Rational Pharmacotherapy in Cardiology

Advanced search


Full Text:


Background. Vitamins В6 В12 and folic acid (FA) therapy to reduce cardiovascular risk appears to be unreasonable. Negative results of recent large-scale trials might be due to high daily doses of the vitamins and widespread FA fortification programmes. Russian population is known to have high prevalence of FA and vitamin B12 deficiency. Aim. To evaluate the effect of FA, B6 and B12 vitamins (in doses approximate to daily maintenance) on long-term prognosis after elective percutaneous coronary intervention (PCI) in stable ischemic heart disease patients. Material and methods. 264 patients (213 male, age 58.8±1.0 years) after successful PCI were involved into the trial. Patients with clinical signs of the vitamins deficiency were not included. Patients were randomly assigned to receive combination of FA (0.6 mg/day), B12 (10 μg/day), and B6 (4 mg/day) vitamins along with the conventional therapy (n=97) or the conventional therapy only (n=167) for 20 months. The groups were comparable in age, gender and prevalence of coronary risk factors. Composite endpoint was defined as cardiovascular death, acute coronary syndrome, stroke or transient is- chemic attack and need for coronary/carotid revascularization. Results. The vitamins prescription to all of the patients did not reduce composite endpoint incidence according to multivariable regression analysis (RR 0,7; 95%CI 0,4-1,4; p=0,3). Subgroup analysis showed significantly lower composite endpoint incidence in patients who received vitamins and had initially low B12 blood level (<260 pg/ml) as compared to the control group (RR 0.09; 95%CI 0.01-0.9; p=0.04). Conclusion. Treatment with FA, B and B vitamins improves prognosis after PCI in patients with initially low blood vitamin B level.

About the Authors

O. O. Shakhmatova
Russian Cardiology Research and Production Complex
Russian Federation

A. L. Komarov
Russian Cardiology Research and Production Complex
Russian Federation

A. N. Samko
Russian Cardiology Research and Production Complex
Russian Federation

T. I. Kotkina
Russian Cardiology Research and Production Complex
Russian Federation

D. V. Rebrikov
”DNA-Technology” Research and Production Company General Genetics Institute named after N.I. Vavilov
Russian Federation

A. D. Deev
State Research Center for Preventive Medicine
Russian Federation

E. P. Panchenko
Russian Cardiology Research and Production Complex
Russian Federation


1. McCully K.S. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969;56:111-128.

2. Wilcken D.E., Wilcken B. The pathogenesis of coronary artery disease. A possible role for methionine metabolism. J Clin Invest 1976;57:1079–1082.

3. Nygard O., Nordrehaug J.E., Refsum H. et al. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997;337:230–236.

4. Schnyder G., Flammer Y., Roffi M. et al. Plasma homocysteine levels and late outcome after coronary angioplasty. J Am Coll Cardiol 2002;40:1769-1776.

5. Durand P., Prost M., Loreau N. et al. Impaired homocysteine metabolism and atherothrombotic disease. Lab Invest 2001;81:645–672.

6. The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354:1567-1577.

7. Schnyder G., Roffi M., Flammer Y. et al. Effect of homocysteine-lowering therapy with folic acid, vitamin B12 and vitamin B6 on clinical outcome after percutaneous coronary intervention. The Swiss Heart Study: a randomized controlled trial. JAMA 2002;288:973-979.

8. Bonaa K.H., Njolstad I., Ueland P.M. et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006;354:1578-1588.

9. Albert C.M., Cook N.R., Gaziano J.M. et al. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk of cardiovascular disease: a randomized trial. JAMA 2008;299:2027-2036.

10. Clarke R., Armitage J., Lewington S. et al. Homocysteine-lowering trials for prevention of vascular disease: protocol for a collaborative meta-analysis. Clin Chem Lab Med. 2007;45:1575-1581.

11. Kothekar M.A. Homocysteine in cardiovascular disease: A culprit or an innocent bystander? Indian J Med Sci 2007;61:361-371.

12. Homocysteine, folic acid and B vitamins as secondary prophylaxis. A commentary on current therapy trials by Olaf Stanger. (German, Austrian, and Swiss Homocysteine Society). Available on:

13. Shakhmatova O.O., Komarov A.L., Rebrikov D.V. et al. Factors determining homocysteine level in Russian patients with stable coronary heart disease. Cardiovascular therapy and prevention. 2010; 4:49-58. Russian (Шахматова О.О., Комаров А.Л., Ребриков Д.В. и др. Факторы, определяющие уровень гомоцистеина, в когорте российских пациентов со стабильной ИБС. Кардиоваскулярная терапия и профилактика, 2010; 4: 49-58).

14. Kaul S., Zadeh A.A., Shah P.K. Homocysteine Hypothesis for Atherothrombotic Cardiovascular Disease: Not Validated. J. Am. Coll. Cardiol. 2006;48;914-923.

15. Volkov I., Rudoy I., Machagna M. et al. Modern society and prospects of low vitamin B12 intake. Ann Nutr Metab. 2007;51:468-470.

16. Boden W.E., O'Rourke R.A., Teo K.K. et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007;356:1503-1516.

17. Carmel R. How I treat cobalamin (vitamin B12) deficiency. Blood 2008;112:2214-2221.

18. Lechner K., Födinger M., Grisold W. et al. Vitamin B12 deficiency. New data on an old theme. Wien Klin Wochenschr. 2005;117:579-591.

19. Lee M, Hong K.S, Chang S.C, Saver J.L. Efficacy of homocysteine-lowering therapy with folic Acid in stroke prevention: a meta-analysis. Stroke. 2010; 41(6):1205-1212.

For citation:

Shakhmatova O.O., Komarov A.L., Samko A.N., Kotkina T.I., Rebrikov D.V., Deev A.D., Panchenko E.P. HOMOCYSTEINE-LOWERING THERAPY AND LONG-TERM PROGNOSIS AFTER ELECTIVE PERCUTANEOUS CORONARY INTERVENTION. Rational Pharmacotherapy in Cardiology. 2011;7(5):524-535. (In Russ.)

Views: 485

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)