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Choice of antihypertensive

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. Christchurch.

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Choice of antihypertensive

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  1. 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

  2. Christchurch

  3. PRE-EMPT(PRE-eclampsia-Eclampsia Monitoring, Prevention & Treatment) • Five objective, LMIC community intervention-focussed, pre-eclampsia project • Funding: • Bill & Melinda Gates Foundation

  4. Why use antihypertensives? • Maternal stroke risk associated with both severe systolic and/or diastolic hypertension • sBP >160mmHg • dBP >110mmHg CEMACH2007 • Severe hypertension associated with placental abruption and attendant maternal and perinatal risks • Severe hypertension is included in most definitions of ‘severe’ pre-eclampsia, although such classification systems are flawed Menzies et al. Hypertens Pregnancy 2007

  5. Why use antihypertensives? • In non-severe pregnancy hypertension • No clear evidence of benefit other than to reduce the frequency of episodes of severe hypertension • May adversely effect fetal growth velocity von Dadelszen et al. Lancet 2000 • Therefore, my focus will be on the pharmacological management of severe hypertension

  6. 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

  7. From what can we choose? • Hydralazine • Beta-blockers (& alpha-/beta-blockers) • Atenolol • Labetalol • Calcium channel blockers • Nifedipine • Alpha-methyldopa • Angiotensin converting enzyme inhibitors • Angiotensin-II receptor blockers

  8. From what can we choose? • Hydralazine • Beta-blockers (& alpha-/beta-blockers) • Atenolol • Labetalol • Calcium channel blockers • Nifedipine • Alpha-methyldopa • Angiotensin converting enzyme inhibitors • Angiotensin-II receptor blockers • Risks of fetal renal toxicity and IUFD

  9. From what can we choose? • MgSO4 is NOT an antihypertensive

  10. 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

  11. Oral administration • Atenolol • No adverse effects on fetal growth when used acutely • Labetalol • Methyldopa • Nifedipine capsules • Nifedipine intermediate acting • PA/Retard • Hydralazine Modified from: Magee & Abdullah. Expert Opin Drug Saf 2004

  12. 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

  13. Reliable reduction in BPsevere hypertension • CCBs are more reliable than hydralazine in lowering BP in pregnant women with severe hypertension Magee et al. BMJ 2004 Duley et al. CDSR 2006 • Hydralazine appears more reliable than labetalol Magee et al. BMJ 2004 • Methyldopa may be an agent of choice for severe hypertension

  14. Duley et al. CDSR 2006

  15. Reliable reduction in BPsevere hypertension • CCBs are more reliable than hydralazine in lowering BP in pregnant women with severe hypertension Magee et al. BMJ 2004 Duley et al. CDSR 2006 • Hydralazine appears more reliable than labetalol Magee et al. BMJ 2004 • Methyldopa may be an agent of choice for severe hypertension

  16. Magee et al. BMJ 2004

  17. Reliable reduction in BPsevere hypertension • CCBs are more reliable than hydralazine in lowering BP in pregnant women with severe hypertension Magee et al. BMJ 2004 Duley et al. CDSR 2006 • Hydralazine appears more reliable than labetalol Magee et al. BMJ 2004 • Methyldopa may be an agent of choice for severe hypertension • Widely used – routinely on EMLs

  18. 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

  19. 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

  20. Normal Pregnancy Early-onset pre-eclampsia

  21. 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

  22. ‘Rapid’ onset of action Modified from: Magee & Abdullah. Expert Opin Drug Saf 2004

  23. 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

  24. 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

  25. 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

  26. 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?

  27. CLIP • Intervention • CLIP package of care • Case recognition & triage • Treatment of severe hypertension (sBP ≥160mmHg) • Oral antihypertensive ? Atenolol; ? Nifedipine, ? Methyldopa • Intramuscular MgSO4 (5g each buttock) • Treatment of eclampsia • Intramuscular MgSO4 (5g each buttock) • Transfer into facilities offering evidence-based care • Setting • Community – community health workers • Primary health units (not repeated)

  28. 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

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