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Complete Revascularization in Multivessel CAD Remains Vexing
Experts discuss benefits, drawbacks of complete revascularization for multivessel disease and STEMI.
Patients with multivessel CAD are at higher risk for worse short- and long-term outcomes after STEMI. Although primary PCI is the preferred treatment for STEMI, questions persist about how to approach revascularization in patients with STEMI in one lesion and at least one nonculprit lesion.
Recent data from clinical trials, including CvLPRIT, PRAMI and DANAMI3-PRIMULTI, indicate that complete revascularization may be beneficial. Some evidence also suggests that performing the procedure in multiple stages — addressing the culprit lesion during the index procedure and treating the nonculprit lesions during a separate procedure — may lead to better outcomes. Additionally, an update to the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guideline on primary PCI in patients with STEMI now gives a class IIb recommendation, as opposed to a class III recommendation, to stenting nonculprit lesions in patients who are hemodynamically stable.
Even so, physicians must consider multiple factors, such as patient characteristics and complexity of lesions, before deciding to pursue complete revascularization.
Four experts in the field — Lloyd W. Klein, MD; Deepak L. Bhatt, MD, MPH; Eric R. Bates, MD; and Anthony H. Gershlick, MD — spoke with Cardiology Today’s Intervention to give insight into this complicated issue.
Q: What is your current approach and what guidance do you have for others?
Until 5 years ago, the guidelines and clinical studies were very clear that pursuing nonculprit lesions was risky at STEMI presentation and led to worse outcomes. There was also evidence from COURAGE that lesions which were not clinically active might be managed medically. More recently, results from small randomized trials, such as PRAMI and CvLPRIT, suggest that complete revascularization may be beneficial in patients with STEMI and multivessel disease.
However, we must put the trials into perspective. First, despite being randomized, they involved selected patients at the time, and we do not fully understand how they were selected. Second, the data have not shown a benefit in terms of MI or death individually. They have shown an improvement in MACE, but that is primarily driven by urgent revascularization. Third, the culprit-only arm was generally based on development of symptoms as opposed to early detection by stress testing, which is what the guidelines suggest. It is also interesting to note that the studies do not show that complete revascularization prevents MI in the short term.
There are substantial problems with these new trials, including the use of composite endpoints without significance relating to death and MI, and lack of differentiation among timing of PCI strategies. Multiple meta-analyses show markedly different results, and the new trials include fewer than 800 total patients.
The data are also less clear on the benefit of performing complete revascularization in one stage vs. multiple stages because the studies are not exactly comparable. For instance, CvLPRIT evaluated both an index procedure and a staged procedure during index hospital admission while PRAGUE 13 evaluated an index and post-discharge staged procedure. This highlights a major problem in the field: There are multiple rational treatment strategies for complete revascularization, and it is difficult to design a trial that compares all of them.
Another issue is the potential for performing unnecessary procedures. COMPARE-ACUTE shows that as many as 56% of nonculprit lesions are overestimated at the time of index PCI.
Ultimately, the new guidelines and updated appropriate use criteria leave the decision to perform complete revascularization up to the clinician’s judgment, which I think is best at this time. Personally, I have performed complete revascularization in the most concerning patients; in some I have performed the PCI before hospital discharge; and in others I’ve brought patients back several weeks after the initial procedure. In my view, there is no single right strategy that covers everyone. Each patient must be evaluated individually.
At present, clinician judgment is key. Ultimately, the complexity of the patient, the complexity of the lesion and other logistical factors, such as time of the primary PCI, all must inform the decision about optimal timing and need for completing revascularization.
There have been a lot of provocative data, particularly from medium-sized randomized clinical trials, that, in aggregate, support the concept of complete percutaneous revascularization vs. culprit-only revascularization in the setting of STEMI, even in patients who are not in cardiogenic shock. In the United States, that approach is being widely adopted in a more selective fashion. It is clear that the strategy reduces the future need for revascularization, but it is not clear whether early complete revascularization reduces subsequent rates of MI and/or death. Results from larger, ongoing randomized clinical trials will be necessary before we have an answer to that question.
The issue of one-stage vs. multistage complete revascularization is also an important unresolved question. Most operators in the United States believe complete revascularization should be performed in stages, such as later during the index hospitalization or after a few weeks when the patient is fully recovered from the initial procedure. That said, when looking strictly at the pooled, randomized clinical data, the signal of reduction in hard endpoints — death or MI — occurred only when complete revascularization was performed during the index procedure. However, it is important to note that the numbers of patients and events were small, and the estimates, statistically speaking, were not very stable or secure.
My default strategy is complete revascularization in stages while the patient is still in the hospital, typically without an intervening functional study. Nevertheless, there are times when I might perform complete revascularization during the index procedure — for example, if the procedure is being performed early in the day and the lesion appears to be straightforward with no concern about bifurcation stenting. If the lesion is complex or borderline, however, then I might get a functional study first and then perform revascularization in the next few days or so.
For patients with STEMI undergoing primary PCI, there are three choices. A clinician can treat the culprit lesion only, monitor the patient medically and then only treat the nonculprit lesion if they have spontaneous or stress-induced myocardial ischemia. The second option is to perform multivessel primary PCI all in one setting. The third option is to perform a staged procedure where only the culprit lesions are treated during the initial primary PCI and then, based on anatomic criteria, perform PCI on the nonculprit lesions several days later, usually before hospital discharge. At present, there are 30 meta-analyses on this topic with conflicting conclusions about which option is best.
Overall, complete revascularization appears to be safe and feasible in select patients, as recommended in the guidelines. First, the nonculprit lesion PCI indication should match elective PCI standards. Second, it should be a very simple stenosis, not an intermediate stenosis, chronic total occlusion or complex lesion. Third, the patient must have no complications from their MI, needs to have tolerated the initial PCI without complications and should have normal hemodynamics and normal renal function.
In the United States, most clinicians have been performing the staged procedure, although there are some patients in whom performing the procedure all in one setting may be more efficient. The decision may depend on whether the lesion is simple or complex and where it is located. However, in some centers, such as some of the larger European centers where there is a long waiting list for patients, it may be more efficient throughput to do it all in one procedure. Patient safety, patient characteristics and operator comfort should all be taken into account.
Still, the issue is very complicated. There are at least eight other studies, including the COMPARE trial, in which the topic is being further examined. Even so, this isn’t a question that is going to be answered by randomized trials or clinical guidelines. This question will have to be answered by the interventional cardiologist each time he or she is treating one of these patients. It’s going to be an individualized decision, not a global recommendation.
PRAMI, CvLPRIT and DANAMI3-PRIMULTI have all demonstrated benefit with complete revascularization, but these trials, though robustly and ethically done with appropriately chosen patients, are not without faults. PRAMI and CvLPRIT were small, and patients in DANAMI3-PRIMULTI were part of a deferred trial and a preconditioning trial before assignment to single-vessel or multivessel intervention. Additionally, all three trials were not powered to show benefit for hard endpoints, such as death, MI or readmission for HF. When viewed together in meta-analyses, there is enough power to demonstrate a benefit for hard endpoints, but questions do remain without results from an appropriately powered, single trial.
If total revascularization is to be performed, the decision about whether to perform it in one stage or multiple stages is more about the reasons not to do it than the reasons to do it. One downside to performing total revascularization in multiple stages is that a second arterial access carries a risk, particularly with a femoral approach. On the other hand, if it’s late at night or there are more patients waiting, then it may be best to bring the patient back later.
That said, completing revascularization before hospital discharge may be preferable. We have to follow up CvLPRIT, but one of the most important findings was that events occurred early, with a significant number of events occurring within the first 30 days. Therefore, bringing back the patient for a second procedure after 2 months, for example, may mean you miss an opportunity to treat the noninfarct-related lesion. However, we will need appropriately powered trials before we can answer this question.
There are several important things we also need to know. First, are there trials that are going to definitely show benefit for hard endpoints? Second, how do we choose which noninfarct-related arteries to treat? Finally, which groups of patients are most likely to benefit from total revascularization? Should our decision be based on SYNTAX score, complexity of the lesions, size of the original infarct, diabetes, age or other factors?
Presently, there is no one right answer, and total revascularization may not be appropriate for every case. What these trials have done is open the debate, and it is important that we have the discussion. – by Melissa Foster
- References:
- Engstrøm T, et al. Lancet. 2015;doi:10.1016/S0140-6736(15)60648-1.
- Gershlick, et al. J Am Coll Cardiol. 2015;doi:10.1016/j.jacc.2014.12.038.
- Hlinomaz O, et al. Hot Line: Late-Breaking Trials and Innovations. Presented at: EuroPCR; May 19-22, 2015; Paris.
- Levine GN, et al. J Am Coll Cardiol. 2015;doi:10.1016/j.jacc.2015.10.005.
- Wald DS, et al. N Engl J Med. 2013;doi:10.1056/NEJMoa1305520.
- For more information:
- Eric R. Bates, MD, is professor of internal medicine at University of Michigan Health System and a member of the Cardiology Today’s Intervention Editorial Board. He can be reached at ebates@umich.edu.
- Deepak L. Bhatt, MD, MPH, is executive director of interventional cardiovascular programs at Brigham and Women’s Hospital Heart and Vascular Center, professor of medicine at Harvard Medical School and Cardiology Today’s Intervention Chief Medical Editor. He can be reached at dbhatt@bwh.harvard.edu.
- Anthony H. Gershlick, MD, is professor of interventional cardiology at University Hospitals of Leicester, United Kingdom. He can be reached at agershlick@aol.com.
- Lloyd W. Klein, MD, is professor of medicine at Rush Medical College in Chicago and a member of the Cardiology Today’s Intervention Editorial Board. He can be reached at lloyd_klein@rush.edu.
Disclosure: Bates, Gershlick and Klein report no relevant financial disclosures. Bhatt reports being on the data safety monitoring committee of the COMPLETE trial.