Effect of Ramipril in Reducing Sudden Deaths and Nonfatal Cardiac Arrests in High-Risk Individuals Without Heart Failure or Left Ventricular Dysfunction (original) (raw)
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European heart journal, 1997
The importance of the effects of ACE inhibitors on sudden death, progressive heart failure and recurrent infarction to the reduction in overall mortality in heart failure and after myocardial infarction is disputed. The AIRE study randomized 2006 patients with clinical or radiological evidence of heart failure within 2-9 days of a myocardial infarction to receive ramipiril 5 mg b.d. or matching placebo. Outcomes were assessed independently by members of an end-points committee blinded to treatment allocation. Fewer patients developed severe resistant heart failure as their first validated end-point on rampril, despite the greater number of at-risk survivors, compared to placebo (n = 143 vs 178; risk reduction 23%; CI 5 to 39%; P = 0.017). Ramipril did not alter the rate of reinfarction or stroke. Irrespective of treatment allocation 182 (46%) patients developed resistant heart failure prior to death. A validated acute or remote myocardial reinfarction occurred in 76 (19%) patients p...
European Heart Journal, 1997
Background The importance of the effects of ACE inhibitors on sudden death, progressive heart failure and recurrent infarction to the reduction in overall mortality in heart failure and after myocardial infarction is disputed. Methods The AIRE study randomized 2006 patients with clinical or radiological evidence of heart failure within 2-9 days of a myocardtal infarction to receive ramipril 5 mg b.d. or matching placebo. Outcomes were assessed independently by members of an end-points committee blinded to treatment allocation. Results Fewer patients developed severe resistant heart failure as their first validated end-point on ramipril, despite the greater number of at-risk survivors, compared to placebo (n= 143 vs 178; risk reduction 23%; CI 5 to 39%; P=O•Ol7). Ramipril did not alter the rate of reinfarction or stroke. Irrespective of treatment allocation 182 (46%) patients developed resistant heart failure prior to death. A validated acute or remote myocardial reinfarction occurred in 76 (19%) patients prior to death and chest pain occurred in 90 (23%) patients around the time of death suggesting an ischaemic element to these deaths. Eighty deaths occurred on the index admission, 167 during re-admission and 145 out-of-hospital. Sudden death accounted for 54% of all deaths and 93% of out-of-hospital
Circulation, 2001
on behalf of the HOPE Investigators Background-In trials of patients with left ventricular dysfunction or heart failure, ACE inhibitor use was unexpectedly associated with reduced myocardial infarction (MI). Using the Heart Outcomes Prevention Evaluation (HOPE) trial data, we tested prospectively whether ramipril, an ACE inhibitor, could reduce coronary events and revascularization procedures among patients with normal left ventricular function. Methods and Results-In the HOPE trial, 9297 high-risk men and women, Ն55 years of age with previous cardiovascular disease or diabetes plus 1 risk factor, were randomly assigned to ramipril (up to 10 mg/d), vitamin E (400 IU/d), their combination, or matching placebos. During the mean follow-up of 4.5 years, there were 482 (10.4%) patients with clinical MI and unexpected cardiovascular death in the ramipril group compared with 604 (12.9%) in the placebo group [relative risk reduction (RRR), 21% (95% CI) (11,30); PϽ0.0003]. Ramipril was associated with a trend toward less fatal MI and unexpected death [4.0% versus 4.7%; RRR, 16% (Ϫ3, 31)] and with a significant reduction in nonfatal MI [5.6% versus 7.2%; RRR, 23% (9,34)]. Risk reductions in MI were documented in participants taking or not taking -blockers, lipid lowering, and/or antiplatelet agents. Although ramipril had no impact on hospitalizations for unstable angina [11.9% versus 12.2%; RRR, 3% (Ϫ9,14)], it reduced the risk of worsening and new angina [27.2% versus 30.0%; RRR, 12% (5,18); PϽ0.0014] and coronary revascularizations [12.5% versus 14.8%; RRR, 18%; (8,26) PϽ0.0005]. Conclusions-In this high-risk cohort, ramipril reduced the risk of MI, worsening and new angina, and the occurrence of coronary revascularizations. (Circulation. 2001;104:522-526.)
Circulation, 2001
Background-Electrocardiographic markers of left ventricular hypertrophy (LVH) predict poor prognosis. We determined whether the ACE inhibitor ramipril prevents the development and causes regression of ECG-LVH and whether these changes are associated with improved prognosis independent of blood pressure reduction. Methods and Results-In the Heart Outcomes Prevention Evaluation (HOPE) study, patients at high risk were randomly assigned to ramipril or placebo and followed for 4.5years. ECGs were recorded at baseline and at study end. We compared prevention/regression and development/persistence of ECG-LVH in the two groups and related these changes to outcomes. At baseline, 676 patients had LVH (321 in the ramipril group and 355 in the placebo group) and 7605 patients did not have LVH (3814 in the ramipril group and 3791 in the placebo group). By study end, 336 patients in the ramipril group (8.1%) compared with 406 in the placebo group (9.8%) had development/persistence of LVH; in contrast, 3799 patients in the ramipril group (91.9%) compared with 3740 in the placebo group (90.2%) had regression/prevention of LVH (Pϭ0.007). The effect of ramipril on LVH was independent of blood pressure changes. Patients who had regression/prevention of LVH had a lower risk of the predefined primary outcome (cardiovascular death, myocardial infarction, or stroke) compared with those who had development/persistence of LVH (12.3% versus 15.8%, Pϭ0.006) and of congestive heart failure (9.3% versus 15.4%, PϽ0.0001). Conclusions-The ACE inhibitor ramipril decreases the development and causes regression of ECG-LVH independent of blood pressure reduction, and these changes are associated with reduced risk of death, myocardial infarction, stroke, and congestive heart failure. (Circulation. 2001;104:1615-1621.)
Circulation, 2005
Background-We have previously demonstrated that ramipril reduces vascular events and new diagnoses of diabetes when given for a 4.5-year period. However, it is not known whether the benefits are observed in subgroups of patients at varying risk or on other proven therapies and whether the benefits are sustained beyond the current trial. The 2 aims of this investigation were to assess whether the benefits observed during the HOPE trial were (1) maintained after trial cessation during an additional 2.6 years of follow-up and (2) observed in subgroups based on risk and ancillary treatments. Methods and Results-Of the initial 267 study centers and 9297 patients, 174 centers and 4528 patients agreed to further follow-up. The rates of use of angiotensin-converting-enzyme inhibitors (ACEIs) in the 2 groups (72% ramipril versus 68% placebo) were similar after the end of the trial. During the posttrial follow-up, patients allocated to ramipril had a 19% further lower relative risk (RR) of myocardial infarction (95% confidence interval [CI], 0.65 to 1.01), a 16% lower RR (95% CI, 0.70 to 0.99) of revascularization, and a 34% lower RR of a new diagnosis of diabetes (95% CI, 0.46 to 0.95). Similar RR reductions in vascular events were observed during and after the active phase of the trial, regardless of baseline risk (RR of 0.76, 0.89, and 0.83 for low-, medium-, and high-risk patients, respectively) or ancillary treatments (RR of 0.90 for aspirin, 0.76 for -blockers, and 0.84 for lipid-lowering medication). Conclusions-The benefits of ramipril observed during the active period of the HOPE trial were maintained during posttrial follow-up for cardiovascular death, stroke, and hospitalization for heart failure. Additional reductions in myocardial infarction, revascularization, and the development of diabetes were observed during the follow-up phase despite similar rates of ACEI use in the 2 randomized groups. These benefits were consistent regardless of patient risk or ancillary treatments.