New England Journal of Medicine December 21, 2017

PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock

Holger Thiele, Ibrahim Akin, Marcus Sandri, Georg Fuernau, Suzanne de Waha, Roza Meyer-Saraei, et al.

Bottom Line

In patients with acute myocardial infarction and cardiogenic shock, an initial strategy of culprit-lesion-only PCI, compared with immediate multivessel PCI, significantly reduces the 30-day risk of death or severe renal failure requiring renal-replacement therapy.

Key Findings

1. At 30 days, the composite primary endpoint of death or renal-replacement therapy occurred in 45.9% of patients in the culprit-lesion-only PCI group versus 55.4% in the multivessel PCI group (RR 0.83; 95% CI 0.71-0.96; P=0.01) [3.1.4].
2. All-cause mortality at 30 days was significantly lower with culprit-lesion-only PCI than with immediate multivessel PCI (43.3% vs. 51.6%; RR 0.84; 95% CI 0.72-0.98; P=0.03).
3. The requirement for renal-replacement therapy occurred in 11.6% of the culprit-lesion-only group compared to 16.4% of the multivessel PCI group (RR 0.71; 95% CI 0.49-1.03; P=0.07).
4. There were no significant between-group differences regarding the time to hemodynamic stabilization, requirement or duration of catecholamine therapy, rates of bleeding, or stroke.

Study Design

Design
Randomized Controlled Trial
Open-Label
Sample
706
Patients
Duration
30 days
Median
Setting
Multicenter, Europe
Population Patients with acute myocardial infarction (STEMI or NSTEMI) complicated by cardiogenic shock, who had multivessel coronary artery disease (≥70% stenosis in ≥2 major epicardial vessels) identified on early diagnostic angiography.
Intervention Initial percutaneous coronary intervention (PCI) of the culprit lesion only, with the option of staged revascularization of nonculprit lesions.
Comparator Immediate multivessel percutaneous coronary intervention (PCI) of all clinically significant lesions during the index primary PCI procedure.
Outcome Composite of death from any cause or severe renal failure leading to renal-replacement therapy within 30 days.

Study Limitations

The trial utilized an open-label design, which inherently carries a risk of bias in post-procedural intensive care management, although hard objective endpoints (death and dialysis) were selected to minimize this.
A crossover rate existed, where some patients assigned to the culprit-only group ultimately required non-culprit intervention due to hemodynamic instability.
The use of mechanical circulatory support was relatively low and left to investigator discretion, which may alter the hemodynamic landscape compared to modern centers employing early advanced mechanical support protocols.
Staged revascularization of non-culprit lesions occurred in roughly 17% of the culprit-only group, complicating the isolation of pure early vs. delayed strategies.

Clinical Significance

The CULPRIT-SHOCK trial instigated a paradigm shift in the management of cardiogenic shock. Prior guidelines historically supported immediate complete revascularization, hypothesizing that treating all ischemic territories would optimize global myocardial function. By demonstrating that routine immediate multivessel PCI actually increases early mortality and the need for dialysis—likely due to prolonged procedural times, higher contrast loads, and delayed ICU stabilization—this trial established culprit-lesion-only PCI as the definitive standard of care. Consequently, major societal guidelines (ESC/ACC/AHA) downgraded routine immediate multivessel PCI in cardiogenic shock to a Class III (harm) recommendation.

Historical Context

The 1999 SHOCK trial established early revascularization as the cornerstone of therapy for cardiogenic shock complicating acute myocardial infarction. Given that up to 80% of these patients present with multivessel coronary artery disease, operators frequently attempted to intervene on all significant stenoses in a single setting to salvage maximal myocardium and reverse the downward hemodynamic spiral. Prior to CULPRIT-SHOCK, no appropriately powered randomized trial had tested whether complete immediate revascularization was actually superior to targeting only the infarct-related artery, leaving the field largely dependent on conflicting observational registry data.

Guided Discussion

High-yield insights from every perspective

Med Student
Medical Student

In the context of the CULPRIT-SHOCK trial, why might attempting to open all blocked coronary arteries (multivessel PCI) immediately during the initial procedure actually worsen outcomes, such as increasing the need for renal replacement therapy, in a patient with cardiogenic shock?

Key Response

This tests foundational pathophysiology. In a patient with cardiogenic shock, systemic perfusion is already critically low. Prolonging the procedure for multivessel PCI increases the duration of hemodynamic instability and significantly increases the contrast dye load, directly exacerbating contrast-induced nephropathy and the subsequent need for renal replacement therapy.

Resident
Resident

You are admitting a patient to the CCU who presented with an acute STEMI, cardiogenic shock, and multivessel disease. The interventionalist performed a culprit-lesion-only PCI based on CULPRIT-SHOCK data. What is the clinical strategy for the remaining non-culprit lesions, and what parameters dictate your management over the next 48-72 hours?

Key Response

The resident must understand that culprit-only PCI does not mean ignoring the other lesions; it means staging them. Management involves stabilizing the patient hemodynamically with mechanical support and/or vasopressors, monitoring renal function recovery, and evaluating for staged revascularization of non-culprit lesions once shock and acute systemic inflammation have resolved.

Fellow
Fellow

The CULPRIT-SHOCK trial demonstrated a survival benefit for culprit-lesion-only PCI, but allowed for staged revascularization of non-culprit lesions. From an interventional and advanced heart failure perspective, how do you determine the optimal timing for this staged procedure, and what specific angiographic or physiological features might compel you to deviate from the protocol and treat a non-culprit lesion during the index procedure?

Key Response

Challenges the fellow to integrate advanced clinical judgment. Staged PCI timing relies on lactate clearance, inotrope weaning, and renal recovery. Deviations to perform immediate non-culprit PCI are justified if the non-culprit lesion is highly unstable (e.g., TIMI 0/1 flow, angiographic thrombus) and actively contributing to ongoing ischemia and hemodynamic collapse.

Attending
Attending

CULPRIT-SHOCK fundamentally overturned the long-held belief that immediate multivessel revascularization was beneficial in cardiogenic shock. What underlying pathophysiological assumptions and cognitive biases led the cardiology community astray prior to this trial, and how can we apply this lesson to avoid iatrogenic harm in other areas of critical care cardiology?

Key Response

Encourages high-level reflection on the 'oculostenotic reflex' and the 'more is better' fallacy. The community assumed that restoring perfusion to all ischemic myocardium would improve global left ventricular function and reverse shock. However, they underestimated the iatrogenic harm of prolonged procedural time, contrast toxicity, and the risk of periprocedural infarction in an already profoundly unstable patient.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD
PhD

The primary endpoint of the CULPRIT-SHOCK trial was a 30-day composite of all-cause mortality and severe renal failure requiring renal replacement therapy. Methodologically, what are the statistical implications and potential biases of combining a terminal event (death) with a non-terminal, provider-dependent event (RRT) as a composite outcome in a critical care trial?

Key Response

Focuses on study design and competing risks. Death acts as a competing risk for renal replacement therapy (a patient must survive long enough to receive RRT). Furthermore, initiating RRT involves subjective clinical judgment, which can introduce ascertainment bias. A critical evaluation must assess whether the composite outcome was driven by the harder or softer endpoint and how competing risks were statistically modeled.

Journal Editor
Journal Editor

Approximately 17% of patients randomized to the culprit-lesion-only arm crossed over to receive immediate multivessel PCI. As an editor reviewing this manuscript, how does this degree of crossover impact the interpretation of the intention-to-treat (ITT) analysis, and what supplementary analyses would you require to ensure the primary findings are robust?

Key Response

Evaluates methodological rigor and threats to validity. Crossover in an ITT analysis typically biases the results toward the null hypothesis (making the two groups look more similar). Because the trial still found a significant benefit for the culprit-only strategy despite this crossover, the finding is highly robust. An editor would demand a per-protocol or as-treated sensitivity analysis, and an examination of the reasons for crossover, to ensure unmeasured confounding did not drive the effect.

Guideline Committee
Guideline Committee

Prior to the CULPRIT-SHOCK trial, international guidelines (e.g., 2015 ACC/AHA STEMI guidelines) gave a Class IIa recommendation for multivessel PCI in cardiogenic shock. Based on the robust findings of increased mortality and renal failure with the immediate multivessel strategy, how specifically should the class of recommendation be updated, and should any specific patient phenotypes be exempted?

Key Response

Directly addresses evidence translation into guidelines. Based on this trial, routine immediate multivessel PCI in cardiogenic shock was downgraded to a Class III (Harm) recommendation in subsequent guidelines (e.g., 2021 ACC/AHA revascularization guidelines). The committee must note that exceptions still apply for patients where a non-culprit lesion is unequivocally driving ongoing hemodynamic instability.

Clinical Landscape

Noteworthy Related Trials

1999

SHOCK Trial

n = 302 · NEJM

Tested

Early revascularization (PCI or CABG)

Population

Patients with acute myocardial infarction complicated by cardiogenic shock

Comparator

Initial medical stabilization

Endpoint

30-day overall mortality

Key result: There was no significant difference in 30-day mortality, but early revascularization significantly improved 6-month and long-term survival.
2012

IABP-SHOCK II Trial

n = 600 · NEJM

Tested

Intraaortic balloon pump (IABP) support

Population

Patients with AMI complicated by cardiogenic shock undergoing early revascularization

Comparator

No IABP support (medical therapy)

Endpoint

30-day all-cause mortality

Key result: The use of an intraaortic balloon pump did not significantly reduce 30-day mortality compared to medical therapy alone.
2019

COMPLETE Trial

n = 4,041 · NEJM

Tested

Complete multivessel PCI

Population

Patients with STEMI and multivessel coronary artery disease without cardiogenic shock

Comparator

Culprit-lesion-only PCI

Endpoint

Composite of cardiovascular death or new myocardial infarction

Key result: Complete revascularization significantly reduced the risk of cardiovascular death or myocardial infarction compared to culprit-lesion-only PCI.

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