The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.
Summary To assess the reliability of salivary theophylline concentrations for patient monitoring, concentrations of theophylline in sera and saliva of 50 patients (ages 6–81 years) receiving oral or parenteral theophylline were determined by two methods: a rapid dry-phase apoenzyme reactivation system (ARIS) and fluorescence polarization immunoassay (FPIA). Saliva production was stimulated by both citric acid (CA) and parafilm (PF). With both analytical methods, there were excellent correlations between salivary theophylline concentration, Cs, and unbound serum theophylline concentration Cu (r2 > 0.95), and between Cs and total serum theophylline concentration, CT (r2 > 0.85). CA- and PF-stimulated Cs by FPIA resulted in concentrations within 2.0 μg/ml of the actual Cu for 100% of the samples measured (n = 47). By ARIS, 100% of the PF-stimulated Cs and 93.6% of the CA-stimulated Cs determinations were within 2.0 μg/ml of the Cu (n = 47). To evaluate the predictive capabilities of PF- and CA-stimulated saliva, one-half (n = 24) of the patients were randomly selected and their data used to predict the CT for the remaining patients. FPIA PF-CS predicted 83.3% (20/24) of CT within ±2 μg/ml, while ARIS CA-CS predicted 75.0% within ±2 μg/ml. There was no difference between FPIA Cs and ARIS Cs results by multivariate analysis of variance (MANOVA), but there was a difference between PF-CS and CA-Cs (p < 0.05). However, when Cu was used as a covariant, there was no significant difference. Using appropriate saliva collection procedures and the FPIA system, we conclude that Cs provides adequate reliability for therapeutic drug monitoring of theophylline.
Background The objectives were to investigate the factors influencing signal-averaged ECGs (SAECGs) recorded in patients after myocardial infarction (MI) and to develop criteria for predicting arrhythmic events (AEs) that account for these factors. Methods and Results SAECGs were recorded 5 to 15 days after MI in 2461 patients without bundle-branch block. The duration (QRSd), terminal potential (VRMS), and terminal duration (LAS) of the filtered QRS were measured. During follow-up (17±8 months), AEs (arrhythmic death; ventricular tachycardia, VT; ventricular fibrillation, VF) occurred in 80 patients (3.3%). Receiver operating characteristic curves showed that QRSd discriminated patients with all types of AEs, but VRMS and LAS discriminated only VT patients; QRSd minus LAS also discriminated AE patients. Sex, age, and MI location significantly affected the SAECG; survivors without VT or VF were divided into subgroups (2 sex×4 age×2 MI), and QRSd values exceeding the 70th percentile in each subgroup predicted AEs with a sensitivity of 65.4%. An unadjusted QRSd criterion showed the same overall sensitivity and specificity but with less uniform values for each subgroup. A Cox model was constructed by use of multiple prognostic indicators, and in rank order, QRSd, previous MI, and Killip class were predictive of AEs. Conclusions SAECG adjustments for sex, age, and MI location did not improve sensitivity and specificity but produced a more uniform predictive performance. The proposed criteria are based only on QRSd, because late potentials (VRMS and LAS) did not discriminate patients with sudden death. Duration of high-level activity during QRS (QRSd−LAS) can predict AEs, suggesting that the arrhythmogenic substrate involves a large mass of myocardium.
