KT Evidence Bite: Rapid blood pressure lowering in intracerebral hemorrhage

In Knowledge Translation by Eve Purdy1 Comment

Editor’s note: This is a series based on work done by three physicians (Patrick ArchambaultTim Chaplin, and our BoringEM Managing editor Teresa Chan)  for the Canadian National Review Course (NRC). You can read a description of this course here.

The NRC brings EM residents from across the Canada together in their final year for a crash course on everything emergency medicine. Since we are a specialty with heavy allegiance to the tenets of Evidence-Based Medicine, we thought we would serially release the biggest, baddest papers in EM to help the PGY5s in their studying via a spaced-repetition technique. And, since we’re giving this to them, we figured we might as well share those appraisals with the #FOAMed community! We have kept much of the material as drop downs so that you can quiz yourself on the studies.

Paper: Rapid blood pressure lowering in patients with acute intracerebral hemorrhage

Citation: 

Anderson, C. S., Heeley, E., Huang, Y., Wang, J., Stapf, C., Delcourt, C., … & Chalmers, J. (2013). Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. New England Journal of Medicine368(25), 2355-2365. doi: 10.1056/NEJMoa1214609

Nickname of study: 
INTERACT-2

Summarized by: Teresa Chan
Reviewed by:Patrick Archambault & Tim Chaplin

Clinical Question

Does rapid lowering of blood pressure improve the outcome in patients with intracerebral haemorrhage?

PopulationPatients included had:

1) spontaneous intracerebral haemorrhage within the previous 6 hours
AND
2) Elevated Systolic BP (i.e. BP between 150-220 mmHg)
InterventionLower BP to target systolic level of < 140 mmHg within 1 hour with agents of physician’s choosing
Control Lower BP to target systolic level of < 180 mmHg (per guidelines) with agents of physician’s choosing
OutcomePrimary Outcome: Death or Major Disability (modified Rankin score of 3-6) at 90 days

Methods

This was a multicenter, randomized controlled trial. Patients were randomized to low target (>140) or high target (<180) and unblinded physicians then chose treatments to meet these targets. Primary outcomes were death and severe disability (as evaluated by the modified Rankin score) Intention to treat analysis was performed.

Results

719 of 1382 patients (52%) of those receiving intensive treatment vs. 785 of 1412 (55.6%) patients in guideline-targets had death or severe disability. This yielded an odds ratio for death or severe disability of 0.87 (95% CI 9.75-1.01 p=0.06) favouring the lower target group.

The performance of some mathematical acrobatics (bimodal ‘ordinal’ analysis of the patients stratifying them by their modified Rankin Score) yielded a significant difference (p=0.04) between the lower and higher target.

Conclusions

“In patients with intracerebral haemorrhage, intensive lowering of blood pressure did not result in a significant reduction in the rate of the primary outcome of death or severe disability. An ordinal analysis of modified Rankin scores indicated improved functional outcomes with intensive lowering of blood pressure.”

Take Home Point

There is no difference in ICH patients if you intensively lower their BP to targets of 140mmHg vs. the guidelines-suggested target of 180 mmHg.

There may be some interaction between BP targets and severity of outcomes as per the modified Rankin Score, but it is unclear if there is a clinically significant difference or merely a statistical anomaly.

EBM Considerations

  • Lack of blinding: Of note, half of the patients in the guideline group had an SBP > 180mmHg at baseline, and only 303 of them received ANY anti-hypertensive agent in the first group. This is concerning since the intervention group received IV therapy was much more common (p < 0.0001). This difference could have been associated with a lack of blinding, which we appreciate would have been difficult to do.
  • Multiple comparisons: The authors completed many comparisons in this study between the two groups, and the only difference in outcome they were able to find was in the ordinal comparison (which lumps several comparisons into one), and yet their significance threshold was only set at p=0.05. While the Bonferroni correction is likely too conservative in its adjustments, some sort of correction for the number of comparisons might have been warranted.
  • External validity: The majority of patients (~60%) in this study were males in China. This demographic is not representative of the population seen in Canadian emergency departments and as such external validity may be compromised in our context.

To learn more about blood pressure in intracerebral hemorrhage check out:

To download a copy of this summary click here NRC – BoringEM – The INTERACT2 study.

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Eve Purdy

Eve Purdy

Senior Editor at BoringEM
Senior emergency medicine resident and anthropology student-happily consuming, sharing, creating and researching #FOAMed.
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