With a dataset encompassing 1.2 million patients with T2DM, this is one of the largest analyses to have assessed total healthcare utilization and costs in patients with T2DM in the US stratified by the presence or absence of ASCVD. It found that almost one-half (45.2%) of all adults with T2DM had concomitant ASCVD during the analysis period of 2014–2015. As would be expected, the prevalence of ASCVD increased with age, from 15% of the youngest cohort (18–44 years) to 71% of the oldest cohort (≥ 65 years). Patients with ASCVD used more healthcare resources and had higher costs related to healthcare for every evaluated resource category (outpatient office visits, inpatient hospital admissions, ER visits) than patients without ASCVD. The mean total healthcare cost per patient with T2DM with concomitant ASCVD ($22,977) was more than double the mean total healthcare cost per patient with T2DM but without ASCVD ($9735), with concomitant ASCVD adding a mean $13,242 per patient per year. Medical (non-pharmacy) costs were almost tripled in patients having T2DM with ASCVD, while pharmacy costs were about 40% higher.
These findings corroborate those from a smaller (N = 138,018) US study by Mehta et al. which used linked EMR-claims data and identified CVD (defined as a history of stroke, transient ischemic attack, MI, unstable angina, or coronary revascularization) in 12% of patients with T2DM. This was lower than the 45.2% prevalence of ASCVD noted in the present study, for which the definition of ASCVD included additional indications of peripheral arterial disease or acute coronary syndrome, which were the ASCVD indications with highest prevalence. Mehta et al. reported that unadjusted monthly total treatment costs per patient were significantly higher, by almost twice, for patients with CVD compared with patients without CVD ($2655 vs $1435) [13], similar to the 2.4-times higher costs for patients with versus without ASCVD in our study. Interestingly, both the Mehta study and our study observed an apparent disproportionate increase in ASCVD-related cost burden in younger relative to older age groups. In our study, the youngest age group (18–44 years) demonstrated the largest difference in costs between patients with vs without concomitant ASCVD (+ 143%); corresponding costs differences in the 45–64 and ≥ 65 year age groups were + 127% and 114%, respectively. Although not directly comparable with unadjusted costs in the present study, it is worth noting that adjusted costs associated with CVD in the Mehta 2018 study were the highest (56% higher) in patients aged less than 45 years and lowest (2% higher) in patients aged more than 64 years [13].
A study by Johnston et al. [11] used MarketScan data (2009–2010) to quantify the cost of major adverse cardiovascular events (MACE; MI and stroke) in 1,415,598 patients with T2DM. Patients were assigned risk categories (lowest, medium, highest) based upon age, sex, number of baseline claims for atherosclerosis, stroke, MI, unstable angina, coronary revascularization, heart failure, dyslipidemia, hypertension, and tobacco use disorder, and were followed 301 to 343 days for occurrence of MACE. Healthcare costs were substantially higher for 10,399 (0.73%) patients with MACE, although costs varied with CVD risk category and payer (commercial, Medicare with supplemental insurance, Medicaid). Among patients with the highest CVD risk, expected per patient per month costs associated with MACE events alone (not all-cause healthcare) ranged from $9574–$18,727, depending on insurance type.
Li et al. [12] analyzed data from 7109 patients with T2DM from the Translating Research Into Action for Diabetes study and used a generalized linear regression model to estimate associations between medical costs and various patient characteristics, including comorbidities. Based on modeling findings, the presence of coronary heart disease increased direct medical costs 1.8-fold in patients with T2DM.
Thus, existing data confirm the substantial cost burden of ASCVD and related comorbidities in patients with T2DM, and there is growing momentum to address cardiovascular complications within the scope of diabetes care. The primary goals of T2DM management, in addition to maintenance of patient quality of life, are to prevent the development or progression of diabetes-related complications through glycemic control and management of cardiovascular risk [21]; as such, the treatment of patients with diabetes is evolving in order to focus more intently on CVD risk reduction. While some older pharmacological agents used to manage diabetes, such as sulfonylureas, may increase CV risk [22, 23], newer classes of agents such as GLP-1RAs and SGLT2is have been shown to reduce the risk of MACE in patients with established CVD independent of their glucose-lowering benefits [24,25,26,27]. Thus, current ADA guidelines recommend that, in patients with T2DM and established CVD who require therapy beyond lifestyle management and metformin, agents with proven cardiovascular benefit should be incorporated as part of glycemic management. Antidiabetic agents with dual impact on both glycemia and CVD risk reduction have the potential to improve health outcomes, limit the number of drugs administered, and possibly reduce overall costs.
Of note, 15% of patients in the youngest age category in the current study (18–44 years) had established ASCVD, and 36% of those in the middle age group (45–64 years). The development of serious comorbidities at a relatively young age can translate into substantial medical cost implications over time and aggressive preventive measures are warranted for both economic and health reasons. Some data suggest that early-onset T2DM in younger patients carries a particularly high cardiovascular risk, including a 14-fold increased risk of MI compared with matched, non-T2DM controls [27].
The findings of this analysis, while robust, are not without limitations. Despite the large nationwide sample, no data were obtained from patients insured by Medicaid or from uninsured patients, thus the results may not be completely generalizable to the entire US population. Nonetheless, generalizability to the US population is enhanced by the sheer size of the study sample (over one-half million patients in each cohort) and diverse geographical sampling distribution. Substantial differences in insurance coverage patterns on healthcare resource use and costs were not assessed. As the prevalence of ASCVD increases with age group and as commercial insurance is replaced by Medicare in older patients, it is possible that the availability of healthcare resources and pharmacological therapies would not be equivalent between insurance carriers across age cohorts. There was a substantial difference between groups in the distribution of types of insurance carriers; approximately 50% of patients with concomitant ASCVD had commercial insurance, as compared to 84% of patients without ASCVD. Not all patients had detailed cost data available; yet this situation was similar for both cohorts and reflected < 15% of either group, and thus should not have impacted the study findings substantially. Propensity score matching was performed based on patient age, sex, region, and insurance, and did not factor in comorbidity variables. It should be noted that the propensity score-matched ASCVD cohort had higher mean DCSI (2.41 vs 0.85) and CCI (2.93 vs 1.76) scores as compared to the non-ASCVD cohort, suggesting greater overall comorbidity burden in the ASCVD cohort. The excess mean prevalence of any non-ASCVD comorbidity/complication in the matched ASCVD cohort versus the non-ASCVD cohort was less than 10% with the exception of hypertension: hypertension (10.1%), dyslipidemia (6.8%), metabolic (2.2%), nephropathy (7.3%), and retinopathy (2.6%). While these differences appear to be relatively minor, a confounding effect of higher comorbidity prevalence in the ASCVD cohort on cost differences between the groups cannot be ruled out and the reader should interpret the study findings with this in mind. Finally, the current analysis is dependent upon the coding practices of providers, which may be subject to coding error, and upon ICD codes alone to document ASCVD and comorbidities, which could also have been subject to coding error. Indirect costs, such as loss of productivity, were not captured.