RESUMO
BACKGROUND: Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have neuroprotective effects in patients with type 2 diabetes (T2D). However, their comparative effectiveness in preventing dementia remains uncertain. OBJECTIVE: To compare the risk for dementia between SGLT2 inhibitors and dulaglutide (a GLP-1 RA). DESIGN: Target trial emulation study. SETTING: Nationwide health care data of South Korea obtained from the National Health Insurance Service between 2010 and 2022. PATIENTS: Patients aged 60 years or older who have T2D and are initiating treatment with SGLT2 inhibitors or dulaglutide. MEASUREMENTS: The primary outcome was the presumed clinical onset of dementia. The date of onset was defined as the year before the date of dementia diagnosis, assuming that the time between the onset of dementia and diagnosis was 1 year. The 5-year risk ratios and risk differences comparing SGLT2 inhibitors with dulaglutide were estimated in a 1:2 propensity score-matched cohort adjusted for confounders. RESULTS: Overall, 12 489 patients initiating SGLT2 inhibitor treatment (51.9% dapagliflozin and 48.1% empagliflozin) and 1075 patients initiating dulaglutide treatment were included. In the matched cohort, over a median follow-up of 4.4 years, the primary outcome event occurred in 69 participants in the SGLT2 inhibitor group and 43 in the dulaglutide group. The estimated risk difference was -0.91 percentage point (95% CI, -2.45 to 0.63 percentage point), and the estimated risk ratio was 0.81 (CI, 0.56 to 1.16). LIMITATION: Residual confounding is possible; there was no adjustment for hemoglobin A1c levels or duration of diabetes; the study is not representative of newer drugs, including more effective GLP-1 RAs; and the onset of dementia was not measured directly. CONCLUSION: Under conventional statistical criteria, a risk for dementia between 2.5 percentage points lower and 0.6 percentage point greater for SGLT2 inhibitors than for dulaglutide was estimated to be highly compatible with the data from this study. However, whether these findings generalize to newer GLP-1 RAs is uncertain. Thus, further studies incorporating newer drugs within these drug classes and better addressing residual confounding are required. PRIMARY FUNDING SOURCE: Ministry of Food and Drug Safety of South Korea.
RESUMO
AIMS: Protein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are novel lipid-lowering agents used in patients with cardiovascular disease. Despite reassuring safety data from pivotal trials, increasing evidence from real-world studies suggests that PCSK9i increase the risk of bacterial and viral infections. Therefore, this study aimed to identify signals of infection-related adverse events (AEs) associated with PCSK9i. METHODS: We performed an observational pharmacovigilance study using the World Health Organization's VigiBase, recorded up to December 2022. We included individual case safety reports (ICSRs) of PCSK9 inhibitors, alirocumab and evolocumab, and compared them with those of other drugs. Infection-related ICSRs were retrieved from the Medical Dictionary for Regulatory Activities System Organ Class 'infections and infestations.' RESULTS: Among 114,293 reports (258,099 drug-AE pairs) related to PCSK9 inhibitors, 54% included female patients, 41% included patients aged ≥65 years, and 82% included patients who received evolocumab. Additionally, beyond AEs recognized by regulatory authorities, organ infections such as influenza (reporting odds ratio [ROR] 2.89, 95% confidence interval [CI] 2.74-3.05), gastric infections (ROR 2.47, 95% CI 1.63-3.75), and kidney infections (ROR 1.36, 95% CI 1.06-1.73) were observed. Sensitivity analysis indicated a heightened risk of infection-related AEs associated with PCSK9i regardless of the specific drug type. CONCLUSIONS: In addition to the labelled respiratory infections, six infection-related symptoms in the gastrointestinal, urinary, and renal organs were identified. Our findings support the need for systematic surveillance of infections among PCSK9i users.
RESUMO
BACKGROUND AND AIMS: Concerns about the safety of coronavirus disease 2019 (COVID-19) vaccines in patients with atrial fibrillation/flutter (AF/AFL) have arisen due to reports of thrombo-embolic events following COVID-19 vaccination in the general population. This study aimed to evaluate the risk of thrombo-embolic events after COVID-19 vaccination in patients with AF/AFL. METHODS: This was a modified self-controlled case-series study using a comprehensive nationwide-linked database provided by the National Health Insurance Service in South Korea to calculate incidence rate ratios (IRRs) of thrombo-embolic events. The study population included individuals aged ≥12 years who were either vaccinated (e.g. one or two doses) or unvaccinated during the period from February to December 2021. The primary outcome was a composite of thrombo-embolic events, including ischaemic stroke, transient ischaemic attack, and systemic thromboembolism. The risk period was defined as 0-21 days following COVID-19 vaccination. RESULTS: The final analysis included 124 127 individuals with AF/AFL. The IRR of thrombo-embolic events within 21 days after COVID-19 vaccination, compared with that during the unexposed control period, was 0.93 [95% confidence interval (CI) 0.77-1.12]. No significant risk variations were noted by sex, age, or vaccine type. However, patients without anticoagulant therapy had an IRR of 1.88 (95% CI 1.39-2.54) following vaccination. CONCLUSIONS: In patients with AF/AFL, COVID-19 vaccination was generally not associated with an increased risk of thrombo-embolic events. However, careful individual risk assessment is required when advising vaccination for those not on oral anticoagulant, as these patients exhibited an increased risk of thrombo-embolic events post-vaccination.
Assuntos
Fibrilação Atrial , Vacinas contra COVID-19 , COVID-19 , Tromboembolia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Fibrilação Atrial/epidemiologia , Flutter Atrial/epidemiologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , COVID-19/complicações , Vacinas contra COVID-19/efeitos adversos , Incidência , República da Coreia/epidemiologia , Tromboembolia/prevenção & controle , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Vacinação/efeitos adversosRESUMO
BACKGROUND: Although the effectiveness and safety of ticagrelor versus clopidogrel may differ in patients with chronic liver disease, there is a scarcity of evidence comparing ticagrelor and clopidogrel in patients with chronic liver disease. We aimed to evaluate the risk of major adverse cardiovascular events (MACE) and major bleeding associated with ticagrelor versus clopidogrel in patients undergoing percutaneous coronary intervention (PCI) due to acute coronary syndrome by chronic liver disease status. METHODS: Using the Korean healthcare claim database, we included adult patients who underwent PCI and initiated ticagrelor or clopidogrel treatment within 7 days of an acute coronary syndrome diagnosis. Patients were classified into 2 mutually exclusive groups: patients with chronic liver disease and patients without chronic liver disease. Within each group, the hazard ratios (HRs) with 95% confidence intervals (CIs) of MACE and major bleeding associated with ticagrelor versus clopidogrel were calculated using a Cox proportional hazards model within a 1:1 propensity score (PS) matched cohort. RESULTS: The final cohort included 14,261 and 148,535 patients with and without chronic liver disease, respectively. After PS matching, the risk of MACE (with chronic liver disease, HR: 1.01, 95% CI: 0.91-1.13; without chronic liver disease, HR: 1.02, 95% CI: 0.98-1.05; P for homogeneity: 0.865) and major bleeding (with chronic liver disease, HR: 1.07, 95% CI: 0.71-1.61; without chronic liver disease, HR: 1.32, 95% CI: 1.15-1.53; P for homogeneity: 0.342) for ticagrelor versus clopidogrel do not vary with chronic liver disease status. CONCLUSIONS: Among acute coronary syndrome patients undergoing PCI, the use of ticagrelor versus clopidogrel was associated with a similar risk of MACE and an increased risk of major bleeding, but these risks did not vary with chronic liver disease status.
Assuntos
Síndrome Coronariana Aguda , Clopidogrel , Hepatopatias , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Ticagrelor , Humanos , Ticagrelor/uso terapêutico , Ticagrelor/efeitos adversos , Clopidogrel/uso terapêutico , Clopidogrel/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Hemorragia/induzido quimicamente , República da Coreia , Estudos de Coortes , Doença Crônica , Pontuação de Propensão , Modelos de Riscos ProporcionaisRESUMO
OBJECTIVES: The clinical importance of adhering to the regimen in tuberculosis patients has been widely investigated, but most studies were conducted in controlled settings and in limited populations. We aimed to measure the level of real-world adherence during intensive phase and investigate the predictors and the risk of mortality and health outcomes of intensive phase non-adherence in tuberculosis patients. STUDY DESIGN: We conducted a nationwide cohort study by linking the Korean National Tuberculosis Surveillance System and the National Health Information Database. METHODS: We included all incident drug-susceptible tuberculosis patients who initiated the regimens recommended by the World Health Organization from 2013 to 2018. Adherence was measured using the proportion of days covered (poor [<50%], moderate [50%-79%], and high [≥80%]). We used logistic regression model to assess predictors and the Cox proportional hazard model to evaluate the risk of mortality and health outcomes with intensive phase non-adherence. RESULTS: Of 46,818 patients, there were 8% and 11% with poor and moderate adherent groups, respectively. Age ≥45 years, insulin use, and history of renal failure were predictors of non-adherence. Compared with high adherent group, poor and moderate adherent groups were associated with a substantial risk of mortality (poor: hazard ratio, 2.14 [95% confidence interval, 1.95-2.34]; moderate: 1.76 [1.62-1.92]). Similar trends were observed for health outcomes. Stratified analyses showed a higher risk of mortality in patients with medical aid, low income, and history of renal failure, systematic corticosteroids, and immunomodulators. CONCLUSIONS: Non-adherence during intensive phase increased mortality risk by twofold, underscoring targeted intervention for high-risk population, including advanced diabetes, and immunocompromised patients.
Assuntos
Insuficiência Renal , Tuberculose , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Tuberculose/tratamento farmacológico , Fatores de Risco , Avaliação de Resultados em Cuidados de Saúde , Adesão à MedicaçãoRESUMO
PURPOSE: Following the withdrawal of propacetamol in Europe owing to safety issues, the regulatory authority of South Korea requested a post-marketing surveillance study to investigate its safety profile. MATERIALS AND METHODS: We conducted nested case-control and case-time-control (CTC) analyses of cases and controls identified for outcomes of interest, including anaphylaxis, thrombosis, and Stevens-Johnson syndrome (SJS), using the claims database of South Korea, 2010-2019. Risk-set sampling was used to match each case with up to 10 controls for age, sex, cohort entry date, and follow-up duration. Exposure to anaphylaxis, thrombosis, and SJS was assessed within 7, 90, and 30 days of the index date, respectively. We calculated odds ratios (OR) with 95% confidence intervals (CIs) using conditional logistic regression to assess the risk of outcomes associated with propacetamol. RESULTS: We identified cases of anaphylaxis (n=61), thrombosis (n=95), and SJS (n=1) and matched them to controls (173, 268, and 4, respectively). In the nested case-control analysis, the ORs for anaphylaxis and SJS were inestimable given the small number of propacetamol users during the risk period; meanwhile, the OR for thrombosis was 1.60 (95% CI 0.71-3.62). In the CTC design, the effect estimate was only estimated for thrombosis (OR 0.56, 95% CI 0.09-3.47). CONCLUSION: In both nested case-control and CTC analyses, propacetamol was not associated with an increased risk of anaphylaxis, thrombosis, or SJS. The findings from this study, which used routinely collected clinical data, provide reassuring real-world evidence regarding the safety of propacetamol in a nationwide population to support regulatory decision-making.
Assuntos
Anafilaxia , Síndrome de Stevens-Johnson , Trombose , Humanos , Anafilaxia/induzido quimicamente , Anafilaxia/epidemiologia , Estudos de Casos e Controles , Acetaminofen/efeitos adversos , Síndrome de Stevens-Johnson/etiologia , Trombose/complicaçõesRESUMO
PURPOSE: Owing to adverse event following immunization (AEFI) related to autoimmune disorders and coronavirus disease 2019 (COVID-19) vaccines sharing common biological mechanisms, identifying the risk of AEFIs associated with COVID-19 vaccines remains a critical unmet need. We aimed to assess the potential safety signals for 16 AEFIs and explore co-reported adverse events (AEs) and drugs using the global database of the World Health Organization, VigiBase. METHODS: We assessed the occurrence of 16 AEFIs following COVID-19 vaccination through the Standardized MedDRA Queries group "Immune-mediated/Autoimmune Disorders" from MedDRA and performed a disproportionality analysis using reporting odds ratio (ROR) and information component (IC) with 95% confidence intervals (CIs). RESULTS: We identified 25,219 events associated with COVID-19 vaccines in VigiBase. Although rare, we detected four potential safety signals related to autoimmune disorders following COVID-19 vaccination, including ankylosing spondylitis or psoriatic arthritis (ROR 1.86; 95% CI 1.53-2.27), inflammatory bowel disease (ROR 1.77; 95% CI 1.60-1.96), polymyalgia rheumatica (ROR 1.42; 95% CI 1.30-1.55), and thyroiditis (ROR 1.40; 95% CI 1.30-1.50), with positive IC025 values. The top co-reported AEs were musculoskeletal disorders, and immunosuppressants were the most representative co-reported drugs. CONCLUSION: In addressing the imperative to comprehend AEFI related to autoimmune disorders following COVID-19 vaccination, our study identified four potential safety signals. Thus, our research underscores the importance of proactive safety monitoring for the identification of the four AEFIs following COVID-19 vaccination, considering the associated advantages.
Assuntos
Doenças Autoimunes , COVID-19 , Humanos , Vacinas contra COVID-19/efeitos adversos , Farmacovigilância , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/epidemiologia , Sistemas de Notificação de Reações Adversas a MedicamentosRESUMO
Concomitant use of sodium glucose cotransporter-2 inhibitors (SGLT-2i) and overactive bladder (OAB) drugs potentially poses a risk of urinary tract infections (UTIs) due to the urinary retention of highly concentrated glucose in the urine. Thus, this study aimed to investigate the risk of UTIs among patients who initiated SGLT-2i treatment while taking OAB drugs. This population-based cohort study included new-users of SGLT-2i or comparator antidiabetics (dipeptidyl peptidase-4 inhibitor (DPP-4i); glucagon-like peptide-1 receptor agonist (GLP-1RA)) with OAB drugs between 2014 and 2020 using claim data from Korea. Primary outcome was a composite UTI event composite end point comprising pyelonephritis, cystitis, and urethritis, using both inpatient and outpatient diagnoses. Propensity score fine stratification was used to adjust for potential confounding factors. Weighted hazard ratios (HR) were calculated using the Cox proportional hazards model. In the first cohort, 796 and 9,181 new-users of SGLT-2i and DPP-4i with OAB drugs were identified, respectively. This study found a similar risk of UTIs in concomitant users of SGLT-2i and DPP-4i (weighted HR 1.08, 95% confidence interval: 0.88-1.32) with OAB drugs. In the second cohort, 2,387 and 280 new-users of SGLT-2i and GLP-1RA with OAB drugs were identified, respectively. Initiation of SGLT-2i while on OAB treatment was not associated with increased risk of UTI (0.89, 0.50-1.60), compared with initiation of GLP-1RA. These results show that the concomitant use of SGLT-2i with OAB drugs was not associated with an increased risk of UTI compared with the concomitant use of DPP-4i or GLP-1RA with OAB drugs.
Assuntos
Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Bexiga Urinária Hiperativa , Infecções Urinárias , Humanos , Estudos de Coortes , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Glucose/metabolismo , Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária Hiperativa/induzido quimicamente , Infecções Urinárias/induzido quimicamente , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologiaRESUMO
BACKGROUND: Finasteride is commonly prescribed for androgenic alopecia and benign prostatic hyperplasia. However, concerns regarding its safety have been growing as cases of cognitive dysfunction have been reported. METHODS: A disproportionality analysis was conducted on data collected between 1967 and 2022 to explore the potential association. Cases of cognitive dysfunction associated with finasteride use were identified, and the reporting odds ratio (rOR) was calculated with 95% confidence intervals to determine the strength of the association between the two variables. Sensitivity analyses were conducted to account for confounding by indication. RESULTS: Among the 54,766 cases of adverse events reported for finasteride use, 1,624 (2.97%) were associated with cognitive dysfunction. The study found a significant disproportionality for cognitive dysfunction related to finasteride use (rOR 5.43, 95% CI 5.17-5.71). Most cases were considered serious (65.83%), with no signs of recovery (58.37%). Sensitivity analyses showed that patients younger than 45 years (rOR 7.30, 95% CI 6.39-8.35) and those with alopecia (rOR 5.52, 95% CI 5.15-5.91) reported more cognitive dysfunctions than their counterparts. CONCLUSION: This study showed an increased reporting of cognitive dysfunction associated with finasteride use, especially among younger alopecia patients. Finasteride should be prescribed with caution, especially to younger alopecia patients.
Assuntos
Inibidores de 5-alfa Redutase , Sistemas de Notificação de Reações Adversas a Medicamentos , Alopecia , Disfunção Cognitiva , Bases de Dados Factuais , Finasterida , Farmacovigilância , Hiperplasia Prostática , Finasterida/efeitos adversos , Finasterida/administração & dosagem , Humanos , Masculino , Alopecia/induzido quimicamente , Alopecia/epidemiologia , Inibidores de 5-alfa Redutase/efeitos adversos , Inibidores de 5-alfa Redutase/administração & dosagem , Pessoa de Meia-Idade , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/epidemiologia , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Hiperplasia Prostática/tratamento farmacológico , Adulto , Idoso , Fatores Etários , Adulto Jovem , Feminino , Adolescente , Idoso de 80 Anos ou maisRESUMO
AIMS: To determine the potential association between the use of either glucagon-like peptide-1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase-4 (DPP-4) inhibitors, and the risk of thyroid cancer in individuals with type 2 diabetes. MATERIALS AND METHODS: This population-based cohort study used claims data from the Korean National Health Insurance Database, 2014-2020. Two distinct cohorts were established to compare each incretin-based drug with sodium-glucose cotransporter-2 (SGLT2) inhibitors, chosen as active comparators because of their previous non-association with thyroid cancer, and their common usage as add-on therapy to metformin along with GLP-1RAs and DPP-4 inhibitors. The first cohort included 21 722 new users of GLP-1RAs and 326 993 new users of SGLT2 inhibitors, whereas the second cohort included 904 300 DPP-4 inhibitor new users and 112 017 SGLT2 inhibitor new users. The outcome was the time to incident thyroid cancer. Weighted Cox proportional models were used to estimate hazard ratios of thyroid cancer incidence associated with incretin-based drugs of interest. RESULTS: The use of GLP-1RAs was not associated with an increased risk of thyroid cancer (weighted hazard ratio 0.98, 95% confidence interval 0.62-1.53) compared with that of SGLT2 inhibitors. Using DPP-4 inhibitors was also not associated with an increased risk of thyroid cancer (0.95, 0.79-1.14) compared with that of SGLT2 inhibitors. No significant effect modifications were observed across subgroup analyses. Sensitivity analyses, including alternative outcome definition analysis of medullary thyroid cancer, were consistent with the primary analysis results. CONCLUSIONS: GLP-1RAs and DPP-4 inhibitors were not associated with an increased risk of thyroid cancer in individuals with type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Neoplasias da Glândula Tireoide , Humanos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Incretinas/uso terapêutico , Estudos de Coortes , Hipoglicemiantes/efeitos adversos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Neoplasias da Glândula Tireoide/epidemiologia , Dipeptidil Peptidases e Tripeptidil Peptidases/uso terapêuticoRESUMO
INTRODUCTION: To estimate herpes zoster (HZ) incidence rate (IR) and economic burden in individuals with immunocompromised conditions and autoimmune diseases (IC/AID) in the Republic of Korea (ROK). METHODS: The nationwide Health Insurance Review and Assessment Service database was used to identify HZ cases from 2016 to 2020 in ROK. HZ and non-HZ IC/AID cases were matched 1:3 using age, sex, institution, Charlson comorbidity index, IC/AID, and index date. Annual HZ IRs/1000 persons and 1-year HZ-associated all-cause direct medical costs for IC/AID cases were calculated. RESULTS: Among 65,976 individuals with IC/AID (mean age 57.14 years [standard deviation 14.1]; 64.94% female), annual HZ IR (95% confidence interval) fluctuated from 2016 to 2020, averaging 23.41/1000 persons (22.21-24.62) and was higher in women (26.85 [25.40-28.31]) than men (18.96 [18.03-19.89]). IRs were highest in individuals aged ≥ 50 years, and in those with transplants (including solid organ and hematopoietic stem cell transplants; 37.12 [35.45-38.79]) and hemato-oncology conditions (35.5 [31.6-39.3]). Mean 12-month all-cause direct medical costs were higher in individuals with IC/AID and HZ (4,759,671 Korean Republic won [KRW]; approximately 4046 United States dollar [USD; according to the 2020 conversion rate from UNCTAD; 1 KRW = 0.00085 USD]) than those without HZ (3,786,658 KRW; 3219 USD). CONCLUSION: Individuals with IC/AID have a substantial disease and economic burden from HZ in ROK, highlighting the need for appropriate HZ prevention measures in the IC/AID population.
RESUMO
Importance: Nonalcoholic fatty liver disease (NAFLD) is a cardiovascular risk factor, but whether sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with reduced cardiovascular risk in patients with type 2 diabetes (T2D) and concomitant NAFLD remains uncertain. Objective: To investigate the outcomes of SGLT-2i and GLP-1RA therapy among patients with T2D varied by the presence or absence of NAFLD. Design, Setting, and Participants: This retrospective, population-based, nationwide cohort study used an active-comparator new-user design. Two distinct new-user active-comparator cohorts of patients aged 40 years and older who initiated SGLT-2i or GLP-1RA were propensity score matched to patients who initiated dipeptidyl peptidase-4 inhibitors (DPP-4i). The study was conducted in South Korea from January 2013 to December 2020, and data analysis was conducted from October 2022 to March 2023. Main Outcomes and Measures: The main outcomes were (1) major adverse cardiovascular events (MACE), a composite end point of hospitalization for myocardial infarction, hospitalization for stroke, and cardiovascular death, and (2) hospitalization for heart failure (HHF). Cox proportional hazards models were used to estimate hazard ratios (HRs). The Wald test was applied to assess heterogeneity by NAFLD. Results: After 1:1 propensity score matching, 140â¯438 patients were retrieved in the first cohort (SGLT-2i vs DPP-4i; mean [SD] age, 57.5 [10.3] years; 79â¯633 [56.7%] male) and 34â¯886 patients were identified in the second cohort (GLP-1RA vs DPP-4i; mean [SD] age, 59.5 [10.5] years; 17â¯894 [51.3%] male). Compared with DPP-4i, SGLT-2i therapy was associated with a lower risk of MACE (HR, 0.78 [95% CI, 0.71-0.85]) and HHF (HR, 0.62 [95% CI, 0.48-0.81]). GLP-1RA therapy was associated with a decreased risk of MACE (HR, 0.49 [95% CI, 0.39-0.62]) but had statistically nonsignificant findings regarding HHF (HR, 0.64 [95% CI, 0.39-1.07]). Stratified analysis by NAFLD status yielded consistent results for SGLT-2i (MACE with NAFLD: HR, 0.73 [95% CI, 0.62-0.86]; without NAFLD: HR, 0.81 [95% CI, 0.72-0.91]; HHF with NAFLD: HR, 0.76 [95% CI, 0.49-1.17]; without NAFLD: HR, 0.56 [95% CI, 0.40-0.78]) and for GLP-1RA (MACE with NAFLD: HR, 0.49 [95% CI, 0.32-0.77]; without NAFLD: HR, 0.49 [95% CI, 0.37-0.65]; HHF with NAFLD: HR, 0.82 [95% CI, 0.38-1.76]; without NAFLD: HR, 0.54 [95% CI, 0.27-1.06]). Conclusions and Relevance: In this population-based cohort study, SGLT-2i therapy was associated with a decreased risk of MACE and HHF, while GLP-1RA therapy was associated with a decreased risk of MACE among patients with T2D, irrespective of baseline NAFLD status.
Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Insuficiência Cardíaca , Hepatopatia Gordurosa não Alcoólica , Inibidores do Transportador 2 de Sódio-Glicose , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Coortes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos Retrospectivos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , IdosoRESUMO
Importance: Postmenopausal individuals with type 2 diabetes are susceptible to fractures due to the interaction of elevated blood glucose levels and a deficiency of the hormone estrogen. Despite continued concerns of fracture risks associated with sodium-glucose cotransporter 2 inhibitors (SGLT2i), existing evidence in this high-risk population is lacking. Objective: To assess the risk of fractures associated with SGLT2i vs incretin-based drugs of dipeptidyl-peptidase 4 inhibitors (DPP4i) and glucagon-like peptide 1 receptor agonists (GLP1RA), separately, in postmenopausal individuals with type 2 diabetes. Design, Setting, and Participants: This active-comparator, new-user cohort study used nationwide claims data of Korea and took place from January 1, 2013, to December 31, 2020. Postmenopausal individuals (aged ≥45 years) with type 2 diabetes were included. Exposures: New users of SGLT2i or comparator drugs. Main Outcomes and Measures: The primary outcome was overall fractures, comprising vertebral, hip, humerus, and distal radius fractures. Patients were followed up from the day after drug initiation until the earliest of outcome occurrence, drug discontinuation (90-day grace period) or switch, death, or end of the study period. After propensity score fine stratification, hazard ratios (HRs) with 95% CIs were estimated using weighted Cox models. Results: Among 37â¯530 (mean [SD] age, 60.6 [9.7] years) and 332â¯004 (mean [SD] age, 60.6 [9.9] years) new users of SGLT2i and DPP4i, respectively, a lower rate of incident overall fractures was presented with SGLT2i vs DPP4i (weighted HR, 0.78; 95% CI, 0.72-0.84). Among 111â¯835 (mean [SD] age, 61.4 [9.8] years) and 8177 (mean [SD] age, 61.1 [10.3] years) new users of SGLT2i and GLP1RA, respectively, no association with an increased risk of overall fractures was presented with SGLT2i vs GLP1RA (weighted HR, 0.92; 95% CI, 0.68-1.24). Results from several subgroup and sensitivity analyses presented consistent results from main analysis. Conclusions and relevance: This population-based cohort study suggests that SGLT2i was not associated with an increased rate of incident fractures compared with DPP4i and GLP1RA, separately, among postmenopausal individuals with type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Fraturas Ósseas , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Fraturas Ósseas/induzido quimicamente , Fraturas Ósseas/epidemiologia , Incretinas/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , IdosoRESUMO
AIM: To assess the risk of amputation associated with sodium-glucose co-transporter-2 inhibitors (SGLT2is) among patients with type 2 diabetes, across categories of baseline cardiovascular disease (CVD) and diuretic use (DU). MATERIALS AND METHODS: We conducted an active comparator, new-user cohort study using Korea's nationwide claims data (2015-2020). The study cohort consisted of patients with type 2 diabetes who initiated SGLT2is or dipeptidyl peptidase-4 inhibitors (DPP4is). Cohort entry was defined by first prescription date. We then classified patients into four discrete subcohorts based on their baseline status of CVD and DU as (1) CVD+/DU+, (2) CVD+/DU-, (3) CVD-/DU+ and (4) CVD-/DU-. We performed 1:1 propensity score (PS) matching within each cohort and estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of amputation with SGLT2is versus DPP4is using Cox models. RESULTS: We identified 219 900 PS-matched pairs of SGLT2is and DPP4is (CVD+/DU+, n = 11 719; CVD+/DU-, n = 26 092; CVD-/DU+, n = 26 894; and CVD-/DU-, n = 155 195), with well-balanced baseline covariates across all cohorts. Significantly lower risks of amputation with SGLT2is versus DPP4is were found in CVD+/DU+ (HR 0.36, 95% CI 0.14-0.90), CVD+/DU- (0.45, 0.21-0.99) and CVD-/DU- (0.48, 0.33-0.70), but not in CVD-/DU+ (0.54, 0.26-1.12). Consistent trends in estimates were found across various sensitivity analyses. CONCLUSIONS: Initiating SGLT2is against DPP4is did not increase the risk of amputation across patient populations of varying vulnerability. These findings based on routine practice will reassure clinicians of the safety of SGLT2is with regard to amputation risk in selected high-risk patients with type 2 diabetes.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Simportadores , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Doenças Cardiovasculares/complicações , Estudos de Coortes , Diuréticos , Fatores de Risco , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Amputação Cirúrgica , Glucose , Sódio , HipoglicemiantesRESUMO
AIM: To explore the risk of breakthrough infection among patients with type 2 diabetes (T2D) and risk of severe clinical outcomes after SARS-CoV-2 infection according to vaccination status. MATERIALS AND METHODS: We conducted a population-based cohort study using South Korea's linked database of nationwide COVID-19 registry and claims data between 2018 and 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breakthrough infections were measured in 1:1 propensity-score (PS)-matched fully vaccinated patients with versus without T2D (full-vaccination cohort), and HRs for all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) use, and hospitalizations after SARS-CoV-2 infection were measured in 1:1 PS-matched T2D patients with versus without full-vaccination (T2D cohort). RESULTS: After 1:1 PS matching, 2 109 970 patients with and without T2D were identified (age 63.5 years; 50.9% male). Patients with T2D showed an increased risk of breakthrough infections compared to those without T2D (HR 1.10, 95% CI 1.06-1.14). The increased risk of breakthrough infections was more notable among T2D patients receiving insulin treatment. However, the risk of severe COVID-19 outcomes was lower in fully vaccinated T2D patients compared with unvaccinated T2D patients (all-cause mortality: HR 0.54, 95% CI 0.43-0.67; ICU admission/MV use: HR 0.31, 95% CI 0.23-0.41; hospitalization: HR 0.73, 95% CI 0.68-0.78). CONCLUSIONS: While patients with T2D remain a vulnerable population to SARS-CoV-2 infection even after full-vaccination, full-vaccination was associated with a lower risk of adverse clinical outcomes after SARS-CoV-2 infection. These findings support the guidelines recommending patients with T2D as a priority vaccination group.
Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , SARS-CoV-2 , Infecções IrruptivasRESUMO
BACKGROUND: To eliminate tuberculosis (TB), World Health Organization (WHO) initiated "The End TB Strategy" with the goal of a 95% reduction in deaths. While many resources are contributed to eradicating TB, a substantial number of TB patients are still unlikely to receive timely treatment. Thus, we aimed to measure healthcare delay and its association with clinical outcomes from 2013 to 2018. METHODS: We conducted a retrospective cohort study using linked data of the National Tuberculosis Surveillance Registry and the health insurance claims data of South Korea. We included incident TB patients, and healthcare delay was defined as the period between the first medical visit with TB-related symptoms and the initiation of an anti-TB regimen. We described the distribution of healthcare delay, and the study population was classified into two groups with mean as a cutoff. The association between healthcare delay and clinical outcomes (all-cause mortality, pneumonia, progression to multi/extensively drug-resistant, intensive care unit admission, and mechanical ventilation use) was evaluated using the Cox proportional hazard model. Several stratified and sensitivity analyses were also conducted. RESULTS: Among 39,747 patients with pulmonary TB, mean healthcare delay was 42.3 days and delayed and non-delayed groups, classified by mean (or average), were 10,680 (26.9%) and 29,067 (73.1%), respectively. Healthcare delay was associated with an increased risk of all-cause mortality (HR 1.10, 95% CI 1.03-1.17), pneumonia (HR 1.13, 95% CI 1.09-1.18), and mechanical ventilation use (HR 1.15, 95% CI 1.01-1.32). We also observed the duration-response of healthcare delay. Stratified analyses showed patients with respiratory diseases were at higher risk, and consistent results were observed in sensitivity analyses. CONCLUSIONS: We observed a substantial number of patients experiencing healthcare delays, and it was associated with the deterioration of clinical outcomes. Our findings suggest that attention from authorities and healthcare professionals is needed to attenuate the preventable burden caused by TB through timely treatment.
Assuntos
Tuberculose Pulmonar , Tuberculose , Humanos , Estudos Retrospectivos , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Tuberculose/diagnóstico , Atenção à Saúde , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Instalações de SaúdeRESUMO
BACKGROUND: Regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB) have been changed from injectable-containing regimens to all-oral regimens. The economic effectiveness of new all-oral regimens compared with conventional injectable-containing regimens was scarcely evaluated. This study was conducted to compare the cost-effectiveness between all-oral longer-course regimens (the oral regimen group) and conventional injectable-containing regimens (the control group) to treat newly diagnosed MDR-TB patients. METHODS: A health economic analysis over lifetime horizon (20 years) from the perspective of the healthcare system in Korea was conducted. We developed a combined simulation model of a decision tree model (initial two years) and two Markov models (remaining 18 years, six-month cycle length) to calculate the incremental cost-effectiveness ratio (ICER) between the two groups. The transition probabilities and cost in each cycle were assumed based on the published data and the analysis of health big data that combined country-level claims data and TB registry in 2013-2018. RESULTS: The oral regimen group was assumed to spend 20,778 USD more and lived 1.093 years or 1.056 quality-adjusted life year (QALY) longer than the control group. The ICER of the base case was calculated to be 19,007 USD/life year gained and 19,674 USD/QALY. The results of sensitivity analyses showed that base case results were very robust and stable, and the oral regimen was cost-effective with a 100% probability for a willingness to pay more than 21,250 USD/QALY. CONCLUSION: This study confirmed that the new all-oral longer regimens for the treatment of MDR-TB were cost-effective in replacing conventional injectable-containing regimens.
Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Análise Custo-Benefício , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Protocolos Clínicos , República da Coreia , Anos de Vida Ajustados por Qualidade de VidaRESUMO
BACKGROUND/PURPOSE(S): Bedaquiline and delamanid were recently approved for multidrug resistant tuberculosis (MDR-TB). Bedaquiline carries a black box warning of increased risk of death compared to the placebo arm, and there is a need to establish the risks of QT prolongation and hepatotoxicity for bedaquiline and delamanid. METHODS: We retrospectively analyzed data of MDR-TB patients retrieved from the South Korea national health insurance system database (2014-2020) to assess the risks of all-cause death, long QT-related cardiac event, and acute liver injury associated with bedaquiline or delamanid, compared with conventional regimen. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Stabilized inverse probability of treatment weighting based on propensity score was used to balance characteristics between the treatment groups. RESULTS: Of 1998 patients, 315 (15.8%) and 292 (14.6%) received bedaquiline and delamanid, respectively. Compared with conventional regimen, bedaquiline and delamanid did not increase risk of all-cause death at 24-month (HR 0.73 [95% CI, 0.42-1.27] and 0.89 [0.50-1.60], respectively). Bedaquiline-containing regimen increased risk of acute liver injury (1.76 [1.31-2.36]), while delamanid-containing regimen increased risk of long QT-related cardiac events (2.38 [1.05-3.57]) within 6 months of treatment. CONCLUSION: This study adds to the emerging evidence refuting the higher mortality rate observed in the bedaquiline trial population. Association between bedaquiline and acute liver injury needs careful interpretation considering for other background hepatotoxic anti-TB drugs. Our finding on delamanid and long QT-related cardiac events suggest careful risk-benefit assessment in patients with pre-existing cardiovascular disease.
Assuntos
Doenças Cardiovasculares , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Ensaios Clínicos como AssuntoRESUMO
Background 2018 American Heart Association/American College of Cardiology cholesterol guideline recommends statin in patients with chronic and/or stable liver disease for secondary prevention of atherosclerotic cardiovascular disease yet remains equivocal on the adequate intensity of statin for patients with chronic liver disease (CLD). We aimed to assess the association between statin intensity and mortality among patients with CLD with atherosclerotic cardiovascular disease. Methods and Results We conducted a population-based cohort study in South Korea. We assessed the risk of survival and clinical outcomes using inverse probability of treatment-weighted Cox proportional hazards regression. We also estimated the absolute risk difference between treatment groups based on the Poisson distribution. During an average of 2.35 person-years, 10 442 patients with CLD with atherosclerotic cardiovascular disease were identified. Among those patients, 5515 (52.8%) received high-intensity statin, and 4927 (47.2%) received low/moderate-intensity statin. High-intensity statin was associated with lower risk for all-cause mortality (hazard ratio [HR], 0.83 [95% CI, 0.75-0.92]), cardiovascular-cause mortality (HR, 0.85 [0.71-1.01]), liver-cause mortality (HR, 0.72 [0.54-0.97]) compared with low/moderate-intensity statin. Although both hospitalizations for recurrent myocardial infarction and stroke were shown to be increased among high-intensity statin users, effect estimate was homogeneous in the absolute scale (myocardial infarction: HR, 1.12 [1.04-1.19], risk difference, 7.57 [-0.69 to 15.84] per 1000 person-years; stroke: HR, 1.11 [0.97 to 1.27]; risk difference, -1.70 [-5.19 to 1.78]). Conclusions Among patients with CLD with atherosclerotic cardiovascular disease, high-intensity statin was significantly associated with a lower risk of mortality. These findings herein support the guidelines for statin use in patients with CLD while demonstrating potential benefit of optimal intensity use.