China Antihypertensive Trial in Acute Ischemic Stroke - CATIS

Nov 17, 2013
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Tulane University and Collins C. Diboll Private Foundation, both in New Orleans, LA; Soochow University, a Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions, China, and the National Natural Science Foundation of China. The Changzhou Pharmaceutical Factory provided the study drug (enalapril) for this trial.
Date Presented:
01/01/2013
Date Published:
01/01/2013
Date Updated:
11/17/2013
Original Posted Date:
11/17/2013
References

Description:

It is unclear if early blood pressure (BP) reduction is associated with improved outcomes in patients presenting with acute ischemic stroke. The current trial sought to assess whether moderate lowering of BP within the first 48 hours after the onset of an acute ischemic stroke would reduce short-term death and major disability.

Hypothesis:

Moderate lowering of BP 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, as compared with control.

Study Design

  • Randomized
  • Parallel

Patient Populations:

  • Ischemic stroke confirmed by brain computed tomography or magnetic resonance imaging within 48 hours of symptom onset
  • Elevated systolic BP between ≥140 and <220 mm Hg

    Number screened: 22,230
    Number of enrollees: 4,071
    Duration of follow-up: 3 months
    Mean patient age: 62 years
    Percentage female: 36%

Exclusions:

  • Severe heart failure (New York Heart Association class III and IV), acute myocardial infarction, unstable angina, atrial fibrillation, aortic dissection, and cerebrovascular stenosis
  • Patients in a deep coma
  • BP >220/120 mm Hg
  • Resistant hypertension
  • Intravenous thrombolytic therapy
  • Current pregnant women
  • Unable to participate in the follow-up examination

Primary Endpoints:

  • Combination of death within 14 days after randomization and major disability at 14 days or
    at hospital discharge (if earlier than 14 days)

Secondary Endpoints:

  • Combination of all-cause mortality and major disability at the 3-month post-treatment follow-up

Drug/Procedures Used:

Patients presenting with an acute ischemic stroke were randomized in a 1:1 fashion to either antihypertensive treatment or control. Several antihypertensive agents, including intravenous angiotensin-converting enzyme inhibitors (enalapril, first-line), calcium channel blockers (second-line), and diuretics (third-line), could be used individually or in combination in the intervention group to achieve the targeted BP reduction according to a prespecified treatment algorithm. Patients in the control group discontinued home antihypertensive medications. After their hospital discharge, patients in both groups were prescribed antihypertensive medications according to clinical guidelines.

Principal Findings:

A total of 4,071 patients were randomized, 2,038 to antihypertensive treatment and 2,033 to control. Baseline characteristics were fairly similar between the two arms. The median National Institutes of Health Stroke Scale (NIHSS) score was 4. Approximately 79% of patients had a history of hypertension, and close to 48% were on antihypertensive treatment; the mean BP on admission was 166/97 mm Hg. The ischemic stroke type was thrombotic in 78%, lacunar in 20%, and embolic in the rest.

Within 24 hours, the absolute BP was significantly lower in the antihypertensive arm as compared with the control arm (-21.8/-11.0 mm Hg vs. -12.7/-6.9 mm Hg, mean difference -9.1/-4.1 mm Hg, p < 0.001). BP was also lower at 7 days (137.3/82.4 mm Hg vs. 146.5/86.4 mm Hg, p < 0.001) and 14 days (135.2/81.4 mm Hg vs. 143.7/85.3 mm Hg, p < 0.001). The primary outcome of death or major disability at 14 days or hospital discharge was similar between the two arms (33.6% vs. 33.6%; hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.88-1.14; p = 0.98). Other outcomes including mortality (1.2% vs. 1.2%, p = 0.99), median score on modified Rankin scale (2.0 vs. 2.0, p = 0.70), and median duration of hospitalization (13.0 vs. 13.0 days, p = 0.28) were similar between the two arms. Among patients who received antihypertensive treatment 24 hours or more after stroke onset, BP lowering was associated with a significant reduction in the primary outcome (odds ratio, 0.73; 95% CI, 0.55-0.97; p for interaction = 0.03).

Interpretation:

The results of the CATIS trial indicate that antihypertensive treatment within 48 hours is not superior to routine management in patients with an acute ischemic stroke in reducing mortality and morbidity. This is one of the largest trials on this topic. Contrary to most other trials on antihypertensive treatment in acute stroke, this trial focused on a strategy (BP reduction) rather than a particular agent (to lower BP such as nimodipine). It is important to note that patients receiving thrombolytics were excluded from this trial. This may limit the generalizability of the trial to some extent.

References:

He J, Zhang Y, Xu T, et al., on behalf of the CATIS Investigators. Effects of Immediate Blood Pressure Reduction on Death and Major Disability in Patients With Acute Ischemic Stroke: The CATIS Randomized Clinical Trial. JAMA 2013;Nov 17:[Epub ahead of print].

Presented by Dr. Jiang He at the American Heart Association Scientific Sessions, Dallas, TX, November 17, 2013.

Keywords: Stroke, Enalapril, Nimodipine, Tomography, X-Ray Computed, Diuretics, Hypotension, Blood Pressure, Magnetic Resonance Imaging, Calcium Channel Blockers, Hospitalization, Hypertension


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