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PubMed1998

Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropathy.

BACKGROUND: The Ramipril Efficacy In Nephropathy (REIN) study found that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, ramipril safely reduced the rate of decline of the glomerular filtration rate (GFR) and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF), as compared with placebo plus conventional antihypertensive drugs at the same level of blood pressure control. At the end of the core study patients continued on or shifted to ramipril and were formally enrolled into the REIN follow-up study. METHODS: 97 patients entered the follow-up study. Patients originally randomised to ramipril continued with the same daily dose (n=51), whereas those originally on placebo plus conventional antihypertensive drugs switched to ramipril after the first visit of the follow-up study (n=46). Ramipril (1.25 to 5.00 mg/day) and conventional antihypertensive therapy were targeted at achieving diastolic blood pressure under 90 mm Hg. The main efficacy variables were GFR decline and ESRF (need for dialysis). Analysis was by intention to treat. FINDINGS: During the follow-up study the mean rate of GFR decline per month decreased from 0.44 (SD 0.54) mL/min per 1.73 m2 in the core study to 0.10 (0.50) mL/min per 1.73 m2 in patients originally randomised to ramipril (p=0.017), and from 0.81 (1.12) to 0.14 (0.87) mL/min per 1.73 m2 in those originally randomised to placebo plus conventional antihypertensive therapy (p=0.017). At the final visit, mean absolute GFR values were 12 mL/min per 1.73 m2 higher (33% better) in patients randomised to ramipril than in those assigned placebo (n=26 and 17, respectively: 35.5 [19.0] vs 23.8 [9.4] mL/min per 1.73 m2, p=0.01). 19 of the patients originally on ramipril versus 35 switched from placebo to ramipril progressed to ESRF (p=0.027) during the whole observation period; of these, six (8%) versus 14 (16%) reached that endpoint during the follow-up study; and the risk ratios were 1.86 (95% CI 1.07-3.26) over the whole observation period and 2.95 (1.13-7.68) during follow-up. Beyond follow-up at month 36, the incidence of ESRF was zero in patients originally randomised to ramipril but 30% in patients on placebo plus conventional antihypertensive therapy. INTERPRETATION: In patients with chronic nephropathy and high risk of rapid progression to ESRF, ramipril reversed the tendency of GFR to decline with time. Moreover, a treatment period of sufficient duration (> or =36 months) eliminated the need for dialysis. Even patients previously treated with antihypertensive drugs other than angiotensin-converting-enzyme inhibitors benefited from shifting to ramipril.

Adult↗

PubMed1992

Combination of ramipril and hydrochlorothiazide in the treatment of mild to moderate hypertension: Part 1--A double-blind, comparative, multicenter study in nonresponders to ramipril monotherapy.

In a parallel-group multicenter study, the efficacy and safety of combination therapy with ramipril 5 mg plus hydrochlorothiazide 25 mg were compared double-blind with those of 5 mg and 10 mg ramipril monotherapy in patients with mild to moderate hypertension who had not responded adequately to ramipril 5 mg alone. Patients were initially treated single-blind for 1 week with ramipril 2.5 mg and 3 weeks with ramipril 5 mg. Of 240 patients enrolled, 165 were subsequently classed as nonresponders (diastolic blood pressure > 90 mmHg) and were randomized to one of the three double-blind treatments for a further 4 weeks. In the double-blind phase, the mean reductions in supine systolic and diastolic blood pressures at end point were significantly greater in the 5 mg plus 25 mg combination group (11.6/10.6 mmHg) than in the groups receiving ramipril 5 mg (6.2/5.9 mmHg; both p < 0.01) and ramipril 10 mg (7.4/7.1 mmHg; both p < 0.05). The proportion of responders at end point was also higher for combination therapy (72%) than for monotherapy (48% for ramipril 5 mg and 62% for ramipril 10 mg). All three treatments were well tolerated. Analysis of laboratory values revealed no clinically important changes.

Adult↗

PubMed2006

Mitigation of radiation-induced optic neuropathy in rats by ACE inhibitor ramipril: importance of ramipril dose and treatment time.

PURPOSE: Radiation-induced optic nerve damage was reduced by ramipril, a prodrug angiotensin-converting enzyme inhibitor (ACEI). This study was to determine the optimum dose and administration time of ramipril for mitigating radiation-induced optic neuropathy. MATERIALS AND METHOD: Adult Fischer 344 male rats were treated with a single dose radiation 30 Gy by using radiosurgical technique. After irradiation, the animals were randomly assigned into groups of different ramipril doses and administration time; control (no treatment), radiation alone, radiation+ramipril in different doses and starting times of drug. Ramipril was given 0.5-1.5 mg/kg/day and AT1R blocker Losartan 20 mg/kg/day in drinking water for 180 days. Functional endpoint with visual evoked potential (VEP) and anatomical endpoint with gross and histological analysis with immunohistochemical (IHC) stain were used. RESULTS: Normal VEP measurements in un-irradiated rats were 46.2+/-7.9 ms. There was no change of VEP value until 4 months, but was lengthened to 188.1+/-58.7 ms at 6 months after radiation. By ramipril treatment with the dose of 1.5 mg starting at 2 weeks after radiation, VEP was significantly shortened to 105.7+/-88.5 ms at 6 months. Gross and microscopic structure of the irradiated optic nerve was well preserved in the ramipril-treated group. CONCLUSION: Ramipril can mitigate the radiation-induced optic nerve damage and preserve the functional integrity of the nerve. The results support early treatment with a high dose of ramipril after radiation.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1994

Absence of effect on exercise capacity of 12-weeks treatment with ramipril in patients with moderate congestive heart failure. Ramipril Study Group.

Pharmacological therapy in cases of chronic congestive heart failure (CHF) is usually evaluated by maximal exercise time. To assess the effect of an angiotensin converting enzyme inhibitor, ramipril, 223 patients with moderate CHF were studied in 24 centres in four Nordic countries in a randomized, double-blind, placebo-controlled, parallel group design. The study drug was titrated from 1.25 mg to a maximum of 10 mg once daily (o.d) over a period of 4 weeks (mean dose 8 mg). A symptom-limited bicycle exercise test, starting at 30 watts and increasing by 10 watts.min-1, was used to evaluate exercise capacity. Reproducible tests were required at baseline, and the test was repeated after 4, 8 and 12 weeks of treatment. Seven deaths were recorded in the placebo group and one death in the ramipril group. A total of 195 patients completed 12 weeks of treatment (placebo group n = 91, ramipril group n = 104). The groups had similar baseline characteristics. Maximal exercise time was increased by mean (SD) 35 s (9) and 41 s (8) in the placebo and ramipril groups, respectively. The adjusted difference between the groups at 12 weeks was 9 s (12) (ns). A significant decrease in blood pressure and rate-pressure product at rest and at end of exercise was obtained by ramipril as compared with placebo. Significantly fewer patients deteriorated in NYHA class from baseline to 12 weeks of ramipril treatment compared to placebo (P = 0.012). Concomitant medication for CHF increased significantly in the placebo group as compared with ramipril-treated patients (P = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output, Low↗

PubMed2001

Cost effectiveness of ramipril in patients with non-diabetic nephropathy and hypertension: economic evaluation of Ramipril Efficacy in Nephropathy (REIN) Study for Germany from the perspective of statutory health insurance.

BACKGROUND: In the Ramipril Efficacy In Nephropathy (REIN) trial, ramipril significantly lowered the rate of reaching the combined end-point of doubling of baseline serum creatinine levels or end-stage renal failure (ESRF). OBJECTIVE: To determine the additional cost per patient-year of chronic (long term) dialysis avoided (PYCDA) when the ACE inhibitor, ramipril, was added to conventional treatment of patients with non-diabetic nephropathy and hypertension. STUDY PERSPECTIVE: Statutory Health Insurance (SHI) provider in Germany. DESIGN AND SETTING: Data from the REIN Study were used in a cost-effectiveness analysis (CEA). A modelling approach was used, which was based on secondary analysis of published data, and costs were those incurred by the SHI provider (i.e. SHI expenses). In the base-case analysis, average case-related SHI expenses were applied and PYCDA were quantified using the cumulative incidence of ESRF as observed in the REIN trial. MAIN OUTCOME MEASURES AND RESULTS: The incremental cost-effectiveness ratios (ICERs) of ramipril varied between about -76,700 deutschmarks (DM) and -DM81,900 per PYCDA (DM 1 approximately equals 0.55 US dollars; 1999 values), according to the treatment periods of 1 year and 3 years, respectively. In the sensitivity,analysis, the robustness of the model and its results were shown when the extent of influence of different model variables on the base-case results was investigated. First, probabilities of ESRF and PYCDA were estimated according to the Weibull method. Second, the influence of the model variables on the target variable was quantified using a deterministic model. Third, the dependency of the target variable (ICER) on random variables was described in a simulation. The cost for chronic dialysis had by far the greatest impact on the target variable, which was 28 times greater than the impact of clinical effectiveness of ramipril, i.e. the number of PYCDA. There were net savings per PYCDA with ramipril treatment after 1, 2 and 3 years: 95% of the 10,000 simulation steps resulted in savings of between DM69 500 and D94,600 per PYCDA after 3 years. CONCLUSIONS: Results from this evaluation show that ramipril offers enormous savings from the perspective of the SHI provider (third-party payer) in Germany when added to the conventional treatment of patients with non-diabetic nephropathy and hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Follow-up study of patients randomly allocated ramipril or placebo for heart failure after acute myocardial infarction: AIRE Extension (AIREX) Study. Acute Infarction Ramipril Efficacy.

BACKGROUND: In the Acute Infarction Ramipril Efficacy (AIRE) Study, the effect of angiotensin-converting-enzyme (ACE) inhibition on the survival of patients with clinical heart failure after acute myocardial infarction (AMI), was assessed. At an average follow-up time of 15 months after randomisation, all-cause mortality was reduced from 22.6% (placebo group) to 16.9% (ramipril group) representing an absolute mortality reduction of 5.7% and a relative risk reduction of 27% (95% CI 11-40%; p = 0.002). Our aim in this study was to assess the long-term (3 years after the AIRE Study closed) magnitude, duration, and reliability of the survival benefits observed after treatment with ramipril (target dose 5 mg twice a day) when compared with placebo. METHODS: We investigated the mortality status of all 603 patients recruited from the 30 UK centres involved in the AIRE Study. Through government records we were able to confirm the death or survival of all 603 patients exactly 3 years after the close of the AIRE Study. Follow-up was for a minimum of 42 months and a mean of 59 months. The average duration of treatment with masked trial medication was 13.4 months for placebo and 12.4 months for ramipril. FINDINGS: By 0000 h March 1, 1996, death from all causes had occurred in 117 (38.9%) of 301 patients randomly assigned placebo and 83 (27.5%) of 302 patients randomly assigned ramipril, representing a relative risk reduction of 36% (95% CI 15-52%; p = 0.002) and an absolute reduction in mortality of 11.4% (114 additional 5-year survivors per 1000 patients treated for an average of 12.4 months). INTERPRETATION: Our data provide robust evidence that administration of ramipril to patients with clinically defined heart failure after AMI results in a survival benefit that is not only large in magnitude, but also sustained over many years.

Aged↗

PubMed1995

ACE inhibitor ramipril is more effective than the beta-blocker atenolol in reducing left ventricular mass in hypertension. Results of the RACE (ramipril cardioprotective evaluation) study on behalf of the RACE study group.

OBJECTIVES: To compare the effect of the angiotensin converting enzyme (ACE) inhibitor ramipril with that of the beta-blocker atenolol on reversal of left ventricular hypertrophy, on blood pressure and on other echocardiographic parameters. DESIGN: The study was conducted in accord with the PROBE (prospective randomized open blinded endpoint) design. Randomized treatment either with ramipril or with atenolol was continued for 6 months, and echocardiograms were recorded before and after 3 and 6 months of treatment. The echo tracings were blindly evaluated in a single reading centre. METHODS: M-mode, two-dimensional guided echocardiography was used to measure left ventricular wall thicknesses and dimensions, from which left ventricular mass was calculated, according to the Penn convention. RESULTS: Of 193 patients at 16 centres, 111 had echocardiograms that could be quantitatively evaluated. The primary analysis of the study was performed using data from those patients. In addition, echocardiograms of 88 patients were analysed on an 'according to protocol' basis (patients with preset values of left ventricular mass). Systolic and diastolic blood pressures were significantly reduced both by ramipril and by atenolol without any significant difference between the two drug treatments. The heart rate was significantly reduced by atenolol only. Both the 'primary' and the 'according to protocol' analyses showed that the left ventricular mass was significantly reduced by ramipril only. Comparison between treatments according to a multivariate analysis demonstrated a significantly greater reduction in left ventricular mass during ramipril than during atenolol treatment. CONCLUSIONS: The present study is the first of suitably large size in which a direct comparison of the effects of an ACE inhibitor and a beta-blocker on echocardiographic left ventricular mass has been performed. It has demonstrated that ramipril is more effective than atenolol in reversing left ventricular hypertrophy in essential hypertensive patients.

Adrenergic beta-Antagonists↗

PubMed2001

Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE).

BACKGROUND: Activation of the renin-angiotensin-aldosterone system and oxidative modification of LDL cholesterol play important roles in atherosclerosis. The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E (SECURE), a substudy of the Heart Outcomes Prevention Evaluation (HOPE) trial, was a prospective, double-blind, 3x2 factorial design trial that evaluated the effects of long-term treatment with the angiotensin-converting enzyme inhibitor ramipril and vitamin E on atherosclerosis progression in high-risk patients. METHODS AND RESULTS: A total of 732 patients >/=55 years of age who had vascular disease or diabetes and at least one other risk factor and who did not have heart failure or a low left ventricular ejection fraction were randomly assigned to receive ramipril 2.5 mg/d or 10 mg/d and vitamin E (RRR-alpha-tocopheryl acetate) 400 IU/d or their matching placebos. Average follow-up was 4.5 years. Atherosclerosis progression was evaluated by B-mode carotid ultrasound. The progression slope of the mean maximum carotid intimal medial thickness was 0.0217 mm/year in the placebo group, 0.0180 mm/year in the ramipril 2.5 mg/d group, and 0.0137 mm/year in the ramipril 10 mg/d group (P=0.033). There were no differences in atherosclerosis progression rates between patients on vitamin E and those on placebo. CONCLUSIONS: Long-term treatment with ramipril had a beneficial effect on atherosclerosis progression. Vitamin E had a neutral effect on atherosclerosis progression.

Aged↗

PubMed1998

Cost-effectiveness analysis of ramipril in heart failure after myocardial infarction. Economic evaluation of the Acute Infarction Ramipril Efficacy (AIRE) study for Germany from the perspective of Statutory Health Insurance.

OBJECTIVE: Data from the Acute Infarction Ramipril Efficacy (AIRE) study were used in a cost-effectiveness analysis to determine the incremental cost per life-year gained (LYG) when the ACE inhibitor ramipril was added to conventional treatment in patients with heart failure after acute myocardial infarction. In the AIRE trial, the addition of ramipril significantly lowered rates of total mortality and rehospitalisation due to heart failure. DESIGN AND SETTING: The cost-effectiveness analysis was conducted from the perspective of the Statutory Health Insurance (SHI) provider in Germany. A modelling approach was used which was based on secondary analysis of existing data, and costs were those incurred by SHI (i.e. expenses of SHI). In the base-case analysis, average case-related expenses of SHI were applied and LYG were quantified by the method of Kaplan and Meier. MAIN OUTCOME MEASURES AND RESULTS: The incremental cost-effectiveness ratios of ramipril varied between 2500 and 8300 deutschmarks (DM) per LYG (1993 values for inpatient and 1995 values for outpatient treatment; DM1 approximately $US0.70), according to the treatment periods of 3.8 years and 1 year, respectively. In the sensitivity analysis, the robustness of the model and its results was shown when the extent of influence of different model variables on the base-case results was investigated. First, survival probability and LYG were estimated according to the Weibull method. Second, the dependency of the target variable (i.e. incremental cost per LYG) on random variables was described in a simulation. Third, the influence of the model variables on the target variable was quantified using a deterministic model. The variance of the target variable was broad and the hospitalisation impact of adding ramipril to conventional treatment was an independent variable with much greater influence on the target variable than the parameter of clinical effectiveness, i.e. the number of LYG. CONCLUSION: Results of this evaluation showed that ramipril has a favourable incremental cost-effectiveness ratio for the treatment of heart failure in post myocardial infarction patients and can be considered an economical therapeutic agent from the perspective of SHI (third-party payer) in Germany.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1991

24-hour blood pressure profiles in hypertensive patients administered ramipril or placebo once daily: magnitude and duration of antihypertensive effects. Ramipril Multicenter Study Group.

Ramipril is a new, potent nonsulfhydryl inhibitor of angiotensin converting enzyme. The magnitude and duration of its antihypertensive effect were evaluated in a multicenter, placebo-controlled, randomized clinical trial conducted in 100 patients with mild to moderate essential hypertension. Ramipril significantly reduced both supine and standing blood pressures measured 24 h after dosing. Automated blood pressure monitoring showed that ramipril significantly reduced systolic and diastolic pressures for 24 h after dosing. The peak effect occurred between 3 and 6 h after dosing, with approximately 50% of this effect retained after 24 h. Ramipril was well tolerated; there was no significant difference between active drug and placebo in the overall incidence of side effects. Ramipril is an effective and well-tolerated antihypertensive agent, which reduces both supine and standing blood pressure over the entire 24-h period after dosing.

Adult↗

PubMed1999

The prognostic significance of a history of systemic hypertension in patients randomised to either placebo or ramipril following acute myocardial infarction: evidence from the AIRE study. Acute Infarction Ramipril Efficacy.

BACKGROUND: After acute myocardial infarction (AMI), patients with a history of arterial hypertension (AH) have a worse prognosis than normotensives. Whether this adverse risk is beneficially modulated by treatment with angiotensin-converting enzyme (ACE) inhibitors is unknown. We evaluated the prognostic value of antecedent hypertension in post-AMI patients given ACE inhibitor therapy. METHODS: We analysed retrospectively data from the AIRE study (randomised, placebo-controlled trial of ramipril in 2006 post-AMI patients with clinical heart failure). A history of AH was present in 28% of the patients. We examined the prognostic value of antecedent hypertension separately among placebo and ramipril treated patients and also the effect of ramipril on clinical outcomes according to whether or not a history of AH was present. RESULTS: Antecedent hypertension was a significant indicator of adverse prognosis in the placebo (P) treated patients (Hazard Ratio 1.49, 95% Confidence Intervals 1.13 to 1.97, P = 0.005) but not in the ramipril (R) treated patients (1.17, 0.84 to 1.61, P = 0.34). A similar pattern was observed for the risks of sudden death (P: 1.75, 1.21 to 2.54, P = 0.003; R: 1.34, 0.86 to 2.07, P = 0.18) and severe/resistant heart failure (P: 1.48, 1.08 to 2.03, P = 0.014; R: 1.18, 0.83 to 1.68, P = 0.37). Treatment with ramipril reduced the all-cause mortality risk in both hypertensive (0.63, 0.44 to 0.89, P = 0.009) and normotensive patients (0.78, 0.61 to 0.99, P = 0.041). CONCLUSION: Antecedent hypertension is not a significant prognosticator in patients with AMI and clinical heart failure given ACE inhibitor therapy.

Aged↗

PubMed1994

Neurohormonal activation in patients with mild or moderately severe congestive heart failure and effects of ramipril. The Ramipril Trial Study Group.

OBJECTIVES: To describe neurohormonal activation in patients with mild or moderate heart failure and how it may be modified by treatment with ramipril. SETTING: Cardiology departments at 24 hospitals in Denmark, Finland, Norway, and Sweden. PATIENTS: 223 patients with mild or moderately severe congestive heart failure who were taking diuretics with or without digitalis. DESIGN: Randomised, double bind, multicentre, placebo controlled comparison of ramipril and placebo. Venous blood samples were drawn at rest, before blind treatment, and after 12 weeks of treatment with the study drug. A probability prediction score for mortality derived by stepwise linear discriminant from neurohormone data in the first cooperative north Scandinavian enalapril survival study (CONSENSUS I) was used to assess combined activity of the different neurohormonal systems. RESULTS: Plasma concentrations of atrial natriuretic peptide were raised at baseline but angiotensin II, aldosterone, and noradrenaline concentrations were within normal limits. There was, however, a wide interindividual variation. Plasma noradrenaline concentration and prediction score were higher among patients with class III congestive heart failure according to the New York Heart Association's classification than among patients with class II congestive heart failure (P < 0.05). There was a modest but significant inverse correlation between exercise duration at baseline and plasma noradrenaline concentration (r = -0.21, P = 0.0023), aldosterone concentration (r = -0.14, P = 0.04), and prediction score (r = -0.24, P = 0.0004). Prediction score at baseline was significantly higher among those who died (n = 10) than among survivors (P = 0.03). Angiotensin converting enzyme activity was suppressed and plasma concentrations of aldosterone and atrial natriuretic peptide were reduced after 12 weeks of treatment with ramipril compared with placebo. In patients with the most pronounced neurohormonal activation at baseline (highest third of noradrenaline concentration or prediction score), noradrenaline concentration and prediction score were significantly lower after 12 weeks of taking ramipril compared with placebo. Patients with a prediction score in the highest third at baseline had a higher heart rate than to those in the lowest third (P = 0.003). CONCLUSIONS: Neurohormonal activation is associated with the degree of symptoms and the severity of disease in mild or moderately severe congestive heart failure. Treatment with ramipril attenuates neurohormonal activation. This effect is most pronounced among patients with the highest circulating concentrations of neurohormones before the start of treatment.

Adult↗

PubMed1995

Effects of 12 weeks of ramipril treatment on the quality of life in patients with moderate congestive heart failure: results of a placebo-controlled trial. Ramipril Study Group.

The assessment of quality of life (QoL) has become recognized as an important tool for evaluating heart failure therapy. The angiotensin-converting enzyme inhibitor ramipril (mean dose 8 mg) was evaluated in 223 patients with moderate chronic congestive heart failure at 24 centers in 4 Nordic countries following a randomized, double-blind, placebo-controlled, parallel group design. The follow-up period was 12 weeks. QoL was evaluated using a questionnaire with 47 items, including the disease-specific Severe Heart Failure Questionnaire, the Sleep Dysfunction Scale, and the Psychological General Well-Being Index. In both treatment groups the total score increased from baseline to 12 weeks for both the Severe Heart Failure Questionnaire and for the Psychological Well-Being Index, reflecting relief of symptoms and improved well-being. However, no significant differences between the placebo and ramipril groups could be detected. Only a trend toward improvement in sleep on ramipril compared with placebo therapy was observed. In conclusion, in this placebo-controlled trial no significant effects of 12-week ramipril treatment of QoL could be demonstrated in patients with moderate congestive heart failure.

Adult↗

PubMed2004

Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, myocardial infarction, stroke, heart failure, need for revascularization, nephropathy, and diabetes and its complications. Although angiotensin-II receptor blockers (ARBs) have been less extensively evaluated, theoretically they may have "protective" effects similar to those of ACE inhibitors, but with better tolerability. Currently, there is uncertainty about the role of ARBs when used alone or in combination with an ACE inhibitor in high-risk populations with controlled hypertension. OBJECTIVES: Primary objectives of the ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) are to determine if the combination of the ARB telmisartan and the ACE inhibitor ramipril is more effective than ramipril alone, and if telmisartan is at least as effective as ramipril. The Telmisartan Randomized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease (TRANSCEND) will determine if telmisartan is superior to placebo in patients who are intolerant of ACE inhibitors. The primary outcome for both trials is the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. METHOD: High-risk patients with coronary, peripheral, or cerebrovascular disease or diabetes with end-organ damage are being recruited and followed for 3.5 to 5.5 years in 2 parallel, randomized, double-blind clinical trials. PROGRESS: Recruitment from 730 centers in 40 countries for ONTARGET (n = 25,620) was completed in July 2003. For TRANSCEND, 5776 patients (out of a projected total of 6000) have been recruited (by May 10, 2004). Baseline patient characteristics are comparable to the Heart Outcomes Prevention Evaluation (HOPE) trial, the basis of the design of the current study, confirming that patients are at high-risk.

Aged↗

PubMed2000

Randomized, placebo-controlled trial of the angiotensin-converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease. PART-2 Collaborative Research Group. Prevention of Atherosclerosis with Ramipril.

OBJECTIVES: The primary objective of this study was to investigate the effects of the angiotensin-converting enzyme (ACE) inhibitor, ramipril, on carotid atherosclerosis in patients with coronary, cerebrovascular or peripheral vascular disease. BACKGROUND: Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of coronary events in various patient groups and to prevent the development of atherosclerosis in animal models. It has been hypothesized that the clinical benefits of ACE inhibitors may, therefore, be mediated by effects on atherosclerosis. METHODS: Six hundred seventeen patients were randomized in equal proportions to ramipril (5-10 mg daily) or placebo. At baseline, two years and four years, carotid atherosclerosis was assessed by B-mode ultrasound, and left ventricular mass was assessed by M-mode echocardiography. RESULTS: Blood pressure (BP) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the ramipril group compared with the placebo group (p<0.001). There was no difference between groups in the changes in common carotid artery wall thickness (p = 0.58) or in carotid plaque (p = 0.93). Left ventricular mass index decreased by 3.8 g/m2 (4%) in the ramipril group compared with the placebo group (2p = 0.04). CONCLUSIONS: The results provide no support for the hypothesis that reduced atherosclerosis is responsible for the beneficial effects of ACE inhibitors on major coronary events. It is more likely that the benefits are due to lower BP, reduced left ventricular mass or other factors such as reversal of endothelial dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

[Remission of left ventricular hypertrophy with ramipril independently of blood pressure changes: the HYCAR study (cardiac hypertrophy and ramipril)].

Most studies of the regression of left ventricular hypertrophy by antihypertensive treatment have methodological weaknesses and have not shown if regression of left ventricular hypertrophy can be obtained independently of blood pressure reduction. In the HYCAR study, after an inclusion phase of 4 to 6 weeks on furosemide (20 mg/day), 115 patients with left ventricular hypertrophy were randomised in a double blind manner to placebo group (N = 40), ramipril, 1.25 mg/day, (N = 38) or 5 mg/day (N = 37) for a period of 6 months. Furosemide was continued during the double blind treatment period. Echocardiography and ambulatory blood pressure monitoring were performed just before the randomisation and at 6 months. At the end of the study, there was no significant difference between the casual and ambulatory blood pressure changes. Expressed in g/m, the left ventricular mass index decreased significantly with respect to placebo in the ramipril 5 mg group (-12.2 +/- 3.9 versus +5.5 +/- 4.3 g/m2, p = 0.003) and in the 1.25 mg group (-7.5 +/- 4.6 g/m2, p = 0.04). The reduction in left ventricular mass index expressed in g/m2 was significant in the 5 mg ramipril (p = 0.008) but not in the 1.25 mg ramipril group (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1997

Cost effectiveness in the treatment of heart failure with ramipril. A Swedish substudy of the AIRE study. Acute Infarction Ramipril Efficacy.

We estimated the cost effectiveness of adding the ACE inhibitor ramipril to conventional treatment in patients with heart failure after acute myocardial infarction. These estimates were based on the Acute Infarction Ramipril Efficacy (AIRE) study and on complementary Swedish healthcare resource use data for a subset of patients. The average follow-up period was 15 months (minimum 6 months, maximum 3.8 years). The perspective of the analysis was that of the county councils (third-party payers), and we focused on the cost of drugs and hospitalisation. The marginal cost effectiveness of the treatment was estimated over 3 treatment periods: 1, 2 and 3.8 years. The cost-effectiveness ratios varied between SEK14,148 and SEK33,033 per life-year gained ($US1 = SEK7.70. Pounds 1 = SEK12.40) for the 3 treatment periods. Adding ramipril to conventional treatment for heart failure after acute myocardial infarction is therefore cost effective, and compares favourably with the cost effectiveness of other common medical therapies in the cardiovascular field.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators.

Survival after acute myocardial infarction has been enhanced by treatment with thrombolytic agents, aspirin, and beta-adrenoceptor blockade. However there remains a substantial subgroup of patients who manifest clinical evidence of heart failure despite the first two of these treatments, and for whom beta-adrenoceptor antagonists are relatively or absolutely contraindicated. These patients have a greatly increased risk of fatal and non-fatal ischaemic, arrhythmic, and haemodynamic events. In this selected high-risk subset of patients we investigated the effect of therapy with the angiotensin converting enzyme (ACE) inhibitor rampiril, postulating that it would lengthen survival. 2006 patients who had shown clinical evidence of heart failure at any time after an acute myocardial infarction (AMI) were recruited from 144 centres in 14 countries. Patients were randomly allocated to double-blind treatment with either placebo (992 patients) or ramipril (1014 patients) on day 3 to day 10 after AMI (day 1). Patients with severe heart failure resistant to conventional therapy, in whom the attending physician considered the use of an ACE inhibitor to be mandatory, were excluded. Follow-up was continued for a minimum of 6 months and an average of 15 months. On intention-to-treat analysis mortality from all causes was significantly lower for patients randomised to receive ramipril (170 deaths; 17%) than for those randomised to receive placebo (222 deaths; 23%). The observed risk reduction was 27% (95 % Cl 11% to 40%; p = 0.002). Analysis of prespecified secondary outcomes revealed a risk reduction of 19% for the first validated outcome (i.e., first event in an individual patient)--namely, death, severe/resistent heart failure, myocardial infarction, or stroke (95% Cl 5% to 31%; p = 0.008). Oral administration of rampiril to patients with clinical evidence of either transient or ongoing heart failure, initiated between the second and ninth day after myocardial infarction, resulted in a substantial reduction in premature death from all causes. This benefit was apparent as early as 30 days and was consistent across a range of subgroups.

Adult↗