Dietary prevention of post-angioplasty restenosis. From illusion and disillusion to pragmatism

Prevention of restenosis and major cardiac events after percutaneous coronary intervention (PCI) is of enormous public health importance. Despite the considerable decrease in the restenosis rate in relation to the advent of the drug-eluting stents, it is likely that the complication will still occur in some patients and/or after a certain delay. Thus, dietary or systemic drug prevention will probably have a role in the drama in the future, although the way they can be used is not clear at present. This discussion focuses on the dietary approach of post-PCI restenosis because, among the many drugs that have been tested, none has been consistently shown to be helpful—with the exception of the potent antioxidant drug probucol—, whereas the results of several dietary trials have been encouraging. As discussed in the present issue of NMCD, vitamins of the B group were recently shown to decrease the risk of restenosis, supposedly through an effect on homocysteine metabolization. It seems, however, that homocysteine is a minor risk factor of post-PCI restenosis. On the other hand, 5-methyltetrahydrofolate (the active form of folic acid) was shown to improve endothelial function independently from homocysteine. Thus, folic acid could prevent restenosis not only by reducing homocysteine, but also by promoting nitric oxide formation. Because of their potential to prevent post-PCI restenosis and acute cardiac complications, n-3 fatty acids have been the most widely studied post-PCI medical intervention. Taken together, trial data suggest that if n-3 fatty acids can be useful in certain populations to prevent restenosis, their effects are probably weak. However, according to recent studies on endothelial nitric oxide synthase (eNOS) gene polymorphisms, it is likely that only certain patients could benefit from n-3 fatty acid supplementation. The same reasoning can probably apply to the folic acid and eNOS issue. In conclusion, although none has been concluding, the studies about n-3 fatty acids and folic acid after PCI suggest that certain nutrients (or more probably a combination of nutrients) may be useful for the prevention of post-PCI restenosis. Any future trial involving these nutrients should combine them and take into account some major genetic confounders. In the meantime, it is medically and ethically justified to supplement our CHD patients after PCI. They should receive n-3 fatty acids to prevent sudden cardiac death, and B group vitamins (at the dosages tested in the Swiss Heart Study) to decrease the risk of restenosis. This would be, at least, a low cost intervention, and there is no fear of adverse side effects, contrary to those one can expect from drug treatments.