Author + information
- †Cedars-Sinai Heart Institute, Los Angeles, California
- ‡Department of Cardiovascular Sciences, University of Leicester and National Institute of Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom
- ↵∗Reprint requests and correspondence:
Dr. Timothy D. Henry, Cedars-Sinai Heart Institute, 127 South San Vicente Boulevard, Suite A3100, Los Angeles, California 90048.
We have made remarkable progress in the treatment of ST-segment elevation myocardial infarction (STEMI) over the last 2 decades, mostly through the introduction of acute percutaneous coronary intervention (PCI). However, important issues remain, including how we should manage the approximate 40% to 60% of patients shown to have multivessel coronary artery disease (MVCAD). To date, clinicians presented with this common clinical problem have surprisingly little robust evidence-based guidance on optimal management. Until recently, most data came from observational studies, registries, or selected patients from randomized clinical trials designed to answer different questions. Based on these limited (and confounded) data, PCI of a noninfarct vessel in hemodynamically stable STEMI patients remains a Class 3 indication, meaning there is no evidence to support the practice and it may be harmful, despite the recent publication of a number of randomized trials showing benefit. In contrast, for STEMI patients with MVCAD and cardiogenic shock, complete revascularization has a Class 1 indication (1,2). It is perhaps this belief that multivessel PCI in higher-risk patients leads to better outcomes that potentially drives interventionalists to select sicker patients for this strategy; outcomes are then determined by the patients being sicker rather than as a result of the treatment strategy itself, with the consequence that biased patient selection and biased patient outcomes affect the guidelines. Large randomized trials are underway to determine whether multivessel PCI in the STEMI setting improves morbidity and mortality.
While we await their results, a different slant on the potential value of a complete revascularization strategy is provided by Jang et al. (3) in this issue of the Journal. They report the influence of complete versus culprit artery–only revascularization on quality of life (QoL) using data from 1,829 STEMI patients enrolled in the TRIUMPH registry (The Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status) at 24 U.S. hospitals from 2005 to 2008 (3).
What is actually meant by “QoL” and how important it is as a metric in clinical trials remain the topic of much debate. Although no one would doubt the importance of hard clinical endpoints, once the patient has experienced an event-free survival, most are seeking a good QoL. To some, this is spending time with family and friends, but to a significant proportion, relief of their debilitating angina is central. They value no longer having to stop unnecessarily whilst their pain subsides. On the other side, at times the lay public and healthcare professionals automatically afford QoL a status well beyond any comprehension of its definition, which can differ, and so it is of utmost importance that we understand exactly what is being measured. For example, QoL will be a different measure in patients with intellectual difficulties or where there are dependency issues.
In the current paper, the TRIUMPH study investigators used an established definition for symptom relief, the Seattle Angina Questionnaire with embedded angina frequency and QoL domains (scores range 0 to 100, with higher scores indicating less angina and better QoL) (3). However, determining the effect of any therapy or treatment strategy on QoL depends clearly on the quality of the source data, and herein lie 2 problems for this group—the overall lack of certainty that multivessel PCI is beneficial, and some inherent weaknesses in data available to these investigators.
In the 664 (36.3%) patients with multivessel disease, 251 (38%) had complete revascularization; including 70 (28%) during the initial PCI, 161 (64%) staged during the initial hospital setting, and 20 (8%) staged within the first 6 weeks following discharge. At 1-year post-STEMI, patients who underwent complete revascularization had less angina and improved QoL, but with no difference in mortality (low at 3.6% vs. 3.4%), recurrent myocardial infarction (3.5% vs. 1.4%), or repeat revascularization (7.5% vs. 9.1%). “Severe angina” (≥3 episodes/week) was present in only 4.4% of patients with multivessel PCI compared to 6.3% in culprit vessel–only patients. The patients’ health status was measured by the Seattle Angina Questionnaire at the time of STEMI and 1 year later; however, one-third of data were missing, and further, it is unclear whether “baseline” reflected 1 week before STEMI, time of STEMI, or the day after PCI (3). In addition, the data are nearly a decade old, with significant changes in practice patterns and outcomes for STEMI patients over that period. It emphasizes the importance of robust QoL proforma prospectively applied to robust trials.
Studies enrolling STEMI patients with MVCAD are challenging to design and conduct. Patients present acutely ill with considerable heterogeneity regarding myocardium at risk for both the culprit and nonculprit vessels. The severity and complexity of the lesion and comorbidities, such as renal disease, anemia, bleeding risk, and left ventricular function, all influence complex decision making. Additionally, it is not simply an issue of culprit-only versus complete revascularization; the timing of revascularization (same setting, same hospital stay, or staged as an outpatient), and presence or absence of ischemia (on the basis of symptoms, fractional flow reserve, or stress testing) require consideration. We thus are faced with important variables making it challenging to study even hard clinical endpoints in homogenous groups in a randomized trial, let alone QoL in a registry; how do you determine accurate prior baseline, for example, in the acutely presenting patient? Further, the event itself will change QoL in a heterogeneous way irrespective of the effect of any therapeutic comparisons.
Clearly, QoL is important to patients and their families after surviving an STEMI; yet, there are almost no data regarding health status in STEMI patients with MVCAD. Actually, we have insufficient data regarding QoL or angina in most patients undergoing PCI, with the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial being an exception (4). Therefore, Jang et al. (3) are to be congratulated in trying to pin down an important aspect of a difficult strategic consideration—if you undertake multivessel PCI at the time of STEMI do the patients feel better? Although the study is based on nonrandomized data (so the selection criterion for who underwent multivessel revascularization is uncertain), the paper provides interesting food for thought. One of the most fascinating results is the significant practice variation (from 0% to >70% revascularization at study sites). This remarkable variation likely reflects our as yet lack of robust evidence for this common but challenging patient population. What this group has done well is to highlight (again) that there is more to clinical research studies than hard endpoints, with QoL often felt to be “soft and unimportant”—something our patients (and families) would contest vigorously. Quality assessment of clearly defined markers of QoL in robust trials is imperative for the development of a holistic management strategy. These results remind us this should be an important goal for all clinical trials.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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