SHOCK: Early Revascularization for Cardiogenic Shock (1999)

“Although a strategy of initial medical stabilization with intra-aortic balloon counterpulsation and subsequent revascularization did not result in a significant difference in 30-day mortality, as compared with a strategy of initial medical stabilization alone, the mortality rates were lower at 6 months in the group assigned to early revascularization.”

— The SHOCK Trial Investigators

1. Publication Details

  • Trial Title: Early Revascularization in Acute Myocardial Infarction Complicated by Cardiogenic Shock.
  • Citation: Hochman JS, Sleeper LA, Webb JG, et al; for the SHOCK Investigators. Early Revascularization in Acute Myocardial Infarction Complicated by Cardiogenic Shock. N Engl J Med. 1999;341(9):625-634. doi:10.1056/NEJM199908263410901.
  • Published: August 26, 1999, in The New England Journal of Medicine.
  • Author: Judith S. Hochman, M.D.
  • Funding: National Heart, Lung, and Blood Institute (NHLBI).

2. Keywords

Cardiogenic Shock, Acute Myocardial Infarction, Revascularization, Percutaneous Coronary Intervention (PCI), Coronary Artery Bypass Grafting (CABG), Intra-aortic Balloon Pump (IABP).

3. The Clinical Question

In patients with cardiogenic shock complicating an acute myocardial infarction (Population), does a strategy of emergency/early revascularization (by PCI or CABG) (Intervention) compared to a strategy of initial medical stabilization (including IABP and fibrinolytics) (Comparison) reduce 30-day all-cause mortality (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Cardiogenic shock complicating acute myocardial infarction (AMI) was a highly lethal condition with in-hospital mortality rates exceeding 70-80%. The standard of care consisted of medical stabilization with inotropes, vasopressors, and often an intra-aortic balloon pump (IABP) to support circulation.
  • Knowledge Gap: While restoring blood flow to the ischemic myocardium with revascularization was a logical approach to reverse the underlying cause of shock, its effectiveness had not been proven in a large, randomized trial. It was unknown if the risks of an early invasive procedure outweighed the potential benefits.
  • Proposed Hypothesis: The authors hypothesized that a strategy of early revascularization would reduce all-cause mortality compared to a strategy of initial medical stabilization.

5. Study Design and Methods

  • Design: A prospective, multicenter, randomized, controlled trial.
  • Setting: 30 clinical centers in the United States and other countries.
  • Trial Period: Enrollment from April 1993 to August 1998.
  • Population:
    • Inclusion Criteria: Patients with AMI complicated by cardiogenic shock, defined by clinical (e.g., hypotension, signs of hypoperfusion) and hemodynamic criteria.
    • Exclusion Criteria: Age >75 years was initially an exclusion but later removed, shock not due to left ventricular failure, and contraindications to revascularization.
  • Intervention: Emergency revascularization, to be performed within 6 hours of randomization. The method (PCI or CABG) was chosen by the clinical team.
  • Control: Initial medical stabilization, which included fibrinolytic therapy (if eligible) and IABP insertion. Delayed revascularization was permitted for refractory ischemia or failure to stabilize.
  • Management Common to Both Groups: All patients were recommended to have IABP insertion for hemodynamic support.
  • Power and Sample Size: The trial was designed to enroll 600 patients to detect a 20% relative reduction in mortality. Due to slow enrollment, the sample size was later revised.
  • Outcomes:
    • Primary Outcome: All-cause mortality at 30 days.
    • Secondary Outcomes: All-cause mortality at 6 months and 1 year, and survival status.

6. Key Results

  • Enrollment and Baseline: 302 patients were randomized (152 to early revascularization, 150 to initial medical stabilization). The groups were well-matched at baseline.
  • Trial Status: The trial was completed, but enrollment was slower than anticipated.
  • Primary Outcome: There was no statistically significant difference in 30-day mortality between the early revascularization and medical stabilization groups (46.7% vs 56.0%; P=0.11).
  • Secondary Outcomes: Mortality at 6 months was significantly lower in the early revascularization group (50.3% vs 63.1%; P=0.027). This survival benefit was maintained at 1 year.
  • Adverse Events: The rates of major adverse events like reinfarction, stroke, and severe bleeding were similar between the two groups.

7. Medical Statistics

  • Analysis Principle: An intention-to-treat analysis was performed.
  • Statistical Tests Used: The primary outcome was analyzed using a chi-square test. Survival over time was analyzed using the Kaplan-Meier method and log-rank test.
  • Primary Outcome Analysis: The proportion of deaths at day 30 was compared between the two groups.
  • Key Statistic(s) Reported:
    • 30-Day Mortality: RR 0.83 (95% CI, 0.67 to 1.04); P=0.11.
    • 6-Month Mortality: RR 0.80 (95% CI, 0.65 to 0.98); P=0.027.
  • Interpretation of Key Statistic(s):
    • P-value: The p-value of 0.11 for the primary outcome did not meet the conventional threshold for statistical significance. However, the p-value of 0.027 for the 6-month outcome was statistically significant.
  • Clinical Impact Measures (based on 6-month mortality):
    • Absolute Risk Reduction (ARR): 12.8% (63.1% – 50.3%).
    • Number Needed to Treat (NNT): 8 (1 / 0.128). To save one life at 6 months, approximately 8 patients with cardiogenic shock need to be treated with a strategy of early revascularization.
  • Subgroup Analyses: The survival benefit at 6 months was consistent across most subgroups, including patients older than 75 years.

8. Strengths of the Study

  • Study Design and Conduct: This was a landmark randomized controlled trial that addressed a critical, high-mortality clinical condition.
  • Generalizability: The multicenter design and broad inclusion criteria increase the applicability of the findings.
  • Long-term Follow-up: The inclusion of 6-month and 1-year follow-up was crucial and ultimately revealed the true benefit of the intervention.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The primary outcome at 30 days was not statistically significant. A significant number of patients (20%) in the medical stabilization group crossed over to receive revascularization.
  • External Validity (Generalizability): The technologies for PCI (e.g., stents, antiplatelet agents) have evolved significantly since the trial was conducted, which may affect the applicability of the exact results today, although the principle remains valid.
  • Other: The trial was underpowered due to slower-than-expected enrollment.

10. Conclusion of the Authors

“For patients with cardiogenic shock due to myocardial infarction, a strategy of early revascularization did not lead to a significant reduction in 30-day mortality as compared with initial medical stabilization. However, a survival benefit with early revascularization was evident at six months.”

11. To Summarize

  • Impact on Current Practice: Despite not meeting its primary 30-day endpoint, the SHOCK trial was practice-changing. The clear and significant mortality benefit at 6 months was compelling enough to establish early revascularization as the standard of care for patients with cardiogenic shock complicating AMI.
  • Specific Recommendations:
    • Patient Selection: Patients with acute myocardial infarction complicated by cardiogenic shock.
    • Actionable Intervention: Pursue an immediate invasive strategy with coronary angiography and prompt revascularization (usually PCI) as the first-line treatment.
    • Expected Benefit: A significant reduction in 6-month mortality, with an NNT of approximately 8.
  • What This Trial Does NOT Mean: This trial does not mean that medical stabilization is unimportant. Hemodynamic support with IABP (though its role is now debated) and vasoactive drugs remains a critical bridge to revascularization.
  • Implementation Caveats: This strategy requires rapid diagnosis and transfer to a center with 24/7 cardiac catheterization capabilities.

12. Context and Related Studies

  • Building on Previous Evidence: The SHOCK trial was the definitive study that moved the field beyond observational data and established a new standard of care.
  • Influence on Subsequent Research: This trial cemented the “open-artery hypothesis” for cardiogenic shock. Subsequent research has focused on optimizing the revascularization strategy (e.g., culprit-lesion only vs. multivessel PCI, studied in the CULPRIT-SHOCK trial, 2017) and the role of more advanced mechanical circulatory support devices.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: The optimal revascularization strategy (culprit-vessel only vs. complete) and the role of various mechanical circulatory support devices (e.g., Impella, ECMO) in addition to revascularization remain areas of active investigation.
  • Future Directions: Research is focused on improving outcomes further by optimizing hemodynamic support, minimizing reperfusion injury, and developing better risk stratification tools.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The question was of the highest clinical importance, addressing an intervention with the potential to dramatically reduce mortality in a condition that was previously almost uniformly fatal.
  • Methods: The randomized, multicenter design was appropriate. The main methodological issue was being underpowered, which likely contributed to the non-significant 30-day result.
  • Results: This is a classic example of a trial where the totality of the evidence, particularly the robust and significant 6-month mortality benefit, outweighed the non-significant primary endpoint. The p-value of 0.11 at 30 days suggested a strong trend, which matured into a clear benefit over time.
  • Conclusions and Applicability: The authors’ conclusion is a precise reflection of the data. Despite the statistical nuance of the primary endpoint, the clinical community correctly interpreted the trial as a clear mandate for an early invasive strategy. The results are highly applicable and form the basis of all modern international guidelines for the management of cardiogenic shock.

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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