE-inhibitor perindopril with several of the most common long-term diseases was evaluated. Patients and Methods: In a multicenter, doubleblind, randomized, placebo-controlled trial, the effect of perindopril was evaluated in 490 patients with mild essential hypertension and any one of the following concomitant diseases: hyperlipidemia, type II diabetes mellitus, ischemic heart disease, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, chronic obstructive pulmonary disease, or degenerative joint disease treated with nonsteroidal anti-inflammatory drugs NSAIDs). After a 3-week single-blind placebo run-in, the patients received either perindopril (4 mg/d) or matching placebo for 6 weeks. Results: Blood pressure was effectively reduced by perindopril irrespective of the associated disease. The rate of spontaneously reported side effects was low. Treatment with perindopril was free from adverse interactions with the concomitant diseases and therapies. Moreover, favorable actions could be observed in patients with ischemic heart disease (reduction of maximal ST-segment depression during peak exercise and decrease in the number of angina attacks), in patients with proteinuria (decrease in albuminuria in patients with normal serum creatinine levels), and in patients with NSAID-treatment (increase in prostaglandin [E.sub.2] concentration in gastric mucosa suggesting gastric cytoprotection). Conclusion: This trial shows that ACE-inhibition with perindopril represents a simple, safe, and effective short-term therapeutic option for the large proportion of patients with mild essential hypertension and concomitant diseases and therapies.

A multicenter, double-blind, randomized, and placebo-controlled trial, the Perindopril Therapeutic Safety Study (PUTS), was designed to assess the interaction between angiotensin-converting enzyme (ACE) inhibition and the diseases and therapies commonly found associated with mild hypertension. A total of 480 male and female patients aged 30-70 years with a diastolic pressure of 90-104 mm Hg were included after a 3-week placebo run-in if they satisfied standard criteria for any of the following: hyperlipidemia, type II diabetes, ischemic heart disease, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, chronic obstructive lung disease or treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). At the end of the placebo run-in period, patients were randomly assigned to either placebo or perindopril 4 mg once daily. A total of 460 patients completed the 6-week double-blind phase, comprising 3 assessments at 1, 3, and 6 weeks. In this report, the principal results obtained in 5 disease groups (hyperlipidemia, type II diabetes, ischemic heart disease, nephropathy with proteinuria, and NSAID treatment) will be reported. A total of 269 patients belonging to one of the aforementioned 5 disease groups completed the double-blind phase of the study and were included for statistical evaluation. In the perindopril group, systolic and diastolic blood pressures decreased significantly more than in the placebo group, and a sitting diastolic blood pressure of 90 mm Hg was achieved in 65% of patients in the perindopril group and 30% of patients in the placebo group. The incidence of symptoms spontaneously reported by the patients was low: 2 patients of the perindopril group complained of cough. Seven patients were withdrawn from the study during active treatment: 1 patient because of resistant cough, 2 for poor compliance, and the others for therapeutic inefficacy, intercurrent illness, or patient's request. Laboratory investigations did not show any significant differences between the 2 groups before and at the end of the treatment. Analyses of the data obtained in the 5 subgroups of patients with concomitant diseases showed that ACE inhibition with perindopril was free from adverse interactions with the concomitant pathologic conditions of the patients, had no unfavorable impact on serum lipid and apolipoprotein concentrations in the patients with hyperlipidemia, did not adversely affect measures of midterm glycemic control, such as serum fructosamine and hemoglobin [A.sub.1c] in type II diabetes patients, had an anti-ischemic and antianginal action in the patients with ischemic heart disease, reduced urinary albumin excretion in a subgroup of patients with nephropathy, stimulated prostaglandin [E.sub.2] in gastric mucosa af NSAID-treated patients, and reduced blood pressure irrespective of the associated disease or therapy. The data show that ACE inhibition with perindopril 4 mg once daily represents a simple, safe, effective, and comprehensive step I therapeutic option suitable for the significant proportion of hypertensive patients with concomitant diseases and therapies. (Am J Cardiol 1993; 71:32E-37E)

Despite a marked reduction in cardiovascular morbidity and mortality, treated hypertensive patients remain at increased risk of coronary artery disease and its complications compared with untreated normotensive subjects. Mild hypertension is often associated with other, usually chronic, diseases. The failure of first-ante antihypertensive therapy to deal adequately with concomitant disease and associated therapy might account for the poor improvement in the cardiovascular prognosis. This possibility has been addressed in an ongoing trial of novel design, the Perindopril Therapeutic Safety Study, a multicenter, double-rannd, randomized and placebo-controlled trial to determine the safety, efficacy, and interaction of angiotensin-converting enzyme (ACE) inhibition with eight of the most common concomitant diseases and their therapies. A total of 480 male and female patients (60 per disease group) aged 30-70 years, with a diastolic pressure of 90-104 mm Hg, were included after a 3-week placebo run-in if they satisfied standard criteria for any of the following: hyperlipidemia, type II diabetes, ischemic heart disease, cardiac arrhythmia, peripheral arterial disease, nephropathy with proteinuria, chronic obstructive lung disease, or rheumatoid arthritis. Of these, 460 patients have completed the 6-week double-blind phase (comprising two assessments, at 3 and 6 weeks), and are currently undergoing assessments every 3 months over a 1-year follow-up period. The end points include the incidence of progression or improvement in concomitant disease, the incidence of positive or negative interaction between ACE inhibition and concomitant therapy, change in blood pressure, adverse biochemical and hemodynamic reactions, self-reported side effects, and quality of life indices. Interim results for the 6-week double blind phase will shortly be available. However, the desirability and feasibility of conducting a study according to this novel design have already been proved.