Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage "ATACH-2"

 

Qureshi AI, Palesch Y Y, Barsan WG, Daniel HF, Hsu CY etal. 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 Jun 8. [Epub ahead of print].

 

 

CLINICAL QUESTION

Can intensive systolic blood pressure control (SBP 110-139 mm Hg) in intracranial haemorrhage can improve neurological and mortality outcome?

 

METHOD

Design

Randomised, multicentred, two group, open levelled trial conducted in 110 sites in the United States, Japan, China, Taiwan, South Korea, and Germany. 1000 patients were screened out of 8532 through a time period of 52 months (500 patients in each group).

Intervention

Intensive treatment group:-

Target SBP 110-139 mm Hg

Intravenous Nimodepine (first line) followed by Labetalol/Diltiazem/ Urapidil

Standard treatment group:-

Target SBP 150 to 179 mm Hg.

Treatment initiated within 4.5 hrs of symptom onset and continued till 24 hrs in both the groups.

Initially, the window period was confined to 3 hrs of symptoms which was extended to 4.5 hrs based on recent evidence.

Inclusion criteria:-

  1. At least one SBP reading in excess of 180 mm of Hg between symptom onset & initiation of antihypertensive

  2. Age > 18 years

  3. Glasgow Coma Score 5 to 15 on presentation

  4. Haematoma size <60cm3 on Initial CT scan

Primary treatment failure:-

Not able to achieve with in 2 hrs of treatment initiation-

  1. target SBP <140 mm Hg in the intensive-treatment group

  2. target SBP<180 mm Hg in the standard- treatment group

Secondary treatment failure:-

Hourly minimum SBP remaining higher than the upper limit of the target range for 2 consecutive hours during the period of 2 to 24 hours after randomization. 

Baseline and 24-hour CT scans were evaluated in core image analysis center which was blinded from the intervention.

Volume of hematoma was calculated by a software.

Follow up was done at 1 month by telephone and clinical attendance at 3 months. Modified Rankin scale (assesses the degree of disability or dependence in daily activities, with scores ranging from 0 [no symptoms] to 6 [death]); quality of life as assessed by means of the European Quality of Life–5 Dimensions (EQ-5D) questionnaire i.e. (range from −0.109 [least favorable health state] to 1 [most favorable health state], with 0 imputed for death) at 3 months)

Primary outcome

  1. Moderately severe or severe disability or death (modified Rankin scale score, 4 to 6) at 3 months.

Secondary outcomes

  1. EQ-5D utility index

  2. Visual-analogue scale (VAS) at 3 months

  3. Proportion of participants with hematoma expansion of >/=33% on the CT scan obtained at 24 hours.

  4. The 3-month EQ-5D utility index (on which scores range from −0.109 [least favorable health state] to 1 [most favorable health state], with 0 imputed for death)

Safety outcomes

  1. Neurologic deterioration (decrease from baseline of 2 or more points in the GCS score or an increase of 4 or more points in the score on the National Institutes of Health Stroke Scale (on which scores range from 0 to 42, with higher scores indicating more severe stroke)

 

RESULTS

Primary outcome:-

  1. There was no significant difference in modified Rankin scale score at 3 months.

Secondary outcomes:-

  1. No significant difference between EQ-5D measures, the percentages of hematoma expansion, death rate at 3 months or in neurologic deterioration at 24 hours after randomization.

  2. The percentage of patients with any serious adverse event at 3 months & rate of renal adverse events within 7 days after randomization was significantly higher in the intensive-treatment group.

 

CONCLUSION

Intensive treatment of BP to a target of 110 to 139 mm Hg was not associated with any mortality benefit nor it was associated with objective reduction in hematoma size.

 

STRENGTHS:-

  1. The intervention window was 4.5 hours compared to earlier studies which was with in 6 hours. This implies that even with early intensive BP control, the outcome remained the same.

WEAKNESS:-

  1. Unblinded

  2. Different antihypertensive agents were used in different participating center. This could possibly affect the outcome of the intervention (related to beneficial or adverse effect of individual drugs). Though the blood pressure target was same for all the participating center.

 

TAKE HOME MESSAGE

 ATACH2 study did not show any difference in objective evidence (hematoma expansion) or overall outcome with intensive BP control (SBP<140 mm Hg). So the the current practice for management of BP control should continue to be same i.e as per AHA/American Stroke Association guidelines (see below).

 

 

 

Literature before the study & existing guideline

 

INTERACT trial:-

In 2010, Anderson CS demonstrated intensive BP-lowering treatment (within 6 hours of hemorrhage) attenuated hematoma growth over 72 hours in intracerebral hemorrhage.(1)

 

INTERACT-2 trial:- A multicenter randomized trial (2013) including 2839 patients, reported a favorable functional outcome (low modified Rankin scores) in intensive treatment group (target SBP <140 mm Hg) compared to conventional treatment group (SBP<180 mm Hg), though there was no significant difference of death or severe disability between the groups.(2)

 

Guideline (3) proposed by American Heart Association/American Stroke Association suggested the following

  • If SBP is 􏰂200 mm Hg or MAP is 􏰂150 mm Hg, then consider aggressive reduction of BP with continuous intravenous infusion, with frequent BP monitoring every 5 min.

  • If SBP is 180 mmHg or MAP is 130mm Hg and there is the possibility of elevated ICP, then consider monitoring ICP and reducing BP using intermittent or continuous intravenous medications while maintaining a cerebral perfusion pressure 􏰆60 mm Hg.

  • If SBP is 180 mmHg or MAP is 130 mmHg and there is not evidence of elevated ICP, then consider a modest reduction of BP (eg, MAP of 110 mm Hg or target BP of 160/90 mm Hg) using intermittent or continuous intravenous medications to control BP and clinically reexamine the patient every 15 min.

 

REFERENCES

  1. Anderson CS, Huang Y, Arima H, et al. Effects of early intensive blood pressure- lowering treatment on the growth of hematoma and perihematomal edema in acute intracerebral hemorrhage: the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT). Stroke 2010;41:307-12.

  2. Delcourt C, Huang Y, Wang J, et al. The second (main) phase of an open, randomized, multicenter study to investigate the effectiveness of an INTEnsive blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT2). Int J Stroke 2010;5:110-6.

  3. Morgenstern LB, Hemphill JC III, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for health- care professionals from the American Heart Association/American Stroke Association. Stroke 2010;41:2108-29.

DR Sananta K Dash

MD, FNB, FCCP,EDIC

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