J Interv Cardiol. 2004 Dec;17(6):375-85

Which parameter should be chosen as primary endpoint for randomized drug-eluting stent studies?

Silber S.

Dr. Muller Hospital, Munich, Germany.

In Europe, 1,108 percutaneous coronary interventions (PCIs) per one Mio inhabitants are currently annually performed, most of them with stent implantation. Drug-eluting stents have been the focus of attention of interventional coronary therapy since the RAVEL study was first presented in September 2001 at the European Society of Cardiology Meeting. Ever since, numerous studies have assessed the effects of various antiproliferative and anti-inflammatory substances and a variety of different stents was used as platform, either covered with polymer carriers of different chemical and physical properties or without a polymer carrier. CE- or FDA-certified drug-eluting stents are increasingly replacing the use of bare metal stents to reduce in-stent restenosis. Today, physicians have a choice of several approved drug-eluting stents and, therefore, need some evidence-based guidance through the "jungle of information" to make the right decisions. Even when focusing on randomized trials, differences between the studies regarding primary endpoints and sample sizes exist, making it difficult to compare the various drug-eluting stent studies. Randomized studies use either nonclinical (i.e., angiographic diameter stenosis, in-stent MLD, or in-stent late lumen loss) or clinical (i.e., TVF, TVR, and MACE) parameters as primary endpoints. Choosing an angiographic parameter as primary endpoint results in two major limitations: first, a significant improvement of an angiographic "surrogate" parameter does not necessarily translate into a better clinical outcome (DELIVER-I); second, conclusions regarding possible improvements of clinical outcome are underpowered, because the sample size calculation is based on the primary endpoint. Usually the number of patients needed is lower for angiographic than for clinical endpoints. Until today, only three trials with a primary clinical endpoint have shown a significantly positive impact on patients' outcome: the SIRIUS trial (Cypher stent) with its reduction of primary endpoint TVF (21.0% vs 8.6%), the TAXUS-IV trial (Taxus stent) with its reduction of primary endpoint TVR (12.0% vs 4.7%) and TAXUS-VI in long lesions with its reduction of primary endpoint TVR (19.4% vs 9.1%). Although the angiographic results of other drug-eluting stents are encouraging, they will have to prove their clinical impact based on adequately powered randomized trials with a primary clinical endpoint at an adequate time interval.

PMID: 15546289