麻豆传媒

DENVER -- Early outcomes are better with culprit lesion-only revascularization in acute MI patients with multivessel disease in cardiogenic shock, the CULPRIT-SHOCK trial showed.

The 30-day rate of death or renal replacement therapy was 45.9% with the limited approach to percutaneous coronary intervention (PCI) versus 55.4% with multivessel PCI (RR 0.83, 95% CI 0.71-0.96), Holger Thiele, MD, of Heart Center Leipzig in Germany, and colleagues reported here at the Transcatheter Cardiovascular Therapeutics meeting.

The difference was driven by mortality, which significantly favored single-vessel PCI (RR 0.84) in the findings, released simultaneously .

"The lack of benefit of immediate multivessel PCI in this trial might be related to the significantly higher dose of contrast material that was used in the multivessel PCI group than in the culprit-lesion-only PCI group and a consequent decline in renal function," the researchers suggested as the mechanism, although severe renal failure leading to dialysis showed only a nonsignificant trend (HR 0.71, P=0.07).

‘Landmark Trial’

“This largest randomized European multicenter trial in cardiogenic shock complicating myocardial infarction therefore challenges current guideline recommendations,” Thiele said at a press conference for the late-breaking clinical trial.

include a level IIa recommendation to do multivessel PCI of all lesions in the acute setting. While American guidelines don’t specifically recommend the same, appropriate use criteria support it.

“I think this is going to change the guidelines,” said Leif Thuesen, MD, of Aarhus University in Denmark, although suggesting “still there might be subgroups where it might not be good to leave the vessel occluded.”

However, registry data suggests that clinical practice is already largely in line with the trial, he said. In Europe and the U.S., “we perform multivessel PCI currently in approximately only one-fifth of patients despite having these guideline recommendations.”

Johnathan Hill, MD, while calling it a “very important study,” agreed: “It’s already being implemented from a practical perspective. Most of this middle-of-the night decision-making about multivessel revascularization is made on a pragmatic basis. Taking on complex CTO [chronic total occlusion] lesions, which may require new techniques, retrograde and dissection reentry, in the middle of night is not practical.”

Cindy Grines, MD, of Hofstra Northwell School of Medicine in Manhasset, New York, called it a “landmark study that absolutely will change our practice in the U.S. We jumped on the bandwagon of multivessel PCI after some of the trials in Europe in this study population. … With this landmark trial, I think we are going to take a step back and really try to limit the patients we treat with multivessel acute PCI.”

David Cohen, MD, of Saint Luke’s Mid-America Heart Center in America Heart Institute in Kansas City, Missouri, said it seemed like a health economic slam-dunk. “It seems like a clear place where less is more.”

“Keep it simple, this is the major message from our trial,” Thiele told reporters. “Do the PCI of the infarct-related artery, then look how the patient does later on and then you can do staged revascularization.”

'Compelling Evidence'

These findings fit with a subgroup analysis of the nearly 20-year-old evidence from the SHOCK trial and a subsequent meta-analysis, both suggesting greater mortality risk to complete revascularization in such cardiogenic shock patients.

Prior studies in the acute MI setting not limited to cardiogenic shock have shown greater benefit to multivessel PCI, such as the and trials, and changed guidelines to make it an "acceptable" approach. A meta-analysis suggested no greater risk of contrast-induced nephropathy compared with stenting only the infarct-related artery.

CULPRIT-SHOCK did not have 12-month data yet, but time didn't change the CvLPRIT findings, with an early advantage that was durable to 12 months.

The well-conducted CULPRIT-SHOCK trial provided "compelling evidence" that would be unlikely to reverse course no matter what advances in PCI technique and periprocedural management come along in the future, Judith Hochman, MD, and Stuart Katz, MD, both of NYU Langone Health in New York City, wrote in an accompanying editorial.

Indeed, they noted: "Despite major advances in PCI technique and antithrombotic pharmacology during the approximately 20 years between the SHOCK trial and the CULPRIT-SHOCK trial, 30-day mortality among patients who underwent initial culprit-lesion-only PCI was nearly identical in the two trials (approximately 45%)."

One potential direction for exploration to improve the prognosis could be initial revascularization with coronary artery bypass grafting, Hochman and Katz suggested.

However, there are some practical limitations, most notably the 6- to 8-hour window typically considered best for CABG in multivessel disease with cardiogenic shock, said Vinod Thourani, MD, of Medstar Heart and Vascular Institute in Washington, D.C., and past chair of the ACC Surgeons’ Council.

“That’s where the rubber meets the road,” he told 麻豆传媒. “If they’re presenting outside of that window, then I think therapy that seems reasonable is the culprit lesion plus or minus ECMO support.”

Routine intraaortic balloon pump use and percutaneous mechanical circulatory support haven't shown promise. Venoarterial extracorporeal membrane oxygenation (ECMO) and its known complication of death due to brain injury were numerically more common in the multivessel PCI group. "ECMO for cardiogenic shock should be subjected to the same rigorous randomized clinical-trial methodology that was used by Thiele et al. in the CULPRIT-SHOCK trial," the editorialists argued.

Trial Design

CULPRIT-SHOCK was a multicenter, open-label trial with 706 patients who had two or more major vessels blocked by at least 70% and who were in acute myocardial infarction and cardiogenic shock. Participants were randomized to PCI of the culprit lesion only (with staged revascularization of nonculprit lesions encouraged, and done for 17.7%) or immediate PCI of all major coronary arteries with more than 70% stenosis.

For the multivessel group, efforts to recanalize chronic total occlusions acutely were encouraged, leading to 81% having complete revascularization overall. The crossover rate was 12.5% in the culprit-lesion-only group and 9.4% with multivessel PCI.

Secondary and safety endpoints came out similar between groups for recurrent MI, rehospitalization for congestive heart failure, bleeding, and stroke.

Findings were consistent across prespecified subgroups, including by presence of chronic total occlusion. "The consistent risk estimates for the primary endpoint in the intention-to-treat, per-protocol, and as-treated analyses support the robustness of the findings," the editorialists noted.

Among patients with cardiogenic shock, the acute hazards of a prolonged procedure time (including the increased dose of contrast material) seem to outweigh any potential negative aspects of repeat revascularization.

“Among patients with cardiogenic shock, the acute hazards of a prolonged procedure time (including the increased dose of contrast material) seem to outweigh any potential negative aspects of repeat revascularization,” the researchers concluded.

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