Publications

Glucagon-like peptide 1 receptor agonists (GLP1-RA) are antidiabetic agents recently approved for weight loss. Obesity is an established risk factor for venous thromboembolism (VTE). Moreover, preclinical studies have shown that GLP1-RA may attenuate thromboxane-induced platelet activation. Therefore, we hypothesized that GLP1-RA use may reduce the risk of VTE. We performed a target trial emulation (TTE) using a population-based database of electronic health records to evaluate whether GLP1-RA use is associated with a reduction in VTE in patients with type 2 diabetes mellitus (T2DM) compared with dipeptidyl peptidase-4 inhibitors (DPP4i). Patients who were newly initiated on GLP1-RA were propensity score matched to patients who were newly initiated on DPP4i. We evaluated the primary outcome, composite VTE, identified using ICD-10 (International Classification of Diseases, Tenth Revision) codes, within 12 months of the initiation of GLP1-RA or DPP4i. The study cohort comprised 540 258 patients with 270 129 individuals receiving either GLP1-RA or DPP4i. Over 12 months of follow-up, patients who received GLP1-RA had a lower incidence of VTE compared with patients who received DPP4i (6.1 vs 7.6 events per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.73-0.83). This was similar for pulmonary embolism (2.9 vs 3.8 events per 1000 patient-years; HR, 0.74; 95% CI, 0.68-0.82) and deep vein thrombosis (3.9 vs 4.7 events per 1000 patient-years; HR, 0.81; 95% CI, 0.75-0.88). In this propensity score-matched, TTE study, patients with T2DM who received a GLP1-RA had a lower risk of VTE at 1 year compared with patients who received DPP4i.

BACKGROUND: Obesity is an established risk factor for venous thromboembolism (VTE). Observational data suggest that glucagon-like peptide 1 receptor agonists (GLP-1RAs) may reduce the risk of VTE. However, the effects of GLP-1RAs on VTE have not been tested in randomized controlled trials (RCTs).

OBJECTIVES: To investigate the impact of GLP-1RAs on VTE risk using data from RCTs.

METHODS: We conducted a systematic review and meta-analysis of placebo-controlled RCTs focusing on GLP-1RA use in patients with type 2 diabetes mellitus (T2DM) or obesity. Five databases were searched from inception to October 2024. The primary outcome was VTE, which was a composite of pulmonary embolism (PE), deep vein thrombosis (DVT), and VTE at other sites, and the secondary outcomes were the individual events.

RESULTS: Twenty-seven RCTs with 84,003 patients were analyzed. The median incidence of VTE was 1.1 and 2.5 per 1,000 patient-years in the GLP-1RA and placebo groups, respectively. There was no statistically significant difference in overall VTE risk between GLP-1RA and placebo groups (RR 0.70, 95% CI 0.46-1.07). However, GLP-1RAs were associated with a significantly lower risk of PE (RR 0.60, 95% CI 0.39-0.94). In contrast, there were no significant differences in the risk of DVT (RR 1.24, 95% CI 0.67-2.27) or VTE at other sites (RR 0.56, 95% CI 0.25-1.26).

CONCLUSIONS: In this meta-analysis of randomized trials, GLP-1RAs were not associated with a significant reduction in overall VTE risk but were associated with a lower risk of PE among patients with T2DM or obesity.

BACKGROUND: High and rising prescription drug costs for asthma and chronic obstructive pulmonary disease (COPD) contribute to medication nonadherence and poor clinical outcomes. The recently enacted Inflation Reduction Act includes provisions that will cap out-of-pocket prescription drug spending at $2,000 per year and expand low-income subsidies. However, little is known about how these provisions will impact out-of-pocket drug spending for Medicare beneficiaries with asthma and COPD.

OBJECTIVE: To estimate the impact of the Inflation Reduction Act's out-of-pocket spending cap and expansion of low-income subsidies on Medicare beneficiaries with obstructive lung disease.

DESIGN: We calculated the number of Medicare beneficiaries ≥ 65 years with asthma and/or COPD and out-of-pocket prescription drug spending > $2,000/year, and then estimated their median annual out-of-pocket savings under the Inflation Reduction Act's spending cap. We then estimated the number of beneficiaries with incomes > 135% and ≤ 150% of the federal poverty level who would become newly eligible for low-income subsidies under this policy.

PARTICIPANTS: Respondents to the 2016-2019 Medical Expenditure Panel Survey (MEPS).

MAIN MEASURES: Annual out-of-pocket prescription drug spending.

KEY RESULTS: An annual estimated 5.2 million Medicare beneficiaries had asthma and/or COPD. Among them, 360,160 (SE ± 38,021) experienced out-of-pocket drug spending > $2,000/year, with median out-of-pocket costs of $3,003/year (IQR $2,360-$3,941). Therefore, median savings under the Inflation Reduction Act's spending cap would be $1,003/year (IQR $360-$1,941), including $738/year and $1,137/year for beneficiaries with asthma and COPD, respectively. Total annual estimated savings would be $504 million (SE ± $42 M). In addition, 232,155 (SE ± 4,624) beneficiaries would newly qualify for low-income subsidies, which will further reduce prescription drug costs.

CONCLUSIONS: The Inflation Reduction Act will have major implications on out-of-pocket prescription drug spending for Medicare beneficiaries with obstructive lung disease resulting in half-a-billion dollars in total out-of-pocket savings per year, which could ultimately have implications on medication adherence and clinical outcomes.

BACKGROUND: Although Medicare Advantage (MA) plans provide coverage to >50% of Medicare beneficiaries, it is unclear whether MA claims can be used similarly to Medicare Fee-For-Service (FFS) claims for clinical outcomes assessment. In this study, we evaluate the accuracy of claims algorithms previously validated in FFS to assess comorbidities and outcomes in MA patients after aortic valve replacement.

METHODS: We compared the concordance of 11 claims-based covariates (diabetes, hypertension, atrial flutter/fibrillation, myocardial infarction) and outcomes (stroke, disabling stroke, transient ischemic attack, major vascular complication, bleeding, permanent pacemaker implantation, death) among FFS and MA patients with the covariates and adjudicated outcomes in the multinational Evolut Low-Risk Trial (2016-2018). We used claims algorithms for 1-year outcomes and calculated sensitivity, specificity, positive predictive value, negative predictive value, and kappa, using adjudicated outcomes as the reference. We compared the kappa for MA versus FFS using the 2-sample z-test with a significance level of P<0.05.

RESULTS: Among 1139 US patients aged 65+ years old in the Evolut Low-Risk Trial, 782 patients (175 MA and 607 FFS) were linked to claims data and had complete comorbidity data. Among all covariates, claims algorithms for covariates had sensitivities ≥85% for identifying diabetes, atrial flutter/fibrillation, and hypertension in MA and FFS. For the outcomes, sensitivities were ≥85% for bleeding (comprehensive), permanent pacemaker implantation, and death. The kappa was higher in MA versus FFS for diabetes (P=0.03) and hypertension (P=0.025) but was lower in myocardial infarction (P<0.0001). There was no statistically significant difference in the kappa agreement between MA versus FFS for any of the selected outcomes.

CONCLUSIONS: Medicare claims have a similar level of kappa agreement in MA versus FFS for most covariates and outcomes. As patients shift to MA, ascertainment of outcomes using Medicare claims in postapproval studies remains valid for select outcomes.