Comparison of Inappropriate Shocks and Other Health Outcomes Between Single- and Dual-Chamber Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death: Results From the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter-Defibrillators

BACKGROUND: In US clinical practice, many patients who undergo placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death receive dual-chamber devices. The superiority of dual-chamber over single-chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single- and dual-chamber ICDs for primary prevention. METHODS AND RESULTS: We identified patients receiving a single- or dual-chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health delivery systems in the Longitudinal Study of Implantable Cardioverter-Defibrillators from 2006 to 2009. The primary outcome was time to first inappropriate shock. ICD shocks were adjudicated for appropriateness. Other outcomes included all-cause hospitalization, heart failure hospitalization, and death. Patient, clinician, and hospital-level factors were accounted for using propensity score weighting methods. Among 1042 patients without pacing indications, 54.0% (n=563) received a single-chamber device and 46.0% (n=479) received a dual-chamber device. In a propensity-weighted analysis, device type was not significantly associated with inappropriate shock (hazard ratio, 0.91; 95% confidence interval, 0.59-1.38 [P=0.65]), all-cause hospitalization (hazard ratio, 1.03; 95% confidence interval, 0.87-1.21 [P=0.76]), heart failure hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.72-1.21 [P=0.59]), or death (hazard ratio, 1.19; 95% confidence interval, 0.93-1.53 [P=0.17]). CONCLUSIONS: Among patients who received an ICD for primary prevention without indications for pacing, dual-chamber devices were not associated with lower risk of inappropriate shock or differences in hospitalization or death compared with single-chamber devices. This study does not justify the use of dual-chamber devices to minimize inappropriate shocks

Device Therapies Among Patients Receiving Primary Prevention Implantable Cardioverterâ Defibrillators in the Cardiovascular Research Network

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143721/1/jah33061_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143721/2/jah33061.pd

Assessing the impact of censoring of costs and effects on health-care decision-making: an example using the atrial fibrillation follow-up investigation of rhythm management (AFFIRM) study

AbstractObjectivesLosses to follow-up and administrative censoring can cloud the interpretation of trial-based economic evaluations. A number of investigators have examined the impact of different levels of adjustment for censoring, including nonadjustment, adjustment of effects only, and adjustment for both costs and effects. Nevertheless, there is a lack of research on the impact of censoring on decision-making. The objective of this study was to estimate the impact of adjustment for censoring on the interpretation of cost-effectiveness results and expected value of perfect information (EVPI), using a trial-based analysis that compared rate- and rhythm-control treatments for persons with atrial fibrillation.MethodsThree different levels of adjustment for censoring were examined: no censoring of cost and effects, censoring of effects only, and censoring of both costs and effects. In each case, bootstrapping was used to estimate the uncertainty incosts and effects, and the EVPI was calculated to determine the potential worth of further research.ResultsCensoring did not impact the adoption decision. Nevertheless, this was not the case for the decision uncertainty or the EVPI. For a threshold of $50,000 per life-year, the EVPI varied between$626,000 (partial censoring) to $117 million (full censoring) for the eligible US population.ConclusionsThe level of adjustment for censoring in trial-based cost-effectiveness analyses can impact on the decisions to fund a new technology and to devote resources for further research. Only when censoring is taken into account for both costs and effects are these decisions appropriately addressed

Evaluation of Genetic Factors for Warfarin Dose Prediction

Objectives: Warfarin is a commonly prescribed anticoagulant drug used to prevent thromboses that may arise as a consequence of orthopedic and vascular surgery or underlying cardiovascular disease. Warfarin is associated with a notoriously narrow therapeutic window where small variations in dosing may result in hemorrhagic or thrombotic complications. To ultimately improve dosing of warfarin, we evaluated models for stable maintenance dose that incorporated both clinical and genetic factors. Method: A model was constructed by evaluating the contribution to dosing variability of the following clinical factors: age, gender, body surface area, and presence or absence of prosthetic heart valves or diabetes. The model was then sequentially expanded by incorporating polymorphisms of cytochrome P450 (CYP) 2C9; vitamin K 2,3 epoxide reductase complex, subunit 1 (VKORC1); gamma carboxylase; factor VII; and apolipoprotein (Apo) E genes. Results: Of genetic factors evaluated in the model, CYP2C9 and VKORC1 each contributed substantially to dose variability, and together with clinical factors explained 56% of the individual variability in stable warfarin dose. In contrast, gamma carboxylase, factor VII and Apo E polymorphisms contributed little to dose variability. Conclusion: The importance of CYP2C9 and VKORC1 to patient-specific dose of warfarin has been confirmed, while polymorphisms of gamma carboxylase, factor VII and Apo E genes did not substantially contribute to predictive models for stable warfarin dose