CULPRIT-SHOCK Trial Challenges Routine Multivessel PCI in MI With Shock

October 30, 2017

DENVER, CO — Same-session multivessel PCI is usually a bad idea in patients with acute MI and cardiogenic shock who have obstructive lesions in multiple coronaries, suggests a major randomized trial that seems to challenge common practice[1]. It saw significantly better survival after culprit-lesion-only PCI compared with the more aggressive approach in close to 700 such patients at centers throughout Europe.

The 30-day risk of death from any cause or renal-replacement therapy, the primary end point of the Culprit Lesion Only PCI vs Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial, was reduced by 17% (P=0.01) with the culprit-only approach.

The difference seemed to be driven by significantly fewer deaths in the culprit-lesion-only group, while the higher rate of renal-replacement therapy in the multivessel-PCI group fell short of significance.

Dr Holger Thiele

"In a larger trial, this difference in renal-replacement therapy may have turned out to be significant," Prof Holger Thiele (Heart Center Leipzig–University Hospital, Germany) told theheart.org | Medscape Cardiology.

"We strongly believe that the higher dose of contrast agent in this unstable situation led to more renal impairment" in the multivessel-PCI group, said Thiele, who is lead author on CULPRIT-SHOCK study published today in the New England Journal of Medicine to coincide with his presentation of the trial here at TCT 2017.

The message for operators when confronted with such patients, he said, is to "do acutely only the culprit artery, then consider staged multivessel treatment after the patient is stable."

In the trial, staged revascularization of nonculprit lesions was an option for patients assigned to the culprit-lesion-only approach, and in fact 17.8% of such patients had further PCI beyond the culprit lesion and vessel at a later session.

While the trial and its findings have impressed observers, some point to quirks in the methodology that keep it from being the definitive guide to using PCI in acute MI with cardiogenic shock.

Unconventional Wisdom

Dr Deepak Bhatt

In such patients, conventional wisdom generally says to perform PCI acutely on the culprit lesion, and if the patient remains unstable or is badly off in other ways, to also treat obstructive lesions in nonculprit coronaries during the same session, observed Dr Deepak Bhatt (Brigham & Women's Hospital, Boston, MA), who was not involved in CULPRIT-SHOCK.

"But this very well-done randomized trial says that conventional thinking is wrong," Bhatt said in an interview. "It has a good message. It actually says to simplify care instead of making it more complex: just go after that culprit vessel as quickly as you can, and get as good a result as you can, and get out of there as quickly as you can."

Dr George Vetrovec

Bhatt said CULPRIT-SHOCK "has a high likelihood of being immediately practice changing."

Dr George Vetrovec (Virginia Commonwealth University, Richmond) said in an interview, "This is important information, but I think we need a lot more information. It's a population that we've not really moved the needle on, so anything we can learn is good.

"I think physicians will feel less required to do multivessel PCI in the setting of shock, whereas in the past if the patient wasn't doing well, they felt like there was a mandate to do it. So this will reduce that stress," Vetrovec said.

But, he said about same-session multivessel PCI in this population, "I'd hate to see it totally go away just based on this." It will likely find some continued use in, for example, patients with MI, shock, and multivessel disease who have normal renal function, according to Vetrovec.

"There's still room for that strategy," agreed Dr Anthony Gershlick (University of Leicester and Glenfield Hospital, Leicester, UK). CULPRIT-SHOCK, he told theheart.org | Medscape Cardiology, does not definitively answer whether some patients should undergo complete revascularization at the time of acute culprit-artery PCI, "but it does tell us it shouldn't be mandated that they have complete revascularization."

Giving the operator discretion, case-by-case, to extend PCI beyond the culprit vessel if the patient doesn't stabilize after the culprit lesion is treated "makes a lot of sense, but not necessarily during the same procedure, because it might take a while for the benefit to manifest," Bhatt pointed out.

"If the patient continues to do poorly in the next few days, consider going back as a staged procedure instead of just forging ahead all at once," he said.

An accompanying editorial[2] says that "The CULPRIT-SHOCK trial provides compelling evidence that a strategy of culprit-lesion-only PCI is preferred over initial multivessel PCI for patients with cardiogenic shock." The possible mechanisms of the mortality increase with the multivessel approach "remain speculative," write Drs Judith S Hochman and Stuart Katz (New York University Langone Health, NY).

Was the Deck Stacked Against Multivessel PCI?

Of note, CULPRIT-SHOCK did not exclude patients with chronic total occlusions (CTO), which is common in patients with cardiogenic shock, the publication notes. Moreover, "In the multivessel PCI group, immediate recanalization of a CTO was recommended."

That could complicate interpretation of the study, as CTOs are usually avoided in actual practice when multiple coronaries are treated in this setting, some say.

Chronic occlusions are probably beyond what most operators do with multivessel PCI, Vetrovec said. "That's a problem with this sort of study;" it can force operators "to do things they might not have done."

According to Bhatt, "if it's pretty clear, based on the clinical presentation and the angiogram, that there is an old CTO that's going to take more than a few minutes to cross, most operators I don't think would go after it in the setting of shock."

But with treating CTOs in CULPRIT-SHOCK, "I think the risk is prolonging the procedure and giving contrast and raising the risk of renal failure," Bhatt said.

On the other hand, "I wouldn't have necessarily expected that more complete revascularization, even more complete than I do, to be associated with a higher risk of death. For that reason, I was surprised by the findings," Bhatt said.

"Maybe if they hadn't gone after the CTOs, there would have been less imbalance in terms of renal failure. But in my mind that still doesn't completely explain the mortality imbalance significantly going the wrong way."

The inclusion of CTOs, Bhatt said, "does leave a little bit of uncertainty, but no one's actually proved that opening up all the vessels in cardiogenic shock is actually a good idea in a large randomized trial. So in the absence of data supporting that approach, the data saying that approach is bad, even if there are some potential holes in it, I think rules the day."

Gershlick said, "Doing CTOs influenced this data negatively. So I think that's a major fault with the trial."

CTO's aren't generally included in multivessel PCI for MI and shock, Thiele acknowledged in an interview. "However, we know that CTO presence is one of the strongest predictors of outcome in cardiogenic shock. Therefore, we decided that a CTO isn't an exclusion criterion and that CTOs should be tried to be reopened if easily possible without an excess in contrast dye."

The published report says operators were "advised to pursue recanalization attempts cautiously and to limit the total dose of contrast material to 300 mL," with the result that multivessel PCI achieved complete revascularization in 81% of that group.

"We looked for a difference in CTO or no CTO, but did not find any difference in outcome between these two groups," Thiele said. So if CTOs had not been treated, "it is unlikely that the multivessel-PCI group would have had better outcomes than observed in our trial."

STEMI and NSTEMI

The trial randomized 706 patients with multivessel CAD and acute ST-segment-elevation MI (STEMI) or non-STEMI with shock to culprit-lesion only PCI (n=351), with staged further PCI an option or to immediate multivessel PCI (n=355). Data were evaluable for the primary end point for 344 and 342 patients, respectively.

The population presenting at 83 centers excluded patients with an indication for emergent CABG, onset of shock more than 12 hours before potential randomization, massive pulmonary embolism, or severe renal insufficiency.

Aspiration thrombectomy was used in significantly more culprit-lesion-only cases (17.5% vs 11.4%, P=0.02). Such cases had significantly shorter fluoroscopy time (median 13 min vs 19 min, P<0.001) and contrast load (median 190 mL vs 250 mL, P<0.001).

The 30-day rates of the primary end point, a composite of death or renal-replacement therapy, were significantly lower in the culprit-lesion-only group, 45.9% vs 55.4%. The rates of death were 43.3% in the culprit-lesion group and 51.6% in the multivessel group, and the rates of renal-replacement therapy were 11.6% and 16.4%, respectively.

Relative Risk (RR, 95% CI) for 30-day Clinical Outcomes, Culprit-Lesion-Only vs Multivessel PCI in CULPRIT-SHOCK

End points RR (95% CI) P
Death from any cause or renal-replacement therapy*              0.83 (0.71–0.96) 0.01
Death from any cause 0.84 (0.72–0.98) 0.03
Renal-replacement therapy 0.71 (0.49–1.03) 0.07
Staged or urgent repeat revascularization 7.43 (3.61–15.31) <0.001
Any actionable bleeding 0.75 (0.55–1.03) 0.07
*Primary end point

The relative risk for the primary end point varied slightly but remained significantly different in per-protocol and as-treated analyses, according to the report.

Other Possible Confounders

Outcomes in the multivessel-PCI group may have been worse for the inclusion of CTO, Vetrovec agreed, but possibly in other ways too.

For example, "there are at least some data that suggest that unloading the patients before revascularization in shock makes a big difference," possibly protecting the kidneys, he said. So if operators performing multivessel PCI had routinely engaged circulatory support before going ahead with the procedure, it might have improved their outcomes.

In the published report, mechanical circulatory support was used in about 28% of patients in both groups, and time to hemodynamic stabilization didn't differ significantly between them. But there were intergroup differences in the use of different circulatory-support devices, such as intra-aortic balloon pump, extracorporeal membrane oxygenation, and several ventricular assist devices.

Also, the entry criteria allowed patients to be treated up to 12 hours after the start of cardiogenic shock, Vetrovec pointed out. "That's a long time." The later PCI is initiated, the less likely the patient will recover, regardless of the PCI strategy, he said.

Thiele reports grants from the European Union, German Cardiac Society, and German Heart Research Foundation during the conduct of the study. Disclosures for the coauthors are listed on the journal website. Katz reports personal fees from Novartis, grants and personal fees from Amgen, grants from Janssen, personal fees from Regeneron, and nonfinancial support from Thoratec (St Jude Medical) outside the submitted work. Hochman has no relevant financial relationships. Gershlick said that he helped referee the CULPRIT-SHOCK report in its peer review prior to publication. Vetrovec said in the past year he has consulted for Corindus, Quintiles, and Abiomed. Bhatt serves on the data safety and monitoring committee of the COMPLETE trial and has received research funding from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Ironwood, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi, and the Medicines Company.

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