Effect of statin treatment on the risk of cancer in patients with heart failure: A target trial emulation study.

PURPOSE: A recent observational study suggested statins could reduce cancer diagnosis in patients with heart failure (HF). The findings need to be validated using robust epidemiological methods. This study aimed to evaluate the effect of statin treatment on the risk of cancer in patients with HF. METHODS: We conducted two target trial emulations using primary care data from IQVIA Medical Research Database-UK (2000 to 2019) with a clone-censor-weight design. The first emulated trial addressed the treatment initiation effect: initiating within 1 year versus not initiating a statin after the HF diagnosis. The second emulated trial addressed the cumulative exposure effect: continuing a statin for ≤3 years, 3-6 years, and >6 years after initiation. The study outcomes were any incident cancer and site-specific cancer diagnoses. Weighted pooled logistic regression models were used to estimate 10-year risk ratios (RR). 95% confidence intervals (CIs) were estimated using non-parametric bootstrapping. RESULTS: The first emulated trial showed that, compared to no statin, statins did not reduce the cancer risk in patients with HF (RR, 1.05; 95% CI, 0.94-1.15). The second emulated trial showed that, compared to treatment ≤3 years, statins with longer durations did not reduce the cancer risk (3-6 years: RR, 0.94; 95% CI, 0.70-1.33. >6 years: RR, 0.97; 95% CI, 0.79-1.26). No significant risk difference was observed on any site-specific cancer diagnoses. CONCLUSIONS: The results from the target trial emulations suggest that statin treatment is not associated with cancer risk in patients with HF.

Impact of ACEIs and ARBs-related adverse drug reaction on patients' clinical outcomes: a cohort study in UK primary care.

BACKGROUND: Adverse drug reaction (ADR) related to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may negatively affect patients' treatment outcomes. AIM: To investigate the impact of ACEIs/ARBs-related ADR consultation on cardiovascular disease (CVD) events and all-cause mortality. DESIGN AND SETTING: Propensity score-matched cohort study of ACEIs/ARBs between 2004 and 2019 using UK IQVIA medical research data. METHOD: ADR consultations were identified using standardised designated codes. Propensity scores were calculated based on comorbidities, concomitant medications, frailty, and polypharmacy. Cox's proportional hazard regression model was used to compare the outcomes between patients in ADR and non-ADR groups. In the secondary analysis, treatment- pattern changes following the ADR were examined and the subsequent outcomes were compared. RESULTS: Among 1 471 906 eligible users of ACEIs/ARBs, 13 652 (0.93%) patients had ACEIs/ARBs- related ADR consultation in primary care. Patients with ACEIs/ARBs-related ADR consultation had an increased risk of subsequent CVD events and all- cause mortality in both primary prevention (CVD events: adjusted hazard ratio [aHR] 1.22, 95% confidence interval [CI] = 1.05 to 1.43; all-cause mortality: aHR 1.14, 95% CI = 1.01 to 1.27) and secondary prevention cohorts (CVD events: aHR 1.13, 95% CI = 1.05 to 1.21; all-cause mortality: aHR 1.15, 95% CI = 1.09 to 1.21). Half (50.19%) of patients with ADR continued to use ACEIs/ARBs, and these patients had a reduced risk of mortality (aHR 0.88, 95% CI = 0.82 to 0.95) compared with those who discontinued using ACEIs/ARBs. CONCLUSION: This study provides information on the burden of ADR on patients and the health system. The findings call for additional monitoring and treatment strategies for patients affected by ADR to mitigate the risks of adverse clinical outcomes.

Global trends in the consumption of benzodiazepines and Z-drugs in 67 countries and regions from 2008 to 2018: a sales data analysis.

STUDY OBJECTIVES: To investigate the trends in the consumption of benzodiazepines (BZDs) and Z-drugs at global, regional, and national levels from 2008 to 2018, across 67 countries and regions. METHODS: This cross-sectional descriptive study investigated the consumption of BZDs and Z-drugs analyzed by global pharmaceutical sales data from the IQVIA-Multinational Integrated Data Analysis System database between 2008 and 2018. Consumption was measured in defined daily dose (DDD) per 1000 inhabitants per day (DDD/TID). The global, regional, and national trends were estimated using linear mixed models. Additional analyses were conducted by grouping countries by income level. The association between consumption and Gross Domestic Product (GDP) and the prevalence of different medical conditions was explored in univariable linear models. RESULTS: BZD consumption decreased annually by -1.88% (95% CI: -2.27%, -1.48%), and Z-drugs increased by + 3.28% (+2.55%, +4.01%). In 2008, the top ten countries for BZD and Z-drug consumption were all European, ranging from 63.69 to 128.24 DDD/TID. Very low levels were found in Russia, Kuwait, United Arab Emirates, Saudi Arabia, French West Africa, and the Philippines, with DDD/TID < 1. The consumption in high-income countries was much higher than in middle-income countries. The results showed that increased consumption of BZDs and Z-drugs was statistically associated (p < 0.05) with higher GDP and increased prevalence of anxiety, self-harm, neurological disorders, chronic respiratory diseases, cardiovascular diseases, and cancers. CONCLUSIONS: Distinct differences in consumption and trends of BZDs and Z-drugs were found across different countries and regions. Further exploration is needed to understand the association and safety of the use of BZDs and Z-drugs in patients with comorbidities.

Global, regional, and national trends in opioid analgesic consumption from 2015 to 2019: a longitudinal study.

BACKGROUND: Previous studies have reported an extremely unbalanced global access to opioid analgesics. We aimed to determine contemporary trends and patterns of opioid analgesic consumption at the global, regional, and national levels. METHODS: We analysed the global pharmaceutical sales data of 66 countries or regions from the IQVIA-Multinational Integrated Data Analysis System database on opioid analgesics between 2015 and 2019. Opioid analgesic consumption was measured in milligram morphine equivalent per 1000 inhabitants per day (MME per 1000/day). The global, regional, and national trend changes were estimated using linear regressions. Factors associated with consumption patterns and trend changes were explored in multivariable linear regression analyses. FINDINGS: Overall opioid analgesic sales in the 66 countries or regions increased from 27·52 MME per 1000/day (16·63-45·54) in 2015 to 29·51 MME per 1000/day (17·85-48·79) in 2019 (difference per year 3·96%, 95% CI 0·26 to 7·80). Sales reduced yearly in North America (-12·84%; 95% CI -15·34 to -10·27) and Oceania (-2·96%; -4·20 to -1·70); increased in South America (28·69%; 7·18 to 54·53), eastern Europe (7·68%; 3·99 to 11·49), Asia (5·74%; 0·61 to 11·14), and western and central Europe (1·64%; 0·52 to 2·78); and did not differ in Africa or central America and the Caribbean. The global opioid consumption patterns were associated with country-level Human Development Index (p=0·040), cancer death rate excluding leukaemia (p=0·0072), and geographical location (p<0·0001). In 2019, opioid analgesic consumption ranged from 0·01 MME per 1000/day to 5·40 MME per 1000/day in the 17 countries and regions in the lowest consumption quartile, despite high income levels and cancer death rates in some of them. INTERPRETATION: Global opioid analgesic consumption increased from 2015 to 2019. The trend changes were distinctive across regions, which could reflect the different actions in response to known issues of opioid use and misuse. Disparities in opioid analgesic consumption remained, indicating potential inadequate access to essential pain relief in countries with low consumption. FUNDING: None.

Comparative cardiovascular risk in users versus non-users of xanthine oxidase inhibitors and febuxostat versus allopurinol users.

OBJECTIVES: The aim of this study is to determine major adverse cardiovascular events (MACE) and all-cause mortality comparing between xanthine oxidase inhibitors (XOIs) and non-XOI users, and between allopurinol and febuxostat. METHODS: This is a retrospective cohort study of gout patients prescribed anti-hyperuricemic medications between 2013 and 2017 using a territory-wide administrative database. XOI users were matched 1:1 to XOI non-users using propensity scores. Febuxostat users were matched 1:3 to allopurinol users. Subgroup analyses were conducted based on colchicine use. RESULTS: Of the 13 997 eligible participants, 3607 (25.8%) were XOI users and 10 390 (74.2%) were XOI non-users. After propensity score matching, compared with non-users (n = 3607), XOI users (n = 3607) showed similar incidence of MACE (hazard ratio [HR]: 0.997, 95% CI, 0.879, 1.131; P>0.05) and all-cause mortality (HR = 0.972, 95% CI 0.886, 1.065, P=0.539). Febuxostat (n = 276) users showed a similar risk of MACE compared with allopurinol users (n = 828; HR: 0.672, 95% CI, 0.416, 1.085; P=0.104) with a tendency towards a lower risk of heart failure-related hospitalizations (HR = 0.529, 95% CI 0.272, 1.029; P=0.061). Concurrent colchicine use reduced the risk for all-cause mortality amongst XOI users (HR = 0.671, 95% 0.586, 0.768; P<0.001). CONCLUSION: In gout patients, XOI users showed similar risk of MACE and all-cause mortality compared with non-users. Compared with allopurinol users, febuxostat users showed similar MACE and all-cause mortality risks but lower heart failure-related hospitalizations.