比较胺碘酮加β受体阻断剂、单用索他洛尔与单用β受体阻断剂预防埋藏式复律除颤器电击的随机试验:OPTIC研究

Context: Implantable cardioverter defibrillator(ICD) therapy is effective but is associated with high-voltage shocks that are painful. Objective: To determine whether amiodarone plus β -blocker or sotalol are better than β -blocker alone for prevention of ICD shocks. Design, Setting, and Patients: A randomized controlled trial with blinded adjudication of events of 412 patients from 39 outpatient ICD clinical centers located in Canada, Germany, United States, England, Sweden, and Austria, conducted from January 13, 2001, to September 28, 2004. Patients were eligible if they had received an ICD within 21 days for inducible or spontaneously occurring ventricular tachycardia or fibrillation. Intervention: Patients were randomized to treatment for 1 year with amiodarone plus β -blocker, sotalol alone, or β -blocker alone. Main Outcome Measure: Primary outcome was ICD shock for any reason. Results: Shocks occurred in 41 patients(38.5% ) assigned to β -blocker alone, 26(24.3% ) assigned to sotalol, and 12(10.3% ) assigned to amiodarone plus β -blocker. A reduction in the risk of shock was observed with use of either amiodarone plus β -blocker or sotalol vs β -blocker alone(hazard ratio[HR], 0.44; 95% confidence interval[CI], 0.28- 0.68; P< .001). Amiodarone plus β -blocker significantly reduced the risk of shock compared with β -blocker alone(HR, 0.27; 95% CI, 0.14- 0.52; P< .001) and sotalol(HR, 0.43; 95% CI, 0.22- 0.85; P=.02). There was a trend for sotalol to reduce shocks compared with β -blocker alone(HR, 0.61; 95% CI, 0.37- 1.01; P=.055). The rates of study drug discontinuation at 1 year were 18.2% for amiodarone, 23.5% for sotalol, and 5.3% for β -blocker alone. Adverse pulmonary and thyroid events and symptomatic bradycardia were more common among patients randomized to amiodarone. Conclusions: Despite use of advanced ICD technology and treatment with a β -blocker, shocks occur commonly in the first year after ICD implant. Amiodarone plus β -blocker is effective for preventing these shocks and is more effective than sotalol but has an increased risk of drug-related adverse effects. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT00257959.

消炎痛预防动脉导管未闭及其引发支气管肺发育不良的风险:早产儿消炎痛预防性试验的进一步分析

Objectives: To determine the risk of bronchopulmonary dysplasia(BPD) in subgroups of infants with and without patent ductus arteriosus (PDA) who were randomized to indomethacin prophylaxis or placebo, and to examine whether adverse drug effects on edema formation and oxygenation may explain why indomethacin prophylaxis does not reduce BPD. Study design:We studied 999 extremely low birth weight infants who participated in the Trial of Indomethacin Prophylaxis in Preterms(TIPP) and who survived to a postmenstrual age of 36 weeks.Results: The incidence of BPD in the 2 subgroups of infants with PDA was 52%(55/105) after indomethacin prophylaxis and 56%(137/246) after placebo. In contrast, rates of BPD in the 2 subgroups without a PDA were 43%(170/391) after indomethacin prophylaxis and 30%(78/257) after placebo (P[interaction] = 0.015). Logistic regression analysis with adjustment for prognostic base line factors showed that adverse and independent effects of indomethacin prophylaxis on the need for supplemental oxygen and on weight loss by the end of the first week of life may increase the risk of BPD in infants without PDA. Conclusions: Harmful side effects on oxygenation and edema formation may explain why indomethacin prophylaxis does not prevent BPD even though it reduces PDA.

吲哚美辛在早产儿应用中的性别差异

To test whether indomethacin prophylaxis has sex-mediated effects on severe intraventricular hemorrhage (grade III and IV) and on long-term outcomes in extremely-low-birth-wei-ght infants. A secondary analysis was performed in the entire “Trial of Indomethacin Prophylaxis in Preterms study”cohort. The results suggest a weak differential treatment effect of indomethacin by sex.