Canadian Society of Internal Medicine Annual Meeting 2017 Toronto, - - PowerPoint PPT Presentation

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Canadian Society of Internal Medicine Annual Meeting 2017 Toronto, - - PowerPoint PPT Presentation

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Canadian Society of Internal Medicine Annual Meeting 2017 Toronto, ON Hypertension in Pregnancy (workshop) Dr. Shital Gandhi University of Toronto CSIM Annual Meeting 2017 The following presentation represents the views of the speaker at

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Canadian Society of Internal Medicine

Annual Meeting 2017

Toronto, ON

Hypertension in Pregnancy (workshop)

  • Dr. Shital Gandhi

University of Toronto

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SLIDE 2

CSIM Annual Meeting 2017

  • Dr. Shital Gandhi-HTN in pregnancy- Nov 1

The following presentation represents the views of the speaker at the time of the presentation. This information is meant for educational purposes, and should not replace other sources

  • f information or your medical judgment.

Learning Objectives:

  • Master the classification to hypertensive disorders in pregnancy
  • Appreciate the role of the internist in the management and treatment of

hypertension in pregnancy, preeclampsia, and post-pregnancy care

  • Discuss preeclampsia prevention
  • Understand early models of preeclampsia prediction
  • Review the medications that can be used safely to treat hypertension in pregnancy
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SLIDE 3

CSIM Annual Meeting 2017

Conflict Disclosures

Definition: A Conflict of Interest may occur in situations where the personal and professional interests of individuals may have actual, potential or apparent influence over their judgment and actions.

“I have no conflicts to declare”

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CLASSIFICATION OF HYPERTENSIVE DISORDERS IN PREGNANCY (SOGC 2014)

Pre-existing (chronic) HTN

  • With co-morbid conditions
  • With preeclampsia

Gestational HTN

  • With comorbid conditions
  • With preeclampsia

Preeclampsia (PET=Preeclampsia-Toxemia) Other (transient, white coat, masked)

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CASE 1 QUESTION 1

35 G1P0 at 8 weeks gestation with BP 145/95 mm Hg Which of the following is CORRECT? 1) She has Pre-existing or Chronic HTN 2) She has Gestational HTN 3) Lowering blood pressure will prevent Preeclampsia 4) There are no therapies to prevent Preeclampsia

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HEMODYNAMIC CHANGES IN PREGNANCY

  • 20

40 100 160 10 20 30 40 50

Systolic BP

Systolic BP

Gestational age

Hypertension defined as BP > 140/90 mm Hg

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SLIDE 7

CLASSIFICATION OF HYPERTENSIVE DISORDERS IN PREGNANCY (SOGC 2014)

Pre-existing (chronic) HTN: HTN (> 140/90) detected prior to 20 weeks

  • With co-morbid conditions
  • With preeclampsia: risk is ~ 20%

Gestational HTN

  • With comorbid conditions
  • With preeclampsia

Preeclampsia Other (transient, white coat, masked)

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CONTROL OF HTN IN PREGNANCY STUDY (CHIPS, NEJM 2015)

No difference: pregnancy loss or NICU

  • RCT of 987 women with HTN
  • Non-proteinuric HTN (14-34 wks)
  • Intervention: “Tight” (DBP 85 mm Hg) vs “Less Tight” (DBP 100 mm Hg)
  • Rates of preeclampsia similar in both groups
  • Secondary outcome: serious maternal complications up to 6 weeks PP or until

hospital discharge

Target 130-155/80-105 mm Hg Target 130-140/80-90 mm Hg if diabetes, renal disease, etc

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CASE 1 QUESTION 2 (TREATMENT)

Which of the following are CORRECT?

  • 1. Atenolol can be used to treat HTN in pregnancy
  • 2. Labetalol can be used to treat HTN in pregnancy
  • 3. Nifedipine is contra-indicated
  • 4. Methyldopa dosing is once a day
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SOGC 2014

Drug Typical Maximum per day Methyldopa 250-500 mg BID-QID 2 grams Labetalol 100-400 mg BID-QID 1200 mg Nifedipine XL 20-60 mg OD-BID 120 mg Hydralazine 10-50 mg TID ~200 mg

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CASE 1 QUESTION 2 (TREATMENT)

Which of the following are correct?

  • 1. Atenolol can be used to treat HTN in pregnancy
  • Increased risk of growth restriction; cases of neonatal bradycardia
  • 2. Labetalol can be used to treat HTN in pregnancy
  • 3. Nifedipine is contra-indicated
  • Fine choice, just don’t have as much volume of data in pregnancy
  • 4. Methyldopa dosing is once a day
  • Fine choice, cheap, but should be at least BID. Significant fatigue
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CASE 1 QUESTION 3 (PREVENTION)

Which of the following is CORRECT?

  • 1. Aspirin prevents preeclampsia
  • 2. Calcium supplementation prevents preeclampsia
  • 3. Salt restriction does NOT prevent preeclampsia
  • 4. Bedrest does NOT prevent preeclampsia
  • 5. All of the above are CORRECT
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ASPIRIN FOR THE PREVENTION OF PET

Author Journal/Yr N Dose ASA GA (wks) Outcome Benigni NEJM/1986 35 60 mg <20 Longer pregnancy Higher birthweight Schiff NEJM/1989 35 100mg 28 Less “PIH” McParland Lancet/1990 100 75 mg <20 Less Proteinuric HTN Less low birth weight Italian Lancet/1993 1100 50 mg 16-32 No difference CLASP Lancet/1994 9364 60 mg 12-32 No difference in preeclampsia Less preterm NIH NEJM/1998 2539 60 mg 13-26 No difference

Over 37,000 women in 55 trials have tried to address this question

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ASPIRIN FOR PREECLAMPSIA

What dose?

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META-ANALYSIS OF INDIVIDUAL PATIENT DATA

ASKIE ET AL. LANCET 2007

RR 0.90 (95% CI 0.84-0.97) Reduced PET Reduced delivery <34 wks Reduced serious adverse outcome

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EARLY ADMINISTRATION OF LOW DOSE ASA FOR THE PREVENTION OF TERM AND PRE-TERM PREECLAMPSIA: SYSTEMATIC REVIEW

FETAL DIAGNOSIS AND THERAPY 2012

If initiated < 16 weeks gestation, RR 0.11, NNT 19

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RECOMMENDATIONS REGARDING ASA ARE UNIVERSAL

Governing body Who What When ACOG Prior early onset PET 60-80 mg Late first trimester NICE All high risk 75 mg < 16 weeks USPSTF High risk 81 mg 12 weeks AHA HTN, or prior gestational HTN 81 mg 12 weeks SOGC All high risk 81 mg < 16 weeks

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PREECLAMPSIA: RISK FACTORS

Demographics Before this Pregnancy This pregnancy T2/T3

Age >40 or <20 Previous PET Multiples Gestational HTN Family history Medical conditions Hypertension Diabetes Renal disease Obesity Abnormal uterine dopplers Family history CAD Antiphospholipid antibody syndrome BP > 130/80 at initial visit Excessive weight gain Low maternal BMI Short duration of sexual relationship > 10 years between pregnancies Reproductive technologies

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IS MORE ASA BETTER?

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CALCIUM SUPPLEMENTATION REDUCES THE RISK OF PREECLAMPSIA

Cochrane Database of Systematic Reviews 4 AUG 2010 DOI: 10.1002/14651858.CD001059.pub3 http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001059.pub3/full#CD001059-fig-0003

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CASE 1 QUESTION 3 (PREVENTION)

Which of the following is correct? 1. Aspirin prevents preeclampsia

  • We can debate the magnitude of effect, but it does help

2. Calcium supplementation prevents preeclampsia

  • In women with low calcium intake

3. Salt restriction does NOT prevent preeclampsia

  • True

4. Bedrest does NOT prevent preeclampsia

  • True

5. You can’t fool me. All of the above are CORRECT

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CASE #1 (REVIEW)

35 G1P0 at 8 weeks gestation with BP 145/95 mm Hg Which of the following is CORRECT? 1) She almost certainly has Pre-existing or Chronic HTN

  • Yes, given the timing of detection

2) She almost certainly has Gestational HTN

  • No, it’s too soon

3) Anti-hypertensive medication will prevent Preeclampsia

  • No. RCT’s have shown that this will not effect rates of PET

4) There is nothing we can do to prevent Preeclampsia

  • Not true: ASA 81-150 mg, calcium if intake is low
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CASE #2

35 G2P1L0 at 17 weeks gestation with BP 145/95 mm Hg (new) Which of the following is correct? 1) She has Pre-existing or Chronic HTN 2) She has Gestational HTN 3) I need more information

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HEMODYNAMIC CHANGES IN PREGNANCY

  • 20

40 100 160 10 20 30 40 50

Systolic BP

Systolic BP Gestational Age

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WHEN GUIDELINES DON’T ENCOMPASS PHYSIOLOGIC EXPECTATIONS

In this situation, 3 possibilities:

  • 1. There is a new medical cause of hypertension
  • Other secondary causes of HTN
  • SLE, HUS, APS, TTP
  • 2. There is an atypical/early placental-mediated disorder
  • Very early onset preeclampsia
  • Molar pregnancy
  • 3. Transient Hypertension
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EARLY ONSET PREECLAMPSIA

  • High perinatal morbidity and mortality
  • Treatment of hypertension is important, but will not

really affect fetal outcome

  • The internist should be aware of guarded fetal

prognosis

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CASE #2

35 G2P1L0 at 17 weeks gestation with BP 145/95 mm Hg (new) Which of the following is correct? 1) She has Pre-existing or Chronic HTN

  • Technically, the guidelines would lead us to this conclusion,

but physiologically, it doesn’t fit 2) She has Gestational HTN

  • Technically, the guidelines would rule this out, but…

3) I need more information

  • Yes. Reviewing the course of blood pressure is important
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CASE #3

35 G1P0 at 28 weeks gestation, BP 145/95 mm Hg (new) Which of the following is FALSE?

  • 1. She has Gestational Hypertension
  • 2. She is at increased risk of Preeclampsia
  • 3. No proteinuria = No preeclampsia
  • 4. The fetus requires additional monitoring
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SLIDE 29
  • 20

40 100 160 10 20 30 40 50

Systolic BP

Systolic BP Gestational Age

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OUTCOMES IN “GESTATIONAL HYPERTENSION”

Outcome Gestational HTN (= no proteinuria) Preeclampsia (= proteinuria) Mild Severe Mild Severe Delivery < 34 1 25 1.9 18.5 SGA (%) 6.9 21 10.2 18.5 Abruption 0.3 4.2 0.5 3.7 Perinatal death 0.5 1.0 1.8 Buchbinder Am J Ob Gynecol 2002 Hauth Obstet Gynecol 2000

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NEW ONSET OF NON-PROTEINURIC HTN < 34 WEEKS PREDICTS HIGH RISK OF PREECLAMPSIA

Gestational Hypertension at “Term” (> 37 weeks)

  • Outcome excellent

Gestational Hypertension “remote from term”

  • Outcomes similar to preeclampsia
  • Time from diagnosis of Hypertension to diagnosis of

preeclampsia ~ 5 weeks

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PREECLAMPSIA (SOGC 2014)

Gestational Hypertension

(new onset after “20-ish” weeks)

+

  • New proteinuria
  • One or more adverse conditions
  • One or more severe complications
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SLIDE 33

SOMANZ SOGC ACOG Chronic HTN

Essential Secondary White coat

Pre-existing

Co-morbid conditions Preeclampsia

Chronic HTN Gestational Gestational

Co-morbid conditions Preeclampsia

Gestational Preeclampsia-eclampsia Preeclampsia Preeclampsia Other

Transient White coat

Chronic + PET Chronic + PET Diagnostic Criteria for Preeclampsia

Hypertension + Organ involvement and/or Fetal involvement

Gestational HTN +

Proteinuria or Adverse conditions or Severe complications

HTN + proteinuria

  • r

HTN +

plts < 100, AST > twice ULN, AKI, neurologic, pulm edema

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CASE #3

35 G1P0 at 28 weeks gestation, BP 145/95 mm Hg (new) Which of the following is FALSE? 1. She has Gestational Hypertension

  • Yes

2. She is at increased risk of Preeclampsia

  • Yes

3. No proteinuria = No preeclampsia

  • No

4. The fetus requires additional monitoring

  • Yes
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CASE #4

35 G1P0 at 30 weeks gestation with BP 160/100 (new) Asked to assess in obstetric triage Your assessment for proteinuria can include any of the following EXCEPT?

  • 1. Urine dipstick
  • 2. Urine protein/creatinine ratio
  • 3. 24 hour urine collection
  • 4. Serum PlGF
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  • 20

40 100 160 10 20 30 40 50

Systolic BP

Systolic BP

Gestational Age

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ASSESSMENT OF PROTEINURIA

Protein to creatinine ratio <30 mg/mmol has a good negative predictive value Sensitivity 84%, specificity 76%, PLR 3.5, NLR 0.21

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WHAT THE PLGF?!?

REVIEWING PREECLAMPSIA PATHOPHYSIOLOGY

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ANGIOGENIC FACTORS AND PREECLAMPSIA

MAYNARD, SEMINARS IN NEPHROLOGY 2011 Explains the multi-systemic nature of this disease (akin to sepsis)

  • Renal
  • Hematologic
  • Hepatic
  • Neurologic
  • Cardiac
  • Respiratory
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CASE #4

35 G1P0 at 30 weeks gestation with BP 160/100 (new) Asked to assess in obstetric triage Your assessment for proteinuria can any of the following EXCEPT? 1. Urine dipstick 2. Urine protein/creatinine ratio 3. 24 hour urine collection 4. Serum PlGF

  • No, but maybe one day this will replace proteinuria

altogether!

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CASE #4

(NO QUESTION)

Assessment of potential preeclamptic:

  • 1. Rule out other “imitators” (TTP, nephritides, DIC)
  • Blood film, urinalysis
  • 2. Multi-system assessment
  • Neuro: reflexes/clonus, fundoscopy, screen
  • CVS: fluid balance, pulmonary edema
  • Renal: function
  • Magnitude of proteinuria does not predict risk
  • Heme: platelets, hemoglobin
  • Hepatic: liver enzymes
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SLIDE 43

CASE #4

35 G1P0 at 30 weeks gestation with BP 160/100 (new) Hyper-reflexic with clonus, edema, headache 3+ protein on dipstick, Urine PCR 320, creatinine 168, AST/ALT 450, platelets 100 Which of the following regarding acute treatment is CORRECT? 1. Intravenous labetalol, hydralazine or oral nifedipine can be used 2. She should be delivered for maternal safety 3. She may benefit from magnesium sulfate 4. All of the above

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RISK OF STROKE INCREASES WITH SYSTOLIC BP >160 MM HG

MARTIN, OBSTET GYNECOL 2005

Measurement (mm Hg)

Pre-pregnancy Pre-stroke Change

Mean systolic 110 175 64

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ECLAMPSIA:

MAGNESIUM SULFATE TREATMENT OF CHOICE FOR PREVENTION AND TREATMENT

  • The Eclampsia Trial Collaborative Group
  • MgSO4 lower risk of recurrence compared to dilantin or

benzo

  • The MAGPIE trial (MAGnesium in the Prevention In Eclampsia)
  • Lancet 2002: 58% reduction in eclampsia
  • Mortality reduced: RR 0.55, but CI (0.26-1.14)
  • No adverse effects on babies
  • 4-6 g in 100 mls D5W over 15 mins, then 1-2 g/hour for 24 hours
  • Toxicity?
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SLIDE 46

CASE #4

35 G1P0 at 30 weeks gestation with BP 160/100 (new) Hyper-reflexic with clonus, edema, headache 3+ protein on dipstick, Urine PCR 320, creatinine 168, AST/ALT 450, platelets 100

Which of the following regarding acute treatment is CORRECT? 1. Intravenous labetalol, hydralazine or oral nifedipine can be used

  • Yes. Avoid labetalol if in heart failure

2. She should be delivered for maternal safety

  • This should be discussed with OB, but yes

3. She may benefit from magnesium sulfate

  • Yes

4. All of the above

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CASE #5

35 G1P1 Postpartum day #3, headache, BP 160/100 mm Hg (new) Which of the following is CORRECT?

  • 1. This could be Preeclampsia presenting postpartum
  • 2. She is no longer at risk of serious complications
  • 3. All antihypertensives are contra-indicated in lactation
  • 4. She can be discharged home with follow up in 6 weeks
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CASE #5

35 G1P1 Postpartum day #3 with headache and BP 160/100 mm Hg Which of the following is CORRECT? 1. This could be Preeclampsia presenting postpartum

  • Yes. 5-10% of PET presents postpartum
  • Take care to stop NSAID’s

2. She is no longer at risk of serious complications

  • False. Consider looking for retained products of conception

3. All antihypertensives are contra-indicated in lactation

  • False. Labetalol, nifedipine, hydralazine, methyldopa, enalapril can be

used 4. She can be discharged home with follow up in 6 weeks

  • False. She should be discharged once BP is controlled. F/U in a week
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SLIDE 49

LONGTERM ASSOCIATIONS WITH PREECLAMPSIA

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WOMEN WITH PREECLAMPSIA HAVE 2-4 FOLD INCREASED RISK FOR: CHRONIC HYPERTENSION ISCHEMIC HEART DISEASE STROKE PERIPHERAL ARTERIAL DISEASE DVT END-STAGE (RR 4.3) WOMEN WITH PREECLAMPSIA MAY HAVE A LOWER RISK OF CANCER

Williams, Obstetric Medicine 2012

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WOMEN WITH EARLY ONSET PREECLAMPSIA HAVE THE HIGHEST RISK

Relative risk of 8 for ischemic heart disease

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SLIDE 52

PREECLAMPSIA INCREASES THE RISK OF ENDSTAGE RENAL DISEASE

Vikse, NEJM 2008 PET in 3 pregnancies, RR 17

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PREECLAMPSIA: GLIMPSE INTO THE FUTURE? HOW TO INTERVENE? CIRCULATION 2011

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SUMMARY

  • Hypertension in pregnancy is a very heterogeneous disease
  • BP drops physiologically in the first half of pregnancy
  • Beware the patient whose BP is rising at this point!
  • Drug: labetalol, methyldopa, nifedipine, hydralazine
  • Target BP is 130-155/80-105 mm Hg
  • Definitely 130-140/80-90 if “co-morbid” conditions
  • Otherwise, target to be decided between you and patient
  • Personal opinion: suggest target 130-140/80-90 mm Hg
  • Prevention: ASA 81 mg OD, calcium supplementation if intake low
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SUMMARY

  • Preeclampsia is a very distinct placental cause of

HTN

  • Consider the management in phases:
  • Acutely: multi-system management
  • Short-term follow up: BP monitoring
  • Long-term follow up: assessment of CV risk
  • The general internist has much to offer and can be a

valuable colleague and consultant to obstetrics