Heart Outcomes Prevention Evaluation HOPE

The Heart Outcomes Prevention Evaluation (HOPE) Study Investigators (2000). Lancet 355, 253-259. 

In addition to their benefits in patients with established heart failure, ACE inhibitors also are effective for prevention of heart failure. The SOLVD prevention trial showed that enalapril decreased the risk of hospitalization for worsening heart failure and reduced the composite end point of death and heart failure hospitalization in patients with asymptomatic left ventricular dysfunction. The development of diabetes mellitus, an important risk factor for cardiovascular disease that also increases morbidity and mortality in heart failure patients, is reduced by enalapril in patients with chronic heart failure. In a post-hoc analysis of the Heart Outcomes Prevention Evaluation (HOPE) trial, ramipril reduced the development of new-onset heart failure by nearly 25% in patients with normal EFs and no symptoms of heart failure. ... 

More recent data suggest that all patients with CAD, not just ACS or heart failure patients, benefit from an ACE inhibitor. In the Heart Outcome Prevention Evaluation (HOPE) trial, ramipril significantly reduced the risk of death, MI, or stroke in high-risk patients aged 55 years or older with chronic CAD or with diabetes and one cardiovascular risk factor. The more recent European trial On Reduction Of Cardiac Events With Perindopril In Stable Coronary Artery Disease (EUROPA) extended the benefit of chronic therapy with ACE inhibitors to patients with stable CAD at lower risk of cardiovascular events compared with patients from the HOPE trial. In the EUROPA trial, patients randomized to perindopril experienced a lower risk of the combined end point of cardiovascular death, MI, or cardiac arrest compared with patients randomized to placebo. Therefore, based on the extensive benefit of ACE inhibitors in patients with CAD, their routine use should be considered in all patients following an ACS in the absence of a contraindication. 

Another class of vasoactive agents with demonstrated benefit in secondary MI prevention are the angiotensin-con-verting enzyme (ACE) inhibitors. Several large trials of angiotensin receptor blockers as secondary prevention agents are now also underway. Most of the evidence for benefit from ACE inhibitors has centered on patients with heart failure (59). An exception to this was the Heart Outcomes Prevention Evaluation (HOPE) trial, which excluded patients with ejection fractions <40%, and involved 9297 patients (60). There was a 25% reduction in cardiac mortality in patients receiving the ACE inhibitor ramipril. 

In addition, the results of the Heart Outcomes Prevention Evaluation (HOPE-2) study showed that combined daily administration of 2.5 mg of folic add, 50 mg of vitamin Bg and Img of vitamin B12 for five years had no ben-efidal eflects on major vascular events in a high-risk vascular disease population (Lonn et al. 2006), although fewer patients assigned to adive treatment than to placebo had a stroke (relative risk, 0.75 95 percent confidence interval, 0.59 to 0.97). Recent findings from this study show that lowering of Hey with folic add and vitamins Bg and B12 did reduce the risk of overall stroke, but not stroke severity or disability (Saposnik et al. 2009). 

Form, E., Yusuf, S., Arnold, M.J., Sheridan, P., Pogue, J., Micks, M., McQueen, M.J., Probstlield, J., Fodor, G., Held, C., Genest, J., and the Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators, 2006. Homocysteine lowering with folic acid and B vitamins in vascular disease. The New England Journal of Medicine. 354 1567-1577. 

The ability of a-tocopherol supplementation to prevent cardiovascular events in different populations was tested in four larger prospective clinical trials The a-Tocopherol, yS-Carotene Cancer Prevention (ATBC) study, the Cambridge Heart Antioxidant Study (CHAOS), the Gruppo Italiano per lo studio della Sopravvivenza nell Infarto Miocar-dito (GISSI) trial, and the Heart Outcome Prevention Evaluation (HOPE) study. In addition, at least two smaller prospective clinical trials have been completed the Secondary Prevention with... 

Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and mi-crovascular outcomes in people with diabetes melli-tus results of the HOPE study and MICRO-HOPE substudy. Lancet 2000 355 253-9. 

Abbreviations. CAD. coronary artery diseases CVA, cerebrovascular accident HOPE, heart outcomes prevention evaluation LTA. light transmittance aggregometry MI. myocardial infarction PCI. percutaneous coronary intervention PVD. peripheral vascular diseases RPFA, rapid platelet function analyzer TxB2, thromboxane B2. 

In the Heart Outcomes Prevention Evaluation 2 (HOPE-2) study, 5522 patients aged 55 or older with vascular disease or diabetes were randomized to treatment with either placebo or a combination 2, 5 mg of folic acid, 50 mg vitamin B6, and I mg vitamin B 2, for an average of five years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, and stroke. Mean plasma homocysteine levels decreased by 2.4 jimol/L in the treatment group and increased by 0.8 jimol/L in the placebo group. The primary outcome occurred in 18.8% of patients assigned to active therapy and in 19.8% of those assigned to placebo (relative risk = 0.95 95% Cl = 0.84-1.07 P = 0.41) (68). 

Cambridge Heart Antioxidant Study DATATOR Deprenyl and Tocopherol Antioxidative Therapy of Rarkinsonism FMC, Finnish Mobile Clinic Health Examination Survey GISSI, Gruppo Italiano Studio Soprawivenza Infarto HOPE, Heart Outcome Prevention Evaluation HPFS, Health Professional Follow-up Study NHS, Nurses Health Study PPR Primary Prevention Project SPACE, Secondary Prevention with Antioxidants of Cardiovascular disease in End-stage renal disease VEAPS, Vitamin E Atherosclerosis Prevention Study VECAT Vitamin E Cataract Age-related maculopathy Trial. 

HOPE (Heart Outcomes Prevention Evaluation Study Investigators) (2000) Effect of an angiotensin converting enzyme inhibitor, ramipril, on cardiovascular events in high risk patients. New England journal of Medicine 342 145-152. 

EUROPA European trial On Reduction Of Cardiac Events With Perindopril In Stable Coronary Artery Disease GRACE Global Registry of Acute Coronary Events GUSTO Global Use of Strategies to Open Occluded Arteries HOPE Heart Outcomes Prevention Evaluation INR international normalized ratio... 

HOPE Heart Outcomes Prevention Evaluation study... 

Anon. Effects of ramipril on cardiovascular and microvas-cular outcomes in people with diabetes meUitus Results of the hope study and micro-hope substudy. Heart outcomes prevention evaluation study investigators. Lancet. 2000 355 253-259... 

Heart Outcomes Prevention Evaluation Study (HOPE) Investigators (2000) Vitamin E Supplementation and Cardiovascular Events in High-Risk Patients, N. Engl. J. Med. 342, 154-160. 

Dagenais, G.R., Yusuf, S., Bourassa, M.G., Yi, Q., Bosch, J., Lonn, EM., Kouz, S., Grover, J., and the HOPE Investigators (2001) Effects of Ramipril on Coronary Events in High-Risk Persons Results of the Heart Outcomes Prevention Evaluation Study, Circulation 104(5), 522-526. 

Heart Outcomes Prevention Evaluation Study Investigators (2000) Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes meUitus results of the HOPE study and MICRO-HOPE substudy. Lancet 355 253-259 Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350 2335-2342 Kozloff M, Yood MU, Berlin J et al (2009) Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer the BRiTE observational cohort study. Oncologist 14 862-870... 

ACE, angiotensin converting enzyme ATBC, Alpha Tocopherol Beta Carotene Prevention Study CHAOS, Cambridge Heart Antioxidant Study GiSSi, GiSSI Prevenzione Triai HOPE, Heart Outcomes Prevention Evaluation Study HPS, Heart Protection Study CHD, Coronary Heart Disease CVD, cardiovascuiar disease Ml, myocardial infarction PUPA, polyunsatutated fatty acids. 

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