Houten, Holly K. Van

Abstract Background Recent studies suggested that treating obesity and its comorbidities with glucagon-like peptide-1 (GLP-1) receptor agonists may improve outcomes in patients with heart failure with preserved ejection fraction (HFpEF). The randomized SUMMIT trial found that tirzepatide use was associated with a lower risk of heart failure (HF) events or cardiovascular death in adults with HFpEF and obesity compared with placebo. Purpose We aimed to examine whether tirzepatide use in clinical practice was associated with risks of HF events and all-cause mortality among adults with HFpEF and obesity. Methods This was a retrospective cohort study leveraging the Optum Labs Data Warehouse (OLDW), a de-identified administrative claims database of commercial and Medicare Advantage enrollees across the United States. We identified all adults with HFpEF and obesity from January 1, 2022, to December 31, 2024. Our primary exposure was tirzepatide use, and our primary outcome was a composite of a HF event (ED visits or hospitalization for HF) or mortality. Secondary outcomes included hospitalization for angina, atrial fibrillation or atrial flutter (AF/AFL), acute myocardial infarction (MI), cardiac arrest, and cardiogenic shock. Patients were followed from the index date, defined as the tirzepatide treatment start date after HFpEF diagnosis or pseudo-index date in tirzepatide non-users, to the end of enrollment or death using the intention-to-treat framework. Inverse probability of treatment weighting (IPTW) was used to balance groups. Fracture, conjunctivitis, ear infection, and fungal skin infection were used as falsification endpoints. Cox-proportional and Fine-Gray subdistribution hazard models were used to estimate a hazard ratio (HR) and subdistribution hazard ratio (SHR), respectively. Results Among our total cohort of 99,270 patients, the mean age was 73 years, 58,616 (59.1%) were female, 8,839 (8.9%) used tirzepatide, and the mean follow-up time was about 385 days. Patients using tirzepatide had a significantly lower risk of a HF event or mortality (HR=0.73; 95% confidence interval [CI]=0.66–0.80; p<0.001) compared to patients not using tirzepatide. Patients using tirzepatide had a lower risk of a HF event (SHR=0.80; 95% CI=0.73–0.88; p<0.001) and all-cause mortality (HR=0.48; 95% CI=0.38–0.60; p<0.001). Tirzepatide use was associated with lower risks of hospitalization for acute MI (SHR=0.67; 95% CI=0.52–0.85; p=0.001) and cardiogenic shock (SHR=0.56; 95% CI=0.38–0.83; p=0.003), but not angina, AF/AFL, or cardiac arrest (Figure 1). Conclusion Among adults with HFpEF and obesity, tirzepatide use in real-world clinical practice was associated with a lower risk of HF events, hospitalizations for acute cardiovascular disease, and all-cause mortality.For image description, please refer to the figure legend and surrounding text.

ImportanceIdentification of factors associated with variation in outpatient surgery may further quality improvement efforts to safely reduce postoperative hospital length of stay nationally.ObjectivesTo explore variation in the use of outpatient surgery, incorporating patient, geographic, and hospital factors.Design, Setting, and ParticipantsThis retrospective cross-sectional study used deidentified administrative claims data from OptumLabs Data Warehouse. Participants included adults who underwent 1 of 10 general, urological, or gynecological operations between January 1, 2015, and June 30, 2021, in the US. Patients who underwent combined procedures or reoperations or had at least 15 Elixhauser comorbidities were excluded. Data were analyzed from July 26 to December 16, 2023.ExposureInpatient or outpatient surgical procedures.Main Outcomes and MeasuresMultilevel logistic regression assessed variation in the use of outpatient surgery rates by hospital characteristics (bed size, presence of trainees, and rural referral center status) and hospital census division, adjusting for patient factors (age, sex, number of Elixhauser comorbidities, year, and rural-urban commuting area). This multilevel model allowed for the sources of variability to be quantitatively attributed to patient characteristics, geography, and hospital characteristics.ResultsA total of 330 424 (72.3%) of 456 954 included patients underwent outpatient surgery. The median age was 54 (IQR, 41-67) years, and of those with data available, most patients were female (268 692 of 414 193 [64.9%]). The likelihood of outpatient surgery varied significantly by hospital census division for all 10 operations (eg, MIS salpingo-oophorectomy range, 29.6%-58.8%; P < .001). Variation in hospital census division contributed most to outpatient surgery for 8 of 10 operations compared with other patient and hospital characteristics. Hospital census division contributed the greatest degree to the variation in outpatient simple mastectomy (20.6%) and the least to outpatient open ventral hernia repair (0.7%). Multivariable analysis showed that the odds of outpatient surgery for patients from metropolitan areas were higher for minimally invasive salpingo-oophorectomy (odds ratio [OR], 1.62; 95% CI, 1.34-1.95) and open ventral hernia repair (OR, 1.16; 95% CI, 1.09-1.24). Hospitals with 400 or more beds were independently associated with decreased odds of outpatient surgery compared with hospitals with 50 to 199 beds for 4 of 7 operations (MIS paraesophageal hernia repair [OR, 0.58; 95% CI, 0.47-0.71; P < .001]; MIS cholecystectomy [OR, 0.73; 95% CI, 0.68-0.78; P < .001]; open ventral hernia [OR, 0.51; 95% CI, 0.46-0.57; P < .001]; MIS ventral hernia repair [OR, 0.66; 95% CI, 0.56-0.77; P < .001]). The presence of a residency training program was independently associated with increased odds of outpatient surgery for simple mastectomy (OR, 1.35; 95% CI, 1.16-1.58; P < .001) and mastectomy with reconstruction (OR, 1.50; 95% CI, 1.27-1.77; P < .001) and decreased odds of outpatient surgery for minimally invasive cholecystectomy (OR, 0.96; 95% CI, 0.92-1.00; P = .04), open ventral hernia repair (OR, 0.93; 95% CI, 0.86-1.00; P = .04), and total thyroidectomy (OR, 0.84; 95% CI, 0.71-1.00; P = .04).Conclusions and RelevanceIn this cross-sectional study, significant variation existed in the use of outpatient surgery in the US and appeared to be driven primarily by hospital geography. Addressing these variations may improve the use of resources.

Background The study aimed to describe the patterns and trends of initiation, discontinuation, and adherence of oral anticoagulation (OAC) in patients with new‐onset postoperative atrial fibrillation (POAF), and compare with patients newly diagnosed with non‐POAF. Methods and Results This retrospective cohort study identified patients newly diagnosed with atrial fibrillation or flutter between 2012 and 2021 using administrative claims data from OptumLabs Data Warehouse. The POAF cohort included 118 366 patients newly diagnosed with atrial fibrillation or flutter within 30 days after surgery. The non‐POAF cohort included the remaining 315 832 patients who were newly diagnosed with atrial fibrillation or flutter but not within 30 days after a surgery. OAC initiation increased from 28.9% to 44.0% from 2012 to 2021 in POAF, and 37.8% to 59.9% in non‐POAF; 12‐month medication adherence increased from 47.0% to 61.8% in POAF, and 59.7% to 70.4% in non‐POAF. The median time to OAC discontinuation was 177 days for POAF, and 242 days for non‐POAF. Patients who saw a cardiologist within 90 days of the first atrial fibrillation or flutter diagnosis, regardless of POAF or non‐POAF, were more likely to initiate OAC (odds ratio, 2.92 [95% CI, 2.87–2.98]; P <0.0001), adhere to OAC (odds ratio, 1.08 [95% CI, 1.04–1.13]; P <0.0001), and less likely to discontinue (odds ratio, 0.83 [95% CI, 0.82–0.85]; P <0.0001) than patients who saw a surgeon or other specialties. Conclusions The use of and adherence to OAC were higher in non‐POAF patients than in POAF patients, but they increased over time in both groups. Patients managed by cardiologists were more likely to use and adhere to OAC, regardless of POAF or non‐POAF.

ImportancePreventing diabetes complications requires monitoring and control of hyperglycemia and cardiovascular risk factors. Switching to high-deductible health plans (HDHPs) has been shown to hinder aspects of diabetes care; however, the association of HDHP enrollment with microvascular and macrovascular diabetes complications is unknown.ObjectiveTo examine the association between an employer-required switch to an HDHP and incident complications of diabetes.Design, Setting, and ParticipantsThis retrospective cohort study used deidentified administrative claims data for US adults with diabetes enrolled in employer-sponsored health plans between January 1, 2010, and December 31, 2019. Data analysis was performed from May 26, 2022, to January 2, 2024.ExposuresAdults with a baseline year of non-HDHP enrollment who had to switch to an HDHP because their employer offered no non-HDHP alternative in that year were compared with adults who were continuously enrolled in a non-HDHP.Main Outcomes and MeasuresMixed-effects logistic regression models examined the association between switching to an HDHP and, individually, the odds of myocardial infarction, stroke, hospitalization for heart failure, lower-extremity complication, end-stage kidney disease, proliferative retinopathy, treatment for retinopathy, and blindness. Models were adjusted for demographics, comorbidities, and medications, with inverse propensity score weighting used to account for potential selection bias.ResultsThe study included 42 326 adults who switched to an HDHP (mean [SD] age, 52 [10] years; 19 752 [46.7%] female) and 202 729 adults who did not switch (mean [SD] age, 53 [10] years; 89 828 [44.3%] female). Those who switched to an HDHP had greater odds of experiencing all diabetes complications (odds ratio [OR], 1.11; 95% CI, 1.06-1.16 for myocardial infarction; OR, 1.15; 95% CI, 1.09-1.21 for stroke; OR, 1.35; 95% CI, 1.30-1.41 for hospitalization for heart failure; OR, 2.53; 95% CI, 2.38-2.70 for end-stage kidney disease; OR, 2.23; 95% CI, 2.17-2.29 for lower-extremity complication; OR, 1.17; 95% CI, 1.13-1.21 for proliferative retinopathy; OR, 2.35; 95% CI, 2.18-2.54 for blindness; and OR, 2.28; 95% CI, 2.15-2.41 for retinopathy treatment).Conclusions and RelevanceThis study found that an employer-driven switch to an HDHP was associated with increased odds of experiencing all diabetes complications. These findings reinforce the potential harm associated with HDHPs for people with diabetes and the importance of affordable and accessible chronic disease management, which is hindered by high out-of-pocket costs incurred by HDHPs.

93 Background: The treatment paradigm for mCSPC patients has rapidly evolved over the last few years with the emergence of triplet therapy and prognostication by volume of disease. However, the health economic implications of triplet therapy by disease volume remain unclear. Methods: A Markov model where patients transitioned between the progression-free, progression and death states was developed. State utilities were derived from the LATITUDE trial. Point probabilities for overall survival, progression-free survival, grade ≥ 3 and 5 toxicities were obtained from the eligible mCSPC phase III clinical trials. Medicare Advantage and commercial total paid amounts (2022 US$) of treatments were obtained from OptumLabs Data Warehouse. Costs and disutilities of adverse events were derived from published literature. Half-cycle corrected costs and utilities were accrued monthly over a 20-year lifetime horizon and were discounted at 3%. Monte Carlo simulation was used to calculate incremental cost-effectiveness ratios (ICERs). A willingness-to-pay (WTP) threshold of US$100,000 was used. Results: In terms of Medicare Advantage payer’s perspective (Table), docetaxel (D)+ADT was observed to provide additional 0.068 QALYs compared to ADT at an ICER of US$16,544 per QALY in high volume disease. Compared to D+ADT, abiraterone (AAP) triplet provided additional 1.03 QALYs at US$56,641 per QALY. Compared to AAP triplet, apalutamide (APA)+ADT provided additional 0.048 QALYs at US$5,846,248 per QALY in high volume disease. In low volume disease, D+ADT provided 0.45 more QALYs at US$20,690 per QALY compared to ADT alone. Compared to D+ADT, AAP triplet provided an additional 1.51 QALYS at US$44,267 per QALY. In terms of total paid commercial costs, AAP triplet provided an additional 1.19 QALYs compared to ADT at US$91,952 per QALY in high volume disease. In low volume, D+ADT provided additional 0.38 QALYs at US$22,058 per QALY compared to ADT. Compared to D+ADT, AAP triplet provided a 0.97 QALY gain at US$105,958 per QALY. Compared to AAP triplet, darolutamide (DARO) triplet provided a 0.47 QALY at US$689,196 per QALY. Compared to DARO triplet, APA+ADT provided an additional 0.49 QALYs at an ICER of US$971,389 per QALY. All other treatments (not reported here) were dominated. Conclusions: At the selected WTP of US$100,000 per QALY, AAP triplet therapy was most likely the cost-effective strategy in overall mCSPC population particularly in patients with high volume disease. However, these results should be interpreted with careful accounting for timing of metastases. [Table: see text]

Background Little is known about outcomes following heart failure (HF) hospitalization among adults with congenital heart disease (CHD) in the United States. We aim to compare the outcomes of HF versus non‐HF hospitalizations in adults with CHD. Methods and Results Using a national deidentified administrative claims data set, patients with adult congenital heart disease (ACHD) hospitalized with and without HF (ACHDHF+, ACHDHF−) were characterized to determine the predictors of 90‐day and 1‐year mortality and quantify the risk of mortality, major adverse cardiac and cerebrovascular events, and health resource use. Cox proportional hazard regression was used to compare ACHDHF+ versus ACHDHF− for risk of events and health resource use. Of 26 454 unique ACHD admissions between January 1, 2010 and December 31, 2020, 5826 (22%) were ACHDHF+ and 20 628 (78%) were ACHDHF−. The ACHD HF+ hospitalizations increased from 6.6% to 14.0% ( P <0.0001). Over a mean follow‐up period of 2.23 ± 2.19 years, patients with ACHDHF+ had a higher risk of mortality (hazard ratio [HR], 1.86 [95% CI, 1.67–2.07], P <0.001), major adverse cardiac and cerebrovascular events (HR, 1.73 [95% CI, 1.63–1.83], P <0.001) and health resource use including rehospitalization (HR, 1.09 [95% CI, 1.05–1.14], P <0.001) and increased postacute care service use (HR, 1.56 [95% CI, 1.32–1.85], P <0.001). Cardiology clinic visits within 30 days of hospital admission were associated with lower 90‐day and 1‐year all‐cause mortality (odds ratio [OR], 0.62 [95% CI, 0.49–0.78], P <0.001; OR, 0.69 [95% CI, 0.58–0.83], P <0.001, respectively). Conclusions HF hospitalization is associated with increased risk of mortality and morbidity with high health resource use in patients with ACHD. Recent cardiology clinic attendance appears to mitigate these risks.

Background Transcatheter closure of patent foramen ovale (PFO) has reduced the risk of recurrent stroke in patients with cryptogenic strokes in randomized clinical trials. Whether PFO closure in clinical practice is associated with similar benefit remains unknown. Methods and Results We identified patients with PFO and a history of ischemic stroke or transient ischemic attack who were treated with PFO closure or medical therapy in the OptumLabs database. The primary end point was recurrent ischemic stroke or systemic embolization. Secondary outcomes included mortality, all stroke, transient ischemic attack, and major bleeding. A total of 6668 propensity‐matched patients were included (PFO closure n=4111; medical therapy n=2557). The incidence of stroke or systemic embolization per 100 person‐years was 2.38 after PFO cohort and 2.99 with medical therapy (hazard ratio [HR], 0.85 [95% CI, 0.68–1.05], P =0.13). Mortality was lower in the PFO closure cohort (1.78 versus 2.59 per 100 person‐years: HR, 0.69 [95% CI, 0.55–0.87], P =0.002). Falsification end points showed that this difference is unlikely to be completely explained by residual confounders. There were no significant differences between the groups in secondary end points including intracranial hemorrhage and major bleeding except for an increase in nonintracranial hemorrhage bleeding among patients treated with oral anticoagulation (1.42 versus 2.16 per 100 person‐years: HR, 0.69 [95% CI, 0.48–0.99], P =0.043). The main end point was consistent in subanalyses including patients <60 years of age, patients with prior stroke, and those treated after the publication of the positive PFO trials in 2017. Conclusions In contemporary US practice, PFO closure is not associated with lower rates of recurrent ischemic stroke or systemic embolization compared with medical therapy. Potential reasons for this discrepancy warrant further investigation.

Background: A recent subanalysis of the EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) suggests a stronger benefit of early rhythm control (ERC) in patients with atrial fibrillation and a high comorbidity burden when compared to patients with a lower comorbidity burden. Methods: We identified 109 739 patients with newly diagnosed atrial fibrillation in a large United States deidentified administrative claims database (OptumLabs) and 11 625 patients in the population-based UKB (UK Biobank). ERC was defined as atrial fibrillation ablation or antiarrhythmic drug therapy within the first year after atrial fibrillation diagnosis. Patients were classified as (1) ERC and high comorbidity burden (CHA 2 DS 2 -VASc score ≥4); (2) ERC and lower comorbidity burden (CHA 2 DS 2 -VASc score 2–3); (3) no ERC and high comorbidity burden; and (4) no ERC and lower comorbidity burden. Patients without an elevated comorbidity burden (CHA 2 DS 2 -VASc score 0–1) were excluded. Propensity score overlap weighting and cox proportional hazards regression were used to balance patients and compare groups for the primary composite outcome of all-cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction as well as for a primary composite safety outcome of death, stroke, and serious adverse events related to ERC. Results: In both cohorts, ERC was associated with a reduced risk for the primary composite outcome in patients with a high comorbidity burden (OptumLabs: hazard ratio, 0.83 [95% CI 0.72–0.95]; P =0.006; UKB: hazard ratio, 0.77 [95% CI, 0.63–0.94]; P =0.009). In patients with a lower comorbidity burden, the difference in outcomes was not significant (OptumLabs: hazard ratio, 0.92 [95% CI, 0.54–1.57]; P =0.767; UKB: hazard ratio, 0.94 [95% CI, 0.83–1.06]; P =0.310). The comorbidity burden interacted with ERC in the UKB (interaction- P =0.027) but not in OptumLabs (interaction- P =0.720). ERC was not associated with an increased risk for the primary safety outcome. Conclusions: ERC is safe and may be more favorable in a population-based sample of patients with high a comorbidity burden (CHA 2 DS 2 -VASc score ≥4).

Background Sepsis is associated with an elevated risk of late cardiovascular events among hospital survivors. Methods and Results We included OptumLabs Data Warehouse patients from 2009 to 2019 who survived a medical/nonsurgical hospitalization lasting at least 2 nights. The association between sepsis during hospitalization, based on explicit and implicit discharge International Classification of Diseases, Ninth Revision ( ICD‐9 )/ Tenth Revision ( ICD‐10 ) diagnosis codes, with subsequent death and rehospitalization was analyzed using Kaplan–Meier survival analysis and multivariable Cox proportional‐hazards models. The study population included 2 258 464 survivors of nonsurgical hospitalization (5 396 051 total patient‐years of follow‐up). A total of 808 673 (35.8%) patients had a sepsis hospitalization, including implicit sepsis only in 448 644, explicit sepsis only in 124 841, and both in 235 188. Patients with sepsis during hospitalization had an elevated risk of all‐cause mortality (adjusted hazard ratio [HR], 1.27 [95% CI, 1.25–1.28]; P <0.001), all‐cause rehospitalization (adjusted HR, 1.38 [95% CI, 1.37–1.39]; P <0.001), and cardiovascular hospitalization (adjusted HR, 1.43 [95% CI, 1.41–1.44]; P <0.001), especially heart failure hospitalization (adjusted HR, 1.51 [95% CI, 1.49–1.53]). Patients with implicit sepsis had higher risk than those with explicit sepsis. A sensitivity analysis using the first hospitalization yielded concordant results for cardiovascular hospitalization (adjusted HR, 1.78 [95% CI, 1.76–1.78]; P <0.001), as did a propensity‐weighted analysis (adjusted HR, 1.52 [95% CI, 1.50–1.54]; P <0.001). Conclusions Survivors of sepsis hospitalization are at elevated risk of early and late post‐discharge death as well as cardiovascular and non‐cardiovascular rehospitalization. This hazard spans the spectrum of cardiovascular events and may suggest that sepsis is an important cardiovascular risk factor.

ImportanceOptimal diabetes care requires regular monitoring and care to maintain glycemic control. How high-deductible health plans (HDHPs), which reduce overall spending but may impede care by increasing out-of-pocket expenses, are associated with risks of severe hypoglycemia and hyperglycemia is unknown.ObjectiveTo examine the association between an employer-forced switch to HDHP and severe hypoglycemia and hyperglycemia.Design, Setting, and ParticipantsThis retrospective cohort study used deidentified administrative claims data for privately insured adults with diabetes from a single insurance carrier with multiple plans across the US between January 1, 2010, and December 31, 2018. Analyses were conducted between May 15, 2020, and November 3, 2022.ExposuresPatients with 1 baseline year of enrollment in a non-HDHP whose employers subsequently forced a switch to an HDHP were compared with patients who did not switch.Main Outcomes and MeasuresMixed-effects logistic regression models were used to examine the association between switching to an HDHP and the odds of severe hypoglycemia and hyperglycemia (ascertained using diagnosis codes in emergency department [ED] visits and hospitalizations), adjusting for patient age, sex, race and ethnicity, region, income, comorbidities, glucose-lowering medications, baseline ED and hospital visits for hypoglycemia and hyperglycemia, and baseline deductible amount, and applying inverse propensity score weighting to account for potential treatment selection bias.ResultsThe study population was composed of 42 326 patients who switched to an HDHP (mean [SD] age: 52 [10] years, 19 752 [46.7%] women, 7375 [17.4%] Black, 5740 [13.6%] Hispanic, 26 572 [62.8%] non-Hispanic White) and 202 729 patients who did not switch (mean [SD] age, 53 [10] years, 89 828 [44.3%] women, 29 551 [14.6%] Black, 26 689 [13.2%] Hispanic, 130 843 [64.5%] non-Hispanic White). When comparing all study years, switching to an HDHP was not associated with increased odds of experiencing at least 1 hypoglycemia-related ED visit or hospitalization (OR, 1.01 [95% CI, 0.95-1.06]; P = .85), but each year of HDHP enrollment did increase these odds by 2% (OR, 1.02 [95% CI, 1.00-1.04]; P = .04). In contrast, switching to an HDHP did significantly increase the odds of experiencing at least 1 hyperglycemia-related ED visit or hospitalization (OR, 1.25 [95% CI, 1.11-1.42]; P &amp;lt; .001), with each year of HDHP enrollment increasing the odds by 5% (OR, 1.05 [95% CI, 1.01-1.09]; P = .02).Conclusions and RelevanceIn this cohort study, employer-forced switching to an HDHP was associated with increased odds of potentially preventable acute diabetes complications, potentially because of delayed or deferred care. These findings suggest that employers should be more judicious in their health plan offerings, and health plans and policy makers should consider allowing preventive and high-value services to be exempt from deductible requirements.