MANAGEMENT OF HTN AND T2DM IN ACUTE STROKE in stroke

1. Dr Rahi kiran
SR I Neurogy
GMC Kota

2. • Stroke is among the three leading causes of death (other two are heart
attacks and cancer)
• Majority of the strokes are ischemic and the rest are of hemorrhagic
type.
• Hypertension is the leading modifiable risk factor for both types of
stroke.
• Appropriate control of blood pressure is required to ensure good
outcome in patients with stroke and to prevent recurrence of stroke.

3.  Acute stroke impairs the autoregulation of the cerebral
circulation so that the blood flow in the ischemic area
becomes passively dependent on mean arterial pressure.
• Pre-existing HTN, Diabetes, high serum creatinine and the
Cushing’s reflex– can all exacerbate HTN.
• Headache, urinary retention, infection, stress - can lead to an
imbalance in the autonomic nervous system, activate the
sympathetic system - hypertensive response

4. • There is a U-shaped relationship between presenting BP and
outcome after ischaemic stroke.
• Both low and high extremes of BP are associated with a
poor outcome.
• For every 10mmHg of SBP below 150mmHg the risk of
death and dependency increased by 17.9%
• For every 10mmHg increase in SBP above 180mmHg the risk
of early death increased by 3.8%.

5. • Elevated BP is present in >80% of patients with AIS,
• Aggressive lowering of BP may lower cerebral perfusion
pressure (CPP), thereby aggravating brain ischemia,
• Very high BP, can worsen cerebral edema, resulting in poorer
outcomes,
• Best outcomes are observed at SBP between 140-180 mmHg.

6.  Patients who have elevated BP and are otherwise eligible for
treatment with intravenous rtPA should have their blood pressure
carefully lowered so that their SBP is <185 mm Hg and DBP is <110
mm Hg (Class I; Level of Evidence B) before fibrinolytic therapy is
initiated.
 If medications are given to lower BP, the clinician should be sure
that the BP is stabilized at the lower level before beginning
treatment with IV rtPA and maintained below 180/105 mm Hg for
at least the first 24 hours after IV rtPA treatment.

7.  In patients with markedly elevated blood pressure who do not receive
fibrinolysis, a reasonable goal is to lower blood pressure by 15% during
the first 24 hours after onset of stroke. The level of blood pressure that
would mandate such treatment is not known, but consensus exists that
medications should be withheld unless the systolic blood pressure is
>220 mm Hg or the diastolic blood pressure is >120 mm Hg (Class I;
Level of Evidence C).

8.  Restarting antihypertensive medications is reasonable after
the first 24 hours for patients who have preexisting
hypertension and are neurologically stable unless a specific
contraindication to restarting treatment is known (Class IIa;
Level of Evidence B)

9.  For patients who are not candidates for fibrinolytic therapy,
current guidelines recommend permitting moderate hypertension
in most patients with acute ischemic stroke.
 Many patients have spontaneous declines in blood pressure during
the first 24 hours after onset of stroke. (Class IIb; Level of
Evidence C).
 exceptions would be patients who have active comorbidities (eg,
aortic dissection, acute myocardial infarction , decompensated
heart failure) that require emergent blood pressure management.

10. • Antihypertensive medications are withheld, as long as SBP is
220 mmHg or lower and DBP is 120 mmHg or lower
(Class I; Level of Evidence C).
• In stroke patients undergoing IV thrombolysis with alteplase or
tenecteplase, anti-hypertensive drugs are not used if the SBP is
185 mmHg or lower and DBP is 110 mmHg or lower.
(Class I; Level of Evidence B)

11.  1. Goal SBP<180 mmHg, DBP<105
 2. SBP 180-230 OR DBP 105-120:
Labetalol 10 mg IV given over 1-2 minutes; may repeat or double
labetalol every 10-20 minutes to maximum dose of 300 mg
or
give initial labetalol dose, then start Nicardipine 5 mg/hour IV
infusion as initial dose and titrate to desired effect by increasing
rate by 2.5 mg/hour every 5 minutes to maximum of 15 mg/hour
or
consider a labetalol drip at 2-8 mg/min.

12.  3. Systolic >230 OR Diastolic 121-140:
Labetalol or give initial labetalol dose, then start Nicardipine
or
consider a labetalol drip at 2-8 mg/min.
 If blood pressure Is not controlled by labetalol or nicardipine,
consider sodium nitroprusside.
 4. Diastolic >140:
Sodium nitroprusside

13.  • Systolic >220 OR Diastolic 121–140:
Labetalol or Nicardipine
 - Aim for a 10% to 15% reduction of blood pressure
 • Diastolic >140
Nitroprusside
 - Aim for a 10% to 15% reduction of blood pressure

14. • HTN in the first 24 hours may be beneficial as it improves CPP,
• Small studies have used phenylephrine or norepinephrine in
the first 24 hours to keep the BP high normal or mildly high,
• Studies showed improvement in ischemic deficits including
aphasia,
• Improved perfusion was also noted on MR perfusion studies,
• Treatment appears promising, however further larger trials are
needed. Not included in guidelines yet. (Class IIb; Level of
Evidence B).

15. CLASS OF DRUG DRUG EFFICACY
ACE inhibitor Perindopril, Ramipril Effective
Diuretic Indapamide Effective
ARB Losartan Effective
ARB Telmisartan Possibly Effective
Ca channel blocker Amlodipine Effective
Beta blocker Atenolol Not effective

16. • Primary prevention :<140/90 mmHg for uncomplicated
hypertensive patients, <130/80 mmHg for those with diabetes
mellitus or chronic kidney disease,
 Secondary prevention :<130/80 mmHg for those with recent
lacunar stroke. (Class IIb; Level of Evidence B).

17. HYPERTENSION
AND
HEMORRHAGIC STROKE

18. • HTN alone or in combination with risk factors accounts for 80%
of ICH cases,
• The risk of developing ICH increases with increasing severity of
HTN

19. • Hematoma expansion is more common in hypertensive ICH, as
compared to ICH due to cerebral amyloid angiopathy (45% vs 19%)
• Neurological deterioration is more common in patients with
hematoma expansion
• Cerebral edema and perihematomal edema are also more in
patients with higher BPs
• Higher BPs lead to higher death rates. 28-day survival rates with
MAP of 118 mmHg or less, 119-132 mmHg, 132-145 mmHg and
>145 mmHg were 71%, 65%, 60% and 30%, respectively.

20. • BP lowering is the single most important predictor for better outcome in
acute ICH,
• Intensive BP lowering is associated with better functional outcomes at
90 days after ICH.
• This is in contrast to Ischemic stroke, where BP lowering is avoided in
the first 24 hours.

21.  BP should be controlled in all ICH patients (Class I; Level of
Evidence A).
 Measures to control BP should begin immediately after ICH
onset (Class I; Level of Evidence A).
 A long-term goal of BP <130 mm Hg systolic and 80 mm Hg
diastolic is reasonable (Class IIa; Level of Evidence B).

22. • For ICH patients with SBP between 150-220 mmHg and without a
contraindication to acute BP treatment, acute lowering of BP to 140
mmHg is safe (Class I; Level of evidence A) and can be effective for
improving functional outcome (Class IIa; level of evidence B)
• For ICH patients presenting with SBP>220 mmHg, aggressive BP
lowering with a continuous IV infusion may be considered (Class
IIb; Level of evidence C)
• Both nicardipine and labetalol infusion are equally safe and
effective.

23.  Acute reduction in BP to < 140mmhg within 1 hour of
presentation – beneficial
 A long-term goal of BP <130/80 mm Hg is reasonable (Class
IIa; Level of Evidence B).
 Target BP of 130/80 mmHg or lower is recommended to
prevent recurrence of ICH.
Antihypertensive Treatment of Acute Cerebral Hemorrhage(ATACH)
Investigators. Antihypertensive treatment of acute cerebral hemorrhage.
Crit Care Med 2010;38:637–48
Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure
lowering in patients with acute intracerebral hemorrhage. N Engl J Med
2013;368:2355–65

24. • Patients with hypertensive ICH have a higher rate of recurrence
of ICH (9% at 1 year, and 14% at 5 years)
• Target BP of 130/80 mmHg or lower is recommended to
prevent recurrence of ICH.
• There is no specific recommendation regarding the choice of
antihypertensive agent, and it depends on age, comorbid
conditions such as DM, renal insufficiency, cardiac disease, etc.
Secondary Prevention of Small Subcortical Strokes (SPS3) study, Am J Hypertens. 2013

26.  Type 2 DM is associated with 2- to 3-fold increase in the risk of
stroke.
 About 10% of newly diagnosed T2DM patients develop stroke
within the first 5 years of diagnosis,
 High glycemic levels may also be seen in the setting of an
acute stroke without a history of diabetes, presumably due to
a sympathetic response to the infarct

27.  Nondiabetic hyperglycemic ischemic stroke patients have a 3-fold
higher 30-day mortality and diabetic patients have a 2-fold 30-day
mortality.
 In several trials involving thrombolytic and anticoagulation therapy
in patients with stroke, hyperglycemia appears to be an
independent risk factor for worsened outcome.
 In addition, hyperglycemia has been suggested as an independent
risk factor in hemorrhagic conversion of the stroke after
administration of thrombolytic therapy.

28.  Age>60
 Proteinuria
 High BP
 FBS > 200 mg%
 HbA1C> 9.5%
 Hyperuricemia

29.  Systematic review and meta-analysis of 64 cohort studies between
1966 to 2013,
 Compared with men with Type 2 DM, women with Type 2 DM had
a 27% greater risk of stroke
 Compared with men with Type 1 DM, women with Type 1 DM had
a 37% greater risk of stroke.
(Lancet Diabetes Endocrinol, 2015)

30.  Prediabetes defined as FBS 110-125 mG% showed a modest
increase in risk of stroke
 Impaired glucose tolerance resulted in modest increase in the
risk of stroke
(BMJ 2012;344:e35)

31.  Among patients admitted with stroke, 40-50% have diabetes
mellitus
 Additional 20% have hyperglycemia without any history of
diabetes - stress hyperglycemia,
 So, a total 0f 60-70% of patients with acute stroke have
hyperglycemia at admission.

32.  Patients with hyperglycemia and acute stroke have prolonged
hospital stay and incur higher hospitalization costs
 Hyperglycemia at admission in patients with stroke results in
poor functional outcome at 3 months
 Hyperglycemia independently increases the risk of death at 90
days, 1 year and 6 years after stroke

33.  Hyperglycemia leads to:
a) Lesser salvage of mismatch tissue from infarction
b) Increase in infarct size/volume over time, thus
resulting in poorer outcomes
 Acute hyperglycemia increases brain lactate production and
facilitates conversion of hypoperfused at-risk tissue into
infarction.

34.  Patients with acute stroke and hyperglycemia are often kept
NPO (nothing by mouth), because of the complicating effects
of feeding on the blood glucose level.
 Typically, hyperglycemia in the setting of acute stroke is
treated with subcutaneous insulin on a sliding scale.
 Refractory hyperglycemia may require the use of intravenous
(IV) insulin; however, IV insulin increases the risk of
hypoglycemia.

35.  Glucose regulation in acute stroke patients (GRASP) trial
 3 arms- tight control (70-110 mg%), loose control (70-
200mg%) and control usual care (70-300mg%)
 Insulin infusion was used to achieve the targets,
 The overall rates of hypoglycemia (<55 mg%) were 5% in loose
and control usual care groups, whereas it was 30% in the tight
group.
(Stroke, 2009)

36.  INSULINFARCT study
 180 patients with ischemic stroke
 Received intensive insulin therapy (IIT) or usual subcutaneous
insulin for 24 hours
 95% within IIT group and 67% in subcutaneous insulin group
had sugar within 126 mg%
 Infarct growth was lower in sc insulin group
 Functional outcome and death rates were similar at 90 days.
(Stroke, 2012)

37.  Maintain plasma glucose levels within 140 to 180 mg% in the first
24 hours,
 Close monitoring should be done to detect hypoglycemia,
 For patients being considered for IV thrombolysis, blood sugar
should be within 50-400 mg% range.
(Stroke,2013)

38.  Hypoglycemia (blood glucose <60 mg/dL) should be treated in
patients with acute ischemic stroke (Class I; Level of Evidence C). The
goal is to achieve normoglycemia.
 Evidence indicates that persistent in-hospital hyperglycemia during
the first 24 hours after stroke is associated with worse outcomes
than normoglycemia, and thus, it is reasonable to treat
hyperglycemia to achieve blood glucose levels in a range of 140 to
180 mg/dL and to closely monitor to prevent hypoglycemia in
patients with acute ischemic stroke (Class IIa; Level of Evidence C).

39.  Patients with ischemic stroke or transient ischemic attack (TIA)
should be screened for diabetes with a fasting plasma glucose,
glycated hemoglobin (A1C) or 75 g oral glucose tolerance test
soon after admission to hospital [Grade D, Consensus].
 All patients with diabetes and ischemic stroke or TIA should
receive the same treatments that are recommended for
patients with ischemic stroke or TIA without diabetes since
they benefit equally [Grade D,Consensus].

40.  sc insulin on a sliding scale
 Refractory hyperglycemia - intravenous (IV) insulin - increases
the risk of hypoglycemia.
 sliding scale insulin may be ineffective for those patients who
had diabetes and were hyperglycemic in the acute stroke
setting.

41.  But, those patients who were hyperglycemic but did not have
a history of diabetes (eg, "stress hyperglycemia") did respond
well to a sliding scale
 Transition from acute therapy to initiation of chronic therapy
depends on persistence of hyperglycemia or evidence that the
patient has diabetes.

42.  delays the onset and slows the progression, but with 3-fold
higher rate of severe hypoglycemia
 For the time being, it appears reasonable to use a sliding scale
in order to maintain reasonable levels of blood glucose (eg,
140 - 180mg/dL), as more aggressive targets may worsen
outcome.

43.  Sugar control is important in patients with stroke to prevent
recurrence of stroke,
 About 9% of recurrent strokes are attributable to diabetes
mellitus,
 Goal for HbA1C level is less than 7%.

44.  High blood glucose on admission predicts an increased risk of
mortality and poor outcome in patients with ICH, independent
of the presence of diabetes mellitus
 tight glucose control (range, 80–110 mg/dL) using insulin
infusions increased incidence of hypoglycemic events and
possibly even an increased risk of mortality

45.  Glucose should be monitored. Both hyperglycemia and
hypoglycemia should be avoided (Class I; Level of Evidence C).
Implementation of evidence-based treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction in acute stroke (QASC):
a cluster randomised controlled trial. Lancet. 2011;

46. • HTN & T2DM is an important risk factor for both AIS and ICH
• BP & sugar control is also important to reduce the future
recurrence of strokes.

47. Ritvij Bowry,Neurology: Clinical Practice , October 2014

48. • Antihypertensive medications are withheld, as long as SBP is
220 mmHg or lower and DBP is 120 mmHg or lower
(Class I; Level of Evidence C).
• In stroke patients undergoing IV thrombolysis with alteplase or
tenecteplase, anti-hypertensive drugs are not used if the SBP is
185 mmHg or lower and DBP is 110 mmHg or lower.
(Class I; Level of Evidence B)

49.  it is reasonable to initiate long-term antihypertensive therapy
after the initial 24 hours from stroke onset in most patients.
(individualized therapy) (Class IIa; Level of Evidence B)

50. • Primary prevention : <140/90 mmHg for uncomplicated
hypertensive patients,
<130/80 mmHg for those with diabetes
mellitus or chronic kidney disease,
 Secondary prevention :<130/80 mmHg for those with recent
lacunar stroke.

51.  Acute reduction in BP to < 140mmhg within 1 hour of
presentation – beneficial
 A long-term goal of BP <130/80 mm Hg is reasonable (Class
IIa; Level of Evidence B).
 Target BP of 130/80 mmHg or lower is recommended to
prevent recurrence of ICH.
Antihypertensive Treatment of Acute Cerebral Hemorrhage(ATACH)
Investigators. Antihypertensive treatment of acute cerebral hemorrhage.
Crit Care Med 2010;38:637–48
Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure
lowering in patients with acute intracerebral hemorrhage. N Engl J Med
2013;368:2355–65

52. Ritvij Bowry,Neurology: Clinical Practice ,October 2014

53.  Glucose should be monitored. Both hyperglycemia and
hypoglycemia should be avoided (Class I; Level of Evidence C).
 tight glucose control (range, 80–110 mg/dL) increased
incidence of hypoglycemia and increased risk of mortality
 it is reasonable to use a sliding scale in order to maintain
reasonable levels of blood glucose (140 - 180 mg/dL), as more
aggressive targets may worsen outcome. (Class IIa; Level of
Evidence C).

54.  Stroke.2015;46:000000.DOI:10.1161/STR.0000000000000069.
 AHA/ASA. Guidelines for management of acute ischemic stroke,
2013
 Canadian Diabetes Association Clinical Practice Guidelines
Expert Committee, Can J Diabetes 37 (2013) S124eS125
 Emedicine : medscape

55. • Primary Outcome: 90-day death and major disability (mRS 3-
6): Not significant (P=0.06)
• Secondary Outcomes:
• Shift in mRS at 90 days: Significant improvement (P=0.04)
• Health related quality of live (EQ-5D): Significant improvement
(p=0.002)
• Rapid blood pressure lowering is safe and may be beneficial