EBQ:INTERACT-2

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Complete Journal Club Article
Anderson C. et al. "Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage". NEJM. 2013. 368(25):2355-2365.
PubMed Full text PDF

Clinical Question

Does aggressive and rapid lowering of blood pressure improve outcomes in patients with acute intracerebral hemorrhage?

Conclusion

Intensive lowering of blood pressure in patients with intracerebral hemorrhage did not result in a significant reduction death or severe disability but does appear to be safe.

Major Points

Prior to INTERACT-2, the INTERACT-1 trial (Intensive blood Bressure Reduction in Acute Cerebral Haemorrhage Trial) functioned as a run-in-phase to the randomized controlled trial for INTERACT-2.[1] INTERACT-1 demonstrated the saftey of intensive BP-lowering and suggested a reduction in hematoma growth with such a strategy paving the way for the subsequent trial focusing on patient centered outcomes.


Similar to INTERACT-1, INTERACT-2 aggressively lowered the systolic blood pressure in emergency department patients with spontaneous atraumatic Intracerebral Hemorrhage (ICH) to a systolic blood pressure of <140 mm Hg within 1 hour and maintained for 7 days. The comparison was made to the current standard care of guideline recommended systolic blood pressure lowering of <180 mm HG within 7 days. The study did not find a death reduction or major disability reduction at 90 days with intensive therapy. Ordinal analysis did suggest improved functional outcomes in the aggressive therapy arm.

Guidelines

AHA Spontaneous ICH BP Guidelines 2015[2]

  1. If SBP is 150-220mmHg without contraindication to BP lowering, it is safe to acutely lower BP to 140mmHg and can be effective for improving functional outcome. (Class I Level A)
  2. For ICH patients presenting with SBP >220 mm Hg, it may be reasonable to consider aggressive reduction of BP with a continuous intravenous infusion and frequent BP monitoring (Class IIb; Level of Evidence C)

AHA Aneurysmal SAH BP Guidelines[3]

  1. No well-controlled studies exist that answer whether BP control influences rebleeding
  2. BP should be controlled to balance the risk of stroke, hypertension-related rebleeding, and maintenance of cerebral perfusion pressure (Class I, Level of Evidence B).
  3. Nicardipine, labetalol, and esmolol are appropriate choices for BP control (Sodium nitroprusside may raise intracranial pressure and cause toxicity with prolonged infusion and should be avoided)

Study Design

  • International, multicenter, prospective, randomized, open-treatment blinded end-point trial.
  • 2839 Emergency Department patients with spontaneous non traumatic intracraneal hemmorage
  • 90 day followup to assess mortality and disability according to the Modified Rankin Scale
  • Secondary ordinal analysis was performed to determine trends toward better functional outcomes

Population

N=2839

Intensive Blood pressure Therapy: 1399
Guideline Recommended Therapy: 1430

Patient Demographics

  • Median Age: 63.5
  • Male: 65.7%
  • Chinese: 68%
  • Systolic blood pressure on presentation: 179 mm Hg
  • Median NIHSS: 11
  • Median GCS: 14

Inclusion Criteria

  • Patients with spontaneous ICH presenting within 6 hours and who had an elevated BP.
  • Age ≥ 18 years

Exclusion Criteria

  • A structural cerebral cause for the intracerebral hemorrhage
  • GCS of 3-5
  • A massive hematoma with a poor prognosis
  • If early surgery to evacuate the hematoma was planned

Interventions

  • Treatment Arm: Intensive BP lowering (target <140mmHg) within 1 hour and for 7 days
  • Comparison Arm: Guideline-recommended BP lowering (<180mm Hg) by oral medication at any time determined by treating physician
  • All patients received oral (or NG tube) within 7 days which included ACE-inhibitor and diuretic if not contraindicated or if different drugs were specifically required with the goal of achieving systolic BP less than 140 mm Hg during follow-up

Outcomes

Primary Outcome

Poor outcome as defined by death or major disability (modified Rankin Scale >2) at 90 days.
  • Intensive BP group: 52%
  • Guideline BP group: 55.6%
p=0.06

Secondary Outcomes

Death or major disability at 7 days
  • Intensive BP group: 76.5%
  • Guideline BP group: 77.3%
p=0.597
Death or major disability at 28 days
  • Intensive BP group: 66.0%
  • Guideline BP group: 68.1
0.219

Subgroup analysis

Intracraneal Hematoma Volume
  • Intensive Group: 15.7ml initially vs 18.2ml at 24hrs
  • Guideline Group: 15.1ml vs 20.6ml at 24hrs
p=0.27
  • Ordinal analysis for the modified Rankin score showed a favorable shift in the distribution of scores on the modified Rankin scale to higher scores with intensive blood-pressure–lowering treatment.

Criticisms & Further Discussion

  • Patients in the intensive BP group started their treatment 20 minutes earlier and IV medications were the major therapy to reach target BP
  • 5% of patients withdrew from the intensive therapy group vs. 3% in the standard group without any clear explanation
  • The treating physicians were unblinded and outcome differences could be due to greater level of attention paid to the treatment group.
  • Although the disability assessment was blinded to treatment and the mRS is standardized, inter-rater reliability often differs by one or more points and makes neurologic disability assessment ambiguous. [4]
  • No difference in morbidity or mortality was found and maintaining such intensive BP control may be an unnecessary use of critical care resources

Funding

Funding from the National Health and Medical Research Council (NHMRC) of Australia

Sources

  1. Anderson C. et al. Intensive blood pressure reduction in acute cerebra haemorrhage trial (INTERACT): a randomised pilot trial
  2. Hemphill JC, et al. AHA/ASA Guideline: Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015.
  3. Bederson J. et al. Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage: A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Heart Association. Stroke. 2009;40:994-1025 PDF
  4. Banks et al. Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis. Stroke. 2007 Mar;38(3):1091-6. Epub 2007 Feb 1.