Low dose aspirin is a wonderful drug in the management of cerebrovascular and cardiovascular disease.However ther is lot of controversies about its use in obstetrics largely due to conclusions drawn on trials with flawed methodology, a reader must always view the evidence critically especially when the not harmful interventions are likely to benefit the patient....

1. Obstetric indications for Low dose aspirin Dr. Veerendrakumar C.M. Associate professor Dept of OBG,VIMS, Bellary, Karnataka

2. Inadequate trophoblastic invasion… Normal abnormal

3. Preeclampsia -Imbalance in favor of vasoconstrictor profile PGI2 TXA2

4. ? The wonder drug aspirin (C9H8O4)

5. Mechanism of action Aspirin is a cyclooxygenase inhibitor… It inhibits production of both PGI2 and TXA2- theoretically no effect must be seen. TXA2 - PlateletsPGI2 - Endothelium

6. Selective inhibition by aspirin Irreversible inhibition of PLT cyclooxygenase. Endothelial cyclooxygenase is quickly regenerated In low doses less aspirin reaches peripheral vessels compared to platelets. Also stimulates production of cytokines which are important for implantation.. Am J ObstetGynecol 157: 123, 1987

7. Net effect on microcirculation-dilatation and no thrombosis TXA2 < PGI2 and no aggregation of PLT No placental infarcts - No ‘factor X’ releasedgood placental flow improved function normal fetal growth- No IUGR

8. For prevention of preeclampsia - 1970’s and 1980’s…… Prof .Wallenberg and RothmansAm J ObstetGynecol 157:123, 1987 Everette and Macdonald J ClinEndocrinolMetab 45:1007,1978

9. CAUGHT BETWEEN EVIDENCE & EXPERIENCE

10. CLASP TRIAL- routine prophylactic administration not recommended 213 centres, 9364 patients -Non significant 12% reduction in proteinuric HTN -significant reduction in PT delivery - no effect on IUGR, stillbirth and NNDLancet. 1994 Mar 12;343(8898):619-29.

11. Cochrane systematic review2000 and 2007 WITHDRAWN: Antiplatelet agents for preventing and treating pre-eclampsia. Knight M, Duley L, Henderson-Smart DJ, King JF. low dose aspirin, have small-moderate benefits when used for prevention of pre-eclampsia. Further information is required to assess which women are most likely to benefit, when treatment should be started, and at what dose.

12. High risk women.. low-dose aspirin is mildly beneficial in terms of reducing the incidence of preeclampsia in women at high risk of developing preeclampsia.Clinics (Sao Paulo). 2005; 60(5):407-14

13. EBM - integrating individual skill with the best available evidence from systematic research J Emeagi criticized L Duley for drawing conclusions on flawed methodologyletter - BMJ.,319,1999 Many large trials in her review did not address timing of starting LDA and trials with low risk women were also included

14. Adopt evidence with pinch of salt

15. Women with abnormal uterine doppler findings ASA treatment initiated early in pregnancy is an efficient method of reducing the incidence of preeclampsia and its consequences. J ObstetGynecol Can. 2009 Sep;31(9):818-26.

16. Women with abnormal uterine doppler findings Low-dose aspirin administered as early as 14-16 weeks of gestation to pregnant women may reduce or modify the course of severe preeclampsia. Its effects on the prevention of IUGR need further evaluation. Croat Med J. 2005 Oct;46(5):826-31.

17. Lancet. Published online May 17, 2007. meta-analysis suggests that antiplatelet therapy …… moderate effect in reducing the risks for preeclampsia …………… Antiplatelet therapy was not associated with significant adverse events.

18. No evidence of harm- Coomarasamy et al ObstetGynecol. 2003 Aspirin reduces the risk of perinatal death and preeclampsia in women with historical risk factors. aspirin therapy should be considered in women with historical risk factors. No increase inplacental abruptionantenatal admissionintraventricular hemorrhage

19. Latest….Obstet Gynecol. August 2010 ;116 Low-dose aspirin initiated in early pregnancy (16 weeks or earlier) is an efficient method of reducing the incidence of preeclampsia and IUGR Preeclampsia 9.3% v/s 21.3%IUGR 7% v/s 16.3% PT birth 3.5% v/s 16.9% Bujold E et al

20. FOGSI experience of 1216 pts in 9 centers 3 groups recruitedTherapeutic prophylacticprimigravidae Significant reduction in need for induction IUGR and PT delivery reduced Primigravidae significant difference not seen FLASP (FOGSI Low Dose Aspirin study)

21. Anti phospholipid antibody syndrome .. Heparin and aspirin therapy improves live birth rate by 54%Empson M et al ObstetGynecol 2002;99 LDA as soon as preg test is positive and LMWH after 7 weeks..

22. No effect on unexplained RPL.. LDA does not increase the live birth rate in women with unexplained recurrent miscarriage51st annual meeting of the American Society of Hematology in New Orleans.Dec 2007

23. Thrombophilia… Combined treatment with LMWH (dalteparin) and low-dose ASA in women with inherited thrombophilia. decreases the risk of preeclampsia by 20% fetal growth restriction by 30% J ObstetGynaecol Can 2007;29(10):787–793

24. Effects of low-dose aspirin in in-vitro fertilization. It is hypothesized that improve blood flow to a woman's implantation site will improve success rates. Conflicting results leave the question of the effects of LDA in IVF unanswered. no need to overturn the current clinical practice for those using LDA in efforts aimed at achieving success with IVF. CurrOpinObstet Gynecol. 2009 Jun;21(3):275-8

25. Thromboprophylaxis- For pts with mechanical heart valves.. A daily low dose aspirin is recommended for patients for pts with high risk for TED.Bonow et al Circulation, 1998;98

26. No adverse effect on infants.. No significant relationship between LDA and any long-term adverse outcome. Furthermore, they reported an association of LDA with a decrease in behavioral difficulties. VinodBhutani et alPediatrics. Published online December 21, 2009.

27. Adverse effects.. Aspirin- an increased risk of vascular disruptions, particularly gastroschisis and possibly premature closure of the ductusarteriosus. large trials demonstrate low-dose aspirin's relative safety and generally positive effects on reproductive outcomes.ObstetGynecolSurv. 2008 Jan;63(1):49-57

28. Dose … Most trials - 50-75 mg / day Greater effect among women treated with doses > 75mg / dayRR 0.49 Villar et al SeminNephrol 2004; 24:607-615