Author: Craig Davidson , Dip Datta / Codes: CC21, CMP6, HMP5 / Published: 09/10/2014
INTERACT 2 – Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage. Anderson et al. N Engl J Med 2013;368:2355-65.
In the management of acute haemorrhagic stroke, does the intensive management of hypertension in the first 6 hours improve outcomes?
International, multicenter, prospective, randomised, open treatment, blinded endpoint trial.
Population: 2839 patients with ICH with elevated BP (150-220 SBP) who could be treated within 6 hours of ICH. Excluded if structural cause of bleed, GCS 3-5, massive ICH, planned surgery.
(Other exclusions premorbid mRS of 3-5). 21 countries. 2008-2012.
Intervention: Intensive management of hypertension (goal <140 at 1 hour of randomisation)
Comparison: Treatment as per guidelines: Treat if over 180mmHg, no target BP or time.
Outcome: Death or major disability (mRS 3-5) at 90 days. Pre-specified ordinal analysis adjusted and unadjusted for various factors similar to IST3. .
Summary: There was no significant difference in primary endpoint of death or major disability (mRScale 3-5) between groups at 90 days. A secondary ordinal analysis found a favourable shift in disability with intensive treatment (OR 0.87 CI 0.77- 1.0). When various other factors were adjusted for this benefit disappeared. Improvement in the secondary endpoint of subjective quality of life/function (EQ-5D), while statistically significant, may not be clinically appreciable. No increase in complications\side effects with intensive management.
- Difference in time to treatment in both groups only 13 mins. BP at 1 hour only differed by 14 mmHg between two groups. This may not be clinically important.
- The intervention resulted in an improvement of 0.05 on the EQ-5D scale – below the 0.074 threshold commonly regarded to be the lowest meaningful difference on this 100 point scale1.
- Open treatment means that subjective endpoints are subject to bias- Hawthorne Effect.
- In subgroup analysis patients who were randomised at >4 hours from onset of symptoms actually appeared to have better outcomes than those whose treatment was started earlier. This was not statistically significant but counterintuitive if you think rapid BP control is worthwhile.
- About 60% study population were chinese and male therefore reducing relevance to UK Population.
- No standardisation of treatment protocols. This is pragmatic decision but may limit generalisability to our own centres.
So now what? UK guidance recommends treatment (IV/Oral/NG) of hypertension in acute intracerebral haemorrhage if SBP >200 mmHg. (NICE 2008) This paper has not identified a benefit to pursuing a more aggressive strategy although it does appear to be safe.
The European Stroke Organisation has this year published new guidelines on the management of intracerebral haemorrhage which gives a weak recommendation for the use of an intensive treatment strategy like the one described in the paper.