Analysis of Dual Combination Therapies Used in Treatment of Hypertension in a Multinational Cohort.

Importance: More than 1 billion adults have hypertension globally, of whom 70% cannot achieve their hypertension control goal with monotherapy alone. Data are lacking on clinical use patterns of dual combination therapies prescribed to patients who escalate from monotherapy. Objective: To investigate the most common dual combinations prescribed for treatment escalation in different countries and how treatment use varies by age, sex, and history of cardiovascular disease. Design, Setting, and Participants: This cohort study used data from 11 electronic health record databases that cover 118 million patients across 8 countries and regions between January 2000 and December 2019. Included participants were adult patients (ages ≥18 years) who newly initiated antihypertensive dual combination therapy after escalating from monotherapy. There were 2 databases included for 3 countries: the Iqvia Longitudinal Patient Database (LPD) Australia and Electronic Practice-based Research Network 2019 linked data set from South Western Sydney Local Health District (ePBRN SWSLHD) from Australia, Ajou University School of Medicine (AUSOM) and Kyung Hee University Hospital (KHMC) databases from South Korea, and Khoo Teck Puat Hospital (KTPH) and National University Hospital (NUH) databases from Singapore. Data were analyzed from June 2020 through August 2021. Exposures: Treatment with dual combinations of the 4 most commonly used antihypertensive drug classes (angiotensin-converting enzyme inhibitor [ACEI] or angiotensin receptor blocker [ARB]; calcium channel blocker [CCB]; ß-blocker; and thiazide or thiazide-like diuretic). Main Outcomes and Measures: The proportion of patients receiving each dual combination regimen, overall and by country and demographic subgroup. Results: Among 970 335 patients with hypertension who newly initiated dual combination therapy included in the final analysis, there were 11 494 patients from Australia (including 9291 patients in Australia LPD and 2203 patients in ePBRN SWSLHD), 6980 patients from South Korea (including 6029 patients in Ajou University and 951 patients in KHMC), 2096 patients from Singapore (including 842 patients in KTPH and 1254 patients in NUH), 7008 patients from China, 8544 patients from Taiwan, 103 994 patients from France, 76 082 patients from Italy, and 754 137 patients from the US. The mean (SD) age ranged from 57.6 (14.8) years in China to 67.7 (15.9) years in the Singapore KTPH database, and the proportion of patients by sex ranged from 24 358 (36.9%) women in Italy to 408 964 (54.3%) women in the US. Among 12 dual combinations of antihypertensive drug classes commonly used, there were significant variations in use across country and patient subgroup. For example starting an ACEI or ARB monotherapy followed by a CCB (ie, ACEI or ARB + CCB) was the most commonly prescribed combination in Australia (698 patients in ePBRN SWSLHD [31.7%] and 3842 patients in Australia LPD [41.4%]) and Singapore (216 patients in KTPH [25.7%] and 439 patients in NUH [35.0%]), while in South Korea, CCB + ACEI or ARB (191 patients in KHMC [20.1%] and 1487 patients in Ajou University [24.7%]), CCB + ß-blocker (814 patients in Ajou University [13.5%] and 217 patients in KHMC [22.8%]), and ACEI or ARB + CCB (147 patients in KHMC [15.5%] and 1216 patients in Ajou University [20.2%]) were the 3 most commonly prescribed combinations. The distribution of 12 dual combination therapies were significantly different by age and sex in almost all databases. For example, use of ACEI or ARB + CCB varied from 873 of 3737 patients ages 18 to 64 years (23.4%) to 343 of 2292 patients ages 65 years or older (15.0%) in South Korea's Ajou University database (P for database distribution by age < .001), while use of ACEI or ARB + CCB varied from 2121 of 4718 (44.8%) men to 1721 of 4549 (37.7%) women in Australian LPD (P for drug combination distributions by sex < .001). Conclusions and Relevance: In this study, large variation in the transition between monotherapy and dual combination therapy for hypertension was observed across countries and by demographic group. These findings suggest that future research may be needed to investigate what dual combinations are associated with best outcomes for which patients.

Transformation of Electronic Health Records and Questionnaire Data to OMOP CDM: A Feasibility Study Using SG_T2DM Dataset.

BACKGROUND: Diabetes mellitus (DM) is an important public health concern in Singapore and places a massive burden on health care spending. Tackling chronic diseases such as DM requires innovative strategies to integrate patients' data from diverse sources and use scientific discovery to inform clinical practice that can help better manage the disease. The Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) was chosen as the framework for integrating data with disparate formats. OBJECTIVE: The study aimed to evaluate the feasibility of converting Singapore based data source, comprising of electronic health records (EHR), cognitive and depression assessment questionnaire data to OMOP CDM standard. Additionally, we also validate whether our OMOP CDM instance is fit for the purpose of research by executing a simple treatment pathways study using Atlas, a graphical user interface tool to conduct analysis on OMOP CDM data as a proof of concept. METHODS: We used de-identified EHR, cognitive, and depression assessment questionnaires data from a tertiary care hospital in Singapore to convert it to version 5.3.1 of OMOP CDM standard. We evaluate the OMOP CDM conversion by (1) assessing the mapping coverage (that is the percentage of source terms mapped to OMOP CDM standard); (2) local raw dataset versus CDM dataset analysis; and (3) Implementing Harmonized Intrinsic Data Quality Framework using an open-source R package called Data Quality Dashboard. RESULTS: The content coverage of OMOP CDM vocabularies is more than 90% for clinical data, but only around 11% for questionnaire data. The comparison of characteristics between source and target data returned consistent results and our transformed data did not pass 38 (1.4%) out of 2,622 quality checks. CONCLUSION: Adoption of OMOP CDM at our site demonstrated that EHR data are feasible for standardization with minimal information loss, whereas challenges remain for standardizing cognitive and depression assessment questionnaire data that requires further work.

Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study.

BACKGROUND: Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis. METHODS: In this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the I 2 value was less than 0·4. FINDINGS: The study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Self-controlled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1·65 [95% CI 1·12-2·44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2·19 [95% CI 1·22-3·95]), chest pain or angina (1·15 [1·05-1·26]), and heart failure (1·22 [1·02-1·45]). INTERPRETATION: Hydroxychloroquine treatment appears to have no increased risk in the short term among patients with rheumatoid arthritis, but in the long term it appears to be associated with excess cardiovascular mortality. The addition of azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term. We call for careful consideration of the benefit-risk trade-off when counselling those on hydroxychloroquine treatment. FUNDING: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, NIHR Senior Research Fellowship programme, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research and Development, IQVIA, Korea Health Industry Development Institute through the Ministry of Health and Welfare Republic of Korea, Versus Arthritis, UK Medical Research Council Doctoral Training Partnership, Foundation Alfonso Martin Escudero, Innovation Fund Denmark, Novo Nordisk Foundation, Singapore Ministry of Health's National Medical Research Council Open Fund Large Collaborative Grant, VINCI, Innovative Medicines Initiative 2 Joint Undertaking, EU's Horizon 2020 research and innovation programme, and European Federation of Pharmaceutical Industries and Associations.