Condition category
Circulatory System
Date applied
06/04/2000
Date assigned
06/04/2000
Last edited
30/07/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Rory Collins

ORCID ID

Contact details

Clinical Trial Service Unit
Radcliffe Infirmary
Oxford
OX2 6HE
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

G9123430

Study information

Scientific title

Acronym

Study hypothesis

1. Providing unequivocal evidence about the effects of cholesterol-lowering drug therapy with simvastatin on total mortality among high-risk patients
2. Demonstrating reliably the effects on coronary heart disease (CHD) within several subgroups where there is still uncertainty (e.g. women, elderly, below-average cholesterol, hypertensive)
3. Providing reliable information about effects on non-cardiac mortality and morbidity (i.e. cancer, trauma, etc.), on vascular surgery and other hospitalisations and any major side-effects
4. Assessing effects of vitamin supplementation on CHD

Ethics approval

Not provided at time of registration

Study design

Randomised placebo controlled factorial design trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Coronary heart disease (CHD)

Intervention

Patients were randomised in a 2 x 2 factorial design to receive:
1. 40 mg simvastatin daily or matching placebo tablets
2. Antioxidant vitamins (vitamins E, C and beta-carotene) or matching placebo capsules

Treatment duration was for five years.

Intervention type

Supplement

Phase

Not Specified

Drug names

Simvastatin, vitamins E and C, beta-carotene

Primary outcome measures

1. Total mortality and cause-specific mortality for statin comparison
2. Total CHD and fatal CHD for vitamin comparison
3. Major vascular events and total CHD for subgroups

Secondary outcome measures

Not provided at time of registration

Overall trial start date

01/01/1994

Overall trial end date

01/10/2001

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients at high risk of CHD (e.g., because of history of vascular disease or diabetes)
2. Without clear indication for or contra-indication to statin
3. Male and female adults
4. Non-fasting blood total cholesterol concentrations of at least 3.5 mmol/L (135 mg/dL)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

20,000

Participant exclusion criteria

1. The patient's doctor considered statin therapy to be clearly indicated or contra-indicated
2. A past history of: stroke, myocardial infarction or angina hospitalisation within the previous six months
3. Chronic liver disease or evidence of abnormal liver function
4. Severe renal disease or evidence of substantially impaired renal function
5. Inflammatory muscle disease or evidence of muscle problems
6. Concurrent treatment with cyclosporin, fibrates or high-dose niacin
7. Child-bearing potential
8. Severe heart failure
9. Life-threatening conditions other than vascular disease or diabetes (including any cancer except non-melanoma skin cancer)
10. Any other condition that might limit long-term compliance

Recruitment start date

01/01/1994

Recruitment end date

01/10/2001

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Clinical Trial Service Unit
Oxford
OX2 6HE
United Kingdom

Sponsor information

Organisation

Medical Research Council (MRC) (UK)

Sponsor details

20 Park Crescent
London
W1B 1AL
United Kingdom
+44 20 7636 5422
clinical.trial@headoffice.mrc.ac.uk

Sponsor type

Research council

Website

http://www.mrc.ac.uk

Funders

Funder type

Research council

Funder name

Medical Research Council (MRC) (UK)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2005 results in http://www.ncbi.nlm.nih.gov/pubmed/15771782
2. 2007 results in http://www.ncbi.nlm.nih.gov/pubmed/17239712
3. 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19442259
4. 2010 genetic variant results in http://www.ncbi.nlm.nih.gov/pubmed/21252144
5. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21277016
6. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21458191
7. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/22539783
8. 2012 sub-study results on cholesterol and risk of vascular events in http://www.ncbi.nlm.nih.gov/pubmed/22539783

Publication citations

  1. Results

    The effects of cholesterol lowering with simvastatin on cause-specific mortality and on cancer incidence in 20,536 high-risk people: a randomised placebo-controlled trial [ISRCTN48489393]., BMC Med, 2005, 3, 6, doi: 10.1186/1741-7015-3-6.

  2. Results

    , Emberson JR, Ng LL, Armitage J, Bowman L, Parish S, Collins R, N-terminal Pro-B-type natriuretic peptide, vascular disease risk, and cholesterol reduction among 20,536 patients in the MRC/BHF heart protection study., J. Am. Coll. Cardiol., 2007, 49, 3, 311-319, doi: 10.1016/j.jacc.2006.08.052.

  3. Results

    , Armitage J, Bowman L, Collins R, Parish S, Tobert J, Effects of simvastatin 40 mg daily on muscle and liver adverse effects in a 5-year randomized placebo-controlled trial in 20,536 high-risk people., BMC Clin Pharmacol, 2009, 9, 6, doi: 10.1186/1472-6904-9-6.

  4. Genetic variant results

    Hopewell JC, Clarke R, Parish S, Armitage J, Lathrop M, Hager J, Collins R, , Lipoprotein(a) genetic variants associated with coronary and peripheral vascular disease but not with stroke risk in the Heart Protection Study., Circ Cardiovasc Genet, 2011, 4, 1, 68-73, doi: 10.1161/CIRCGENETICS.110.958371.

  5. Results

    , Jonathan Emberson, Derrick Bennett, Emma Link, Sarah Parish, John Danesh, Jane Armitage, Rory Collins, C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20,536 patients in the Heart Protection Study., Lancet, 2011, 377, 9764, 469-476, doi: 10.1016/S0140-6736(10)62174-5.

  6. Results

    Hopewell JC, Parish S, Clarke R, Armitage J, Bowman L, Hager J, Lathrop M, Collins R, , No impact of KIF6 genotype on vascular risk and statin response among 18,348 randomized patients in the heart protection study., J. Am. Coll. Cardiol., 2011, 57, 20, 2000-2007, doi: 10.1016/j.jacc.2011.02.015.

  7. Results

    Parish S, Offer A, Clarke R, Hopewell JC, Hill MR, Otvos JD, Armitage J, Collins R, , Lipids and lipoproteins and risk of different vascular events in the MRC/BHF Heart Protection Study., Circulation, 2012, 125, 20, 2469-2478, doi: 10.1161/CIRCULATIONAHA.111.073684.

Additional files

Editorial Notes