Why Is Intravascular Ultrasound Guidance Underutilized in Percutaneous Coronary Intervention?: It Is Not "All About the Benjamins".

Abstract

HomeCirculation: Cardiovascular Quality and OutcomesVol. 14, No. 5Why Is Intravascular Ultrasound Guidance Underutilized in Percutaneous Coronary Intervention?: It Is Not “All About the Benjamins” Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessEditorialPDF/EPUBWhy Is Intravascular Ultrasound Guidance Underutilized in Percutaneous Coronary Intervention?: It Is Not “All About the Benjamins” Khanjan B. Shah, MD, MPH and David J. Cohen, MD, MSc Khanjan B. ShahKhanjan B. Shah Division of Cardiology, Department of Medicine, University of Florida, Gainesville (K.B.S.). Search for more papers by this author and David J. CohenDavid J. Cohen David J. Cohen, MD, MSc, Cardiovascular Research Foundation, 1700 Broadway, New York, NY 10019. Email E-mail Address: [email protected] https://orcid.org/0000-0001-9163-724X Department of Cardiology, St Francis Hospital, Roslyn, NY and the Clinical Trials Center, Cardiovascular Research Foundation, New York, NY (D.J.C.). Search for more papers by this author Originally published18 May 2021https://doi.org/10.1161/CIRCOUTCOMES.121.007844Circulation: Cardiovascular Quality and Outcomes. 2021;14:e007844This article is a commentary on the followingIntravascular Ultrasound Versus Angiography-Guided Drug-Eluting Stent Implantation: A Health Economic AnalysisSee Article by Zhou et alSince its introduction by Gruentzig >40 years ago, percutaneous coronary intervention has been guided by coronary angiography. Angiography has many critical limitations, however, including reliance on 2-dimensional imaging, limited spatial resolution, and inability to fully characterize plaque morphology. Intravascular imaging modalities, such as intravascular ultrasound (IVUS) and optical coherence tomography, allow for more accurate determination of lesion severity, vessel dimensions for optimal stent sizing, and lesion morphology, which can guide the use of adjuvant therapies such as atheroablation.Notwithstanding the advantages of intravascular imaging over angiography alone, evidence of important clinical benefits of these techniques was lacking until recently. Although numerous randomized controlled trials of IVUS-guided percutaneous coronary intervention (PCI) had been performed in a variety of lesion subsets, virtually all of these studies were inconclusive—due, at least in part, to small sample sizes, patient selection, and limited follow-up.1–3 Recently, however, several studies have demonstrated clear clinical benefits of IVUS-guided PCI including the ULTIMATE (Intravascular Ultrasound Guided Drug-Eluting Stents in All-Comers Coronary Lesions) trial, which demonstrated improved outcomes including stent thrombosis and target vessel revascularization (TVR) at 3 years in an all-comers population undergoing drug-eluting stent implantation.4 These benefits were subsequently reinforced by a meta-analysis including randomized controlled trials and observational studies that demonstrated lower rates of cardiovascular death, myocardial infarction, TVR, and stent thrombosis with use of IVUS guidance.5 Despite this growing body of evidence, in much of the world (including the United States), IVUS-guided PCI remains relatively infrequent with recent estimates suggesting that it is used in only ≈10% of all PCI procedures.6 Although numerous explanations have been suggested for this low rate, one common theme among critics of intravascular imaging has been the incremental cost of this approach and a corresponding lack of evidence on its cost-effectiveness.In this issue of Circulation: Cardiovascular Quality and Outcomes, Zhou et al7 provide important new insight into the costs, benefits, and overall value of IVUS guidance for patients undergoing PCI from the perspective of the Australian health care system. The study was based on a state-transition (Markov) model, which was used to simulate the short and long-term outcomes of a hypothetical 66-year-old patient undergoing PCI with or without IVUS guidance. Through a series of linked mathematical equations, the model projects relevant clinical outcomes, including death, stent thrombosis, myocardial infarction, and TVR, and estimates costs and quality-adjusted life years (QALYs) for the 2 strategies over a lifetime horizon.One of the key attributes of a decision-analytic model is that it allows the investigators to synthesize data from a variety of sources. Appropriately, Australian PCI registry data were used as the basis for event rates after PCI in the angiography-guided approach. To project event rates for the IVUS-guided approach, the authors performed a fixed-effects meta-analysis of 12 relevant randomized controlled trials of IVUS-guided versus angiography-guided PCI to estimate the relative risk of each outcome. The additional costs of IVUS-guided PCI (including the IVUS catheter as well as the additional procedural time and resource utilization required for lesion optimization) were assessed from the perspective of the Australian health care system using a variety of data sources.As in virtually all model-based studies, it is critical to understand the specific assumptions on which the model is based. In their study, Zhou et al made several key assumptions. First, they assumed that the clinical benefits of IVUS extend up to 2 years—an assumption that is justified based on recently published data from both the ULTIMATE and IVUS-XPL trials.4,8 The second is that the impact of nonfatal myocardial infarction on both mortality and cost persists indefinitely, whereas the disutility of TVR is transient—a reasonable assumption that is based on numerous observational studies. Finally, the authors assumed that the lower risk of death observed in the randomized trials of IVUS-guided PCI is related solely to lower rates of stent thrombosis and TVR. This is a critical assumption that ensures that any mortality benefit of IVUS-guided PCI was not double counted in the model. Importantly, in areas of uncertainty, the authors generally made assumptions that were conservative with regard to the benefit of IVUS—thus strengthening the validity of their stuxsdy.The main results of the study were that for an all-comers PCI population, IVUS-guided PCI was projected to increase lifetime medical care costs by AUD$823 and to improve quality-adjusted life expectancy by 0.05 QALYs, resulting in an incremental cost-effectiveness ratio (ICER) of $17 539/QALY gained—a favorable value compared with the Australian willingness to pay threshold of AUD$50 000/QALY gained (since lower ICERs are better than higher ICERs). The cost-effectiveness of IVUS-guided PCI took ≈7 years to emerge and was driven both by improved long-term clinical outcomes and reduced downstream costs.Although these results were modestly sensitive to variations in certain model parameters (particularly the cost of IVUS), probabilistic sensitivity analysis, in which all modeling parameters were varied simultaneously, demonstrated that the ICER remained less than AUD$50 000/QALY gained in 99% of iterations, indicating a high degree of confidence in the study’s main findings. Moreover, when the authors performed a worst-case analysis in which all modeling assumptions including the duration of benefit of IVUS and the prognostic impact of nonfatal myocardial infarction were assumed to be time-limited, IVUS-guided PCI remained economically favorable with an ICER of AUD$36 651/QALY gained. Finally, the benefits of IVUS-guided PCI were projected to be most favorable in patients with complex coronary artery disease such as left main disease and long lesions. In these subgroups, adverse clinical events are more likely such that both the clinical and economic benefits of IVUS-guided PCI are magnified, resulting in more favorable ICERs compared with the all-comers population.These findings have several important implications. First, they demonstrate the value of formal economic modeling to understand the cost-effectiveness of a common medical procedure. By incorporating the best available data for treatment effects (in the form of a meta-analysis of contemporary randomized clinical trials) along with registry data to estimate the outcomes of standard treatment, Zhou et al have provided important new insights about the cost-effectiveness of IVUS guidance for PCI. Although their study was based specifically on the Australian health care system, there is little reason to think that these findings would not also apply to the United States and many other Western health care systems. As in most situations, the cost-effectiveness of IVUS guidance for PCI is driven largely by its clinical benefit and resulting QALY gains, which should be generalizable to other health care systems. Moreover, since hospitalization costs are generally higher in the United States than in Australia, it is likely that cost offsets related to adverse events would be even greater, leading to even more favorable ICERs. Finally, it is worth noting that the cost-effectiveness of IVUS modeled in this article is better than the cost-effectiveness of drug-eluting stents when first introduced.9Given these findings, the obvious question then becomes: why is IVUS not used routinely in the United States (or in much of the world)? Potential barriers to universal IVUS adoption are 2-fold. First, cost-effectiveness from a societal perspective must be distinguished from cost-effectiveness from the perspective of hospitals or individual physicians. In the United States, most hospitals (with the exception of the VA system) are reimbursed based on diagnosis-related groups, which do not provide incremental payments for the increased resource utilization associated with IVUS guidance. Additionally, hospitals are reimbursed per episode of care, which incentivizes repeat procedures. As such, hospitals incur the up-front incremental cost of IVUS but the third-party payor derives the downstream financial benefit. Data from Japan (where there is substantial hospital reimbursement for the use of IVUS and virtually all PCI procedures are guided by intravascular imaging) suggest that these differences in economic perspective may be a key barrier to increased use. This mechanism does not explain the reluctance of physicians who practice in public health care systems around the world to more widely embrace IVUS-guided PCI, however.Second, there are physician barriers to widespread IVUS use. In particular, many practicing interventional cardiologists may not be comfortable with the technical aspects of IVUS imaging and image interpretation.10 In addition, despite the growing evidence base, interventional cardiologists may also lack knowledge of or confidence in studies demonstrating the clinical benefits of IVUS. Most contemporary studies are from Asia, so interventional cardiologists in other regions may think that the clinical benefits do not apply to patients in their practice. Finally, although there is additional physician reimbursement for the use of IVUS in the United States, it is relatively modest in comparison to reimbursement for other activities. As such, some physicians may feel that the additional time required for IVUS acquisition and lesion optimization is not worth the trouble. The fact that the clinical benefits of IVUS (reduced stent thrombosis and target lesion revascularization) may occur months after the initial PCI procedure and few interventional cardiologists are aware of their long-term outcomes likely exacerbates this distortion.To overcome these barriers to adoption of IVUS-guided PCI, we suggest several potential solutions. First, additional data are needed to confirm the benefits of imaging guidance for PCI. Ideally, these trials would include patients from a broad range of health care environments, including Western Europe and North America. Two such trials, ILUMIEN-4 (Optical Coherence Tomography Guided Coronary Stent Implantation Compared to Angiography: a Multicenter Randomized Trial) (using optical coherence tomography) and IMPROVE (Impact on Revascularization Outcomes of Intravascular Ultrasound Guided Treatment of Complex Lesions and Economic Impact) (using IVUS), are currently ongoing in the United States.11,12 If these trials demonstrate important clinical benefits, it is likely that both the United States and European PCI guidelines would strongly endorse imaging guidance, leading to substantially greater uptake of these approaches. Indeed, if the guidelines recognize the value of IVUS-guided PCI, this approach should be adopted as a quality metric used in programmatic evaluation at both the institutional and provider level. Third, practicing interventional cardiologists should participate in continuing medical education to become facile in IVUS interpretation and PCI optimization. Ongoing improvements in functionality of imaging software should lead to greater adoption as well. Finally, in recognition of the cost-effectiveness of IVUS-guided PCI, third-party payers should increase reimbursement at both the hospital and physician levels to align incentives for improved patient care.It has taken >2 decades, but it appears that the evidence in favor of IVUS-guided PCI is close to reaching critical mass. In this light, the study by Zhou et al highlighting the favorable cost-effectiveness of this approach represents another important piece of evidence supporting the value of this technology. If these findings are confirmed in the ongoing ILLUMIEN-4 and IMPROVE trials, we can safely conclude that—to paraphrase the rapper Puff Daddy—our failure to adopt imaging-guided PCI is not "all about the Benjamins".Sources of FundingNone.Disclosures Dr Cohen reports research grant support from Abbott, Boston Scientific, Medtronic, Edwards Lifesciences, Phillips, Svelte; Consulting income from Abbott, Boston Scientific, Medtronic, Edwards Lifesciences, Svelte. The other author reports no conflicts.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.David J. Cohen, MD, MSc, Cardiovascular Research Foundation, 1700 Broadway, New York, NY 10019. Email [email protected]org