Firoz_Choice of Anti Hypertensives in Management of PEE

8/2/2019 Firoz_Choice of Anti Hypertensives in Management of PEE

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Tabassum Firoz, MD FRCPCUniversity of British Columbia, Canada

PRE-EMPT [Pre-eclampsia/Eclampsia Evaluation, Monitoring and Treatment]


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1. Definition of severe hypertension

2. Severe hypertension and maternal morbidity

3. Choice of antihypertensive therapy


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2 RCTs (133 women) show that expectant care

of early severe pre-eclampsia was associated

with a mean pregnancy prolongation of 2.0 wk

[1.4, 2.6] 1

A 2009 systematic review found that expectant

care of severe preeclampsia


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MAP of 107mmHg

= 140/90mmHgMAP of 140mmHg=

180/120mmHg

Seems likely that pregnancy shifts the curve to the LEFT and

Possibly also causes increased vascular PERMEABILITY


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Guideline sBP definition dBP definition

Canada: Society ofObstetricians & Gynecologists of

Canada(2008)

160 mmHg 110 mmHg

UK: NICE The Management ofHypertensive Disorders DuringPregnancy (2010)

160 mmHg 110 mmHg

US: ASH Position Article:Hypertension in Pregnancy(2008)

160 mmHg 110 mmHg

Australasia: SOMANZGuidelines for the Managementof Hypertensive Disorders of

Pregnancy (2008)

170 mmHg 110 mmHg


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In a retrospective case series of 28 women with

stroke, right before their stroke1

o96% had a sBP of 160mmHgo13% had a dBP of 110mmHg

1

Obstet Gynecol 2005;105:246-54


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Saving Mothers Lives 2006-2008, published March 2011

The single major

failing in clinical care in

the current triennium

was, again, inadequate

treatment of

hypertension with

subsequent intracranial

hemorrhage


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Women with severe hypertensionshould receive treatment withantihypertensive therapy

Very low quality evidence

Strong Recommendation

WHO Recommendations for Prevention and Treatment of Pre-eclampsia and Eclampsia 2011


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The choice and route of administrationof an antihypertensive drug for severehypertension during pregnancy, inpreference to others, should be basedprimarily on the prescribing clinicians experience

with that particular drug, its cost and local

availability.

Very-low-quality evidence Weak recommendation


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2010: NICE guidelines provide most up-to-date

summary (30 trials 3,446 women)1

2009: Cochrane Database of Systematic Reviews(24 trials, 2,959 women) 2

2003:BMJ (21 trials, 1,085 women) 3

Two approaches differed in regards to inclusion of quasi-randomised trials, use of RR and RD (risk difference)

One antihypertensive therapy vs. another, OR, hydralazine vs.

any other antihypertensive

1http://guidance.nice.org.uk/CG/Wave15/102DOI: 10.1002/14651858.CD001449.pub2

3BMJ 2003;327:955-60


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Maternal hypotension

Persistent severe hypertension


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Adverse FHR effects N=18 trialsRR 1.61 [1.03, 2.56]

Significant heterogeneity isolated to hydralazine vs. LB group

Adverse FHR effects were variably defined, mostly by

inspection, vague definitions

Low 1-min Apgars N=3 trials

RR 2.70 [1.27, 5.88]

Consistent between trials

No difference in 5-min Apgars

Bradycardia N=3 trialsRD -0.24 [-0.42, -0.06];

All hydralazine vs. LB trials


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Nifedipine compared favourably with parenteralhydralazine with no differences seen in BP controlor maternal or perinatal outcomes

The incidence of maternal hypotension in thenifedipine capsule arms of these trials was low(1/102, 3 trials), but hypotension was more

common in both arms of a nifedipine 10mg capsulevs. 10mg PA tablet trialo 11/31 in the capsule arm vs. 3/33 in the tablet arm with a

relative difference of 0.26 [95% CI 0.07, 0.46]

**Unpublished data


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Concerns have been raised about the safety ofnifedipine capsules outside of pregnancy

Case reports in pregnancy describe the temporalassociation between nifedipine use and either

maternal hypotension or neuromuscular blockade

However, risk of NM blockade has been estimated to

be


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Essential medicines are defined by the WorldHealth Organization as drugs that satisfy the

health care needs of the majority of the

population

Essential Medicines List serve as an advocacytool

Inclusion on an EML does not guarantee anations access to a medication, rather, it

supports the argument that the medicationshould be routinely available.


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Lalani et al. Submitted to BJOG 2012


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Lalani et al. Submitted to BJOG 2012


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There is consensus that severe hypertension (BP of 160-

170/110) should be treated

The emphasis is on importance of treatment, rather than a

specific antihypertensive

Hypotension can occur with any agent

BP goal in a hypertensive urgency should be achieved as

outside pregnancy slowly


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Most studied antihypertensive agents are labetalol (IV),

hydralazine (IV), and nifedipine (po capsules)

There are no definitive differences but hydralazine is not

clearly the drug of FIRST choice

Oral antihypertensive agents may be a reasonable choice

in the facility setting

Essential Medicines Lists have at least one option

a ailable for the treatment of se ere h ertension

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Firoz_Choice of Anti Hypertensives in Management of PEE