Comparative Effectiveness and Safety Analysis of Dual Antiplatelet Therapies Within an Integrated Delivery System.

BACKGROUND: Dual antiplatelet therapy is a mainstay of care for percutaneous coronary intervention (PCI) patients; however, uncertainty exists in real-world practice about comparative effectiveness and safety outcomes. OBJECTIVE: To evaluate outcomes of different oral P2Y12 inhibitors in PCI patients. METHODS: We retrospectively studied patients treated between July 1, 2010, and December 31, 2013. Patients received clopidogrel, prasugrel, ticagrelor, or more than 1 antiplatelet (switch) during PCI. Outcomes were evaluated for major adverse cardiovascular events (MACE) and bleeding at 1 year. Propensity score matching with Cox proportional hazards analysis was used to determine predictors of MACE and bleeding. RESULTS: A total of 8127 patients were included: clopidogrel (n = 6872), prasugrel (n = 605), ticagrelor (n = 181), and switch (n = 469). Treatment with prasugrel was associated with the lowest risk of MACE using multivariate regression (odds ratio [OR] = 0.57; 95% CI = 0.36-0.92; P = 0.02). In the propensity score-matched analysis, only the prasugrel group was associated with a lower risk of MACE compared with the clopidogrel group. Clopidogrel was associated with the lowest risk of major bleeding using multivariate regression (OR = 0.64; 95% CI = 0.42-0.98; P = 0.042). Both ticagrelor (hazard ratio [HR] = 2.00; 95% CI = 1.11-3.59) and the switch groups (HR = 1.65; 95% CI = 1.09-2.50) were associated with a greater risk of major bleeding compared with clopidogrel. However, no differences were found in the propensity score-matched analysis. CONCLUSIONS: Dual antiplatelet therapies differed in both MACE and bleeds in a real-world setting of PCI. Prasugrel was associated with fewer MACE, whereas clopidogrel had fewer major bleeding events.

Predictors of Cisatracurium Continuous Infusion Dose in Acute Respiratory Distress Syndrome.

Neuromuscular blockade (NMB) with cisatracurium may improve outcomes in the acute respiratory distress syndrome (ARDS) population; however, optimal dosing strategy remains unknown. Factors affecting pharmacokinetics and pharmacodynamics of cisatracurium may impact the dose required to achieve adequate train-of-four (TOF) response. The aims of this study were to determine cisatracurium dose requirements in a critically ill ARDS population and to identify clinical factors that affect dosing. This was a single-center, retrospective cohort study of medical intensive care patients who received cisatracurium infusion for treatment of ARDS. "Stable dose" was defined as the infusion rate producing 2 consecutive TOFs of 1/4 to 2/4. Factors examined for association with dose were temperature, pH, age, and the presence of acute kidney injury (AKI). The analysis included 39 patients. The median stable dose of cisatracurium was 2.8 (2.0, 3.1) µg/kg/min. Multivariable linear regression model for weight-normalized dose identified AKI as a factor independently associated with steady-state dose requirements (% change -31.4, 95% confidence interval [CI]: -51.9, -2.3). Our study provides information on cisatracurium doses required in patients with ARDS to reduce time required to reach goal TOF. Further studies are needed to determine effect of AKI on cisatracurium dose requirements and clinical outcomes.