Tocolytic Therapy for preterm labor

Atosiban vs Nifedipine: meta-analysis

The perfect tocolytic

is uniformly effective with complete fetomaternal safety does not exist

Types

beta-agonists, Ca(2+) channel blockers oxytocin receptor antagonists. differ in cost, utero-specificity, safety,

efficacy

Tocolytic agents

ß-agonistß2-receptor: uterus, blood vessels,

bronchioles Stimulate receptoren -> adenyl

cyclase -> ↑ cAMP -> ↓ calciumMost important: ritodrine

Side Effects : Maternal

Side Effects: Fetal

RCOG, 2002

If tocolysis is indicated, B2-agonist should not be used

Choice should be either CCB or Atosiban

CCB: Nifdipine (Adalat )

EffectiveSE: Hypotension & tachycardia

especially multiple pregnancy

Tractocile® : uterospecific

Introduced in Europe in 2000

Atosiban = structure similar to oxytocine -> inhibit uterus contractions

Tractocile®

Tractocile vs Nifedipine

Both drugs are effective but maternal adverse events are more with Nifedipine (Al-Omari et al, 2006)

In another RCT

Atosiban was effective in 75% of the cases, and nifedipin in 65% of the cases, for delaying delivery for more than 7 days.

The maternal side effects in the atosiban group were 17.5%, and in the nifedipin group they were 40%, which had a statistically significant difference (p=0.027). (Kanashian et al, 2005)

How to use

Injection

Not longer than 48 hour infusionTotal dose: < 330 mg atosiban

Interesting

Both B2 agonists and Atosiban are registered in Europe for management of preterm labor

Nifedipine: no

Objective of Meta-analysis

to determine the comparative clinical value of atosiban versus nifedipine in women in preterm labor by evaluating both, their comparative effectiveness and safety profiles

Methodology: Meta-analysis

Randomised controlled trials according to the guidelines of the

Cochrane handbook for systematic reviews of interventions (version 5.0.1)

Outcomes

Prolongation of pregnancy prevention of preterm labor maternal and fetal side effects and

infant morbidity and mortality

safety in favor of atosiban:

there were lower incidence of adverse drug reactions, flushing, GIT upset, hypotension, palpitation, and tachycardia in women prescribed atosiban, with the exception of nausea, which was more frequent in such women

So

The balance of evidence indicates that atosiban is as effective as nifedipine and is significantly safer than it

However

We have two major problems: Cost Real value

Cost

Atosiban is extremely expensive compared to Nifidipine

This is a major limiting issue in the use of Atosiban

Sustained Tocolysis? Nifidipine could be better choice

406 women with threatened preterm birth randomised to an additional 12 days of nifedipine or placebo after completion of a 48-hour initial course of tocolysis.

The probability of adverse perinatal outcomes was similar between groups, as were mean gestational age and birth weight and likelihood of neonatal intensive care unit admission .

Moreover

Among participants still using Nifedipine at the time of delivery, mean blood loss was higher in those women assigned to nifedipine (432 mL vs. 307 mL; P=0.045). Journal Watch Women's Health January 17, 2013

Why tocolysis?

To allow for a course of corticosteroids To allow for in utero transfer (women go

to tertiary center)

Questioning Tocolysis!!!!

Patient oriented outcome: neonatal mortality ????

What a surprise!!!

No clear evidence was found for the relative effectiveness of any tocolytic versus placebo being beneficial for neonatal mortality

Fig  Compared to Placebo

Haas D M et al. BMJ 2012;345:bmj.e6226©2012 by British Medical Journal Publishing Group

No evidence !!

No evidence of beneficial effect does not mean Evidence of no value

No evidence could be due to small number of patients (type II error), or heteregeneity of studies, or different entry point at time of study

What to do now??

we have become accustomed to the fact that tocolytics buy us time.

The question is : Does it Worth?

To get an answer

is a large scale multi-centred randomised non-blinded trial, analysed by intention to treat.

Till then

Tocolysis will continue So use the most cost effective

modality : CCB

Thank You