EBQ:INTERACT-2

Under Review Journal Club Article

Anderson C. et al. "Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial.". 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. 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

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

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

Sources

• Study Protocol
• Supplemental Appendix