Strengths and Limitations of Real World Data in Patients Treated With Coronary Stents

HomeCirculation: Cardiovascular InterventionsVol. 11, No. 9Strengths and Limitations of Real World Data in Patients Treated With Coronary Stents Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBStrengths and Limitations of Real World Data in Patients Treated With Coronary Stents Robert A. Byrne, MB, BCh, PhD, Roisin Colleran, MB, BCh and Adnan Kastrati, MD Robert A. ByrneRobert A. Byrne Robert A. Byrne, MB, BCh, PhD, Deutsches Herzzentrum München, Klinik an der Technischen Universität München, Lazarettstrasse 36, Munich 80636, Germany. Email E-mail Address: [email protected] Deutsches Herzzentrum München, Technische Universität München, Munich, Germany (R.A.B., R.C., A.K.). DZHK (German Centre for Cardiovascular Research), Munich Heart Alliance, Germany (R.A.B., A.K.). , Roisin ColleranRoisin Colleran Deutsches Herzzentrum München, Technische Universität München, Munich, Germany (R.A.B., R.C., A.K.). and Adnan KastratiAdnan Kastrati Deutsches Herzzentrum München, Technische Universität München, Munich, Germany (R.A.B., R.C., A.K.). DZHK (German Centre for Cardiovascular Research), Munich Heart Alliance, Germany (R.A.B., A.K.). Originally published17 Sep 2018https://doi.org/10.1161/CIRCINTERVENTIONS.118.007239Circulation: Cardiovascular Interventions. 2018;11:e007239This article is a commentary on the followingUnselected Use of Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Coronary RevascularizationSee Article by Yamaji et alDrug-eluting stents have had a major impact on the treatment of patients with obstructive coronary artery disease.1 Although early generation devices were effective at reducing the risk of restenosis compared with bare metal stents, there was clear evidence of an increased risk of stent thrombosis beyond 1 year after implantation, a serious adverse event leading to major myocardial infarction and death.2 However, newer generation devices with iterative improvement of stent design have addressed this safety issue. As a result, newly published clinical practice guidelines in Europe state that drug-eluting stents are recommended over bare metal stents for all interventions irrespective of clinical presentation, lesion type, whether or not noncardiac surgery is planned, and independent of the anticipated duration of dual antiplatelet therapy and requirement for concomitant anticoagulant therapy.3Important differences in the regulatory approval processes between Europe and the United States mean that the number of stents approved for use in the United States is far less than the number in Europe. A Task Force report published in 2015 identified 29 stents approved for use in Europe.4 By way of comparison, just 5 devices are approved for use in the United States at present. Interestingly, however, approval processes for medical devices are undergoing considerable change in both regions, with a tightening of processes in Europe and a less restrictive approach being adopted by the Food and Drug Administration.5 Indeed, a number of new generation drug-eluting stents are undergoing regulatory evaluation for United States approval at the moment and data with one of these devices—the biodegradable polymer sirolimus-eluting stent (SES, Orsiro; Biotronik, Bülach, Switzerland) is the subject of a study in the current issue of the journal.6In that study Yamaji et al6 present data from a large, single-center registry comparing the outcomes of patients treated with the new generation biodegradable polymer SES compared with those of patients treated with durable polymer everolimus-eluting stents.6 Overall, 4638 patients were treated with the devices over a period of just >4 years. After propensity-score matching of 2902 patients, the main finding was that the primary end point of interest—a composite of cardiac death, target vessel myocardial infarction, and target lesion revascularization (TLR)—was comparable in both treatment groups at 1 year: 6.9% with SES versus 8.0% with everolimus-eluting stents (hazard ratio, 0.85; 95% CI, 0.65–1.11). Other important clinical end points were observed with comparable frequency in both groups.A number of features of the report deserve closer attention. First, although randomized clinical trials are considered the highest standard of evidence for treatment comparisons, real-world registry data has an important complementary role, extending the validity of observations from selected patients included in trials to the patients treated in routine clinical practice. That the patients included in this study are more complex than those of patients included in a recent United States approval study of the SES (which itself had broad inclusion criteria) can be seen at a glance (Figure).6,7 Baseline risk factors speak to a higher risk profile, and the rate of clinical events and overall mortality at 1 year is considerably higher in the registry study. An exception to the trend was myocardial infarction, which was higher in the approval trial, largely because of a higher rate of periprocedural infarction (Figure). This is likely explained by the definition and adjudication of events rather than an excess of clinically relevant events. In terms of comparisons between the 2 stents, broadly concordant findings were seen in both investigations. This gives us confidence on the generalizability of the approval study results. Moreover, individual clinical trials have consistently showed similar clinical performance between these 2 devices with little evidence of heterogeneity of the treatment effect.8Download figureDownload PowerPointFigure. Comparison of selected baseline characteristics (A) and clinical outcomes (B) of patients enrolled in the CARDIOBASE Bern PCI registry6 and the BIOFLOW V clinical trial.7 CABG indicates coronary artery bypass surgery; MI, myocardial infarction; ST, stent thrombosis; and TLR, target lesion revascularization.Second, the design of the registry is of interest. At the institution where patients were treated, the type of stent used is determined by the day of the week, and the choice is independent of who the patient or operator is. This is a worthwhile strategy to reduce allocation bias. However, although such an approach has also been used in clinical trials with drug-eluting stents,9 it is no substitute for a randomized assignment because treatment allocation is not concealed and bias might be introduced by knowledge of the device available for use on a particular day. Indeed, in the study of Yamaji et al6 this method did not circumvent the need to do propensity score matching to account for differences in baseline risk between the treatment groups.Third, the end points assessed were well chosen. Indeed, the primary end point is the preferred end point for evaluation of coronary stents, favored by academic and regulatory authorities.4,10 Moreover, a robust definition of myocardial infarction was used, reducing the representation of smaller, prognostically less important periprocedural infarctions (Figure [B]), which can reduce the signal-to-noise ratios of clinical trials. Finally, stent thrombosis was adjudicated in detail, and TLR was the chosen parameter of efficacy. Indeed, in our opinion, the use of TLR remains preferable to ischemia-driven TLR, which is frequently used in clinical trials. First, all TLR events are serious adverse events, exposing the patient to risk of periprocedural myocardial infarction and bleeding, additional antithrombotic therapy and ultimately a small but measurable risk of death. Second, the risk of bias introduced by the judgment of the treating physician who decides to do TLR must be weighed against the risk of bias is introduced by post hoc adjudication of events.At the same time, when interpreting the findings of the report, a number of limitations must be borne in mind. First, >6% of patients had data missing at 1-year follow-up. This is important to consider when interpreting rates of rarely occurring end point in the registry, such as cardiac death (2.3% with SES versus 3.0% with everolimus-eluting stents). Second, inclusion of noninferiority hypothesis testing is not usual in the setting of nonrandomized data sets and the reason for its use is not well described. Noninferiority investigations are of greater interest for industry trials aimed at regulatory approval because "as good as" can be sufficient for approval. However, physician-initiated studies are generally focused on elucidating differences in treatments or marginal advantages for patient care.11 Third, the follow-up period of the study was short and longer-term surveillance would be important to see if advantages for 1 device emerge over time. At the same time, randomized trials with 5-year follow-up have thus far failed to show any evidence of superiority for stents with self-degrading polymer compared with new generation permanent polymer stents and many doubt that any advantage exists.12–14 Expected results from trials with up to 10-year follow-up will shed more light on this issue.DisclosuresDr Byrne reports lecture fees/honoraria from B. Braun Melsungen AG, Biotronik, Boston Scientific and Micell Technologies and research grants to the institution from Boston Scientific and Celonova Biosciences. The other authors report no conflicts.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.https://www.ahajournals.org/journal/circinterventionsRobert A. Byrne, MB, BCh, PhD, Deutsches Herzzentrum München, Klinik an der Technischen Universität München, Lazarettstrasse 36, Munich 80636, Germany. Email [email protected]mhn.deReferences1. 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Circulation: Cardiovascular Interventions. 2018;11 September 2018Vol 11, Issue 9 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/CIRCINTERVENTIONS.118.007239PMID: 30354605 Originally publishedSeptember 17, 2018 Keywordsdrug-eluting stentssirolimus-eluting stentsEditorialsbiodegradable polymerrandomized trialregistrycoronary artery diseasePDF download Advertisement SubjectsCatheter-Based Coronary and Valvular Interventions