Björkegren K. Future combinations for future trials. Rondel 2001: 7: Editorial (www.rondellen.net, April-June 2001)
The sad message from Dr Hultdin was that ongoing trials of homocysteine lowering will turn out inconclusive concerning risk reduction for vascular events (1). Consequently, Dr Lökk suggested that a future trial should be restricted to patients with established coronary artery disease, aged 70-75 years (2); such patients appeared easier to evaluate than other groups.
Dr Lökk also suggested that homocysteine lowering should be made by oral high-dose cyanocobalamin (Behepan, 1 mg daily) and oral high-dose folic acid (Folacin, 5 mg daily).
One main point of Dr Lökk was that the manufacturer of the leading brands of oral high-dose cyanocobalamin and oral high-dose folic acid should be approached for negotiations concerning the supply of cyanocobalamin and folic acid and corresponding placebo tablets for a future conclusive trial of a possible vascular risk reduction by homocysteine lowering; many previous trials have collapsed due to supply failure (2).
My main objection to the suggestions of Dr Lökk (2) is that a future combination of B vitamins should be designed for future clinical use. Furthermore, the two or three vitamins of the combination should be combined in one tablet for the convenience and compliance of the patients.
From such considerations, I suggest that the leading manufacturer (Pharmacia) is asked if it is possible for the company to provide the researchers with a combination tablet and its corresponding placebo tablet. The proposed composition of a combined tablet might be cyanocobalamin 1 mg and folic acid 1 mg. Alternative combinations might be subject to negotiations with the company.
The proposed combination corresponds to the analyses performed previously in The Rondel (3-5). A conclusive trial of the effect on vascular risk of homocysteine lowering is urgent. If a suitable combination tablet cannot be found, the old reliable Behapan and Folacin will serve well for homocysteine lowering by oral high-dose cyanocobalamin and oral high-dose folic acid.
No one challenges B vitamin treatment in deficiency states. The role of homocysteine as a deficiency marker is established. A role of homocysteine as a causal risk factor for vascular disease remains to be demonstrated.
Dr Karin Björkegren
Department of Primary Health Care
University Hospital
SE-751 85 Uppsala
Sweden
karin.bjorkegren@pubcare.uu.se
References
Published April 22, 2001