Atosiban versus betamimetics in the treatment of preterm labour in Italy: clinical and economic importance of side-effects.

The aim of this study was to determine the cost effectiveness of atosiban compared to betamimetics in the treatment of preterm labour within the Italian setting. A systematic literature review identified randomised controlled trials (RCTs) comparing atosiban with betamimetics. Meta-analysis of nine RCTs determined that atosiban and betamimetics had similar efficacy in delaying preterm birth by at least 48 h (p=0.910). Use of atosiban was associated with significantly fewer adverse events (p<0.008). Results demonstrate that atosiban is cost-saving versus ritodrine or isoxuprine. Atosiban cost savings are €657 per patient from the National Health Service payer's perspective; €299 at 18 h of tocolysis to €189 at 48 h from the hospital's perspective. The respective values versus isoxuprine were €303 and €199. From the combined perspective, using atosiban versus ritodrine saved from €425 to €316; and versus isoxuprine from €429 to €326. Owing to its superior safety profile, atosiban is cost-saving versus betamimetics in the treatment of preterm labour in Italy from the payer's, hospital's and combined perspectives. With the approximate 40,000 annual preterm births in Italy the annual savings could be in excess of €13 million for the payer or €3.8-6.2 million for the hospitals.

The influence of tocolytic drugs on cardiac function, large arteries, and resistance vessels.

PURPOSE: Beta-2 adrenoceptor agonistic drugs like ritodrine have been the reference tocolytic drugs, but are associated with cardiovascular side-effects. Atosiban, a newer drug, is a competitive antagonist of oxytocin and has been claimed to have fewer cardiovascular side effects. Until now, there has mainly been a subjective reporting of adverse reactions and few objective cardiovascular data. Evaluation of the acute effects of therapeutic doses of ritodrine and atosiban compared with placebo on cardiac function, large artery properties, blood pressure, and resistance vessels. METHODS: A double-blind, randomized trial was carried out in 20 non-pregnant female volunteers. Hemodynamic measurements were made under standardized conditions during kinetic steady state. Cardiac output was measured with echocardiography, large artery properties with an echo-tracking device. The effect on the microcirculation was estimated using the total peripheral resistance index (TPRI). RESULTS: Atosiban did not differ from placebo. With ritodrine, cardiac function increased by 79% compared with placebo because of a rise in heart rate (91%). TPRI decreased by 48%. Ritodrine increased the distensibility of the common carotid artery by 62% and the compliance by 83%, independent of blood pressure. Compliance of the common femoral artery increased independently of pressure by 33% and the distensibility by 59%. Aortic pulse wave velocity was not influenced by either medication. CONCLUSIONS: The present study shows potential beneficial vascular effects of ritodrine that are counterbalanced by the cardiac effects. Atosiban has no clinically relevant cardiovascular effects and may be a good alternative for ritodrine in pregnant women at risk of cardiovascular complications.

Optimising maternal-fetal outcomes in preterm labour: a decision analysis.

OBJECTIVE: To compare, using decision analytic techniques, maternal and fetal risk and benefits of three strategies for the management of preterm labour after 32 weeks. These strategies are empiric tocolysis, no tocolysis, or amniocentesis for fetal maturity testing. DATA SOURCES: Published medical literature provided the probabilities, including those for tocolysis efficacy, maternal and neonatal outcomes, and steroid efficacy. DATA: Synthesis Separate decision trees were created for hypothetical cohorts of patients presenting with preterm labour at 32, 34, and 36 weeks of gestation to compare strategies. The primary outcome was the total number of expected adverse maternal and neonatal events for each strategy at each gestational age. RESULTS: At 32 weeks tocolysis yielded the lowest total number of adverse maternal and neonatal events. At 34 weeks, both tocolysis and no tocolysis yielded similar overall outcomes. At 36 weeks most clinical outcomes were good regardless of strategy. CONCLUSIONS: This analysis supports the empiric use of tocolytics at 32 weeks. At 34 weeks, either tocolysis or no tocolysis appear to be reasonable alternatives. At 36 weeks no tocolysis is probably preferred. This analysis also suggests that amniocentesis should not be employed in the management of preterm labour at these gestational ages.

Premature rupture of the membranes--aggressive versus conservative approach: effect of tocolytic and antibiotic therapy.

The purpose of this randomized, prospective study was to evaluate the efficacy of tocolytic and antibiotic therapy in the prolongation of pregnancy and neonatal outcome in the treatment of premature rupture of the membranes without clinical labor. Delivery was delayed for 48 h, 7 days and beyond 35 weeks of gestation in 87, 39 and 18%, respectively, of patients in the treated group (n = 39) compared with 50, 12 and 17% of patients in the nontreated group (n = 42). The incidence of a low Apgar score (< 7 at 5 min), requiring artificial ventilation, and infectious morbidity was more common in the treated group than in the nontreated group (18 vs. 0, 41 vs. 17 and 39 vs. 17%, respectively). There was no significant cost difference in survivors between the treated and nontreated groups, although the mothers in the treated group were significantly more expensive. From these observations, it appears that tocolysis and antibiotics are not effective in PROM cases.

Efficacy and safety of indomethacin versus ritodrine in the management of preterm labor: a randomized study.

One hundred six patients in preterm labor with intact amniotic membranes and gestational age less than or equal to 32 weeks were randomized to receive either ritodrine hydrochloride or a 48-hour course of indomethacin for tocolysis. The relative efficacy, maternal and neonatal safety, and costs were evaluated to determine which may be the more appropriate first-line pharmacologic agent used to manage preterm labor. Fifty-four patients and 52 patients were randomized to receive ritodrine hydrochloride or indomethacin, respectively. Ritodrine hydrochloride and indomethacin were equally effective in inhibiting uterine contractions and delaying delivery. Delivery was delayed for at least 48 hours in 83 and 94%, and for at least 7 days in 70 and 75% of patients receiving ritodrine or indomethacin, respectively. Tocolysis with indomethacin was associated with no maternal side effects, whereas tocolysis with ritodrine hydrochloride was associated with a 24% incidence of serious cardiovascular and metabolic adverse effects prompting discontinuation of the drug. There were no differences in outcome between the infants exposed to indomethacin versus ritodrine hydrochloride when delivered either remote from therapy or during therapy, except for a statistically higher serum glucose in the infants exposed to ritodrine hydrochloride when delivered during tocolytic therapy. There were no cases of premature closure of the ductus arteriosus or pulmonary hypertension. Tocolysis with indomethacin was 17 times less costly than tocolysis with ritodrine hydrochloride. For gestations less than or equal to 32 weeks complicated by preterm labor, indomethacin may be an appropriate alternative as a first-line tocolytic agent.

Retrospective analysis of the effects of ritodrine and terbutaline in the management of preterm labor.

The tocolytic effects, adverse reactions, cost, and duration of therapy of terbutaline and ritodrine used for treating preterm labor were compared using retrospective chart review. Of 614 pregnant women admitted to an obstetrics unit between May 1980 and June 1981 who did not deliver a child during that admission, 48 remained on the unit more than 12 hours, received a tocolytic agent, and had a diagnosis of preterm labor. Of these, 22 women received terbutaline or ritodrine. Eight women were excluded, leaving 14 women in the study group. Maternal and fetal characteristics were tabulated, and patients exposed to terbutaline (seven mothers and seven babies) and ritodrine (seven mothers and eight babies) were compared. There were no significant differences between the terbutaline and ritodrine groups for maternal or fetal characteristics, efficacy of treatment, adverse effects, or duration of therapy. The cost of terbutaline is substantially less than that of ritodrine. Terbutaline and ritodrine appear to be comparable tocolytic agents clinically. The use of terbutaline should be investigated further in view of its lower cost and comparable clinical effects.