Dietary prevention of postangioplasty restenosis

Patients treated with percutaneous transluminal coronary angioplasty (PTCA) have a high (15 to 50 per cent, depending on studies) risk of developing restenosis within the first 6 months after the procedure. At present, with the exception of stents coated with antifibrotic substances113 and probucol (the later with many unacceptable side effects), there is no drug treatment to prevent that complication. On the other hand, a dietary approach with either n-3 fatty acid or folate supplementation has been proposed.

Several small studies have indeed suggested that supplementation with n-3 fatty acids may inhibit restenosis. However, recent larger trials set up to prove that effect failed to do so.114-116 In the Coronary Angioplasty Restenosis Trial, in particular, 500 patients were randomly allocated to 5 g per day of a fish oil concentrate or placebo (corn oil) from at least 2 weeks before until 2 months after PTCA.116 Compliance was documented by measuring the content of n-3 fatty acids in the blood, and patients receiving n-3 fatty acids had a significant reduction in serum triglyceride levels. However, no effect could be demonstrated on the restenosis rate or coronary atherosclerosis assessed by quantitative coronary angiography after 6 months of treatment.

It is noteworthy that in these negative trials, patients were treated with quite high doses of n-3 fatty acids, up to 8 g per day,115 and that no previous data did support the use of such doses in the prevention of CHD. In addition, these studies were all performed in patients having had conventional balloon PTCA, and there are no data on patients receiving any type of stent. One major limitation of the dietary approach of the prevention of restenosis is the theoretic requirement to start supplementation at least a few days before PTCA, while many PTCAs are now performed in emergency or during the sub-acute phase of AMI, with no time for a pre-stenting supplementation.

Finally, recent data suggest that high homocysteine levels could be associated with restenosis and accelerated atherosclerosis117,118 and a combination of folic acid, vitamin B12 and pyridoxine (known to decrease homocysteine levels) was shown to reduce the rate of restenosis in a double-blind randomised trial.118 In that trial, the need for revascularisation was also significantly lower in patients receiving the treatment (10.8 per cent vs. 22.3 per cent). This underlines the potential clinical benefit of the dietary approach of the prevention of restenosis and should be compared with the data of the Lyon Diet Heart Study in which the patients randomised in the experimental group and following a Mediterranean diet, which is typically a folate-rich diet, also had a lower rate of restenosis after PTCA.60 Further studies are however needed to clarify which component of the vitamin cocktail of the Swiss trial118 was preventive and which dosage would be the most appropriate. The potential impact of dietary folates in the various clinical manifestations of CHD is also discussed in section 3.6.3 on 'endothelial dysfunction'.

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