INTERACT2 Trial

[https://www.ncbi.nlm.nih.gov/pubmed/23713578 Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med 2013;368(25):2355–65.]

Clinical Question
In patients with spontaneous intraparenchymal hemorrhage (IPH), does intensive blood pressure (BP) lowering to systolic blood pressure (SBP) <140 mmHg reduce the risk of death or severe disability compared with guideline-recommend treatment with target SBP <180 mmHg.

Trial Data

 * Design
 * Multicenter, prospective, randomized trial
 * N = 2,839 (1,403 to intervention, 1,436 to control)
 * Setting: 144 hospitals in 21 countries
 * Enrollment: 2008-2012
 * Primary Outcome: Death or major disability (score of 3-6 on modified Rankin scale (mRS) at 90 days after randomization)
 * Notable inclusion criteria: Age >18 with spontaneous IPH and SBP 150-220 mmHg on arrival, able to be treated within 6 hours
 * Notable exclusion criteria: severe vascular stenoses, recent ischemic stroke, definitive indication for intensive BP lowering (e.g. hypertensive encephalopathy, aortic dissection)
 * Groups:
 * Intensive: SBP <140 mmHg
 * Guideline: SBP 140-180 mmHg
 * Results:
 * Death or major disability in 52.0% (intensive) vs 55.6% (guideline) (OR 0.87; 95% CI 0.75-1.01; p=0.06).
 * Post-hoc shift analysis of mRS: better functional outcome in intensive group (0.87, 95% CI 0.77-1.00, p=0.04)
 * No difference at all in adverse events

Major Points

 * This trial technically failed to meet its primary endpoint as p=0.06, but there was strong trend towards benefit for primary outcome, benefit on post-hoc analysis, and no adverse events.
 * Common interpretation of this trial after completion was that goal SBP <140 mmHg may be of benefit and is unlikely to cause harm. This is reflected in the 2015 American Heart Association / American Stroke Association Guidelines for Management of Spontaneous Intracerebral Hemorrhage . However, the subsequent publication of the ATACH-2 trial showed contradictory results.
 * Analysis of SBP obtained in this trial (Figure S2 in Supplementary Appendix) shows that the average SBP actually achieved in the intensive group was ~135-145 mmHg, while in the guideline group it was 150-160 mmHg. Thus the intensive group barely achieved its SBP goal, while the guideline group achieved SBPs lower than goal.  As such, this trial actually suggests that, if anything, SBPs in the 130s-140s range has a trend to improved outcomes compared with SBPs in the 150s-160s range.
 * ATACH2 suggested that SBPs in the 120s might have harm compared with 140s, while INTERACT2 suggested that SBPs in the 130s-140s range has a trend to improve outcomes compared with 150s-160s. A reasonable interpretation is that 120s is too low, 130s-140s are probably okay, and SBPs in the 150s-160s may be too high. Taking the two trials together, we therefore aim for SBP 130-150 mmHg in most situations.