This study aimed to determine if early antihypertensive therapy in patients with acute ischemic stroke leads to different outcomes in those with and without a history of hypertension. Over 4 years, 4,071 patients were randomly assigned to either strict blood pressure control or usual care. Strict control led to greater reductions in blood pressure over 24 hours, 7 days and 14 days, with no differences in short-term death or disability regardless of hypertension history. However, early blood pressure reduction was associated with a lower rate of recurrent stroke in patients with a history of hypertension.

1. Journal club presentation
Dr Govind Madhaw
Dept of neurology
Guide: Dr Niraj Kumar

2. Is early antihypertensive therapy associated
with different outcomes among patients with
ischemic stroke with or without a history of
hypertension?

3. • 80% of patients have self-limiting acute hypertensive response after ischemic
stroke most marked in first few hours and resolves during the next several days.
• Benefit of decreasing BP for primary and secondary prevention of stroke has been
well established.
• But the effect of lowering the BP immediately in patients with acute ischemic
stroke has been uncertain.
• What to do with ongoing antihypertensive therapy?
Background: BP in Acute ischemic stroke

4. • ↓vascular damage,
• ↓ cerebral edema,
• ↓ hemorrhagic transformation
↓ secondary injury
• hasten the transition to long-
term antihypertensive therapy.
• ↓ cerebral perfusion of the
ischemic tissue
• ↑ size of the cerebral
infarction.
Decreasing BP

5. Background: Previous clinical trials

7. To determine whether in acute ischemic stroke
• lowering systolic blood pressure by 10-25% within the first 24 hours and
• achieving systolic blood pressure <140 and diastolic blood pressure <90 mm Hg within 7 days after
randomization and
• maintaining this blood pressure level afterwards during hospitalization
AIM
• will reduce short-term case-fatality and major disability within 2-weeks and
• long-term mortality, major disability, stroke recurrence, and vascular
events over 3 months
• as compared to usual care based on current clinical guidelines.

8. Secondary objective:
To test the effect of early blood pressure reduction among patients
with acute ischemic stroke over 3 months on
• long-term mortality and
• major disability
• Recurrent stroke: fatal or non-fatal
• Vascular events (vascular deaths, nonfatal stroke,
nonfatal myocardial infarction, hospitalized and treated
angina, hospitalized and treated congestive heart failure,
and hospitalized and treated peripheral arterial disease)
• All-cause mortality
• Combination of vascular events and all cause-mortality
• Neurological functional status (mRS)
Objectives of CATIS:
Primary objective:
To test the effect of early blood pressure
reduction among patients with acute ischemic
stroke within 2 weeks on:
• short-term case-fatality and
• major disability (mRS >3)
They also collected DNA and serum/plasma specimens for future genomics and clinical studies on the etiology and
prognosis of ischemic stroke.

9. 0: No symptoms at all
1: No significant disability despite symptoms; able to carry out all usual duties and activities
2: Slight disability; unable to carry out all previous activities, but able to look after own affairs without
assistance
3: Moderate disability; requiring some help, but able to walk without assistance
4: Moderately severe disability; unable to walk and attend to bodily needs without assistance
5: Severe disability; bedridden, incontinent and requiring constant nursing care and attention
6: Dead
Modified Rankin scale

10. Exclusion criteria:
 Systolic BP of 220 mm hg or higher,
 Diastolic BP equal to or higher than 120 mm hg,
 Severe heart failure,
 Acute myocardial infarction or unstable angina,
 Atrial fibrillation,
 Aortic dissection,
 Cerebrovascular stenosis,
 Resistant hypertension, or
 Deep coma
 Patients treated with intravenous thrombolytic therapy
at baseline
Trial Design and Participants
 Multicenter: 26 hospitals across China
 Single-blinded,
 Blinded end-points
 Randomized clinical trial (PROC PLAN in SAS)
 August 2009 to may 2013.
Inclusion criteria:
 Aged 22 years or older
 who had ischemic stroke
 confirmed by computed tomography or magnetic
resonance imaging of the brain
 within 48 hours of symptom onset and
 who had systolic BP between 140 and 220 mm Hg.

11. Control group: Discontinue all home blood pressure
medications.
Methods:
Treatment group: Received antihypertensive
treatment aimed at
• ↓ SBP by 10% to 25% within the 1st 24 hours after
randomization,
• SBP to ≤140 mm Hg, DBP to 90 mm Hg within 7
days, and
• maintaining this level of BP control during the
remainder of a patient’s hospitalization.
• prespecified treatment algorithm regarding use of
multiple drugs
• 1st line: ACEi
• 2nd line: CCB
• 3rd line: Diuretics
• Both groups received standard care according to the
China National Guidelines for Prevention and Treatment
of Cerebrovascular Diseases.
• After discharge, all study participants received standard
care provided by their own healthcare providers
according to the national guidelines.
• Antihypertensive medications prescribed to all study
participants by their physicians.
• The treatment was designed to test for BP treatment
strategy rather than the efficacy of specific
antihypertensive drugs.

12. TARGET
SBP lowering by 10% to 25% within the first 24 hours
SBP≤ 140 mm Hg and DBP < 90 mm Hg maintain this blood
pressure level afterwards during the hospitalization.

13. • Stroke severity: NIHSS
• History of hypertension was defined as a yes answer to the question “have you been told by the doctor that you have
high BP?” or to the question “are you currently taking a drug to lower BP?”
• Baseline BP measurements were obtained by trained nurses
• BP was measured in a supine position using a standard mercury sphygmomanometer
• After randomization, 3 BP measurements were obtained every 2 hours for the first 24 hours, every 4 hours during the
second and third days, and 3 times a day thereafter until hospital discharge or death.
Measurements:

14. • Intention-to-treat
• Means between the antihypertensive treatment and control groups: t tests,
• For percentages : χ2 tests, 2-sided α level of 5%,
• For medians: Wilcoxon rank sum test.
• unadjusted odds ratios (ORs) and 95% CIs: Logistic regression.
• To estimate the effect of BP decrease on the full range of the mRS : ordinal logistic regression.
• To adjust age, sex, baseline systolic BP, body mass index, history of diabetes, smoking, stroke subtype, baseline NIHSS
score, and time from onset to randomization to test the robustness of our findings: sensitivity analysis.
• Data analyses were performed from January to October 2018: using SAS, version 9.4
Statistical Analysis

15. RCT of 200 patients of spont ICH: which one is better- surgical or medical
management?
100 patients were randomized to enter neurology and 100 to enter neurosurgery.
10 patients in the surgery arm died before surgery could be arranged.
10 died after surgery.
20 patients died in total in medical arm.
How to analyse the data?
How to analyse the deaths prior to surgery in the neurosurgery arm?
• 20 % died in medical and 10 % in surgical: if we ignore 10 who died before
surgery as drop out. (Surgical is better)
• Total 30 died with medical management 10/90 in surgical.
• If we count them as death in surgical arm, both medical and surgical arm
looks similar – 20 % death in each arm.

19. Blood Pressure Decrease:
24 hours after randomization,
differences in systolic BP between the intervention group and control group
In patients with history of hypertension: −8.4 (95% CI, −9.5 to −7.3) mm Hg (P < .001)
In those without history of hypertension: −7.2 (95% CI, −9.3 to −5.1) mm Hg (P < .001).

20. Time since
enrollment
Intervention Control Intervention Control
At enrollment
Difference in SBP
b/w two groups (I-C)
-8.4mm of Hg
(95% CI: -9.5 to -7.3mm of Hg)
-7.2mm of Hg
(95% CI: -7.3 to -5.1 mm of Hg)
After 24hr, decrease
in SBP with Rx
21.7 (12.6%) 12.4 (7.0%) 22.4 (13.2%) 14.0 (8.1%)
Difference in SBP −9.3 (95%CI, −10.5 to −8.2)mmHg
(P < .001).
−8.4 (95%CI, −10.5 to −6.2)mmHg
(P < .001).
After 7 days,
difference in SBP
−9.4 (95%CI, −10.3 to −8.5)mmHg
(P < .001)
−8.8 (95%CI, −10.6 to −7.0)mmHg
(P < .001)
At 14 days,
difference in SBP
−9.3 (95%CI, −10.6 to −8.0)mmHg
P < .001
−5.8 (95%CI, −8.4 to −3.1)mmHg
P < .001
With h/o HTN Without h/o HTN

24. a Adjusting for age, sex, baseline SBP, BMI, diabetes, cigarette smoking, stroke subtype, baseline NIHSS score and time
from onset to randomization.

25. Limitation
1. Subgroup analysis: Reduced statistical power of study due to confounding factors.
2. No mention of data regarding cerebral blood flow, collateral blood flow, and presence of penumbral tissue.
3. Criteria chosen for ‘history of hypertension’: Self reported answers about previous diagnoses and current use
of antihypertensive medications
4. Exclusively Chinese patients with stroke

26. Critical appraisal

27. Relevance
Did the study ask a clearly-focused question?
P:
I:
C:
O:
Did the intervention and the control groups start with same prognosis?

30. Were the patients randomized?
Was the randomisation concealed?
Were the patients in study groups similar with respect to known prognostic factors?
Validity Assessment

31. Was the prognostic balance maintained as the disease progressed and
at end of the study?
To what extent was the study blinded?
Was the follow up complete?
Were all of the participants who entered the trial accounted for at its
conclusion?
Validity Assessment

32. Was the Analysis Based on ITT or PP?
Were the participants in all groups followed up and data collected in the same
way?
Validity Assessment

33. Result assessment
Did the new treatment make any difference?
How large was the treatment effect?

34. Patient care/ applicability
Were the study patients similar to patients in our practice?
Were all patient important outcomes considered?
 Can we use this for our patient?

35. • After 7days and 14 days, no difference was noted in
outcomes including death or major disability regardless
of preexisting hypertension (HTN).
• However, early BP reduction was associated with a
lower rate of recurrent stroke in those patients with a
previous history of HTN.
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