Association of antipsychotic nonadherence with all-cause mortality in adults with schizophrenia newly treated or reinitiating antipsychotic medication: A retrospective healthcare claims study.

Background:Gout is the most common inflammatory arthritis worldwide with a diverse spectrum of clinical manifestations. Many studies indicated that gout is associated with hypertension, metabolic syndrome, chronic kidney disease and ischaemic heart diseases.Objectives:This study investigated the association between the compliance of urate-lowering agents (ULA) compliance and progression end-stage renal disease (ESRD) and all-cause mortality.Methods:We identified 53,917 patients with incident gout from 2002 to 2012. We followed up these patients till 31DEC2015. The primary data source was the National Health Insurance database of Taiwan. Proportion of days covered (PDC) was used to measure medication adherence. Patients with PDC≧80% more than two years defined adherence to ULA. Cox proportional hazards model was used to estimate difference and hazard ratios (HRs) for ESRD and all-cause mortality.Results:A total of 53,917 patients were included (figure 1). Patient with urate-lowering agent PDC≧80% more than 2 years were 2,371. After propensity score matched 1:4 with age, sex and comorbidities, PDC <80% were 9,484 matched cohort (Table 1). The mean follow-up duration is 12.30±2.45 years in PDC≧80% group and 9.52±3.46 years in PDC <80%. During follow-up, ESRD was detected in 1,349 patients (306 with PDC≧80% and 1,043 with PDC <80%) and all-cause mortality was found 3,430 patients (842 with PDC≧80% and 2,588 with PDC <80%). This matching showed no difference in ESRD (HR, 0.91; 95% CI, 0.80-1.03) and all-cause mortality (HR, 0.96; 95% CI, 0.88-1.03) (Table 2).Table 1.Baseline characteristic of adherence and non-adherence of urate-lowering agent among patients with gout in matched and unmatched cohortUnmatched CohortPropensity-score Matched CohortVariablePDC≧80%N=2371^PDC<80%N=51546^PPDC≧80%N=2371^PDC<80%N=9484^PAge (years) (mean ± standard deviation)59.96±13.4451.52±15.61<0.000159.96±13.4460.23±13.410.3755follow-up duration (years) (mean ± standard deviation)12.30±2.459.52±3.46Gender0.30980.2855Male1929(81.36%)42358(82.18%)1929(81.36%)7624(80.39%)Female442(18.64%)9188(17.82%)442(18.64%)1860(19.61%)ComorbiditiesHypertension406(17.12%)3695(7.17%)1.71E-71406(17.12%)1571(16.56%)0.5138Diabetes Mellitus276(11.64%)2367(4.59%)1.78E-54276(11.64%)1080(11.39%)0.7291Ischemic heart disease109(4.60%)988(1.92%)1.58E-19109(4.60%)444(4.68%)0.8617Cerebrovascular disease113(4.77%)891(1.73%)1.05E-26113(4.77%)481(5.07%)0.5416Peripheral arterial disease20(0.84%)170(0.33%)3.67E-0520(0.84%)74(0.78%)0.7561Congestive heart failure81(3.42%)606(1.18%)1.88E-2181(3.42%)286(3.02%)0.3137Anemia182(7.68%)1559(3.02%)5.22E-36182(7.68%)769(8.11%)0.4882CKD266(11.22%)1978(3.84%)2.61E-69266(11.22%)963(10.15%)0.1281Table 2.hazard ratio of ESRD and all-cause mortality in patients with goutOutcomeHazard ratio (95% Confidence interval)ESRDULA adherence level PDC<80%Reference PDC≧80%0.91 (0.80-1.03)All-cause mortalityULA adherence level PDC<80%Reference PDC≧80%0.96 (0.88-1.03)PDC= Proportion of days coveredFigure 1.Flow chart for study designConclusion:Gout patients with/without two years adherence of urate-lowering agents does not have an impact on ESRD and all-cause mortality.

Background:Evidence has consistently shown that adherence to AM is poor in systemic lupus erythematosus (SLE) patients. However, data on the impact of adherence to AM on mortality is scarce.Objectives:To assess the effect of AM adherence on all-cause mortality in SLE patients from the general population.Methods:This study used administrative databases from British Columbia, Canada. We created an incident SLE cohort between January 01, 1997, and March 31, 2015, using the physician billing data and a 7-year washout period. The inclusion criteria were at least two physician visits, at least two months apart, within two years, with an ICD-9 code (710.0) or ICD-10 code (M32.1, M32.8, M32.9) for SLE. Follow-up started at the first day of having both SLE and AM, i.e., at the SLE index date (second ICD code) for those whose first AM use occurred before the SLE index date, or the date of the first AM use if otherwise. Our outcome was all-cause mortality, obtained from the vital statistics registry. In the analysis, the follow-up time was divided into 30-days windows, for a total of 293,190 person-months. For each window, a measure of adherence, the proportion of days covered (PDC), was calculated and categorized as adherent (PDC≥0.90), non-adherent (0<PDC<0.90), and discontinuer (no drug or PDC = 0). We used both Cox’s proportional hazards models and marginal structural models (MSM) to estimate the effect of AM adherence on all-cause mortality. Both analysis controlled for baseline demographics (age, sex, residence, income quintile), as well as the following baseline and time-varying covariates: immunosuppressive and other medications, hospitalizations, impatient, and other visits, and Charlson comorbidity index. To account for the possibility of a few time-varying covariates being mediators in the causal pathway from AM adherence to mortality, which may cause the Cox model to yield biased estimates of the adherence effects, we conducted the MSM analysis that can produce valid estimates as it balances the distributions of time-varying confounders among the three adherence groups via inverse probability weighting.Results:We identified 3,385 individuals with incident SLE (mean age 47.3 years, 89% were women) who had at least one filled AM prescription. Over the mean follow-up of 6.66 years, 288 (8.5%) incident SLE patients died. The incidence rate (IR) of mortality for AM adherent, non-adherent, and discontinuer patients were 4.31, 11.86, and 19.51 per 1000 person-years, respectively. Using the Cox model, the adjusted hazard ratio (HRs) obtained for AM adherent and non-adherent SLE patients were 0.20 and 0.66, respectively, compared to discontinuer SLE patients (Table 1). Using MSM, those adjusted HRs were found as 0.18 and 0.64. Also, the adjusted HRs for adherers compared to the non-adherers were 0.30 (Cox) and 0.28 (MSM). A statistically significant linear trend in the HRs of mortality risk over the adherence levels was found (Table 1, Linear Trend).Table 1.Adherence LevelsNo. of DeathsIR Ratios (95%CI)Adjusted Cox HRs (95%CI)Adjusted MSM HRs (95%CI)Discontinuer (Reference)198Non-adherent470.61(0.44-0.84)0.66(0.47-0.93)0.64(0.46-0.89)Adherent430.22(0.16-0.31)0.20(0.14-0.28)0.18(0.12-0.25)Contrast: Partial vs. Full0.36(0.24-0.55)0.30(0.19-0.46)0.28(0.18-0.42)Linear Trend0.32(0.25-0.41)0.29(0.23-0.37)Conclusion:SLE patients that adhere to AM therapy have a lower risk of death than patients who do not adhere or who discontinue AM (5 and 3 times, respectively) in both the MSM and Cox analysis. Our findings support the importance of AM adherence to prevent premature deaths in SLE patients.Disclosure of Interests:None declared

Background Therapeutic management of hypertension is a landmark of cardiovascular (CV) risk prevention. Combined therapies with at least 2 anti-hypertensive agents are required in many patients in whom monotherapy and lifestyle interventions failed in blood pressure control. It is well-known that poor medication adherence remains a major barrier to achieving the therapeutic targets for all CV drugs, including anti-hypertensives. Purpose We evaluated the relationship between adherence to perindopril (PER)-based therapeutic regimen prescribed as single-pill combination (SPC) or free-pill and CV outcomes and all-cause mortality in a large Italian population. Methods A retrospective analysis was performed using administrative databases corresponding to around 6.7 million health-assisted residents. Hypertensive adults were first identified through hospitalization discharge diagnosis or exemption codes for hypertension between 2010 and 2021. Patients prescribed PER-based therapies were screened for all combinations of PER with amlodipine (AML) and/or indapamide (IND) (all formulations, single-pill or free-pill). Time of the first prescription of a PER-based regimen during the inclusion period was considered the index-date. The analysis included all hypertensive subjects prescribed a PER-based therapy, having available data at least 12 months before and 24 months after the index-date, respectively. Since the analysis was focused on the possible associations between adherence level and CV outcomes and all-cause mortality, adherence was assessed during the first year of follow-up on alive patients and outcomes were assessed during the second year. Adherence was assessed using the proportion of days covered (PDC) approach on 1-year follow-up, and considering a PDC<80% as poor-to-moderate adherence, and PDC ≥80% as good adherence. The Cox’s proportional hazard model was applied to estimate Hazard Ratio (HR) adjusting for baseline covariates, including comorbidity profile and pill burden. Results The included cohort (N=24,476) was divided into sub-groups according to adherence in poor-to-moderate (N=6,781) and good adherent patients (N=17,695) with a mean age of 64.8±13.3 and 64.6±11.9 years old, respectively. The Cox’s proportional hazard model showed that good adherence was associated with a relative risk reduction of 23% in all-cause mortality (Table 1A), 21% in all CV events (Table 1B), 17% in ischemic heart disease (Table 1C), 33% in cerebrovascular events (Table 1E), and 22% in the composite outcome of CV events/all-cause mortality (Table 1G). Conclusions The present analysis provided evidence from the Italian real clinical practice that good adherence to PER-based anti-hypertensive therapy results in significantly lower cardiovascular risk and all-cause mortality. These data further emphasize the importance of promoting cost-effective measures to increase medication adherence in patients on anti-hypertensive treatment.

In observational studies, the methods used to measure medication adherence may affect assessments of the clinical outcomes of drug therapy. This study estimated medication adherence to multidrug therapy in patients with hypertension using different measurement methods and compared their impacts on clinical outcomes. This was a retrospective cohort study using the Korean National Health Insurance Service-National Sample Cohort database (2006-2015). Adults diagnosed with hypertension who initiated multidrug antihypertensive therapy in the index year 2007 were included. Adherence was defined as over 80% compliance. Adherence to multidrug antihypertensive therapy was measured in 3 ways using the proportion of days covered (PDC) with 2 approaches to the end-date of the study observations: PDC with at least one drug (PDCwith≥1), PDC with a duration weighted mean (PDCwm), and the daily polypharmacy possession ratio (DPPR). The primary clinical outcome was a composite of cardiovascular and cerebrovascular disease-specific hospitalizations or all-cause mortality. In total, 4,226 patients who initiated multidrug therapy for hypertension were identified. The mean adherence according to the predefined measurements varied from 72.7% to 79.8%. Non-adherence was associated with an increased risk of a primary outcome. The hazard ratios (95% confidence intervals, CIs) primary outcomes varied from 1.38 (95% CI, 1.19 to 1.59) to 1.44 (95% CI, 1.25 to 1.67). Non-adherence to multidrug antihypertensive therapy was significantly associated with an increased risk of a primary clinical outcome. Across the varying estimates based on different methods, medication adherence levels were similar. These findings may provide evidence to support decision-making when assessing medication adherence.

Background: Previous studies have reported that women with type 2 diabetes mellitus (T2DM) diagnosed with breast cancer have greater overall morality compared to nondiabetic breast cancer patients, while limited knowledge exists on cause-specific mortality. Among the nonelderly U.S. population, Medicaid-insured individuals have higher breast cancer mortality and elevated risk of T2DM-related complications compared to other insurance types. However, the role of preexisting T2DM on mortality among Medicaid-insured women diagnosed with breast cancer remains unknown. We investigated the influence preexisting T2DM and antidiabetic drugs have on all-cause and cause-specific mortality among Medicaid-insured women diagnosed with breast cancer. Methods: Data for 9,221 women aged <64 years who were diagnosed with breast cancer and reported to the New York State (NYS) Cancer Registry from 2004-2016 were linked with Medicaid claims data. Preexisting T2DM was determined by three diagnosis claims for T2DM with at least one claim prior to breast cancer diagnosis and a prescription claim for an antidiabetic drug within three months following breast cancer diagnosis. Estimated menopausal status was determined by age (premenopausal age <50; postmenopausal age ≥50). Hazard ratios (HR) and 95% confidence intervals (95%CI) were calculated with Cox proportional hazards regression, adjusting for potential confounders. Results: Women with preexisting T2DM had greater all-cause (HR=1.42; 95%CI 1.22, 1.65), cancer-specific (HR=1.26; 95%CI 1.06, 1.50), and cardiovascular-specific (HR=2.45; 95%CI 1.54, 3.89) mortality hazard compared to nondiabetic women. In subgroup analyses, the association between T2DM and all-cause mortality was observed among non-Hispanic White (HR 1.80 95%CI 1.39, 2.32), postmenopausal (HR=1.49; 95%CI 1.24, 1.79) women, but not among other race/ethnicity groups or premenopausal women. Additionally, compared to women prescribed metformin, all-cause mortality hazard was elevated among women prescribed sulfonylurea (HR=1.44; 95%CI 1.07, 1.94) or insulin (HR=1.54; 95%CI 1.12, 2.11). Conclusion: Among Medicaid-insured women with breast cancer, those with preexisting T2DM have an increased mortality hazard, especially when prescribed sulfonylurea or insulin. Further research is warranted to determine the optimal course of treatment for women with preexisting T2DM diagnosed with breast cancer. Citation Format: Wayne R. Lawrence, Akiko S. Hosler, Margaret Gates Kuliszewski, Matthew C. Leinung, Wangjian Zhang, Francis P. Boscoe. All-cause and cause-specific mortality among Medicaid-insured women with preexisting type 2 diabetes diagnosed with breast cancer: A cancer registry-Medicaid linkage [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PR16.

Impact of preexisting type 2 diabetes mellitus and antidiabetic drugs on all-cause and cause-specific mortality among Medicaid-insured women diagnosed with breast cancer

Efficacy and safety of adjunctive pharmacologic treatments for alcohol addiction in patients with schizophrenia and bipolar disorder

Adherence to Statin Treatment and Health Outcomes in an Italian Cohort of Newly Treated Patients: Results From an Administrative Database Analysis

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Servier. Background/Introduction One of the most effective strategies for cardiovascular (CV) disease prevention is lipid level control. To achieve this control, a satisfactory level of adherence to effective lipid-lowering medications is required. Purpose To evaluate and compare medication adherence and plasma levels of low-density lipoprotein cholesterol (LDL-C) among 2 cohorts of patients treated with rosuvastatin and ezetimibe (ROS/EZE) as free (FC) or single-pill combination (SPC), in an Italian real-world setting. Methods A retrospective analysis was performed using administrative databases linked to laboratory database, covering approximately 7 million health-assisted subjects. Adults prescribed with ROS/EZE as SPC or FC during January 2018-June 2020 were included and categorized in 2 cohorts. Index date (ID) was the first prescription of SPC or first simultaneous prescription of the 2 drugs (within 30 days interval). Patients were characterized during all available periods prior to ID and followed-up to end of data availability. Propensity score matching (PSM) was applied to minimize selection bias between cohorts; adherence was calculated as proportion of days covered (PDC): PDC<25% non-adherence; PDC=25-75% partial adherence; PDC>75% adherence, after PSM. Based on ESC/EAS 2019 guidelines, patients were stratified by CV risk profile. For a subgroup of patients (n=3,846) with plasma-LDL-C data availability (at ID and during first year of follow-up), the percentages of patients being above 55 mg/dl LDL-C for very-high risk, 70 mg/dl for high risk, and 116 mg/dl for other CV risk patients, and who reached these levels during follow-up were reported. Results The analysis included 25,886 patients in SPC cohort and 7,309 in FC. Post-PSM cohorts were balanced for their characteristics, including CV risk, and comprised 21,927 (SPC) and 7,309 (FC) patients. A higher percentage of patients were adherent to SPC vs FC (56.8% vs 44.5%, p<0.001). A lower percentage of non-adherent patients was found for the SPC vs FC (12.6% vs 27.4%, p<0.001). Among very-high, high and other CV risk patients, respectively, a 30%, 28% and 21% increase in the number of adherent patients was found for SPC vs FC [65.4% vs 50.4%, p<0.001 (very-high); 54.7% vs 42.7%, p<0.001 (high); 43.5% vs 35.9%, p<0.001 (other CV risk)] (Fig. 1). The proportion of very-high-CV risk patients reaching LDL-C ≤55mg/dl in the first year of follow-up was higher in SPC vs FC (35.4% vs 23.8%, p<0.001) (Fig.2). Similarly, among high-risk patients, 46.9% and 23.1% (p<0.001) of SPC and FC, respectively, reached ≤70 mg/dl LDL-C and among other CV-risk patients, 71.6% and 49.5% (p<0.001) of SPC and FC, respectively, reached ≤116 mg/dl LDL-C levels during first year of follow-up. Conclusions This real-world analysis in patients with hypercholesterolemia showed that treatment with ROS/EZE SPC vs FC could be associated with better medication adherence and lower LDL-C levels, whatever the CV risk category.

Medication Adherence in Patients with Chronic Myelogenous Leukemia Using Tyrosine-Kinase Inhibitors: A Retrospective Analysis

Studies suggest that long-term use of proton pump inhibitors (PPIs) may be associated with an increased risk of fracture. However, the role of medication adherence in this association is not fully understood. A retrospective cohort study was conducted to examine the relationship between PPI use/adherence and fracture risk among elderly subjects by combining administrative pharmacy claims data, survey data, and Medicare data. The study cohort included 1,604 PPI users and 23,672 nonusers who were enrolled in Pennsylvania's Pharmaceutical Assistance Contract for the Elderly program. PPI adherence was measured by the proportion of days covered (PDC). Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) of PPI use/adherence for fracture risk while controlling for demographics, comorbidity, body mass index, smoking, and non-PPI medication use. The overall incidence of any fracture per 100 person-years was 8.7 for PPI users and 5.0 for nonusers. A gradient in fracture risk according to PPI adherence was observed. Relative to nonusers, fracture HRs associated with the highest (PDC ≥ 0.80), intermediate (PDC 0.40-0.79), and lowest (PDC <0.40) adherence levels were 1.46 (p < 0.0001), 1.30 (p = 0.02), and 0.95 (p = 0.75), respectively. In addition, the fracture risk of PPI use was significant for hip (HR = 1.32, p = 0.04) and vertebral (HR = 1.69, p = 0.0005) fractures, and risk was similar between major osteoporotic and other fractures. These results provide further evidence that PPI use may increase fracture risk in the elderly and highlight the need for clinicians to periodically reassess elderly patients' individualized needs for ongoing PPI therapy, while weighing potential risks and benefits.

To assess the association of antimalarial (AM) adherence with premature mortality among incident systemic lupus erythematosus (SLE) patients. All patients with incident SLE and incident AM use in British Columbia, Canada, between January 1997 and March 2015 were identified using the provincial administrative databases. Follow-up started on the first day of having both SLE and AM. The outcome was all-cause mortality. An adherence measure, proportion of days covered (PDC), was calculated and categorized as adherent (PDC ≥ 0.90), nonadherent (0 < PDC < 0.90), and discontinuer (PDC = 0) during 30-day windows. We first used Cox models for time-to-death, adjusting for baseline and time-varying confounders on medication usages, health care utilization, and comorbidities. We then used marginal structural Cox models via inverse probability weighting designed for causal inference with time-varying confounders to assess the effect of AM adherence on premature mortality. We identified 3,062 individuals with incident SLE and incident AM use (mean age 46.9 years). Over the mean follow-up period of 6.4 years, 242 (7.9%) of those patients died. Adjusted hazard ratios (HRadj ) from the Cox model for AM adherent and nonadherent SLE patients were 0.20 (95% confidence interval [95% CI] 0.13-0.29) and 0.62 (95% CI 0.42-0.91), respectively, compared to discontinuers. The corresponding HRadj from the marginal structural Cox model were 0.17 (95% CI 0.12-0.25) and 0.58 (95% CI 0.40-0.85), respectively. A significant trend in the HRadj of mortality risk over the adherence levels was found (P < 0.001). Patients with SLE adhering to AM therapy had a 71% and 83% lower risk of death than patients who do not adhere or who discontinued AMs, respectively.

Adherence to taking medication is essential for patients with chronic diseases such as Type 2 Diabetes Mellitus (T2DM). There have been many studies about the association between medication adherence and HbA1c levels, but few have used Adherence Refills and Medications Scale (ARMS) questionnaire and Proportion of Days Covered (PDC) method to measure adherence in Indonesian population. The aim of this study were to assess the association of medication adherence to HbA1c levels and compare two methods of adherence measurements. This research was conducted at Pasar Minggu Public Health Center, Jakarta using a cross-sectional design. The adherence assessment was conducted using a validated Indonesian version of the ARMS questionnaire and compared to the pharmacy refill adherence method using the PDC calculation. One hundred twenty-seven T2DM patients (75.6% female) with mean age of 58.69 years were recruited. The proportion of adhere patients as measured by ARMS was only 39.4% (50/127). Meanwhile, the proportion of adhere patients as measured by PDC was 77.2% (98/127). Adherence by both measurement showed significant associations with HbA1c <7% (ARMS, OR 4.000 (95% CI 1.705 – 9.386), p = 0.002; PDC, OR 5.674 (95% CI 1.266 – 25.438), p = 0.024). After controlled by covariates, the result remained significant (ARMS, aOR 4.281 (95% CI 1.785 – 10.267, p = 0.001; PDC, aOR 5.83 (95% CI 1.287 – 26.405), p = 0.022). Adherence and HbA1c levels was significantly associated even after controlling covariates. ARMS and PDC generated different proportions of adhere patients and may indicate the need of combining the two methods in measuring adherence.

BackgroundSemaglutide, a once-weekly injection (SOWI), is a glucagon-like peptide-1 receptor agonist for managing type-2 diabetes (T2D). However, it has a high discontinuation rate among users in the first year after treatment initiation. This study investigated the medication adherence level among T2D patients managed with SOWI.MethodsThis cross-sectional study was conducted among T2D patients aged 18 years or above who visited the outpatient pharmacy to refill their prescriptions for SOWI. The patients responded to their sociodemographic characteristics and the Adherence to Refills and Medications Scale (ARMS). The patient’s electronic health record obtained details of the proportion of days covered (PDC), glycosylated hemoglobin (HbA1C), and body mass index (BMI). The association of medication adherence and sociodemographic characteristics, as well as the clinical outcomes between patients with different levels of adherence, were analyzed.ResultsA total of 434 patients were included in this study. According to the ARMS score, only 32.48% (141) of the patients adhered to SOWI. Sociodemographic characteristics had lower odds association for medication non-adherence. However, non-adherent patients had a significant association with BMI (overweight and obese) and HbA1C (>7). The adherence level of PDC for SOWI was significantly associated with the ARMS medication adherence level. The mean HbA1C and BMI between adherents and non-adherents were statistically significant (p<0.001). The patients who adhered to both ARMS and PDC (n = 126) experienced a significant decline in mean BMI (p < 0.001) and HbA1C (p < 0.001) compared to patients who adhered to PDC but not ARMS and those who did not adhere to either ARMS or PDC.ConclusionMedication adherence to the SOWI is subjective to T2D patients and not influenced by sociodemographic characteristics. T2D patients need more motivation to refill and administer the SOWI according to the schedule since medication adherence directly impacts HbA1C and BMI.

Impact of Dosing Frequency of Oral Oncolytics on Refill Adherence Among Patients with Hematological Malignancies