Lowering homocysteine does not reduce CVD (HOPE 2)
Clinical Question:<!–
D([“mb”,”\u003c/h3\u003e\n\u003cp\u003e\n Is supplementation to lower homocysteine levels an effective treatment for cardiovascular disease \nor disease prevention?\n\u003c/p\u003e\n\n\u003ch3\u003eBottom Line:\u003c/h3\u003e\n\u003cp\u003e\n Supplementation with folic acid and B vitamins is ineffective for adults 55 years and older with \nknown cardiovascular disease (CVD) or diabetes. A second report in the same issue found that \nsimilar supplementation in patients with a recent acute myocardial infarction was not helpful and \nmay actually increase the risk of a bad cardiovascular outcome (relative risk \u003d 1.22; 95% CI, 1.0 – \n1.5). \u003ca href\u003d\”http://www.infopoems.com/levels.html\” target\u003d\”_blank\” onclick\u003d\”return top.js.OpenExtLink(window,event,this)\”\u003e(LOE \u003d 1b)\u003c/a\u003e\n\u003c/p\u003e\n\n\u003ch3\u003eReference:\u003c/h3\u003e\n\u003cp\u003e\n \u003ca href\u003d\”http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd\u003dRetrieve\u0026amp;db\u003dPubMed\u0026amp;list_uids\u003d16531613\u0026amp;dopt\u003dAbstract\” target\u003d\”_blank\” onclick\u003d\”return top.js.OpenExtLink(window,event,this)\”\u003eLonn \nE, Yusuf S, Arnold MJ, et al, for the Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. \nHomocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med \n2006;354:1567-1577.\u003c/a\u003e\n\u003c/p\u003e\n\n\u003cdiv\u003e\n\u003ch3\u003eStudy Design:\u003c/h3\u003e\n\u003cp\u003e\n Randomized controlled trial (double-blinded)\n\u003c/p\u003e\n\u003c/div\u003e\n\n\n\u003cdiv\u003e\n\u003ch3\u003eFunding:\u003c/h3\u003e\n\u003cp\u003e\n Government\n\u003c/p\u003e\n\u003c/div\u003e\n\n\n\u003cdiv\u003e\n\u003ch3\u003eSetting:\u003c/h3\u003e\n\u003cp\u003e\n Outpatient (any)\n\u003c/p\u003e\n\u003c/div\u003e\n\n\n\u003cdiv\u003e\n\u003ch3\u003eAllocation:\u003c/h3\u003e\n\u003cp\u003e\n Concealed\n\u003c/p\u003e\n\u003c/div\u003e\n\n\u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eSynopsis:\u003c/h3\u003e\n\u003cp\u003e\n An elevated level of homocysteine is an independent predictor of the risk of developing CVD. The \nleap that many physicians and patients have made (unsubstantiated by any evidence) is that lowering \nhomocysteine levels through the use of B vitamins and folic acid supplements will therefore prevent \nor treat CVD. The current study is the first to evaluate this hypothesis in a prospective, \nrandomized trial. The authors enrolled 5522 patients older than 54 years with known coronary, \ncerebrovascular, or peripheral vascular disease, or diabetes plus one additional risk factor for \nCVD. They then randomized the patients (allocation concealed) to receive either 2.5 mg folic acid, \n50 mg vitamin B6, and 1 mg vitamin B12 or matching placebo daily. Patients came from countries in \nwhich folate fortification of food is mandatory (United States and Canada) and not mandatory \n(Brazil, Western Europe, and Slovakia). Compliance with treatment was good: More than 90% and \npatients were followed up for a mean of 5 years. Groups were balanced at the start of the study and \nanalysis was by intention to treat. As expected, homocysteine levels dropped and vitamin levels \nincreased in the active treatment group. However, there was no difference between groups in the \ncombined risk of cardiovascular death, myocardial infarction, or stroke (18.8% vs 19.8%; relative \nrisk \u003d 0.95; 95% CI, 0.84 – 1.07). There was also no difference regarding this combination of \noutcomes in patients in the top tertile of homocysteine levels (23.9% vs 24%). There was no \ndifference in outcomes between countries that did or did not fortify foods with folate. Regarding \nindividual outcomes, there were slightly fewer strokes (4.0% vs 5.3%), but more hospitalizations \nfor unstable angina (9.7% vs 7.9%) with supplementation. The study was powered to detect a 17% to \n20% relative reduction in the risk of the primary outcome. A second report in the same issue of the \njournal also failed to find any benefit for secondary prevention of cardiovascular events in \npatients with a recent acute myocardial infarction (N Engl J Med 2006;345:1578-1588). In fact, they \nfound evidence of possible harm from B vitamin supplementation in this group of high-risk patients.\n”,1]
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Is supplementation to lower homocysteine levels an effective treatment for cardiovascular disease or disease prevention?
Bottom Line:
Supplementation with folic acid and B vitamins is ineffective for adults 55 years and older with known cardiovascular disease (CVD) or diabetes. A second report in the same issue found that similar supplementation in patients with a recent acute myocardial infarction was not helpful and may actually increase the risk of a bad cardiovascular outcome (relative risk = 1.22; 95% CI, 1.0 – 1.5). (LOE = 1b)
Reference:
Study Design:
Randomized controlled trial (double-blinded)
Funding:
Government
Setting:
Outpatient (any)
Allocation:
Concealed
Synopsis:
An elevated level of homocysteine is an independent predictor of the risk of developing CVD. The leap that many physicians and patients have made (unsubstantiated by any evidence) is that lowering homocysteine levels through the use of B vitamins and folic acid supplements will therefore prevent or treat CVD. The current study is the first to evaluate this hypothesis in a prospective, randomized trial. The authors enrolled 5522 patients older than 54 years with known coronary, cerebrovascular, or peripheral vascular disease, or diabetes plus one additional risk factor for CVD. They then randomized the patients (allocation concealed) to receive either 2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12 or matching placebo daily. Patients came from countries in which folate fortification of food is mandatory (United States and Canada) and not mandatory (Brazil, Western Europe, and Slovakia). Compliance with treatment was good: More than 90% and patients were followed up for a mean of 5 years. Groups were balanced at the start of the study and analysis was by intention to treat. As expected, homocysteine levels dropped and vitamin levels increased in the active treatment group. However, there was no difference between groups in the combined risk of cardiovascular death, myocardial infarction, or stroke (18.8% vs 19.8%; relative risk = 0.95; 95% CI, 0.84 – 1.07). There was also no difference regarding this combination of outcomes in patients in the top tertile of homocysteine levels (23.9% vs 24%). There was no difference in outcomes between countries that did or did not fortify foods with folate. Regarding individual outcomes, there were slightly fewer strokes (4.0% vs 5.3%), but more hospitalizations for unstable angina (9.7% vs 7.9%) with supplementation. The study was powered to detect a 17% to 20% relative reduction in the risk of the primary outcome. A second report in the same issue of the journal also failed to find any benefit for secondary prevention of cardiovascular events in patients with a recent acute myocardial infarction (N Engl J Med 2006;345:1578-1588). In fact, they found evidence of possible harm from B vitamin supplementation in this group of high-risk patients.
Atencion Primaria 