Resumen de Effects of Immediate Blood Pressure Reduction on Death and Major Disability in Patients With Acute Ischemic Stroke

Jiang He, Yonghong Zhang, Tan Xu, Qi Zhao, Dali Wang

• Importance Although the benefit of reducing blood pressure for primary and secondary prevention of stroke has been established, the effect of antihypertensive treatment in patients with acute ischemic stroke is uncertain.

  Objective To evaluate whether immediate blood pressure reduction in patients with acute ischemic stroke would reduce death and major disability at 14 days or hospital discharge.

  Design, Setting, and Participants The China Antihypertensive Trial in Acute Ischemic Stroke, a single-blind, blinded end-points randomized clinical trial, conducted among 4071 patients with nonthrombolysed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were recruited from 26 hospitals across China between August 2009 and May 2013.

  Interventions Patients (n = 2038) were randomly assigned to receive antihypertensive treatment (aimed at lowering systolic blood pressure by 10% to 25% within the first 24 hours after randomization, achieving blood pressure less than 140/90 mm Hg within 7 days, and maintaining this level during hospitalization) or to discontinue all antihypertensive medications (control) during hospitalization (n = 2033).

  Main Outcomes and Measures Primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 14 days or hospital discharge.

  Results Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg (−12.7%) within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg (−7.2%) in the control group within 24 hours after randomization (difference, −5.5% [95% CI, −4.9 to −6.1%]; absolute difference, −9.1 mm Hg [95% CI, −10.2 to −8.1]; P < .001). Mean systolic blood pressure was 137.3 mm Hg in the antihypertensive treatment group and 146.5 mm Hg in the control group at day 7 after randomization (difference, −9.3 mm Hg [95% CI, −10.1 to −8.4]; P < .001). The primary outcome did not differ between treatment groups (683 events [antihypertensive treatment] vs 681 events [control]; odds ratio, 1.00 [95% CI, 0.88 to 1.14]; P = .98) at 14 days or hospital discharge. The secondary composite outcome of death and major disability at 3-month posttreatment follow-up did not differ between treatment groups (500 events [antihypertensive treatment] vs 502 events [control]; odds ratio, 0.99 [95% CI, 0.86 to 1.15]; P = .93).

  Conclusion and Relevance Among patients with acute ischemic stroke, blood pressure reduction with antihypertensive medications, compared with the absence of hypertensive medication, did not reduce the likelihood of death and major disability at 14 days or hospital discharge.

  Trial Registration clinicaltrials.gov Identifier: NCT01840072 Stroke is the second leading cause of death and the leading cause of serious, long-term disability worldwide.1 Clinical trials have documented that lowering blood pressure reduces the risk of stroke in hypertensive2,3 and normotensive patients with a history of stroke or transient ischemic attack.4- 6 Although the benefit of lowering blood pressure for primary and secondary prevention of stroke has been established, the effect of immediate antihypertensive treatment in patients with acute ischemic stroke and elevated blood pressure is uncertain.7,8 Elevated blood pressure is common during acute ischemic stroke. In the US National Hospital Ambulatory Medical Care Survey, 76.5% of patients with acute ischemic stroke had systolic blood pressures of 140 mm Hg or greater on arrival at the emergency department.9 Observational studies have reported that a decrease in blood pressure within the first 48 hours after symptom onset was associated with poorer, better, or no difference in adverse clinical outcomes among patients with acute ischemic stroke.10- 12 There are no published clinical trials with sufficient statistical power to address the question of whether lowering blood pressure reduces adverse clinical outcomes among patients with acute ischemic stroke.

  The China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) was a multicenter randomized controlled trial designed to test whether moderate lowering of blood pressure within the first 48 hours after the onset of an acute ischemic stroke would reduce death and major disability at 14 days or hospital discharge. In addition, we also evaluated the effects of antihypertensive treatment during the acute phase of ischemic stroke on 3-month mortality, major disability, and vascular events, as assessed at a posttreatment follow-up visit.