Newer is Better! New Generation DES outperform older DES and BMS

Abstract & Commentary

By Andrew J. Boyle, MBBS, PhD, Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco.

Source: Sarno G, et al. Lower risk of stent thrombosis and restenosis with unrestricted use of 'new-generation' drug-eluting stents: A report from the nationwide Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Eur Heart J 2012;33:606-613.

For those who perform percutaneous coronary intervention (PCI), the newer generation stents have obvious benefits during the procedure. Newer metal alloys with thinner struts and newer stent designs mean that the newest generation are lower profile and more flexible, and are thus more deliverable to where they need to go. In short, they make the procedure faster, easier, and less traumatic to the patients' coronary arteries. Newer antiproliferative drugs used on these stents have reduced the clinical event rate. The clinical trials that brought the newer drug-eluting stents (n-DES) to market showed equivalence or even superiority to the older generation of drug-eluting stents (o-DES) both in terms of in-stent restenosis (ISR) and stent thrombosis (ST). However, these pivotal clinical trials that brought the newer stents to market tend to enroll less complex coronary lesions than are seen in real-world practice. Furthermore, we are treating more and more complex patient populations as stent technology evolves. Thus, the clinical effectiveness of n-DES in the real world has not been fully defined. In this large registry study, the authors sought to determine the real-world safety and efficacy of bare metal stents (BMS), o-DES, and n-DES.

Using the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), the authors report on all cases of PCI performed in Sweden since the release of n-DES in 2006. This registry is compulsory for all patients undergoing PCI in Sweden and captures these patients wherever follow-up occurs throughout the country. The authors present data on more than 94,000 patients undergoing PCI during that time: 64,631 received BMS, 19,202 received o-DES, and 10,551 received n-DES. They defined o-DES as sirolimus-eluting Cypher, zotarolimus-eluting Endeavor, and paclitaxel-eluting Taxus stents, and n-DES as everolimus-eluting Xience, Xience Prime, Promus and Promus Element stents, and zotarolimus-eluting Endeavor Resolute stents. Patients were followed for 2 years after the index PCI in this study.

Overall, the clinical risk profile was higher in both DES groups than the BMS group, with no difference between the clinical risk profile of o-DES and n-DES. The one exception was that BMS were used more often in ST-elevation myocardial infarction. The baseline clinical and demographic data were similar between groups receiving BMS, o-DES, and n-DES. In addition, the procedural characteristics demonstrate that both DES groups were treating more complex lesions than the BMS group. After multi-variable adjustment for clinical and procedural variables, the use of n-DES was associated with lower rates of ISR, ST, and death compared not only with BMS, but also with o-DES.

The adjusted hazard ratio [HR] for ISR in the n-DES group compared to BMS was 0.29 and compared to o-DES was 0.62. The HR for definite ST (by the academic research consortium definition) in the n-DES group was 0.38 vs BMS and 0.57 vs o-DES. The HR for mortality in n-DES was 0.55 vs BS and 0.77 vs o-DES. All these HRs are statistically significant. The authors conclude that PCI with n-DES is associated with a 38% lower risk of clinically meaningful restenosis, a 43% lower risk of definite ST, and a 23% lower risk of death compared to o-DES in this observational study from a large real-world population.

Commentary

This is a compelling study presenting data from a very large cohort. It comes as no surprise that the use of n-DES is associated with lower rates of ISR. Some prior smaller randomized studies have shown lower rates of ST with some of the newer stents, but not all. It is reassuring to see that the ST rates in the real world are lower. The study is strengthened by the large number of patients enrolled, by the rigorous nationwide follow-up, and by linking the PCI registry with the national death database to ascertain accurate mortality figures. The authors also performed statistical adjustment for a large number of clinical and procedural variables, which strengthens their data further. However, there are several limitations to this study. First, these are retrospective observational data and thus there may be additional confounders that were not accounted for statistically. Second, the duration of, and the compliance with, dual antiplatelet therapy was not stated. This may have a significant effect on the rates of ST and death. Third, whether data from a single European nation can be extrapolated to the heterogeneous U.S. population is not known. Fourth, there was not complete angiographic follow-up, as there often is in prospective studies. Patients were referred for repeat angiography and/or PCI for clinical indications, thus the authors' use of the term "clinically meaningful restenosis" in their conclusion. I don't see that as a significant limitation as that is what we all do in routine clinical practice.

The role of large registries like this one is controversial. We generally consider randomized, controlled trials to be the ultimate in clinical evidence. However, randomized, controlled trials are rarely large enough to compare three treatments like this study does, they usually have many exclusion criteria and that limits their generalizability, and they are often (by necessity) funded by industry. This government-funded large registry, and others like the ACC National Cardiovascular Data Registry, provide important data that never can, nor will, be tested in randomized trials. Large registries, therefore, remain the best way to address certain questions in real-world populations. This study by Sarno and colleagues tells us that the evolution of our PCI technology is saving lives and reducing repeat procedures. A formal cost-effectiveness study based on these data would be most welcome and would likely make an even more compelling case for n-DES in this era of health care reform.