Homocysteine levels and treatment effect in the PROspective Study of Pravastatin in the Elderly at Risk.
OBJECTIVE
To assess the effect of preventive pravastatin treatment on coronary heart disease (CHD) morbidity and mortality in older persons at risk for cardiovascular disease (CVD), stratified according to plasma levels of homocysteine.


METHODS
A post hoc subanalysis in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), started in 1997, which is a double-blind, randomized, placebo-controlled trial with a mean follow-up of 3.2 years.


METHODS
Primary care setting in two of the three PROSPER study sites (Netherlands and Scotland).


METHODS
Individuals (n = 3,522, aged 70-82, 1,765 male) with a history of or risk factors for CVD were ranked in three groups depending on baseline homocysteine level, sex, and study site.


METHODS
Pravastatin (40 mg) versus placebo.


METHODS
Fatal and nonfatal CHD and mortality.


RESULTS
In the placebo group, participants with a high homocysteine level (n = 588) had a 1.8 higher risk (95% confidence interval (CI) = 1.2-2.5, P = .001) of fatal and nonfatal CHD than those with a low homocysteine level (n = 597). The absolute risk reduction in fatal and nonfatal CHD with pravastatin treatment was 1.6% (95% CI = -1.6 to 4.7%) in the low homocysteine group and 6.7% (95% CI = 2.7-10.7%) in the high homocysteine group (difference 5.2%, 95% CI = 0.11-10.3, P = .046). Therefore, the number needed to treat (NNT) with pravastatin for 3.2 years for benefit related to fatal and nonfatal CHD events was 14.8 (95% CI = 9.3-36.6) for high homocysteine and 64.5 (95% CI = 21.4-∞) for low homocysteine.


CONCLUSIONS
In older persons at risk of CVD, those with high homocysteine are at highest risk for fatal and nonfatal CHD. With pravastatin treatment, this group has the highest absolute risk reduction and the lowest NNT to prevent fatal and nonfatal CHD.
Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
Yvonne M
YM
Drewes
Rosalinde K E
RK
Poortvliet
Jeanet W
JW
Blom
Wouter
W
de Ruijter
Rudi G J
RG
Westendorp
David J
DJ
Stott
Henk J
HJ
Blom
Ian
I
Ford
Naveed
N
Sattar
J
J
Wouter Jukema
Willem J J
WJ
Assendelft
Anton J M
AJ
de Craen
Jacobijn
J
Gussekloo
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood* / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D017035:Pravastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D012606:Scotland / Q000453:epidemiology; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006710:Homocysteine; D017035:Pravastatin
cardiovascular risk; homocysteine; older persons; prevention; statins