In Intracerebral Hemorrhage, Intensive BP Lowering Has Little Impact on Outcomes

Early, aggressive blood pressure (BP) lowering treatment was deemed safe in patients with acute intracerebral hemorrhage (ICH) and effective for preventing hematoma expansion. The findings of the recent meta-analysis were reported in Cerebrovascular Diseases.¹

Although ICH represents only 10% to 20% of strokes, it has an extremely high mortality rate — approximately 40% within 1 month — most often associated with secondary expansion of the hematoma.^2-4 Blood pressure lowering is often part of the treatment plan to reduce intracranial pressure and risk of morbidity and mortality.^5,6

Simona Lattanzi, MD, and colleagues from the Neurologic Clinic of Marche Polytechnic University in Ancona, Italy, combined data from 5 large clinical trials conducted between 2008 and 2016^7-10 for a total cohort of 4350 patients; 2162 who had intensive BP-lowering treatment and 2188 who were treated conservatively. All 5 studies were randomized, placebo-controlled, open-label, blinded, comparative trials of BP-lowering therapies in adults treated within 24 hours of acute onset of ICH.

The investigators reported no differences in 3-month mortality rates across all 5 studies evaluating the 2 different approaches (relative risk (RR) 0.99; 95% CI, 0.83-1.17; P =.883). The same was true for 3-month death or major disability (RR 0.96, 95% CI, 0.91-1.01; P =.126). Likewise, there were no differences between strategies for outcomes of early neurological deterioration, hypotension, recurrent stroke, or acute coronary events. Adverse events were similar in both groups with the exception of risk for renal failure, which was higher in patients given intensive treatment (RR 2.18; 95% CI, 1.08-4.41; P =.031).

A secondary end point of the study was preventing growth of the hematoma, which favored aggressive/intensive BP reduction over conservative approaches by a weighted mean difference (WMD) of -1.53 ([-2.94 to -0.12]; P =.033) mL.

The investigators found that although intensive approaches were in most ways as safe as conservative BP-lowering treatments (except for a higher risk of renal failure), benefits in the reduction of hematoma did not produce expected improvements in clinical outcomes. They identified several possible features of the study that may have contributed to this finding, including a patient base more disposed to better outcomes regardless of treatment, or a dilution effect to intensive treatment that was not delivered within the prescribed 3 hours after ICH. Or, they noted, “The relationship between BP and outcome may be more complex than simply linear; the clinical benefit may not increase in parallel to the degree of BP, or it may be attributable to mechanisms other than absolute BP reduction.”

References

1. Lattanzi S, Cagnetti C, Provinciali L, et al. How should we lower blood pressure after cerebral hemorrhage? A systematic review and meta-analysis. Cerebrovasc Dis. 2017;43:207-213.
2. Ikram MA, Wieberdink RG, Koudstaal PJ. International epidemiology of intracerebral hemorrhage. Curr Atheroscler Rep. 2012;14:300-306.
3. Qureshi AI, Mendelow AD, Hanley DF. Intracerebral haemorrhage. Lancet. 2009;373:1632-1644.
4. van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol. 2010;9:167-176.
5. Guan J, Hawryluk GWJ. Targeting secondary hematoma expansion in spontaneous intracerebral hemorrhage – state of the art. Front Neurol. 2016;7:187.
6. Anderson CS, Huang Y, Wang JG, et al. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol. 2008;7:391-399.
7. Koch S, Romano JG, Forteza AM, et al. Rapid blood pressure reduction in acute intracerebral hemorrhage: feasibility and safety. Neurocrit Care. 2008;8:316-321.
8. Anderson CS, Heeley E, Huang Y, et al; for the INTERACT2 Investigators: Rapid blood pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368:2355-2365.
9. Butcher KS, Jeerakathil T, Hill M, et al; for the ICH ADAPT Investigators: The intracerebral hemorrhage acutely decreasing arterial pressure trial. Stroke. 2013;44:620-626.
10. Qureshi AI, Palesch YY, Barsan WG, et al; for the ATACH-2 Trial Investigators and the Neurological Emergency Treatment Trials Network: Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med. 2016;375:1033-1043.