Use of Medication for Cardiovascular Disease During Pregnancy

The following are key points to remember

from this review about the use of

cardiovascular medications during pregnancy:

⛱ General Consideration


1- Several hemodynamic and physiologic

Adaptations occur during pregnancy and

the pharmacokinetics of CVS medications

can change throughout gestation.

2- Data on medication safety are often drawn

from observational studies and expert opinion.

3- Food and Drug Administration has replaced

the ABCDX classification system for labeling

the safety of medications during pregnancy

with a narrative labeling system.

4- The Pregnancy and Lactation Labeling Rule

(PLLR) is intended to provide more information

about available data, clinical considerations,

and differences in degrees of fetal risk.

5- In Emergency Situations Standard medications

should be used for treatment of cardiopulmonary

resuscitation or cardiogenic shock.

⛱ARRHYTHMIA


• Arrhythmia in Unstable Patient should be

treated with electrical cardioversion.

• Antiarrhythmic medications should be

avoided in first trimester if possible, and

the lowest effective dose should be used.

• Amiodarone should be avoided

due to the risk of fetal thyroid and

neurodevelopmental complications.

1- Supraventricular tachycardia (SVT) :-

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• SVT can be treated initially with vagal maneuvers,

then adenosine, beta-blockers, and

verapamil as third-line therapy.

• Beta-blockers (with or without digoxin) or

oral verapamil can be used for suppressive

therapy for SVT in the absence of pre-excitation.

• Sotalol or flecainide can be considered in

the absence of structural heart abnormalities.

• In Wolff-Parkinson-White (WPW) syndrome,

flecainide or propafenone are recommended

for the prevention of SVT.

2- Atrial Fibrillation and Atrial Flutter :-

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• AFib & AFlut can be treated with beta-blockers,

verapamil, and digoxin.

• Sotalol, flecainide, and propafenone can be

considered if rhythm-control is needed.

• Intravenous procainamide is used for the

treatment of atrial fibrillation with pre-excitation

(wide complex tachycardia).

3- Beta-blockers :-

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• Beta-blockers are used frequently for treatment

of several CVS conditions during pregnancy.

• Beta-blockers in Large, retrospective studies

shows no association with major congenital abnormalities.

• Beta-blockers are associated with :-

➰ Intrauterine growth restriction

(small for gestational age infants),

➰ Increased risk of preterm birth, and

➰ Neonatal bradycardia and hypoglycemia.

• Atenolol is not recommended due to

increased risk of fetal growth restriction.

4- DIGITALIS

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• Digoxin can be used during pregnancy.

• Of note, the assay for measuring digoxin levels

during pregnancy can result in falsely elevated

levels due to circulating digoxin-like fragments.

5- ANTI-ARRHYTHMICS

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• Flecainide can be used during pregnancy.

Adverse Effects include :-

  • Maternal visual disturbance,

  • Maternal QT interval prolongation,

  • Neonatal QT intervals prolongation and

  • Heart failure at toxic levels,

  • Cholestasis of pregnancy, and

  • Fetal heart rate variability decreased.

• Limited data exist about the use of propafenone during pregnancy.

• Sotalol portends increased risk of

torsades de pointes due to QT prolongation and

is typically only used for fetal arrhythmias.

6- Ventricular tachycardia (VT):-

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• Electric cardioversion should be performed

for Unstable VT.

• If a pregnant woman is Hemodynamically Stable,

Electric cardioversion or Lidocaine or

Beta-blockers can be considered.

• European Society of Cardiology guidelines

suggest procainamide, flecainide, or sotalol.

• Amiodarone should only be used

if other treatments are ineffective.

⛱ HYPERTENSION


1- The placenta does not autoregulate blood

flow; therefore, acute maternal hypotension

due to antihypertensive treatment may cause

Fetal Distress.

2- First-line agents for chronic or gestational HTN

include Labetalol, Nifedipine, and Methyldopa.

💬 Dose reduction may needed in second trimester

when a 5-10 mm Hg decrease in mean BP

due to the physiologic changes of pregnancy.

💬Diuretics can cause placental Hypoperfusion.

⛱ HEART FAILURE


1- Beta-blockers can be used

2- Digoxin can be considered.

3- Diuretics can be used for pulmonary Edema

(furosemide, bumetanide, hydrochlorothiazide)

but excessive dosing carries risk of placental

hypoperfusion & fetal electrolyte abnormalities.

4- During pregnancy, hydralazine plus nitrates

can be used for afterload reduction

5- ACE inhibitors, Angiotensin-receptor blockers,

Direct renin-inhibitors, Angiotensin receptor

neprysilin inhibitors, spironolactone, and

eplerenone are contraindicated.

6- Enalapril, captopril, and benazepril can be

safely considered during lactation.

⛱ DYSLIPIDEMIA


1- Statins considered Contraindicated during

pregnancy, although no associations with birth

defects were found in , observational,

prospective trial and recent systematic review.

2- Gemfibrozil, Fenofibrate, and Ezetimibe

are also considered potentially teratogenic.

⛱ Anticoagulation for Mechanical Valves


1- Embryopathy, Miscarriage, and Stillbirth

Common with daily doses of warfarin >5 mg.

2- If the warfarin dose is >5 mg/day,

Should Switch to (LMWH) or (UFH) Heparin

By the End of the Sixth week of gestation

To decrease the risk of warfarin embryopathy.

3- LMWH does not cross the placenta.

Meticulous monitoring of peak and

trough anti-Xa levels need to be followed.

4- Transition between warfarin and LMWH

are times of increased risk for valve thrombosis

and thromboembolic risk.

5- Women who are receiving warfarin should be

changed to LMWH or UFH at 36 weeks’

gestation to reduce the risk of fetal hemorrhage

and maternal bleeding at the time of delivery.

6- Regional anesthesia cannot be given

within 24 hours of the last dose of LMWH.

7- Cesarean delivery should be performed

if a mother arrives in labor while on warfarin.

8- Reversal of warfarin with vitamin K in

the mother does not ensure reversal in the fetus.

Antiplatelet Medications


1- Low-dose aspirin is considered safe

during pregnancy and lactation, and

2- ASA commonly used for prevention of pre-eclampsia.

3- High-dose aspirin should be avoided due to

Risk of premature closure of ductus arteriosus.

4- Clopidogrel has been used in pregnancy but

since there are limited data, it is recommended

to use it for the shortest duration possible.

5- Clopidogrel must be discontinued 7 days prior

to neuroaxial anesthesia to decrease the risk

of epidural hematoma.

Pulmonary Arterial Hypertension


1- Parenteral and inhaled prostaglandins can be

used in the appropriate setting and

phosphodiesterase-5 inhibitors may considered.

2- Endothelin receptor blockers

(bosentan, ambrisentan, macitentan)

are teratogenic and should not be used.

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📊FDA Pregnancy Categories

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A: Generally Acceptable.

Controlled studies in pregnant women

Show No evidence of fetal risk.

Example drugs : levothyroxine,

folic acid, liothyronine

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B: May be Acceptable.

Either Animal studies show No risk But

Human studies Not available

-OR-

Animal studies showed Minor risks and

Human studies done and showed No risk.

Example drugs: metformin, amoxicillin

hydrochlorothiazide,cyclobenzaprine

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C: Use with caution if benefits outweigh risks.

Animal studies show risk and

human studies not available

-OR-

Neither Animal Nor Human studies done.

Example drugs: gabapentin, amlodipine, trazodone

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D: Use in LIFE-THREATENING Emergencies

When No safer drug available.

Positive evidence of Human Fetal risk.

Example drugs: losartan

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X: Do Not Use in Pregnancy.

Safer alternatives exist.

Risks involved outweigh potential benefits.

Example drugs: atorvastatin, simvastatin,

methotrexate, finasteride