Trials Prompt Interventionalists to Reconsider Complete Revascularization for STEMI

With almost half of STEMI patients presenting with multivessel disease—a pattern that confers a worse long-term prognosis—interventionalists face an almost daily dilemma: After successful primary PCI of the culprit lesion, should they immediately stent the remaining significant blockages or put off further PCI? If they choose the latter, then should delayed PCI occur during the same hospitalization or be scheduled for weeks ahead?

Or is it safe—and perhaps more prudent—to wait and see how the patient fares on optimal medical therapy?

The question of when to treat noninfarct lesions had been settled in favor of deferral except in cases of hemodynamic instability. But that thinking has lately been shaken up by the results of a pair of randomized trials; PRAMI and CvLPRIT both point toward complete revascularization and away from the stance of the current guidelines.

“These were very provocative trials, and they have prompted many interventionalists to rethink what the guidelines should say and how they should practice,” Jeffrey A. Breall, MD, of Indiana University (Indianapolis, IN), told TCTMD in a telephone interview. The guidelines’ prohibition of simultaneous complete revascularization stemmed from concern that nonculprit intervention, especially in the proinflammatory milieu of STEMI, might trigger a complication, he explained. And with 2 territories in jeopardy, the consequences could be dire.

But given the increased safety of contemporary PCI, “the chances of that happening are very small,” he said. “And [complete revascularization] makes physiologic sense since [during a STEMI] you’re often demanding more of the nonculprit wall of the heart, so if there’s a stenosis there, the patient might be better off getting it revascularized.”

Ajay J. Kirtane, MD, SM, of Columbia University Medical Center (New York, NY), said that the new evidence undercuts the assumption that additional PCI is harmful. “Whereas before, complete revascularization was looked at as something you didn’t want to do, now people are thinking that certainly it’s not wrong to do,” he said in a telephone interview with TCTMD.

Importantly, he added, PRAMI and CvLPRIT highlighted the ongoing risk of STEMI patients with multivessel disease. “The prevailing wisdom had been that once someone had a STEMI, if there was additional, nonculprit disease, they became a COURAGE-type patient who could then be managed medically,” Dr. Kirtane noted. “But these trials [show] that when a patient has already had a significant event, we ought to be more aggressive about revascularization” because rather than being innocent bystanders, nonculprit lesions reflect an underlying disease risk that may have been exacerbated by the STEMI.

ACC/AHA Guidelines Need to Be ‘Loosened Up’

Currently, the American College of Cardiology/American Heart Association (ACC/AHA) STEMI guidelines give multivessel PCI a designation of “Class III: harm” when performed during the index catheterization in a hemodynamically stable patient. The European Society of Cardiology (ESC) guidelines are more liberal, giving immediate nonculprit PCI a Class IIb recommendation (may be considered) and staged revascularization in the presence of symptoms or ischemia a Class IIa recommendation (should be considered)—all with level of evidence B.

The strict prohibition against opening more than the culprit vessel during acute STEMI is “a little out of date,” Dr. Breall said. There may not be enough data to warrant changing the guidelines, but they could at least be “loosened up,” he added, noting that “in this litigious era, many people think of guidelines as synonymous with standard of care and that is not the case.”

Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), was blunter. “The way [the guidelines] are written right now is both unrealistic and unnecessary,” he said in a telephone interview with TCTMD.

Indeed, all of those interviewed agreed that the ACC/AHA “harm” designation should be dropped, giving more leeway for clinical judgment. In a possible signal of upcoming changes, in September 2014 the ACC withdrew its Choosing Wisely warning—aimed more at patients than providers—that immediate complete revascularization should be questioned.

Overturning a Paradigm

In fact, most of the evidence against immediate preventive revascularization was derived from registry studies and meta-analyses having heterogeneous designs and varied endpoints, noted CvLPRIT investigator Anthony H. Gershlick, MD, of the University Hospitals of Leicester NHS Trust, Glenfield Hospital (Leicester, England), in a telephone interview with TCTMD.

Moreover, the conclusions of these retrospective studies were not only inconsistent but were likely tainted by selection bias, he and others asserted. For example, Dr. Gershlick said, most operators stent nonculprit lesions in STEMI patients with cardiogenic shock, trying to improve their chances of good outcome. Unfortunately, many of these patients die, not because of harm done by the extra stenting but because they were very sick. Yet the deaths get counted against PCI. No amount of adjustment can compensate for the confounding, he added.

The results of the randomized trials reverse—or at least cast doubt on—the apparent lesson of the observational data.

In PRAMI, reported at the 2013 ESC Congress and simultaneously published online ahead of print in the New England Journal of Medicine, researchers randomized 465 STEMI patients to infarct-artery primary PCI with or without immediate revascularization of other lesions with at least 50% stenosis. The trial was stopped early when preventive PCI showed a 65% reduction in the primary outcome (cardiac death, nonfatal MI, or refractory angina). There was also a decline in both MI and refractory angina and a trend toward less cardiac death. 

In the CvLPRIT trial, presented at the 2014 ESC Congress and published in the March 17, 2015, issue of the Journal of the American College of Cardiology, Dr. Gershlick and colleagues found in 296 STEMI patients that complete revascularization during the index hospitalization reduced 12-month MACE (death, recurrent MI, heart failure, or ischemia-driven revascularization) by 55%. The individual endpoints were also lower in the preventive PCI group, though only ischemia-driven revascularization was significant.

Solidifying the turnaround, a meta-analysis by Dr. Gershlick of all 4 randomized trials, involving 1,044 patients, demonstrated a similar 66% reduction in MACE and a 64% decrease in cardiovascular mortality with complete revascularization.

With Conflicting Evidence, Practice Varies

In line with the guidelines, there was a consensus among the physicians interviewed by TCTMD that the presence of hemodynamic instability warrants immediate complete revascularization. Outside of that presentation, however, approaches differ.

“If a patient is in frank cardiogenic shock or is bordering on shock, I’m prone to open up everything I can in hopes of giving him the best myocardial blood flow,” Dr. Breall said. “Also, if a patient has ongoing chest pain that I am convinced is ischemic, I would lean toward intervention in the same setting as primary PCI.”

“Short of those [scenarios], I tend to be conservative and bring patients back, either if it is clinically indicated or [to obtain] objective evidence of ischemia,” he added.

One argument for a deferred approach, Dr. Breall noted, is that many patients who present with MI have been on no or minimal medical therapy beforehand. “So after opening up their culprit artery, perhaps the first thing we should do is optimize their medication and then see where the chips fall,” he said, though he acknowledged that that strategy could be risky. At least optimal medical therapy should be mandatory for both arms in any future randomized trials, he said.

For Dr. Kirtane, the presence of severe stenosis or slow flow or angiographic evidence of nonculprit-vessel contribution to the STEMI would be reasons to immediately treat noninfarct disease. “Otherwise, we adopt a staged approach,” he said, “because the incidence of adverse events between primary PCI and the deferred procedure is usually very low.”

According to Dr. Gershlick, the recent data suggest that “if you see a tight lesion in an important epicardial vessel, you should at least consider opening it during the same setting.” But he stressed that for the most part immediate PCI is not mandatory. If there are any concerns—eg, TIMI 3 flow has not been achieved, the patient is hypertensive, or the cath lab team is tired—“you should take a step back. There is nothing wrong with bringing the patient back for a noninvasive test,” Dr. Gershlick advised.

However, citing a landmark analysis from CvLPRIT showing a trend toward a benefit for nonculprit PCI within 30 days, he added: “If you bring patients back at 6 or 8 weeks, you may miss the window for early revascularization.”

Dr. Brenersaid he “quite frequently” treats nonculprit vessels at the time of primary PCI. For example, he said, “if the patient has had angina for quite a while before the STEMI [suggesting the pain is caused by a nonculprit lesion], I do as much as I can in a single setting and certainly finish everything before the patient goes home. Large territories that are at risk and still viable I would not leave alone.”

Still, Dr. Brener advocated thinking about treating noninfarct stenoses apart from the STEMI setting. “If they are lesions you would normally revascularize, then you should do it,” he said. “The timing—whether you treat tomorrow or in 4 weeks—is less important.”

On the other hand, Keith G. Oldroyd, MD, of Golden Jubilee National Hospital (Glasgow, Scotland)—who acknowledges being an outlier in this regard—said in an email with TCTMD that immediate complete revascularization is now his default approach, as long as primary PCI is successful and the patient is stable. A few exceptions, he added, are the presence of renal dysfunction or a chronic total occlusion (CTO).

Noting that patients with cardiogenic shock were excluded from both PRAMI and CvLPRIT, Dr. Oldroyd said the issue of immediate vs staged complete revascularization in this subgroup is being addressed in the ongoing CULPRIT-SHOCK trial.

A Matter of Timing

Yet even those swayed by evidence backing complete revascularization remain uncertain about when to carry it out. PRAMI and CvLPRIT basically tested nonculprit intervention during primary PCI. Although the latter trial allowed additional interventions anytime within the index hospitalization, on average they took place within about 1 day of the initial procedure.

The import of timing turns in large part on whether the risk of recurrent events is high shortly after STEMI—and on that the evidence is unclear, noted Dr. Oldroyd. However, “the event curves in PRAMI and CvLPRIT separate early and argue in favor of immediate or at most a 2- to 3-day delay for opening nonculprit lesions,” he said, noting that reassuringly both studies found no signal of harm from immediate complete revascularization. Besides, he added, “staging—even within the index admission—is clinically and economically inefficient.”

Best Way to Assess Nonculprit Lesions Uncertain


Another open question is how to determine which nonculprit lesions need to be treated. Because not all stenoses are the same, “a cautious way to go would be something analogous to FAME,” Dr. Breall said. “If you have multivessel problems, you fix the culprit, and if you anticipate needing to do more, you use a pressure wire.”

Dr. Kirtane, however, was reluctant to endorse invasive functional testing. “I’m a big proponent of FFR in general,” he said, but in certain scenarios—for example, an RCA infarction with residual 70% to 80% disease in the LAD—“I’m not convinced that it is the right test.” Also, it could be argued that the risk of nonculprit lesions does not always correlate with hemodynamic significance, he said, noting that a 50% lesion, if it is very vulnerable plaque, presents a higher risk than a totally stable lesion with a 70-80% stenosis.

As a rule, “if I see a significant lesion in another territory, I schedule that patient for [staged] revascularization,” he said. “If when the patient returns the lesion no longer looks that severe, then I would advocate doing FFR.”

There is as of yet no definitive answer about when to turn to FFR, Dr. Oldroyd said. He noted that the positive randomized trials used angiographic criteria, which at least makes them universally applicable. Several upcoming studies are using FFR assessment of nonculprit lesions. But, he noted, a drawback of FFR is that it “introduces some delay” into an urgent procedure. Moreover, there are no data on the value of IVUS or OCT, but any recommendation to use those imaging modalities would inhibit adoption of immediate nonculprit stenting, Dr. Oldroyd added.

Effect on Cost Not Straightforward

According to Dr. Breall, because most primary PCI patients with multivessel disease end up returning for further intervention at some point, opening all the vessels in the same setting—provided it is safe—may be cost saving. However, that is contingent on factors like the length of the procedure, the amount of contrast used, and the patient’s baseline renal and hemodynamic status, he added.

Dr. Brener said that the relationship between immediate multivessel stenting and cost is complex. If operators open more than the culprit vessel in the acute setting, the procedure is considered to be of “indeterminate” appropriateness, he explained. On the other hand, if nonculprit PCI is staged, and when the patient returns he does not have angina or there is no objective evidence of ischemia, the procedure becomes “inappropriate.” “That may push some operators to potentially do more PCI upfront,” he commented.

In addition, depending on the insurer and the hospital’s situation, reimbursement may be bundled into 1 STEMI admission with revascularization, with additional charges allowed only for extra materials and technical services but not professional fees, he noted. “In some cases, staged PCI may be deferred to beyond 30 days to get out of the bundling.”

Upcoming Trials May Shed More Light

“PRAMI and CvLPRIT were both robust trials and they have some validity, but they are not definitive,” Dr. Gershlick acknowledged. And importantly, the trials were relatively small and not powered for the hard endpoints of death or MI and admission for heart failure.

Moreover, some critics have noted that given the paucity of events, the play of chance could have led to a different conclusion. In addition, Dr. Gershlick said, some have pointed out that CvLPRIT controls were managed with medical therapy alone, whereas many physicians order follow-up noninvasive tests for ischemia. However, he countered, a nuclear scan performed at 6 weeks in this group showed no evidence of severe ischemia.

Dr. Gershlick asserted that the trial populations reflect the broad range of patients encountered in everyday practice. But, Dr. Kirtane cautioned, a blanket conclusion that immediate complete revascularization is safe does not apply to excluded patient subsets, such as those with CTOs.

Indeed, the safety and efficacy of complete revascularization need confirmation in larger randomized trials powered for hard endpoints, Dr. Gershlick agreed, noting that important ancillary questions related to timing and lesion selection require further exploration. Several trials now underway or about to get started, including COMPLETE, PRIMULTI, COMPARE-ACUTE, and CROSS-AMI, are pursuing these goals.

Meanwhile, PRAMI and CvLPRIT succeeded in that they “raised a red flag and generated interest” in trying to determine the optimal management of STEMI patients with nonculprit disease, Dr. Gershlick concluded.





  • Dr. Breall reports serving on the advisory board for Siemens and as a consultant to Fujifilm.
  • Dr. Brener reports no relevant conflicts of interest.
  • Dr. Gershlick reports serving on the advisory board and speaker’s bureau for Abbott Vascular, Medtronic, and The Medicines Company.
  • Dr. Kirtane reports institutional research support from Abbott Vascular, Abiomed, Boston Scientific, Medtronic, and St. Jude Medical.
  • Dr. Oldroyd reports receiving institutional research support from Biosensors, the British Society of Cardiovascular Imaging, and St. Jude Medical and speaker’s fees from Biosensors, the British Society of Cardiovascular Imaging, St. Jude Medical, and Volcano.


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