HOPE
Heart Outcomes Prevention Evaluation

PROGRESS Perindopril Protection Against Recurrent Stroke Study
Disease Cerebrovascular disease, hypertensive, non-hypertensive, disability, cognitive function, recurrent stroke, transient ischaemic attack, TIA Purpose To determine the effects of blood pressure reduction with an angiotensin converting enzyme (ACE) inhibitor-based regimen on the stroke risk in patients with a history of transient ischaemic attacks or minor stroke Dates Anticipated first presentation: 01/11/2001 Contacts Associate Professor Stephen MacMahon and Dr DJ Chalmers Clinical Trials Research Unit, Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand Tel: [phone] Fax: [phone] Email: Stephen MacMahon Treatment regimen and control Perindopril/placebo 4 mg od 1 indapamide/placebo 2.5 mg od Perindopril/placebo 4 mg in patients with definite indication for or contraindication to a diuretic (Indapamine 2.0 mg in Japan) Follow up: 4 years minimum for every patient, mean 5 years						Description In the PROGRESS study, 6105 patients who had sustained a TIA or stroke in the preceding 5 years were randomized to perindopril, with additional randomization to indapamide at the physician's discretion, or to matching placebos. There were 420 strokes in the placebo group (13.8%) compared with 307 (10.1%) in the active treatment group (28% reduction, p<0.0001). The benefits were largely confined to those taking both drugs, stroke recurrence being reduced by 43% in those taking both drugs and 5% in those taking only one. Comparable figures for fatal or disabling stroke were 149 (4.9%)and 93 (3.0%), and for hemorrhagic stroke 74 and 37. The therapy was effective both in hypertensives and non-hypertensives.
HOPE Disease cardiovascular disease, myocardial infarction, stroke, Purpose To investigate two treatments: ramipril, an angiotensin-converting enzyme (ACE) inhibitor; and vitamin E, a naturally occurring antioxidant vitamin in the prevention of myocardial infarction (MI), stroke or CV death Dates First subject enrollment: 01/12/1993 Actual recruitment completion: 01/06/1995 Contacts Dr. Salim Yusuf, Canadian cardiovascular Project Office, Hamiltin General Hospital, 237 Barton St E, Hamilton, Ontario ON L8L 2X2, Canada. [e-mail]		Description The study was stopped early in March 1999 because of a very clear reduction in cardiovascular deaths, heart attacks and strokes in the ramipril arm.The primary endpoint of a composite of these three events was reduced from 17.8% to 14.0%(p<0.001), myocardial infarction from 12.3% to 9.9%, and stroke from 4.9% to 3.4%. There were comparable reductions in overall mortality, need for hospitalisation and revascularisation. No benefit was observed from the use of Vitamin E. Similar benefits were seen in diabetic patients. Treatment regimen and control A 2x2 factorial design with ramipril (2.5 mg od for 1 week, then 5 mg for 3 weeks, then 10 mg + vitamin E) and vitamin E (400 U od), or placebo + vitamin E, or placebo Follow up: 4-6 years

Hope

CONSENSUS COoperative North Scandinavian ENalapril SUrvival Study
Disease Congestive heart failure, CHF, heart filure, HF Purpose To investigate the effect of enalapril, in addition to conventional therapy, on mortality in severe CHF. To study the activation of hormones related to cardiovascular function and the effect of the overall hormone response to angiotensin converting enzyme (ACE) inhibition.		Description At 6 months, crude mortality was reduced by 40% in the enalapril group compared to the placebo group (p = 0.002); at 1 year, it was reduced by 31% (p = 0.001) and at the end of the study it was reduced by 27% (p = 0.003). The entire reduction in total mortality was in patients with progressive heart failure (a reduction of 50%). There was no difference in the incidence of sudden cardiac death between the two groups. A significant improvement in NYHA classification and a reduction in heart size was also observed in the enalapril group. A significant positive relationship was found between mortality and levels of angiotensin II (p < 0.05), aldosterone (p = 0.003), noradrenaline (p < 0.001), adrenaline (p = 0.001), and a trial natriuretic factor (p = 0.003). No similar relationship was observed among enalapril-treated patients. The difference between the original treatment groups remained at 2-year follow-up. Treatment with enalapril was, however, made available to all surviving patients. The study was terminated prematurely on the recommendation of the Ethical Review Committee, because of the consistent difference in favour of enalapril. Treatment regimen and control Enalapril, 2.5 mg/day up to 20 mg bid Study

CONSENSUS II COoperative New Scandinavian ENalapril SUrvival Study II
Disease Acute myocardial infarction, AMI Purpose To investigate the effect of early enalapril, in addition to conventional therapy, on mortality after AMI		Description At 6 months, the mortality was 11% in the enalapril group and 9.9% in the placebo group. The results were consistent across all subgroups. The study was terminated in May 1991 on the recommendation of the safety committee, because of no difference in favour of enalapril. Treatment regimen and control Enalapril (2.5 mg bid up to 20 mg/day) vs placebo

ELITE Evaluation of Losartan in the Elderly Study
Disease heart failure Purpose To determine the relative safety and efficacy of an angiotensin converting enzyme (ACE-I) vs an angiotensin II type I receptor blocking agent and to compare the safety and efficacy of captopril and losartan in elderly patients with heart failure Contacts Dr Bertram Pitt Division of Cardiology, University Hospital, Ann Arbor, MI 48109-0366, USA Tel [phone] Fax [phone] Email Bertram Pitt		Description Death and/or hospital admission for heart failure was recorded in 9.4% of the losartan compared to 13.2% of the captopril patients. The risk reduction was primarily due to a decrease in all-cause mortality. In this study treatment with losartan was associated with an unexpected lower mortality than that found in captopril. Although there was no difference in renal dysfunction, losartan was generally better tolerated than captopril and fewer patients discontinued losartan therapy. Treatment regimen and control Losartan 50 mg od, captopril 50 mg tds Follow up: 48 weeks

ELITE II The Losartan heart failure survival study-ELITE II

SOLVD Studies Of Left Ventricular Dysfunction
Disease Left ventricular dysfunction, Congestive heart failure, LVD, CHF Purpose To investigate whether enalapril improves long-term survival in patients with LVD, with and without a history of overt CHF, and to demonstrate its effects on diastolic function, echocardiography, exercise, neurohumoral parameters, quality of life, radionuclide studies and sudden death						Description All patients were given at least two test doses of enalapril, 25 mg, before randomisation; 89 of these patients were hospitalised during the administration of the test doses, because of the risk of hypotension. In this highly selected group, symptoms related to a decrease in blood pressure were noted in 13 patients (15%). There were 510 deaths in the placebo group (39.7%) and 452 in the enalapril group (35.2%). This represents a risk reduction of 16% (p = 0.0036). The greatest reduction was seen in the number of deaths that were attributed to progressive heart failure. In the enalapril group there was a significant reduction of 37% in the risk of developing overt heart failure. There were no significant differences in ventricular premature complexes or in runs of non-sustained ventricular tachycardia between the groups at baseline or at 4 or 12 months. Equal numbers of patients in the enalapril and placebo groups developed new ventricular arrhythmias or had comparable reduction in ventricular arrhythmias. The registry of patients has been used to determine patterns of medication use, and the results of SOLVD have been used in conjunction with New Zealand data to determine the costs of adding enalapril to conventional treatment for heart failure.
TRACE TRAndolapril Cardiac Elevation
Disease AMI, Left ventricular dysfunction, LVD, acute myocardial infarction Purpose To determine whether patients who have LVD soon after AMI benefit from long-term angiotensin converting enzyme (ACE) inhibition with trandolapril		Description During the therapeutic intervention study of 1749 patients there were 304 deaths (34.7%) in the trandolapril group and 369 (42.3%) in the placebo group (p = 0.001). Trandolapril also reduced the risk of death from cardiovascular causes (relative risk 0.75), reduced the risk of sudden death (relative risk 0.76) and reduced the frequency of progression to severe heart failure (relative risk 0.71), but did not significantly reduce the risk of recurrent MI (relative risk 0.86). Assessment of the screening data showed that the 1-year and 3-year mortality rates increased sharply with increasing age. There was an excess 3-year mortality of 14% in patients aged ≤ 55 years, 24% in those aged 56-65 years, 25% in those aged 66-75 years and 28% in those aged ≥ 75 years. The absolute excess of 3-year mortality associated with LV systolic dysfunction was 15%, 19%, 25% and 21% in these 4 age groups, respectively, indicating that the relative importance of LV systolic dysfunction and congestive heart failure as causes of death diminished with increasing age.

RALES Randomized Aldactone Evaluation Study
Disease severe congestive heart failure Purpose To assess the benefits of adding spironolactone (vs placebo) to ACE inhibitor therapy in the treatment of heart failure Dates Actual recruitment completion: 01/12/1996 Contacts Dr B Pitt Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48104, USA Tel: [phone] Fax: [phone] Email: Bertram Pitt										Description Among the 1663 patients randomized, 46% of the placebo patients died compared with 35% of those on spironolactone. There was also a 30% reduction in hospitalization.
DIG Digitalis Investigation Group Trial
Disease heart failure, left ventricular dysfunction Purpose To determine the effect of digoxin on all-cause mortality in patients with clinical heart failure who are in sinus rhythm and whose ejection fraction (EF) is = 0.45 Dates First subject enrollment: 01/01/1991 Anticipated first presentation: 01/01/1996 Contacts Dr Richard Gorlin The Digitalis Investigation Group Mount Sinai Medical Center, Division of Cardiology, New York, NY 10029-6574, USA Tel [phone]					Study population Target/actual number of subjects in the trial: 6800 (actual) Gender: Male and female Inclusion criteria: Patients with clinical heart failure who are in sinus rhythm and whose EF is = 0.45 Ancillary Trial: 992 patients with EF > 0.45 Design Randomized, Placebo controlled, Multicentre Treatment regimen and control Digoxin vs placebo Follow up: Mean duration 37 months (range 28-
CURE Clopidogrel in Unstable angina to prevent Recurrent Events
Disease acute coronary syndrome, unstable angina, non-Q wave infarction Purpose To compare the safety and efficacy of the combination of clopidogrel and aspirin with aspirin alone in the treatment of acute coronary syndromes Contacts Prof. Salim Yusuf, Hamilton Health Sciences Corporate-General Division, McMaster Clinic, 237 Barton Street East, Hamilton, Canada L8L 2X2.			Description The primary endpoint (cardiovascular death, MI and stroke) occurred in 11.4% of the aspirin only patients compared with 9.3% in those with the aspirin/clopidogrel combination (p=0.001). There was no significant reduction in cardiovascular death, but MI was reduced from 6.7% to 5.2%. The second primary endpoint of cardiovascular death, MI, stroke and refractory ischemia was reduced from 18.8% to 16.5% (p=0.001). Major bleeding occurred significantly more often in the clopidogrel group (aspirin 2.7%, aspirin/clopidogrel 3.6%(p=0.001). Study

---