Know Cancer

forgot password

HOPE-2 Study (Heart Outcomes Prevention Evaluation-2 Study)

Phase 4
55 Years
Open (Enrolling)
Cardiovascular Disease, Myocardial Infarction, Stroke, Cancer

Thank you

Trial Information

HOPE-2 Study (Heart Outcomes Prevention Evaluation-2 Study)

Cardiovascular disease (CVD) remains a major cause of mortality and morbidity in most
developed countries and accounts for approximately 40% of all deaths in Canada. Reductions
in cholesterol, lowering of blood pressure and smoking cessation have been shown to be
effective strategies in cardiovascular prevention; however, these major "classical
cardiovascular risk factors" along with nonmodifiable risk factors, cannot fully explain why
certain individuals develop atherosclerotic cardiovascular diseases, while others do not.
Other "emerging" cardiovascular risk factors are currently under investigation. There is a
large body of consistent, biologically plausible evidence linking hyperhomocyst(e)inemia to
cardiovascular risk and the association is graded. A simple, nontoxic therapeutic
intervention in the form of multivitamins - folic acid and vitamins B6 and B12 - has been
shown to be highly effective in reducing homocyst(e)ine levels, irrespective of the
underlying cause. To date, however, there are no good clinical trials evaluating the
efficacy of homocyst(e)ine-lowering therapies in reducing major cardiovascular events. The
impact of this simple intervention on cardiovascular morbidity and mortality remains to be

Study Hypothesis: Evaluate if long-term therapy with folic acid and vitamins B6 and B12
compared to placebo reduces the risk of major fatal and nonfatal cardiovascular events.

Importance of the Study: The "homocyst(e)ine theory of atherosclerosis" remains an important
unanswered question in cardiovascular medicine. If indeed a combination of multivitamins is
found to be effective in reducing cardiovascular events, it is expected that this safe,
inexpensive and easily administered therapy would be widely used world-wide. Therefore, the
results of this trial could have a significant public health impact.

Inclusion Criteria:

- Women and men 55 years of age or over with established CVD and at high risk for
future fatal and nonfatal CV events, defined as:

1. Documented coronary artery disease (CAD);

2. Documented peripheral vascular disease (PVD);

3. Documented cerebrovascular disease;

4. Diabetes with one of the following; additional cardiovascular risk factors:

i) hypertension (BP >160 mmHg systolic or >90 mmHg diastolic or on treatment); ii)
total cholesterol >5.2 mmol/L (>200 mg/dl); iii) HDL cholesterol <0.9 mmol/L (3.5
mg/dl); iv) current cigarette smoker; v) any evidence of previous vascular disease

- Provision of informed consent

Exclusion Criteria:

- Current use of any vitamin supplements containing folic acid >200 micrograms/day. The
patients taking such vitamin supplements can be asked if they agree to discontinue
these supplements. If they agree, they can be randomized to the study following a one
month wash-out period.

- Known previous adverse reactions to folic acid and/or vitamin B6 and/or B12.

- Planned cardiac, peripheral or cerebrovascular revascularization, defined as a
decision taken by the patient and his or her physician(s) to perform surgical or
percutaneous transluminal revascularization within the next 6 months.

- Hemodynamically significant primary valvular outflow tract obstruction (e.g. mitral
stenosis, asymmetric septal hypertrophy, malfunctioning prosthetic valve).

- Constrictive pericarditis.

- Complex congenital heart disease.

- Syncopal episodes presumed to be due to uncontrolled life-threatening arrhythmias
(asymptomatic arrhythmias including ventricular tachycardia are not exclusion

- Uncontrolled hypertension.

- Cor pulmonale.

- Heart transplant recipient.

- Other important non-cardiovascular disease(s) expected to limit compliance and/or
impact on patient's ability to complete the study, such as: *history of alcohol or
drug abuse, *psychiatric disorders, *senility, *severe physical disability,
*illnesses including terminal stage of cancer and other major systemic illnesses
expected to limit the patient's ability to comply with the study protocol and to
complete the study.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Outcome Measure:

The composite of cardiovascular death, myocardial infarction (MI) and stroke

Principal Investigator


Investigator Role:

Principal Investigator

Investigator Affiliation:

McMaster University


Canada: Health Canada

Study ID:

HOPE-2, CIHR FRN # MT-15428



Start Date:

December 1999

Completion Date:

October 2005

Related Keywords:

  • Cardiovascular Disease
  • Myocardial Infarction
  • Stroke
  • Cancer
  • homocysteine
  • folic acid
  • micronutrients
  • multivitamins
  • vitamin supplements
  • Cardiovascular Diseases
  • Infarction
  • Myocardial Infarction
  • Stroke