Development and Validation of SCACOMS, a Composite Scale for Assessing Disease Progression and Treatment Effects in Spinocerebellar Ataxia.

Spinocerebellar ataxias (SCA) are rare inherited neurodegenerative disorders characterized by a progressive impairment of gait, balance, limb coordination, and speech. There is currently no composite scale that includes multiple aspects of the SCA experience to assess disease progression and treatment effects. Applying the method of partial least squares (PLS) regression, we developed the Spinocerebellar Ataxia Composite Scale (SCACOMS) from two SCA natural history datasets (NCT01060371, NCT02440763). PLS regression selected items based on their ability to detect clinical decline, with optimized weights based on the item's degree of progression. Following model validation, SCACOMS was leveraged to examine disease progression and treatment effects in a 48-week SCA clinical trial cohort (NCT03701399). Items from the Clinical Global Impression-Global Improvement Scale (CGI-I), the Friedreich Ataxia Rating Scale (FARS) - functional stage, and the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) were objectively selected with weightings based on their sensitivity to clinical decline. The resulting SCACOMS exhibited improved sensitivity to disease progression and greater treatment effects (compared to the original scales from which they were derived) in a 48-week clinical trial of a novel therapeutic agent. The trial analyses also provided a SCACOMS-derived estimate of the temporal delay in SCA disease progression. SCACOMS is a useful composite measure, effectively capturing disease progression and highlighting treatment effects in patients with SCA. SCACOMS will be a powerful tool in future studies given its sensitivity to clinical decline and ability to detect a meaningful clinical impact of disease-modifying treatments.

Exploring the relationship between North Star Ambulatory Assessment and Health Utilities Index scores in Duchenne muscular dystrophy.

BACKGROUND: The North Star Ambulatory Assessment (NSAA) documents motor performance in ambulatory individuals with Duchenne muscular dystrophy (DMD). Health Utilities Index (HUI) scores, reflecting preferences for health-related quality-of-life (HRQoL) implications of health states, are commonly estimated within trials. This study sought to characterize the relationship between the NSAA score and utility in DMD. METHODS: Family members serving as proxy respondents for placebo-treated ambulatory individuals with DMD (NCT01254019; BioMarin Pharmaceuticals Inc) completed the HUI and the NSAA (score range, 0-34). Mean change over time on these measures was estimated, and the correlation between changes in NSAA score and a) HUI utility; b) HUI3 ambulation and HUI2 mobility attribute scores, over 48 weeks was calculated. RESULTS: Baseline mean (range) age was 8.0 years (5-16; n = 61) and mean (standard deviation [SD]) scores were 0.87 (0.13; HUI2), 0.82 (0.19; HUI3), and 21.0 (8.1; NSAA). Mean (SD) change over 48 weeks was -0.05 (0.14; HUI2), -0.06 (0.19; HUI3), and -2.9 (4.7; NSAA). Weak positive correlations were observed between baseline NSAA score and HUI utility (HUI2: r = 0.29; HUI3: r = 0.17) and for change over 48 weeks (HUI2: r = 0.16; HUI3: r = 0.15). Stronger correlations were observed between change in NSAA score and the HUI3 ambulation (r = 0.41) and HUI2 mobility (r = 0.41) attributes. CONCLUSIONS: Among ambulatory individuals with DMD, NSAA score is weakly correlated with HUI utility, suggesting that motor performance alone does not fully explain HRQoL. Stronger relationships were observed between HUI ambulation and mobility attributes, and NSAA. Although unidimensional measures like the NSAA are informative for documenting disease-specific health impacts, they may not correlate well with measures of overall health status; requiring use in conjunction with other patient-reported and preference-based outcomes.

Factors associated with the health-related quality of life among people with Duchenne muscular dystrophy: a study using the Health Utilities Index (HUI).

BACKGROUND: Data on health state utility in Duchenne muscular dystrophy (DMD) are few. This study estimated mean utility values by age, ambulatory status and over time, and investigated which aspects of health-related quality-of-life (HRQoL) are most strongly associated with utility in DMD. METHODS: Data from placebo-treated ambulant boys with DMD with exon 51 skip amenable mutations, (NCT01254019), were included. Ambulatory function assessments were conducted at baseline and every 12 weeks for the trial duration. Family member proxies completed the Health Utility Index (HUI) at baseline, 24 and 48 weeks; and HUI3 and HUI2 utility values were summarized. Changes in HUI attribute level over time, and predictors of changes in utility, were explored. RESULTS: Sixty-one boys (mean [range] age of 8.0 [5-16] years) were included in the analysis. Mean baseline utilities were 0.82 (HUI3) and 0.87 (HUI2); and utilities were 0.35 (HUI3) and 0.55 (HUI2) after loss of ambulation (LOA, where applicable). Over the follow-up period mean utility declined more among the older versus younger boys. Pain accounted for the highest proportion of variability (42%) in change in HUI3 utility from baseline to week 48, while for HUI2, self-care (39%) did. After LOA, change in ambulation levels explained 88% of the decline in mean HUI3 utility and change in mobility levels explained 66% of the decline in mean HUI2 utility. CONCLUSIONS: Utility values among this sample were higher than previously published estimates. In younger boys utility remained relatively stable, but older boys and those losing ambulation experienced important declines over follow-up.

A Method for Reconstructing Individual Patient Data From Kaplan-Meier Survival Curves That Incorporate Marked Censoring Times.

Introduction. Access to individual patient data (IPD) can be advantageous when conducting cost-effectiveness analyses or indirect treatment comparisons. While exact times of censoring are often marked on published Kaplan-Meier (KM) curves, an algorithm for reconstructing IPD from such curves that allows for their incorporation is presently unavailable. Methods. An algorithm capable of incorporating marked censoring times was developed to reconstruct IPD from KM curves, taking as additional inputs the total patient count and coordinates of the drops in survival. The reliability of the algorithm was evaluated via a simulation exercise, in which survival curves were simulated, digitized, and then reconstructed. To assess the reliability of the reconstructed curves, hazard ratios (HRs) and quantiles of survival were compared between the original and reconstructed curves, and the reconstructed curves were visually inspected. Results. No systematic differences were found in HRs and quantiles in the original versus reconstructed curves. Upon visual inspection, the reconstructed IPD provided a close fit to the digitized data from the published KM curves. Inherent to the algorithm, censoring times were incorporated into the reconstructed data exactly as specified. Conclusion. This new algorithm can reliably be used to reconstruct IPD from reported KM survival curves in the presence of extractable censoring times. Use of the algorithm will allow health researchers to reconstruct IPD more closely by incorporating censoring times exactly as marked, requiring as additional inputs the total patient count and coordinates of the drops in survival.

Health expenditures after first hospital admission for heart failure in Nova Scotia, Canada: a retrospective cohort study.

BACKGROUND: Although the frequency of heart failure makes it among the costliest of illnesses, there are scant Canadian data on annual costs of treatment or the costs as the condition advances. Our objective was to estimate mean prevalence- and incidence-based direct medical costs among older adults discharged alive after a first hospital admission for heart failure. METHODS: We conducted a retrospective cohort study using population-based administrative health databases for Nova Scotia. The cohort comprised persons 50 years of age or older with an incident hospital admission for heart failure between 2009 and 2012. We considered the costs (expressed as 2020 Canadian dollars) of hospital admissions, physician visits and, for patients 65 years of age or older, outpatient cardiac medications. We estimated costs for calendar years, longitudinally and in the last 2 years of life. We analyzed costs from the perspective of a third-party public payer. RESULTS: The cohort consisted of 3327 patients (mean age 77.6 yr; 1605 [48.2%] women). Median survival was 2.5 and 2.2 years among men and women, respectively. Annual prevalence-based costs were about $7100. Mean incidence-based costs ranged between $65 000 and $164 000 in the year after diagnosis and decreased by 90% subsequently. Costs were 4 to 7 times higher in the year before death than in the period from 1 to 2 years before death. INTERPRETATION: The direct medical costs of treating patients with heart failure in Nova Scotia displayed a reverse J shape, with costs highest after diagnosis, declining subsequently and then increasing during the final year of life. Strategies designed to improve the quality of care immediately after diagnosis and during more advanced stages of disease might reduce these costs.

Fall/Fracture-Related Healthcare Costs and Their Association with Cumulative Anticholinergic Burden in People with Overactive Bladder.

BACKGROUND: Falls/fractures are major causes of morbidity and mortality among older adults and the resulting health consequences generate a substantial economic burden. Risk factors are numerous and include overactive bladder (OAB) and anticholinergic use. OBJECTIVES: We aimed to estimate the impact of falls/fractures on all-cause healthcare resource utilization and costs, according to levels of cumulative anticholinergic burden, among individuals with OAB. METHODS: Among a US cohort of adults with OAB (identified based on medical claims for OAB or OAB-specific medications), the frequency of resource utilization (outpatients visits, medication use, and hospitalizations) was examined according to level of anticholinergic burden. Anticholinergic burden was assessed cumulatively using a published measure, and categorized as no, low, medium, or high. Resource utilization prior to and after a fall/fracture was compared. Generalized linear models were used to examine overall and incremental changes in healthcare resource utilization and costs by fall/fracture status, and annual costs were predicted according to age, sex, fall/fracture status, and level of anticholinergic burden. RESULTS: The mean age of the OAB cohort (n = 154,432) was 56 years, 68% were female, and baseline mean anticholinergic burden was 266.7 (i.e. a medium level of burden); a fall/fracture was experienced by 9.9% of the cohort. All estimates of resource utilization were higher among those with higher levels of anticholinergic burden, regardless of fall/fracture status, and higher for all levels of anticholinergic burden after a fall/fracture. Among those with a fall/fracture, the highest predicted annual costs were observed among those aged 66-75 years with high anticholinergic burden (US$22,408 for males, US$22,752 for females). CONCLUSIONS: Falls/fractures were associated with higher costs, which increased with increasing anticholinergic burden.

Comparative Safety and Efficacy of Treatments for Overactive Bladder Among Older Adults: A Network Meta-analysis.

BACKGROUND: Cumulative exposure to one or more anticholinergic medications ("anticholinergic burden") is associated with an increased risk of adverse outcomes, particularly among older individuals. Mirabegron, an oral selective ß3-adrenergic receptor agonist, has demonstrated efficacy in managing the symptoms of overactive bladder without contributing to anticholinergic burden. However, it is not known whether the favorable safety profile of mirabegron relative to antimuscarinics varies with increasing age among a patient population who may have a high anticholinergic burden. OBJECTIVE: The primary objective of this study was to indirectly compare the safety and efficacy profile of mirabegron relative to antimuscarinics in older adults with overactive bladder. METHODS: A systematic literature review was conducted to identify randomized controlled trials that reported safety and efficacy endpoints among patients aged ≥ 65 years. Identified randomized controlled trials were subsequently synthesized via a network meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines in designing, performing, and reporting the literature review were followed. In line with current best practices, the network meta-analysis was conducted using a Bayesian approach and according to the overall general guidance for evidence synthesis developed by the National Institute for Health and Care Excellence decision support unit. Estimates of relative safety were assessed via the odds ratio and estimates of relative efficacy were assessed via means and credible intervals. RESULTS: A total of 3078 abstracts, 300 of which underwent full-text screening, were identified using the search criteria. Twenty articles reporting on 21 randomized controlled trials were eligible for data extraction and synthesis. Following review, five safety and five efficacy endpoints were considered for inclusion in the network meta-analysis. Regarding findings typical of anticholinergic exposure in older adults, mirabegron was not associated with an increased odds of dry mouth (odds ratio 95% credible interval 0.76 [0.26-2.37]) or constipation (1.08 [0.39-3.02]) relative to placebo, whereas antimuscarinics were strongly associated with these events (odds ratio range 3.78-7.85 and 2.12-4.66, respectively). In this older population, mirabegron was associated with a similar odds of experiencing adverse event-related treatment discontinuations relative to placebo (0.99 [0.57-1.70]), while the odds of experiencing an adverse event-related treatment discontinuation for antimuscarinics had a range of 1.14-3.03 (in most cases, the association was mild). No increased odds of experiencing overall treatment-emergent adverse events was observed for mirabegron or antimuscarinics (odds ratio range 1.25-1.55), apart from fesoterodine (2.23 [1.37-3.37]). Finally, a similar treatment effect was observed across all efficacy endpoints between mirabegron and antimuscarinics in this older population. CONCLUSIONS: This study indicates that the safety and efficacy profile of mirabegron remains favorable compared with antimuscarinics among older adults. This includes safety outcomes typically associated with anticholinergic burden, which were less frequently observed in patients treated with mirabegron.

Treatment patterns and costs among patients with OAB treated with combination oral therapy, sacral nerve stimulation, percutaneous tibial nerve stimulation, or onabotulinumtoxinA in the United States.

INTRODUCTION: Treatment patterns and costs were characterized among patients with overactive bladder (OAB) receiving later-line target therapies (combination mirabegron/antimuscarinic, sacral nerve stimulation [SNS], percutaneous tibial nerve stimulation [PTNS], or onabotulinumtoxinA). METHODS: In a retrospective cohort study using 2013 to 2017 MarketScan databases, two partially overlapping cohorts of adults with OAB ("IPT cohort": patients with incident OAB pharmacotherapy use; "ITT cohort," incident target therapy) with continuous enrollment were identified; first use was index. Demographic characteristics, treatment patterns and costs over the 24-month follow-up period were summarized. Crude mean (standard deviation [SD]) OAB-specific (assessed by OAB diagnostic code or pharmaceutical dispensation record) costs were estimated according to target therapy. RESULTS: The IPT cohort comprised 54 066 individuals (mean [SD] age 58.5 [15.0] years; 76% female), the ITT cohort, 1662 individuals (mean [SD] age 62.8 [14.9] years; 83% female). Seventeen percent of the IPT cohort were treated with subsequent line(s) of therapy after index therapy; among those, 73% received antimuscarinics, 23% mirabegron, and 1.4% a target therapy. For the ITT cohort, 32% were initially treated with SNS, 27% with onabotulinumtoxinA, 26% with combination mirabegron/antimuscarinic, and 15% with PTNS. Subsequently, one-third of this cohort received additional therapies. Mean (SD) costs were lowest among patients receiving index therapy PTNS ($6959 [$7533]) and highest for SNS ($29 702 [$26 802]). CONCLUSIONS: Costs for SNS over 24 months are substantially higher than other treatments. A treatment patterns analysis indicates that oral therapies predominate; first-line combination therapy is common in the ITT cohort and uptake of oral therapy after procedural options is substantial.

An Evaluation of Longitudinal Measures of Anticholinergic Exposure for Application in Retrospective Administrative Data Analyses.

INTRODUCTION: As continuous exposure to anticholinergics has been associated with adverse outcomes, accurately measuring exposure is important. However, no gold standard measure is available, and the performance of existing measures has not been compared. Our objective was to compare the properties of the Cumulative Anticholinergic Burden (CAB) measure against two existing measures of anticholinergic exposure and to assess their compatibility for use in observational studies based on claims data. METHODS: The average daily dose, cumulative dose and CAB measures were evaluated on: the applicability for use with anticholinergic burden scales, the ability to consider duration and/or accumulation of exposure, and consideration of anticholinergic dose, potency, and residual effect. To calculate each measure empirically, Truven MarketScan claims data from 2012 to 2015 were analyzed. Cumulative anticholinergic exposure over 1-year post-enrollment was calculated for each measure using Anticholinergic Cognitive Burden scale scores. Median [interquartile range (IQR)] and ranges of measure scores, and Spearman's correlation coefficients between measures, were estimated. Due to the differing methods of calculation, the absolute values of each score cannot be compared. RESULTS: The properties of the different measures varied, with only the CAB considering both dose and theoretical potency. The cohort included 99,742 individuals (mean age = 73.1 years; 54.9% female). Among individuals prescribed anticholinergics (n = 55,969), 1-year median (IQR) scores based on average daily dose, cumulative dose and CAB measures were 0.9 (0.3-1.5), 16.9 (7.3-33.9) and 203 (68-500), respectively. Measures were highly inter-correlated (r2 = 0.74-0.83). CONCLUSIONS: Considering both potency and dose, the CAB may prove a more comprehensive measure of anticholinergic burden; however, additional research is necessary to demonstrate whether it has any association with relevant health-related outcomes. FUNDING: Astellas Pharma Global Development, Inc.

Association between cumulative anticholinergic burden and falls and fractures in patients with overactive bladder: US-based retrospective cohort study.

OBJECTIVE: To estimate the association between cumulative anticholinergic burden and falls and fractures in patients with overactive bladder (OAB). DESIGN: A retrospective claims-based study (2007-2015) of patients with OAB; outcomes from a subset were contrasted to a non-OAB comparison. SETTING: United States, commercially and Medicare-insured population. PARTICIPANTS: 154 432 adults with OAB and 86 966 adults without OAB, mean age of 56 years, and 67.9% women. MAIN OUTCOME MEASURES: Cumulative anticholinergic burden, a unitless value representing exposure over time, was estimated over the 12 months pre-index ('at baseline') and every 6 months post index. Burden was categorised as no burden (0), low burden (1-89), medium burden (90-499) or high burden (500+). Unadjusted rates of falls or fractures were estimated, and the increased risk associated with anticholinergic burden (measured at the closest 6-month interval prior to a fall or fracture) was assessed using a Cox proportional hazards model and a marginal structural model. RESULTS: Median (IQR) baseline anticholinergic burden was 30 (0.0-314.0) and higher among older (≥65 years, 183 [3.0-713.0]) versus younger (<65 years, 13 [0.0-200.0]) adults. The unadjusted rate of falls or fractures over the period was 5.0 per 100 patient-years, ranging from 3.1 (95% CI 3.0-3.2) for those with no burden, to 7.4 (95% CI 7.1-7.6) for those with high burden at baseline. The adjusted risk of falls and fractures was greater with higher anticholinergic burden in the previous 6 months, with an HR of 1.2 (95% CI 1.2 to 1.3) for low burden versus no burden, to 1.4 (95% CI 1.3 to 1.4) for high versus no burden. Estimates from marginal structural models adjusting for time-varying covariates were lower but remained significantly higher with a higher anticholinergic burden. Rates of falls and fractures were approximately 40% higher among those with OAB (vs those without). CONCLUSION: Higher levels of anticholinergic burden are associated with higher rates of falls and fractures, highlighting the importance of considering anticholinergic burden when treating patients with OAB.

The Relative Efficacy and Safety of Mirabegron and OnabotulinumtoxinA in Patients With Overactive Bladder who Have Previously Been Managed With an Antimuscarinic: A Network Meta-analysis.

OBJECTIVE: To compare the efficacy and safety of mirabegron and onabotulinumtoxinA in the management of treatment-experienced patients with overactive bladder. METHODS: The network meta-analysis was based on evidence from a systematic literature review of randomized controlled trials and a post-hoc analysis of treatment-experienced subpopulations from mirabegron studies. RESULTS: Nineteen trials described in 21 publications were included. CONCLUSION: Overall, compared to mirabegron, there was some evidence that onabotulinumtoxinA was associated with improved outcomes, including reductions in the number of micturitions in a 24-hour period, and the number of incontinence episodes. However, mirabegron was associated with a lower risk of urinary tract infections compared with onabotulinumtoxinA.

Evaluating adverse drug event reporting in administrative data from emergency departments: a validation study.

BACKGROUND: Adverse drug events are a frequent cause of emergency department presentations. Administrative data could be used to identify patients presenting with adverse drug events for post-market surveillance, and to conduct research in patient safety and in drug safety and effectiveness. However, such data sources have not been evaluated for their completeness with regard to adverse drug event reporting. Our objective was to determine the proportion of adverse drug events to outpatient medications diagnosed at the point-of-care in emergency departments that were documented in administrative data. METHODS: We linked the records of patients enrolled in a prospective observational cohort study on adverse drug events conducted in two Canadian tertiary care emergency departments to their administrative data. We compared the number of adverse drug events diagnosed and recorded at the point-of-care in the prospective study with the number of adverse drug events recorded in the administrative data. RESULTS: Among 1574 emergency department visits, 221 were identified as adverse drug event-related in the prospective database. We found 15 adverse drug events documented in administrative records with ICD-10 codes clearly indicating an adverse drug event, indicating a sensitivity of 6.8% (95% CI 4.0-11.2%) of this code set. When the ICD-10 code categories were broadened to include codes indicating a very likely, likely or possible adverse event to a medication, 62 of 221 events were identifiable in administrative data, corresponding to a sensitivity of 28.1% (95% CI 22.3-34.6%). CONCLUSIONS: Adverse drug events to outpatient medications were underreported in emergency department administrative data compared to the number of adverse drug events diagnosed and recorded at the point-of-care.

The occurrence of adverse events in relation to time after registration for coronary artery bypass surgery: a population-based observational study.

BACKGROUND: Our objective was to evaluate the effect of delays on adverse events while waiting for coronary artery bypass grafting (CABG). METHODS: An observational study that prospectively followed patients from registration on a wait list to removal for planned surgery, death while waiting, or unplanned emergency surgery. The population-based registry provided data on 12,030 patients with a record of registration on a wait list for first-time isolated CABG surgery between 1992 and 2005. RESULTS: In total, 104 patients died and 382 patients underwent an emergency surgery before planned CABG. The death rate was 0.5 per 1000 patient-weeks in the semiurgent group and 0.6 per 1000 patient-weeks the nonurgent group, adjusted OR = 1.07 (95% confidence interval [CI] 0.69-1.65). The emergency surgery rate of 1.2 per 1000 patient-weeks in the nonurgent group was lower compared to 2.1 per 1000 patient-weeks in the semiurgent group (adjusted OR = 0.72, 95% CI 0.54-0.97). However, the nonurgent group had a greater cumulative incidence of preoperative death than the semiurgent group for almost all weeks on the wait list, adjusted OR = 1.92 (95% CI 1.25-2.95). The surgery rate was 1.2 per 1000 patient-weeks in the nonurgent group and 2.1 per 1000 patient-weeks in the semiurgent group, adjusted OR = 0.72 (95% CI 0.54-0.97). The cumulative incidence of emergency surgery before planned CABG was similar in the semiurgent and nonurgent groups, adjusted OR = 0.88, (95% CI 0.64-1.20). CONCLUSION: Despite similar death rates in the semiurgent and nonurgent groups, the longer waiting times in the nonurgent group result in a greater cumulative incidence of death on the wait list compared to that in the semiurgent group. These longer waiting times also offset the lower rate of emergency surgery before planned admission in the nonurgent group so that the cumulative incidence of the emergency surgery was similar in both groups.

Evaluation of supply-side initiatives to improve access to coronary bypass surgery.

BACKGROUND: Guided by the evidence that delaying coronary revascularization may lead to symptom worsening and poorer clinical outcomes, expansion in cardiac surgery capacity has been recommended in Canada. Provincial governments started providing one-time and recurring increases in budgets for additional open heart surgeries to reduce waiting times. We sought to determine whether the year of decision to proceed with non-emergency coronary bypass surgery had an effect on time to surgery. METHODS: Using records from a population-based registry, we studied times between decision to operate and the procedure itself. We estimated changes in the length of time that patients had to wait for non-emergency operation over 14 calendar periods that included several years when supplementary funding was available. We studied waiting times separately for patients who access surgery through a wait list and through direct admission. RESULTS: During two periods when supplementary funding was available, 1998-1999 and 2004-2005, the weekly rate of undergoing surgery from a wait list was, respectively, 50% and 90% higher than in 1996-1997, the period with the longest waiting times. We also observed a reduction in the difference between 90th and 50th percentiles of the waiting-time distributions. Forty percent of patients in the 1998, 1999, 2004 and 2005 cohorts (years when supplementary funding was provided) underwent surgery within 16 to 20 weeks following the median waiting time, while it took between 27 and 37 weeks for the cohorts registered in the years when supplementary funding was not available. Times between decision and surgery were shorter for direct admissions than for wait-listed patients. Among patients who were directly admitted to hospital, time between decision and surgery was longest in 1992-1993 and then has been steadily decreasing through the late nineties. The rate of surgery among these patients was the highest in 1998-1999, and has not changed afterwards, even for years when supplementary funding was provided. CONCLUSIONS: Waiting times for non-emergency coronary bypass surgery shortened after supplementary funding was granted to increase volume of cardiac surgical care in a health system with publicly-funded universal coverage for the procedure. The effect of the supplementary funding was not uniform for patients that access the services through wait lists and through direct admission.

An observational study to evaluate 2 target times for elective coronary bypass surgery.

BACKGROUND: Guidelines for timing of elective bypass surgery were established by expert opinion; yet, there is little evidence to support the recommended target times. OBJECTIVES: To estimate the effect of timing of the procedure on in-hospital mortality by comparing groups of patients that differ in the duration of time between decision to operate and performed procedure. RESEARCH DESIGN: We used a population-based registry to identify patients who underwent surgical coronary revascularization and their hospital discharge summaries to identify in-hospital death. SUBJECTS: We studied 9593 patients who underwent surgical revascularization between 1992 and 2006 after registration on a wait list for first-time isolated coronary artery bypass grafting on an elective basis. MEASURES: The outcome was postoperative in-hospital death. The study variable was the timing of surgery, categorized as short, prolonged, and excessive delays according to the guidelines. METHODS: The probability of in-hospital death in relation to timing of surgery was modeled by logistic regression that included a precalculated risk score for in-hospital death, with weighting observations by inverse propensity scores for the 3 surgery timing groups. RESULTS: In-hospital death among patients with short delays was one third as likely as among those with excessive delays: adjusted odds ratio=0.32 (95% confidence interval 0.20-0.51). The protective effect was smaller and not significant for patients with prolonged delays; odds ratio=0.78 (95% confidence interval, 0.38-1.63). CONCLUSIONS: Our findings suggest a survival benefit from performing elective surgical revascularization within the time frame recommended by the stricter of the 2 guidelines. Our results have implications for health systems that provide universal coverage and that budget the annual number of procedures.