CATIS: Blood Pressure Reduction in Acute Ischemic Stroke (2014)

“Among patients with acute ischemic stroke, immediate blood pressure reduction did not reduce the risk of death and major disability at 14 days or hospital discharge.”

  • The CATIS Investigators

1. Publication Details

  • Trial Title: Effects of Immediate Blood Pressure Reduction on Death and Major Disability in Patients With Acute Ischemic Stroke: The CATIS Randomized Clinical Trial
  • Citation: The China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) Investigators. Effects of Immediate Blood Pressure Reduction on Death and Major Disability in Patients With Acute Ischemic Stroke: The CATIS Randomized Clinical Trial. JAMA. 2014;311(5):479–489. DOI: 10.1001/jama.2013.285479
  • Published: February 5, 2014, in The Journal of the American Medical Association (JAMA)
  • Author: The CATIS Investigators
  • Funding: The Chinese Ministry of Science and Technology and Ministry of Health.

2. Keywords

  • Ischemic Stroke, Blood Pressure, Hypertension, Antihypertensive Therapy, Randomized Controlled Trial

3. The Clinical Question

  • In adult patients with acute ischemic stroke and elevated systolic blood pressure (Population), does a strategy of immediate antihypertensive treatment (Intervention) compared to standard care without antihypertensive treatment (Comparison) reduce the composite risk of death and major disability at 14 days (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Elevated blood pressure is very common in the acute phase of an ischemic stroke and is associated with poor outcomes. However, the optimal management strategy was a major clinical controversy. While lowering blood pressure could theoretically reduce the risk of hemorrhagic transformation and cerebral edema, there were significant concerns that it could also worsen brain injury by reducing cerebral perfusion to the ischemic penumbra.
  • Knowledge Gap: There was no definitive evidence from a large, multicenter randomized controlled trial to guide blood pressure management in acute ischemic stroke patients who were not candidates for thrombolysis.
  • Proposed Hypothesis: The authors hypothesized that immediate blood pressure reduction would be superior to standard care in reducing the risk of death and major disability.

5. Study Design and Methods

  • Design: A large, multicenter, prospective, randomized, open-label, blinded-endpoint trial (used to test the effectiveness of interventions).
  • Setting: 26 academic and community hospitals in China.
  • Trial Period: Enrollment ran from August 2009 to May 2013.
  • Population:
    • Inclusion Criteria: Adult patients (≥22 years) with acute ischemic stroke (confirmed by CT or MRI) who presented within 48 hours of symptom onset and had a systolic blood pressure between 140 mm Hg and 220 mm Hg.
    • Exclusion Criteria: Included patients who received thrombolytic therapy, had a clear indication for immediate antihypertensive treatment (e.g., aortic dissection), or had severe heart failure.
  • Intervention: An antihypertensive treatment strategy. Patients received intravenous antihypertensive medications with a goal of lowering the systolic blood pressure by 10% to 25% within the first 24 hours and achieving a target of <140/90 mm Hg within 7 days.
  • Control: A standard care (control) group, where antihypertensive medications were withheld unless the systolic blood pressure was ≥220 mm Hg or the diastolic was ≥120 mm Hg.
  • Management Common to Both Groups: All patients received standard medical care for acute ischemic stroke, including antiplatelet therapy.
  • Power and Sample Size: The authors calculated that a sample size of 4000 patients would provide 80% power to detect a 2.5% 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 death and major disability (defined as a modified Rankin Scale [mRS] score of ≥3) at 14 days or at hospital discharge.
    • Secondary Outcomes: Included the primary outcome at 3 months, and the individual components of the primary outcome.

6. Key Results

  • Enrollment and Baseline: 4071 patients were randomized (2038 to the intervention group and 2033 to the control group). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: There was no significant difference in the primary composite outcome. The primary outcome occurred in 422 of 2029 patients (20.8%) in the intervention group and in 416 of 2028 patients (20.5%) in the control group (p=0.84).
  • Secondary Outcomes: There was no significant difference in the rate of death and major disability at 3 months.
  • Adverse Events: The incidence of adverse events was similar in both groups.

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: Odds Ratio (OR) for the primary outcome: 1.03 (95% CI, 0.86 to 1.22; P-value: 0.76).
  • Interpretation of Key Statistic(s):
    • Odds Ratio (OR):
      • Formula: Conceptually, OR = (Odds of Poor Outcome in Intervention Group) / (Odds of Poor Outcome in Control Group).
      • Calculation: The paper reports the result as 1.03.
      • Clinical Meaning: An OR of 1.03 suggests a non-significant 3% higher odds of a poor outcome in the antihypertensive treatment group.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The 95% CI was 0.86 to 1.22.
      • Clinical Meaning: Since this range crosses the line of no effect (1.0), it confirms that the result is not statistically significant. Clinically, this means the true effect could range from a 14% benefit to a 22% harm.
    • P-value: The p-value of 0.76 is much higher than the 0.05 threshold, indicating the result is not statistically significant and very likely due to chance (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures: As the trial was neutral, ARR and NNT are not applicable.
  • Subgroup Analyses: No significant differences were found in any of the pre-specified subgroups.

8. Strengths of the Study

  • Study Design and Conduct: The very large, multicenter, randomized controlled design with blinded outcome assessment provided high-quality evidence on a critical clinical question.
  • Generalizability: The pragmatic design and inclusion of a large number of diverse hospitals make the findings highly generalizable to a broad population of patients with acute ischemic stroke.
  • Statistical Power: The very large sample size provided definitive power to confidently rule out even a small but clinically important benefit of the intervention.
  • Patient-Centered Outcomes: The primary outcome was a composite of death and major disability, which are robust and patient-centered endpoints.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was open-label (unblinded), which introduces a risk of performance bias.
  • External Validity (Generalizability): The findings are highly generalizable to the broad population of patients with acute ischemic stroke who are not receiving thrombolysis.
  • Other: The blood pressure difference achieved between the two groups was modest, which may have made it more difficult to detect a true difference in outcomes.

10. Conclusion of the Authors

  • The authors concluded that among patients with acute ischemic stroke, immediate blood pressure reduction did not reduce the risk of death and major disability.

11. To Summarize

  • Impact on Current Practice: This was a landmark “negative” trial that provided strong evidence against the routine, aggressive lowering of blood pressure in the acute phase of ischemic stroke. It supported a more conservative, permissive hypertension approach.
  • Specific Recommendations:
    • Patient Selection: For adult patients with acute ischemic stroke and moderately elevated blood pressure (SBP < 220 mm Hg) who are not receiving thrombolysis.
    • Actionable Intervention: The results do not support the routine use of antihypertensive medications to lower blood pressure in the first 48 hours.
  • What This Trial Does NOT Mean: This trial does NOT mean that hypertension should never be treated in acute stroke. It only argues against routine lowering in patients without a specific, high-risk indication (e.g., SBP ≥ 220 mm Hg, or for patients receiving thrombolysis).
  • Implementation Caveats: The key takeaway is that permissive hypertension is a safe and appropriate strategy for the majority of patients with acute ischemic stroke.

12. Context and Related Studies

  • Building on Previous Evidence: The CATIS trial (2014) was designed to provide a definitive answer to a question that had been based on physiological theory and conflicting observational data for decades.
  • Influence on Subsequent Research: The definitive neutral result of this large trial has been highly influential in shaping international stroke guidelines, which now recommend a more conservative approach to blood pressure management in this population.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: The optimal blood pressure target for patients who do receive thrombolysis or thrombectomy remains an area of active investigation.
  • Future Directions: Future research is focused on identifying which specific subgroups of stroke patients might still benefit from more aggressive blood pressure control.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was of the highest relevance, testing a very common clinical practice for a leading cause of disability and death.
  • Methods: The very large, multicenter, randomized controlled trial design with blinded outcome assessment was of high quality. The main methodological weakness is the open-label design, but the primary outcome was objective and adjudicated by a blinded committee.
  • Results: The study reported a clear neutral finding for its primary outcome, with a narrow confidence interval centered on the null value. This provides strong evidence against a meaningful clinical benefit of routine, immediate blood pressure reduction.
  • 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. This is a classic example of a high-quality “negative” trial that was profoundly practice-changing by providing strong evidence to stop a common but ineffective therapy.

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.
Scroll to Top