The HOPE (Heart Outcomes Prevention Evaluation) Study and its Consequences

The HOPE study was a 19 country, prospective randomized trial in which the ACE‐inhibitor Ramipril but not Vitamin E significantly reduced the risk of future cardiovascular events in a high‐risk population of men and women, including many with diabetes. The benefits were present in all sub‐groups, independent of the presence or absence of diabetes, hypertension, evidence of cardiovascular disease, microalbuminuria, blood pressure lowering, the use of aspirin, lipid‐lowering or antihypertensive medication. It provided clear evidence that Ramipril should safely and cost‐effectively be used in individuals not known to have low ventricular ejection fraction or heart failure but at high‐risk of cardiovascular events. It was also beneficial in patients with renal insufficiency, reducing progression of proteinuria and development of new microalbuminuria. It provided micro‐ and macrovascular benefits in people with diabetes, reduced the development of new cases of diabetes and showed a positive and graded association between the waist‐to‐hip ratio and the risk of developing diabetes. Sub‐studies completed and on‐going into the predictive role of natriuretic peptides, infectious and inflammatory markers, provide insight into possible mechanisms of action of Ramipril.

[1]  J. Mann,et al.  Cardiovascular risk in patients with mild renal insufficiency: implications for the use of ACE inhibitors. , 2005, Presse medicale.

[2]  J. Pogue,et al.  The effect of vitamin E supplementation on cardiovascular risk in diabetic individuals with different haptoglobin phenotypes. , 2004, Diabetes care.

[3]  S. Yusuf,et al.  Effect of Ramipril in Reducing Sudden Deaths and Nonfatal Cardiac Arrests in High-Risk Individuals Without Heart Failure or Left Ventricular Dysfunction , 2004, Circulation.

[4]  S. Yusuf,et al.  Effects of ramipril on left ventricular mass and function in cardiovascular patients with controlled blood pressure and with preserved left ventricular ejection fraction: a substudy of the Heart Outcomes Prevention Evaluation (HOPE) Trial. , 2004, Journal of the American College of Cardiology.

[5]  J. Manson,et al.  Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. , 2004, JAMA.

[6]  S. Yusuf,et al.  Effects of vitamin E on cardiovascular outcomes in people with mild-to-moderate renal insufficiency: results of the HOPE study. , 2004, Kidney international.

[7]  E. Lonn,et al.  Pathophysiologic and Therapeutic Importance of Tissue ACE: A Consensus Report , 2002, Cardiovascular Drugs and Therapy.

[8]  S. Yusuf,et al.  Impact of ramipril in patients with evidence of clinical or subclinical peripheral arterial disease , 2004 .

[9]  S. Yusuf,et al.  Increased occurrence of diabetes in people with ischemic cardiovascular disease and general and abdominal obesity. , 2003, The Canadian journal of cardiology.

[10]  S. Yusuf,et al.  Progression of renal insufficiency in type 2 diabetes with and without microalbuminuria: results of the Heart Outcomes and Prevention Evaluation (HOPE) randomized study. , 2003, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[11]  Salim Yusuf,et al.  Prevention of Heart Failure in Patients in the Heart Outcomes Prevention Evaluation (HOPE) Study , 2003, Circulation.

[12]  S. Yusuf,et al.  Development of renal disease in people at high cardiovascular risk: results of the HOPE randomized study. , 2003, Journal of the American Society of Nephrology : JASN.

[13]  M. Coen,et al.  Economic Impact of Ramipril on Hospitalization of High-Risk Cardiovascular Patients , 2003, The Annals of pharmacotherapy.

[14]  S. Yusuf,et al.  Multiple Infections and Subsequent Cardiovascular Events in the Heart Outcomes Prevention Evaluation (HOPE) Study , 2003, Circulation.

[15]  S. Yusuf,et al.  Mechanisms of cardiovascular risk reduction with ramipril: insights from HOPE and HOPE substudies , 2003 .

[16]  S. Yusuf,et al.  Cost implications of the use of ramipril in high-risk patients based on the Heart Outcomes Prevention Evaluation (HOPE) study. , 2003, Circulation.

[17]  S. Yusuf,et al.  Relationship of Anti-60 kDa Heat Shock Protein and Anti-Cholesterol Antibodies to Cardiovascular Events , 2002, Circulation.

[18]  S. Yusuf,et al.  Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy. , 2002, Diabetes care.

[19]  R. Collins,et al.  Effects of long-term treatment with angiotensin-converting-enzyme inhibitors in the presence or absence of aspirin: a systematic review , 2002, The Lancet.

[20]  S. Yusuf,et al.  Effect of long-term therapy with ramipril in high-risk women. , 2002, Journal of the American College of Cardiology.

[21]  T. Kahan,et al.  The cost‐effectiveness of ramipril in the treatment of patients at high risk of cardiovascular events: a Swedish sub‐study to the HOPE study , 2002, Journal of internal medicine.

[22]  S. Yusuf,et al.  Aspirin-Resistant Thromboxane Biosynthesis and the Risk of Myocardial Infarction, Stroke, or Cardiovascular Death in Patients at High Risk for Cardiovascular Events , 2002, Circulation.

[23]  J. Schrader,et al.  Preventing stroke : High risk patients should receive ramipril irrespective of their blood pressure , 2002 .

[24]  J. Bosch,et al.  Use of ramipril in preventing stroke: double blind randomised trial , 2002, BMJ : British Medical Journal.

[25]  Johan P Mackenbach,et al.  Income inequality and population health , 2002, BMJ : British Medical Journal.

[26]  S. Anand.  Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Eikelboom JW, Hirsh J, Weitz J, Johnston M, Yi Q, Yusuf S. Circulation 2002; 105: 1650- 1655. , 2002 .

[27]  S. Yusuf,et al.  Cardiovascular Risk in Patients with Early Renal Insufficiency , 2002, American Journal of Cardiovascular Drugs.

[28]  Gerstein,et al.  Effects of Vitamin E on Cardiovascular and Microvascular Outcomes in High-Risk Patients With Diabetes , 2002 .

[29]  Salim Yusuf,et al.  Blood-pressure reduction and cardiovascular risk in HOPE study , 2001, The Lancet.

[30]  U. de Faire,et al.  Comparative Effects of Ramipril on Ambulatory and Office Blood Pressures: A HOPE Substudy , 2001, Hypertension.

[31]  S. Yusuf,et al.  Ramipril and the development of diabetes. , 2001, JAMA.

[32]  S. Yusuf,et al.  Reduction of Cardiovascular Risk by Regression of Electrocardiographic Markers of Left Ventricular Hypertrophy by the Angiotensin-Converting Enzyme Inhibitor Ramipril , 2001, Circulation.

[33]  S. Yusuf,et al.  Effects of Ramipril on Coronary Events in High-Risk Persons: Results of the Heart Outcomes Prevention Evaluation Study , 2001, Circulation.

[34]  S. Yusuf,et al.  Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. , 2001, JAMA.

[35]  J. Kooner,et al.  Cost effectiveness of ramipril treatment for cardiovascular risk reduction , 2019 .

[36]  S. Yusuf,et al.  Renal Insufficiency as a Predictor of Cardiovascular Outcomes and the Impact of Ramipril: The HOPE Randomized Trial , 2001, Annals of Internal Medicine.

[37]  Kukin Ml.  The Heart Outcomes Prevention Evaluation Study. , 2001, Current cardiology reports.

[38]  S. Yusuf,et al.  Effects of Ramipril and Vitamin E on Atherosclerosis: The Study to Evaluate Carotid Ultrasound Changes in Patients Treated With Ramipril and Vitamin E (SECURE) , 2001, Circulation.

[39]  M. Boaz,et al.  Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial , 2000, The Lancet.

[40]  W. Lawson,et al.  Does aspirin attenuate the beneficial effects of angiotensin-converting enzyme inhibition in heart failure? , 2000, Archives of internal medicine.

[41]  S. Yusuf,et al.  Prevalence and determinants of microalbuminuria in high-risk diabetic and nondiabetic patients in the Heart Outcomes Prevention Evaluation Study. The HOPE Study Investigators. , 2000, Diabetes care.

[42]  Bruce H. R. Wolffenbuttel,et al.  Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy , 2000, The Lancet.

[43]  S. Yusuf,et al.  Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. , 2000 .

[44]  S. Yusuf,et al.  Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. , 2000 .

[45]  S. Yusuf,et al.  Vitamin E supplementation and cardiovascular events in high-risk patients. , 2000, The New England journal of medicine.

[46]  S. Yusuf,et al.  Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000;342:145-53. , 2000 .

[47]  Gerardo Heiss,et al.  Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study , 1999, The Lancet.

[48]  B. Zinman,et al.  New guidelines for the management of diabetes: a physician's guide. Steering Committee for the Revision of the Clinical Practice Guidelines for the Management of Diabetes in Canada. , 1998, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[49]  Lawrence A Leiter,et al.  1998 clinical practice guidelines for the management of diabetes in Canada. Canadian Diabetes Association. , 1998, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[50]  R. Pini,et al.  Differential effects of angiotensin converting enzyme inhibition and diuretic therapy on reductions in ambulatory blood pressure, left ventricular mass, and vascular hypertrophy. , 1998, American journal of hypertension.

[51]  R. Schmieder,et al.  Reversal of Left Ventricular Hypertrophy in Essential Hypertension: A Meta-Analysis of Randomized Double-Blind Studies , 1997 .

[52]  H. Schunkert,et al.  Effects of estrogen replacement therapy on the renin-angiotensin system in postmenopausal women. , 1997, Circulation.

[53]  J. Kluger.  Beyond cholesterol. , 1997, Time.

[54]  W. Klein.  Gender differences in clinical trials in coronary heart disease: response to drug therapy. , 1996, European heart journal.

[55]  S. Yusuf,et al.  Rationale and Design of a Large Study to Evaluate the Renal and Cardiovascular Effects of an ACE Inhibitor and Vitamin E in High-Risk Patients With Diabetes: The MICRO-HOPE Study , 1996, Diabetes Care.

[56]  S. Yusuf,et al.  Study design and baseline characteristics of the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E: SECURE. , 1996, The American journal of cardiology.

[57]  Janzen,et al.  The HOPE (Heart Outcomes Prevention Evaluation) Study: the design of a large, simple randomized trial of an angiotensin-converting enzyme inhibitor (ramipril) and vitamin E in patients at high risk of cardiovascular events. The HOPE study investigators. , 1996, The Canadian journal of cardiology.

[58]  S. Yusuf,et al.  The Antioxidant Vitamins and Cardiovascular Disease: A Critical Review of Epidemiologic and Clinical Trial Data , 1995, Annals of Internal Medicine.

[59]  S. Yusuf,et al.  Emerging role of angiotensin-converting enzyme inhibitors in cardiac and vascular protection. , 1994, Circulation.

[60]  J. Manson,et al.  Vitamin E consumption and the risk of coronary disease in women. , 1993, The New England journal of medicine.

[61]  E. Rimm,et al.  Vitamin E consumption and the risk of coronary heart disease in men. , 1993, The New England journal of medicine.

[62]  R. Campbell,et al.  ACE inhibitors after myocardial infarction. , 1993, The New England journal of medicine.

[63]  E. J. Brown,et al.  Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. , 1992, The New England journal of medicine.

[64]  S. Yusuf,et al.  Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. , 1992, The New England journal of medicine.

[65]  E. Berry.  The effects of nutrients on lipoprotein susceptibility to oxidation , 1992 .

[66]  Salim Yusuf,et al.  Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. , 1991, The New England journal of medicine.

[67]  P. Puska,et al.  Inverse correlation between plasma vitamin E and mortality from ischemic heart disease in cross-cultural epidemiology. , 1991, The American journal of clinical nutrition.

[68]  S. Ball,et al.  ACE INHIBITORS AFTER MYOCARDIAL INFARCTION , 1989, The Lancet.

[69]  J L Witztum,et al.  Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. , 1989, The New England journal of medicine.

[70]  J. Steinberg.  Book ReviewAmbulatory Pediatric Care , 1989 .

[71]  K. Swedberg,et al.  Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). , 1988, The American journal of cardiology.

[72]  E. Freis,et al.  Low-dose captopril for the treatment of mild to moderate hypertension. , 1983, Hypertension.

[73]  C. Minick,et al.  Brief Definitive Report , 2003 .

[74]  W. Kannel,et al.  Left ventricular hypertrophy by electrocardiogram. Prevalence, incidence, and mortality in the Framingham study. , 1969, Annals of internal medicine.