1、Effects of an Angiotensin-Converting Enzyme Inhibitor, Ramipril, on Death from Cardiovascular Causes, Myocardial Infarction, and Stroke in High-Risk Patients,The Heart Outcomes Prevention Evaluation (HOPE) Study Investigators,N Engl J Med, January 20, 2000,HOPE - Background,ACEIs improve the outcome
2、 in patients with LV dysfunction, whether or not they have symptomatic heart failure. This study assessed the role of an ACEI, ramipril, in patients who were at high risk for cardiovascular events but who did not have LV dysfunction or heart failure.,N Engl J Med, January 20, 2000,HOPE - Design,A to
3、tal of 9,297 high-risk patients, 55 years old, who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low EF or heart failure were randomly assigned to receive ramipril (10 mg per day) or matching placebo for a mean of 5 years. The
4、 primary outcome was a composite of MI, stroke or death from cardiovascular causes. Each of these endpoints were also analyzed separately. Secondary endpoints were death from any cause, the need for revascularization, hospitalization for unstable angina or heart failure, and complications related to
5、 diabetes.,N Engl J Med, January 20, 2000,HOPE - Baseline Characteristics,N Engl J Med, January 20, 2000,Characteristic Ramipril Group Placebo Group(n=4645) (4652)Age- yr 66 66 Blood pressure - mm Hg 139/79 139/79 Heart rate - beats/min 69 69 Female sex - % 27.5 25.8 History of CAD - % 79.5 81.3 Str
6、oke or TIA - % 10.8 11.0 Peripheral vascular disease - % 42.3 44.8 Hypertension - % 47.6 46.1 Diabetes - % 38.9 38.0 Documented elevated TC - % 65.4 66.4 Documented low HDL - % 18.1 19.0 Current cigarette smoking - % 13.9 14.5 LVH on ECG - % 8.2 8.7,HOPE - Baseline Characteristics - Medications -,Ch
7、aracteristic Ramipril Group Placebo Group(n=4645) (n=4652)Medications - %Beta-blockers 39.2 39.8ASA or other platelet agents 75.3 76.9Lipid-lowering agents 28.4 28.8Diuretics 15.3 15.2CCBs 46.3 47.9,N Engl J Med, January 20, 2000,HOPE - Compliance,More patients in the ramipril group versus the place
8、bo group stopped treatment because of cough (7.3% versus 1.8%) or hypotension or dizziness (1.9% versus 1.5%) By contrast, more patients in the placebo group than in the ramipril group stopped treatment because of uncontrolled hypertension (3.9% versus 2.3%) or because of a clinical event - a primar
9、y or secondary outcome (9.0% versus 6.7%) 5.3% of patients in the ramipril group and 7.2% of patients in the placebo group received open label ACEI for heart failure,N Engl J Med, January 20, 2000,HOPE - Kaplan-Meier Estimates of the Composite Endpoint of CV Death, MI or Stroke in the Ramipril and P
10、lacebo Groups,N Engl J Med, January 20, 2000,P0.001,HOPE - Primary Endpoint Results,Endpoint Ramipril Placebo RR P value(n=4645) (n=4652)MI/Stroke/CV Death 14.1% 17.7% 0.78 0.001CV Death 6.1% 8.1% 0.75 0.001MI 9.9% 12.2% 0.80 0.001Stroke 3.4% 4.9% 0.69 0.001 Non CV Death 4.3% 4.1% 1.03 0.78 Total Mo
11、rtality 10.4% 12.2% 0.84 0.006,N Engl J Med, January 20, 2000,HOPE - Primary Endpoint Results,MI/Stroke/ CV Death,CV Death,MI,Stroke,Total Mortality,22% Risk Reduction p0.001,25% Risk Reduction p0.001,20% Risk Reduction p=0.001,31% Risk Reduction p=0.001,16% Risk Reduction p=0.006,N Engl J Med, Janu
12、ary 20, 2000,Non CV Death,0% Risk Reduction p=0.78,HOPE - Secondary and Other Endpoint Results,Endpoint Ramipril Placebo RR P value(n=4645) (n=46532)Secondary Outcomes - %Revascularization 16.0 18.6 0.84 0.001Hospitalization for UA 12.2 12.4 0.98 0.68Complications/DM 6.2 7.4 0.84 0.03Hospitalization
13、 for HF 3.3 3.8 0.87 0.19 Other Outcomes - %Heart failure 9.2 11.7 0.77 0.001Cardiac arrest 0.8 1.2 0.63 0.03Worsening angina 23.8 26.2 0.89 0.003New diagnosis of DM 3.7 5.3 0.68 0.002Unstable angina withECG changes 3.9 4.0 0.96 0.72,N Engl J Med, January 20, 2000,UA = unstable angina; DM = diabetes
14、 mellitus; HF = heart failure,HOPE - Secondary and Other Endpoint Results,Revascularization,DM Complications,New diagnosis of Diabetes Mellitus,16% Risk Reduction p0.001,16% Risk Reduction p=0.03,23% Risk Reduction p0.001,HF Hospitalization,Heart Failure,N Engl J Med, January 20, 2000,13% Risk Reduc
15、tion p=0.19,32% Risk Reduction p=0.002,HOPE - Results in Patients with a Normal EF,Endpoint Ramipril Placebo RR P valuen=2339 n=2337Primary Endpoint 13.6% 18.3% 0.73 0.001 CV Death 5.0% 7.0% 0.7 0.0032 MI 10.3% 13.5% 0.75 0.0009 Stroke 2.9% 4.2% 0.67 0.010 All HF 8.3% 10.4% 0.79,G. Dagenais, ESC 199
16、9,HOPE - Results in Patients with Normal EF,MI/Stroke/ CV Death,CV Death,Stroke,27% Risk Reduction p=0.00002,30% Risk Reduction p=0.0032,33% Risk Reduction p=0.010,MI,25% Risk Reduction p=0.0009,G. Dagenais, ESC 1999,HOPE - Results in Patients with Diabetes,Endpoint Ramipril Placebo RR P valuen=1808
17、 n=1770Primary Endpoint 15.3% 19.6% 0.76 0.0007 CV Death 6.0% 9.6% 0.62,G. Dagenais, ESC 1999,HOPE - Results in Patients with Diabetes,MI/Stroke/CV Death,CV Death,34% Risk Reduction p=0.0007,38% Risk Reduction,G. Dagenais, ESC 1999,HOPE - BP Effects,Outcome Baseline Change at 1 Change at 2 Change at
18、 end(mmHg) month (mmHg) months (mmHg) (mmHg)Ramipril SBP 139 -6.0 -3.0 -2.0 Placebo SBP 139 -2.0 0.00 0.00 Ramipril DBP 79 -3.0 -3.0 -3.00 Placebo DBP 79 -1.0 -1.0 -2.00,N Engl J Med, January 20, 2000,HOPE - Vitamin E Outcomes Results,Vitamin E Placebo RRPrimary Endpoint 16.0% 15.4% 1.04(0.94-1.15)
19、All Cause Mortality 11.0% 11.0%,G. Dagenais, ESC 1999,HOPE - Summary of Results,Patients randomized to ramipril had risk reductions of: MI, stroke, CV death -22% CV death -25% MI -20% Stroke -31% Revascularization procedures* -16% New onset of diabetes -32%,*Revascularization procedures included PTC
20、A, CABG or peripheral angioplasty,N Engl J Med, January 20, 2000,HOPE - Summary of Results (continued),The beneficial effect of treatment with ramipril on the composite outcome was consistently observed among the following predefined subgroups: patients with and without diabetes men and women those
21、with and without evidence of cardiovascular disease those 65 year of age those with and without hypertension at baseline* those with and without microalbuminuria,*A reduction of 2 mm Hg in diastolic blood pressure (as seen in this trial) might at best account for about 40% of the reduction in the ra
22、te of stroke and about 25% of the reduction of MI.,N Engl J Med, January 20, 2000,HOPE - Summary of Results (continued),There was a clear benefit of ramipril among patients: with and without evidence of coronary artery disease at baseline with and without a history of myocardial infarction with a do
23、cumented EF 40% (27% risk reduction, p0.001) Benefits were also observed whether or not patients were also taking (at randomization): ASA or other antiplatelet agents beta-blockers lipid-lowering agents antihypertensive agents,N Engl J Med, January 20, 2000,HOPE - Conclusions,“Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure”,N Engl J Med, January 20, 2000,
