Potential clinical and economic effects of homocyst(e)ine lowering.

Background: Elevated total homocyst(e)ine levels (>/=11 micromol/L) have been identified as a potential risk factor for coronary heart disease. However, the benefits expected from lowering homocyst(e)ine levels with folic acid and vitamin B(12) supplementation have yet to be demonstrated in clinical trials.

Subjects And Methods: We constructed a decision analytic model to estimate the clinical benefits and economic costs of 2 homocyst(e)ine-lowering strategies: (1) "treat all"-no screening, daily supplementation with folic acid (400 microg) and vitamin B(12) (cyanocobalamin; 500 microg) for all; (2) "screen and treat"-screening, followed by daily supplementation with folic acid and vitamin B(12) for individuals with elevated homocyst(e)ine levels. Simulated cohorts of 40-year-old men and 50-year-old women in the general population were evaluated. In the base-case analysis, we assumed that lowering elevated levels would reduce excess coronary heart disease risk by 40%; however, this assumption and others were evaluated across a broad range of potential values using sensitivity analysis. Primary outcomes were discounted costs per life-year saved.

Results: Although the treat-all strategy was slightly more effective overall, the screen and treat strategy resulted in a much lower cost per life-year saved ($13,600 in men and $27,500 in women) when compared with no intervention. Incremental cost-effectiveness ratios for the treat-all strategy compared with the screen and treat strategy were more than $500,000 per life-year saved in both cohorts. Sensitivity analysis showed that cost-effectiveness ratios for the screen and treat strategy remained less than $50,000 per life-year saved under several unfavorable scenarios, such as when effective homocyst(e)ine lowering was assumed to reduce the relative risk of coronary heart disease-related death by only 11% in men or 23% in women.

Conclusions: Homocyst(e)ine lowering with folic acid and vitamin B(12) supplementation could result in substantial clinical benefits at reasonable costs. If homocyst-(e)ine lowering is considered, a screen and treat strategy is likely to be more cost-effective than universal supplementation. Arch Intern Med. 2000;160:3406-3412.