Choice of antihypertensive Peter von Dadelszen BMedSc, MBChB, DipObst, DPhil, FRANZCOG, FRCSC, FRCOG Associate Professor of Obstetrics & Gynaecology, UBC Consultant in Maternal-Fetal Medicine, BC Women’s Co-Director, CFRI Reproduction & Healthy Pregnancy Cluster PRE -eclampsia E clampsia M onitoring, Prevention & T reatment
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Choice of antihypertensive Peter von Dadelszen BMedSc, MBChB, DipObst, DPhil, FRANZCOG, FRCSC, FRCOG Associate Professor of Obstetrics & Gynaecology, UBC.
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Choice of antihypertensive
Peter von DadelszenBMedSc, MBChB, DipObst, DPhil, FRANZCOG, FRCSC, FRCOG
Associate Professor of Obstetrics & Gynaecology, UBCConsultant in Maternal-Fetal Medicine, BC Women’s
Modified from: Magee & Abdullah. Expert Opin Drug Saf 2004
The ‘ideal’ agent in rural & remote settings
• Oral administration• Reliable reduction in BP• Smooth reduction in BP• Rapid onset of action• Minimal overshoot
– BP in target range• sBP 130-160mmHg• dBP 80-110mmHg
Reliable reduction in BPsevere hypertension
• CCBs are more reliable than hydralazine in lowering BP in pregnant women with severe hypertension
Magee et al. BMJ 2004Duley et al. CDSR 2006
• Hydralazine appears more reliable than labetalolMagee et al. BMJ 2004
• Methyldopa may be an agent of choice for severe hypertension
Duley et al. CDSR 2006
Reliable reduction in BPsevere hypertension
• CCBs are more reliable than hydralazine in lowering BP in pregnant women with severe hypertension
Magee et al. BMJ 2004Duley et al. CDSR 2006
• Hydralazine appears more reliable than labetalolMagee et al. BMJ 2004
• Methyldopa may be an agent of choice for severe hypertension
Magee et al. BMJ 2004
Reliable reduction in BPsevere hypertension
• CCBs are more reliable than hydralazine in lowering BP in pregnant women with severe hypertension
Magee et al. BMJ 2004Duley et al. CDSR 2006
• Hydralazine appears more reliable than labetalolMagee et al. BMJ 2004
• Methyldopa may be an agent of choice for severe hypertension– Widely used – routinely on EMLs
The ‘ideal’ agent in rural & remote settings
• Oral administration• Reliable reduction in BP• Smooth reduction in BP• Rapid onset of action• Minimal overshoot
– BP in target range• sBP 130-160mmHg• dBP 80-110mmHg
Smooth reduction in BP
• The ideal agent will reduce BP effectively and over a relatively short period of time– <60min– Stabilise and reduce MAP by 10% per hour
• BP fall will not be precipitous– Adverse maternal CNS effects– Adverse fetal effects
Normal Pregnancy
Early-onsetpre-eclampsia
The ‘ideal’ agent in rural & remote settings
• Oral administration• Reliable reduction in BP• Smooth reduction in BP• Rapid onset of action• Minimal overshoot
– BP in target range• sBP 130-160mmHg• dBP 80-110mmHg
‘Rapid’ onset of action
Modified from: Magee & Abdullah. Expert Opin Drug Saf 2004
Drug Dosage Onset Peak Duration
Atenolol 25 – 50 mg 1hr 2-4hr 24hr
(dose dependent)
Labetalol 200 mg 20min – 2hr 1-4 hr 8-12hr
(dose dependent)
Methyldopa 500 mg – 2 g 40 min 3-6hr 12-24hr
Nifedipine PA (or retard) 10 mg 30min 4hr 12hr
Nifedipine capsule 5 – 10 mg 5-10min 30min 6.5hr
The ‘ideal’ agent in rural & remote settings
• Oral administration• Reliable reduction in BP• Smooth reduction in BP• Rapid onset of action• Minimal overshoot
– BP in target range• sBP 130-160mmHg• dBP 80-110mmHg
Minimal overshoot
• CCBs less likely to cause overshoot than hydralazine Magee et al. BMJ 2004
• Beta-blockers less likely to cause overshoot than hydralazine Magee et al. BMJ 2004
• Nifedipine PA/Retard less likely to cause overshoot than capsules? Brown et al. AJOG 2002
– Small RCT– End-point (‘in range BP’) measured at time PA
approaching maximal effect
On balance• An intervention package should include 1 - 3 oral
antihypertensive agent(s)• The choice for a single antihypertensive lies between
methyldopa, nifedipine, and another beta-blocker, probably atenolol – labetalol is not on EMLs
• Theoretical and practical reasons to have all available– Combined CNS control, beta-blockade and vasodilatation– Second effective agent for women whose BP is resistant to
another agent • Reserve i.v. hydralazine for obtunded/comatose
women
PRE-EMPTObjective 3
• CLIP (Community-Level Interventions for Pre-eclampsia)
– Cluster randomised controlled trial of community level interventions for women with pre-eclampsia
– Aims• Can
– identification, – early risk stratification, and – initiation of life-saving treatment at the community level
• decrease pre-eclampsia-related maternal and perinatal mortality in LMIC?
CLIP• Intervention
– CLIP package of care• Case recognition & triage• Treatment of severe hypertension (sBP ≥160mmHg)