Newark Beth Israel Medical Center, Newark USA
* Correspondence to: Dr. Marc Cohen, Chief Division of Cardiology, Cardiac Cath Lab Administration, Newark Beth Israel Medical Center, 201 Lyons Avenue, Newark, New Jersey 07112, USA. Tel: +1 973-926-7852, Fax: +1 973-282-0839
E-mail address: marcohen{at}sbhcs.com
Received 28 October 2003; accepted 5 November 2003
See doi:10.1016/j.ehj.2003.11.002 for the article to which this editorial refers
A revolution has taken place. We are witnessing a time when medical intervention is quantitatively improving the clinical outcomes of diabetic patients. As physicians we knew that diabetic patients had a worse natural history than non-diabetics. As interventional cardiologists, we knew that diabetic patients suffer from much higher restenosis rates than non-diabetics. In fact over the past several years, there has been a movement to refer diabetics with multivessel coronary artery disease for coronary artery bypass surgery (CABG), and away from percutaneous coronary intervention (PCI).1
In this issue of the European Heart Journal, a very clear forward step has been announced regarding improving outcomes in diabetics undergoing PCI.2The RAVEL investigators analysed the restenosis rates and clinical outcomes of the 49 diabetic patients from their original trial involving 238 patients comparing sirolimus eluting stents (SES), to bare metal stents. In the 19 diabetic patients who received a SES, there was a 0% restenosis rate! In comparison, the restenosis rate in the 20 diabetic patients who were randomized to receive a bare metal stent was 42%. For the most part, the methodology and conclusions from this RAVEL, post-hoc, subgroup analysis appear sound. However, the restensosis rate in the RAVEL diabetic control group, was relatively high compared to the restensosis rates in diabetics in the EPISTENT or SIRIUS trials,3which were in the 2023% range. However, remember that in the higher risk, E-SIRIUS study4that enrolled patients with smaller vessels and longer lesions, the target lesion revascularization rate was also 42%.
The conclusions derived from the RAVEL sub-study appear to be supported by two larger, recently published trials, SIRIUS,3and E-SIRIUS.4Both of these studies were prospective, blinded, randomized comparisons of SES versus bare metal stents. In these studies roughly 25% of the randomized patients were diabetic, and the restenosis rates in the group that received SES was remarkably low, about 4.0%. In the SIRIUS trial 279 of 1058 patients were diabetic. The rate of target lesion revascularization in the diabetic patients who received SES compared to bare metal stents was 6.9% vs 22.3%. This contrasts somewhat with the 0% vs 42% in the RAVEL subgroup analysis but the bottom line is the same: SES drastically reduces restenosis in diabetic patients!
Several questions however, remain unanswered. (1) Is there still a role for glycoprotein IIb/IIIa receptor blockers during PCI of elective diabetic patients?5The excellent result observed in the RAVEL diabetic subgroup treated with SES was achieved with GP IIb/IIIa receptor blockade being administered to only one patient. Keep in mind that every patient in the RAVEL study had a loading dose of 300mg of clopidogrel at least 48h prior to the PCI. The recently presented results from the ISAR REACT trial seem to parallel this experience. (2). Is CABG no longer the automatic path for diabetics with multivessel coronary disease? Based on the RAVEL, SIRIUS, and E-SIRIUS data, I think it is appropriate to consider PCI as initial therapy for diabetic patients with single vessel disease, and to reconsider PCI as initial therapy for diabetic patients with multivessel coronary disease. The FREEDOM trial should address this question in a more definitive manner. (3) The last question is which patients are diabetic, and which are not? Do the results of RAVEL and the pair of SIRIUS trials apply to non-insulin dependent as well as insulin requiring diabetics? Would patients who are only in the insulin resistance-metabolic syndrome phase enjoy the same dramatic results as those who declared they were frankly diabetic on the RAVEL case report form?
References
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