CULPRIT-SHOCK: PCI Strategy in Myocardial Infarction with Cardiogenic Shock (2017)

“In patients with acute myocardial infarction complicated by cardiogenic shock, the risk of a composite of death or severe renal failure at 30 days was lower among those who underwent PCI of the culprit lesion only than among those who underwent immediate multivessel PCI.”

  • The CULPRIT-SHOCK Investigators

1. Publication Details

  • Trial Title: PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock
  • Citation: Thiele H, Akin I, Sandri M, et al. PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock. N Engl J Med. 2017;377(25):2419-2432. DOI: 10.1056/NEJMoa1710261
  • Published: December 21, 2017, in The New England Journal of Medicine
  • Author: Holger Thiele, M.D.
  • Funding: European Union; German Centre for Cardiovascular Research; and others.

2. Keywords

  • Myocardial Infarction, Cardiogenic Shock, Percutaneous Coronary Intervention (PCI), Multivessel Disease, Randomized Controlled Trial

3. The Clinical Question

  • In patients with acute myocardial infarction (AMI) and multivessel coronary disease complicated by cardiogenic shock (Population), does an initial PCI strategy of the culprit lesion only (Intervention) compared to immediate multivessel PCI (Comparison) reduce the composite risk of death or severe renal failure at 30 days (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Cardiogenic shock complicating AMI has a very high mortality rate. Most of these patients have multivessel coronary artery disease. While opening the “culprit” artery that caused the heart attack is the primary goal, it was common practice to also perform immediate percutaneous coronary intervention (PCI) on other significantly blocked, non-culprit arteries at the same time.
  • Knowledge Gap: It was unknown if this immediate multivessel PCI strategy was beneficial or harmful. While it could improve overall blood flow to the heart, it also prolonged the procedure, increased the contrast dye load, and carried a risk of periprocedural complications, all of which could be detrimental to a patient in profound shock.
  • Proposed Hypothesis: The authors hypothesized that a strategy of immediate multivessel PCI would be superior to a culprit-lesion-only PCI strategy in reducing the 30-day risk of death or severe renal failure.

5. Study Design and Methods

  • Design: A multicenter, prospective, open-label, randomized, controlled trial (used to test the effectiveness of interventions).
  • Setting: 83 centers in Europe.
  • Trial Period: Enrollment ran from April 2013 to April 2017.
  • Population:
    • Inclusion Criteria: Adult patients with acute MI, multivessel coronary disease, and cardiogenic shock.
    • Exclusion Criteria: Included cardiac arrest with a duration of resuscitation >30 minutes and an expected survival of less than 6 months.
  • Intervention: A culprit-lesion-only PCI strategy, with the option for staged revascularization of non-culprit lesions at a later time if clinically indicated.
  • Control: An immediate multivessel PCI strategy, where all significant non-culprit lesions were also treated with PCI during the initial procedure.
  • Management Common to Both Groups: All patients received standard medical therapy for AMI and cardiogenic shock, which could include antiplatelet agents, anticoagulation, and mechanical circulatory support.
  • Power and Sample Size: The authors calculated that a sample size of 706 patients would provide 80% power to detect a 10% absolute risk reduction in the primary outcome. (Power is a study’s ability to find a real difference between treatments if one truly exists; 80% is the standard accepted level for clinical trials).
  • Outcomes:
    • Primary Outcome: A composite of all-cause mortality or severe renal failure leading to renal-replacement therapy (RRT) within 30 days of randomization.
    • Secondary Outcomes: Included 30-day mortality, time to hemodynamic stabilization, and rates of bleeding and stroke.

6. Key Results

  • Enrollment and Baseline: 706 patients were randomized (351 to culprit-lesion-only PCI and 355 to multivessel PCI). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: The primary composite outcome occurred in a significantly lower proportion of patients in the culprit-lesion-only group: 158 of 344 patients (45.9%) in the culprit-lesion-only group met the primary endpoint, compared with 189 of 341 patients (55.4%) in the multivessel-PCI group (p=0.01).
  • Secondary Outcomes: 30-day mortality was also significantly lower in the culprit-lesion-only group (43.3% vs. 51.6%). There was no significant difference in the rates of bleeding or stroke.
  • Adverse Events: The primary adverse events were death and the need for RRT, both of which were less common in the culprit-lesion-only group.

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed using a chi-square test.
  • Primary Outcome Analysis: The primary outcome was a comparison of the proportions of patients who met the composite endpoint between the two groups.
  • Key Statistic(s) Reported: Relative Risk (RR) for the primary outcome: 0.83 (95% CI, 0.71 to 0.96; P-value: 0.01).
  • Interpretation of Key Statistic(s):
    • Relative Risk (RR):
      • Formula: Conceptually, RR = (Risk in Intervention Group) / (Risk in Control Group).
      • Calculation: The paper reports the result as 0.83.
      • Clinical Meaning: The RR of 0.83 means that patients in the culprit-lesion-only group had a 17% lower relative risk of death or severe renal failure at 30 days compared to the multivessel-PCI group.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The 95% CI was 0.71 to 0.96.
      • Clinical Meaning: Since this entire range is below the line of no effect (1.0), it confirms that the result is statistically significant and demonstrates a clear benefit for the culprit-lesion-only strategy.
    • P-value: The p-value of 0.01 is below the 0.05 threshold, indicating the result is statistically significant (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures:
    • Absolute Risk Reduction (ARR):
      • Formula: ARR = (Risk in Control Group) – (Risk in Intervention Group)
      • Calculation: ARR = 55.4% – 45.9% = 9.5%.
      • Clinical Meaning: For every 100 patients treated with a culprit-lesion-only strategy, about 9-10 additional patients were saved from death or severe renal failure.
    • Number Needed to Treat (NNT):
      • Formula: NNT = 1 / ARR
      • Calculation: NNT = 1 / 0.095 = 10.5, which is rounded down to 10.
      • Clinical Meaning: You would need to treat 10 patients with a culprit-lesion-only strategy (instead of immediate multivessel PCI) to prevent one additional case of death or severe renal failure.
  • Subgroup Analyses: The benefit of the culprit-lesion-only strategy was consistent across all pre-specified subgroups.

8. Strengths of the Study

  • Study Design and Conduct: The multicenter, randomized, controlled design provided high-quality evidence on an important clinical question.
  • Generalizability: The inclusion of 83 diverse centers increases the applicability of the findings.
  • Statistical Power: The study was adequately powered for its primary outcome.
  • Patient-Centered Outcomes: The primary outcome was a composite of death and severe organ failure, which are highly relevant patient-centered endpoints.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was open-label (unblinded), which introduces a risk of performance bias, as the interventional cardiologists’ knowledge of the assigned strategy could have influenced their technique or decision-making.
  • External Validity (Generalizability): The study population was from a high-income European setting, and the results may not be fully generalizable to all healthcare systems.
  • Other: The trial did not mandate a specific approach to staged revascularization in the culprit-lesion-only group, leaving this to clinical discretion.

10. Conclusion of the Authors

  • The authors concluded that in patients with AMI and cardiogenic shock, an initial PCI strategy of the culprit lesion only was associated with a lower risk of a composite of death or severe renal failure at 30 days than a strategy of immediate multivessel PCI.

11. To Summarize

  • Impact on Current Practice: This was a profoundly practice-changing trial. It provided definitive evidence that a strategy of “less is more” during the acute phase of cardiogenic shock is superior to a more aggressive, immediate multivessel revascularization approach.
  • Specific Recommendations:
    • Patient Selection: For adult patients with AMI, multivessel disease, and cardiogenic shock.
    • Actionable Intervention: The initial PCI should be limited to the culprit lesion only.
    • Expected Benefit: This strategy can be expected to prevent one additional death or case of severe renal failure for every 10 patients treated.
  • What This Trial Does NOT Mean: This trial does NOT mean that non-culprit lesions should never be treated. It only argues against treating them immediately during the index procedure. Staged revascularization after the patient has stabilized remains an important consideration.
  • Implementation Caveats: The key is to stabilize the patient first by opening the culprit artery, and to defer any further interventions on other arteries until a later, safer time.

12. Context and Related Studies

  • Building on Previous Evidence: The CULPRIT-SHOCK trial (2017) was designed to provide a definitive answer to a question that was a major area of debate among interventional cardiologists, with previous evidence being based on weaker, observational data.
  • Influence on Subsequent Research: The definitive positive result of this trial has been highly influential and was rapidly incorporated into international cardiology and critical care guidelines, establishing culprit-lesion-only PCI as the standard of care for this high-risk population.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: The optimal timing and strategy for staged revascularization of the non-culprit lesions after initial stabilization remains an area of investigation.
  • Future Directions: Future research is focused on identifying which patients might still benefit from a more complete revascularization strategy and on the optimal use of mechanical circulatory support in this population.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, addressing a common and high-stakes clinical decision in the management of one of the deadliest cardiac emergencies.
  • Methods: The multicenter RCT design was appropriate and robust. The main methodological weakness is the open-label design. However, the primary outcome was a composite of objective endpoints (death and need for RRT), which mitigates the risk of bias.
  • Results: The study reported a statistically significant and clinically important benefit for the less aggressive strategy (NNT of 10). The findings were consistent and robust.
  • Conclusions and Applicability: The authors’ conclusion is a direct and fair reflection of the data. The high external validity of this pragmatic trial means its findings are broadly applicable to most centers that perform PCI. This is a classic example of a high-quality trial that was practice-changing by providing strong evidence to de-adopt a common but harmful practice in favor of a simpler, safer approach.

16. Disclaimer and Contact

  • This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.
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