Glucagon-like peptide-1 receptor agonists and risk of major adverse liver outcomes in patients with chronic liver disease and type 2 diabetes.

OBJECTIVE: Phase II trials suggest glucagon-like peptide-1 receptor (GLP1) agonists resolve metabolic dysfunction-associated steatohepatitis but do not affect fibrosis regression. We aimed to determine the long-term causal effect of GLP1 agonists on the risk of major adverse liver outcomes (MALO) in patients with any chronic liver disease and type 2 diabetes. DESIGN: We used observational data from Swedish healthcare registers 2010-2020 to emulate a target trial of GLP1 agonists in eligible patients with chronic liver disease and type 2 diabetes. We used an inverse-probability weighted marginal structural model to compare parametric estimates of 10-year MALO risk (decompensated cirrhosis, hepatocellular carcinoma, liver transplantation or MALO-related death) in initiators of GLP1 agonists with non-initiators. We randomly sampled 5% of the non-initiators to increase computational efficiency. RESULTS: GLP1 agonist initiators had a 10-year risk of MALO at 13.3% (42/1026) vs 14.6% in non-initiators (1079/15 633) in intention-to-treat analysis (risk ratio (RR)=0.91, 95% CI=0.50 to 1.32). The corresponding 10-year per-protocol risk estimates were 7.4% (22/1026) and 14.4% (1079/15 633), respectively (RR=0.51, 95% CI=0.14 to 0.88). The per-protocol risk estimates at 6 years were 5.4% (21/1026) vs 9.0% (933/15 633) (RR=0.60, 95% CI=0.29 to 0.90) and at 8 years 7.2% (22/1026) vs 11.7% (1036/15 633) (RR=0.61, 95% CI=0.21 to 1.01). CONCLUSION: In patients with chronic liver disease and type 2 diabetes who adhered to therapy over time, GLP1 agonists may result in lower risk of MALO. This suggests that GLP1 agonists are promising agents to reduce risk of chronic liver disease progression in patients with concurrent type 2 diabetes, although this needs to be corroborated in randomised trials.

Does Cardiovascular Mortality Overtake Cancer Mortality During Cancer Survivorship?: An English Retrospective Cohort Study.

Background: Cancer survivors have a higher risk for developing cardiovascular diseases than the general population. Objectives: The aim of this study was to investigate whether cardiovascular mortality overtakes cancer-specific mortality during cancer survivorship and, if so, at what point cardiovascular disease becomes the dominant cause of death. Methods: This cohort study used linked English electronic health records, including death registration data. The study population included 104,028 adults ≥40 years of age whose first cancer diagnosis was for 1 of 9 common cancers and who were alive and followed up at least 1 year after diagnosis. Age-stratified mortality rates were estimated from cardiovascular disease or cancer by predicting from Poisson models incorporating categorical age at diagnosis and time since diagnosis. Where cardiovascular disease mortality overtook cancer mortality, the crossover point was estimated using interpolation. Results: Mortality from cardiovascular causes overtook mortality due to the primary cancer at 2 to 11 years after cancer diagnosis in survivors of all 9 cancer types ≥80 years of age at diagnosis and after 5 to 17 years in survivors of 7 cancer types 60 to 79 years of age at diagnosis. Cardiovascular mortality overtook all cancer mortality for 6 and 2 cancer sites in the ≥80-year and 60- to 79-year age groups, respectively, over a longer time period. Cardiovascular mortality did not overtake cancer mortality during the observation period in patients aged 40 to 59 years, except among survivors of uterine cancer. Conclusions: In older survivors of 9 common cancers, cardiovascular mortality becomes dominant over mortality from the primary cancer, though not always over total cancer mortality, as time passes since cancer diagnosis.

Risk of Cardiovascular Diseases Among Older Breast Cancer Survivors in the United States: A Matched Cohort Study.

BACKGROUND: It has been suggested that cardiovascular risks are increased in breast cancer survivors, but few studies have quantified the risks of a range of specific clinically important cardiovascular outcomes in detail. PATIENTS AND METHODS: Women aged >65 years with incident breast cancer from 2004 to 2013 in the SEER-Medicare linked database were matched with 5 cancer-free female counterparts (5:1 ratio). Prevalence of specific cardiovascular outcomes at baseline was measured, then Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals for the risk of individual cardiovascular outcomes during follow-up. Modification of the effect was investigated by time since diagnosis, race/ethnicity, prior cardiovascular disease (CVD), and age. RESULTS: In all, 91,473 women with breast cancer and 454,197 without breast cancer were included. Women with breast cancer had lower baseline prevalence of all CVDs. Compared with cancer-free controls, breast cancer survivors had substantially increased risks of deep vein thrombosis (adjusted HR, 1.67; 95% CI, 1.62-1.73; 386,484 person-years of follow-up) and pericarditis (HR, 1.43; 95% CI, 1.38-1.49; 390,776 person-years of follow-up); evidence of smaller increased risks of sudden cardiac arrest, arrhythmia, heart failure, and valvular heart disease (adjusted HRs ranging from 1.05-1.09, lower CI limits all ≥1); and evidence of lower risk of incident angina, myocardial infarction, revascularization, peripheral vascular disease, and stroke (adjusted HRs ranging from 0.89-0.98, upper CI limits all ≤1). Increased risks of arrhythmia, heart failure, pericarditis, and deep vein thrombosis persisted >5 years after cancer diagnosis. CONCLUSIONS: Women with a history of breast cancer were at increased risk of several CVDs, persisting into survivorship. Monitoring and managing cardiovascular risk throughout the long-term follow-up of women diagnosed with breast cancer should be a priority.

Endocrine therapy use and cardiovascular risk in postmenopausal breast cancer survivors.

OBJECTIVE: Examine the effect of tamoxifen and aromatase inhibitors (AIs) on the risk of 12 clinically relevant cardiovascular outcomes in postmenopausal female breast cancer survivors. METHODS: We carried out two prospective cohort studies among postmenopausal women with breast cancer in UK primary care and hospital data (2002-2016) and US Surveillance, Epidemiology and End Results-Medicare data (2008-2013). Using Cox adjusted proportional hazards models, we compared cardiovascular risks between AI and tamoxifen users; and in the USA, between users of both drug classes and women receiving no endocrine therapy. RESULTS: 10 005 (UK) and 22 027 (USA) women with postmenopausal breast cancer were included. In both countries, there were higher coronary artery disease risks in AI compared with tamoxifen users (UK age-standardised incidence rate: 10.17 vs 7.51 per 1000 person-years, HR: 1.29, 95% CI 0.94 to 1.76; US age-standardised incidence rate: 36.82 vs 26.02 per 1000 person-years, HR: 1.29, 95% C I1.06 to 1.55). However, comparisons with those receiving no endocrine therapy (US data) showed no higher risk for either drug class and a lower risk in tamoxifen users (age-standardised incidence rate tamoxifen vs unexposed: 26.02 vs 35.19 per 1000 person-years, HR: 0.74, 95% 0.60 to 0.92; age-standardised incidence rate AI vs unexposed: 36.82 vs 35.19, HR: 0.96, 95% CI 0.83 to 1.10). Similar patterns were seen for other cardiovascular outcomes (arrhythmia, heart failure and valvular heart disease). As expected, there was more venous thromboembolism in tamoxifen compared with both AI users and those unexposed. CONCLUSIONS: Higher risks of several cardiovascular outcomes among AI compared with tamoxifen users appeared to be driven by protective effects of tamoxifen, rather than cardiotoxic effects of AIs.

Burden and prevalence of prognostic factors for severe COVID-19 in Sweden.

The World Health Organization and European Centre for Disease Prevention and Control suggest that individuals over the age of 70 years or with underlying cardiovascular disease, cancer, chronic obstructive pulmonary disease, asthma, or diabetes are at increased risk of severe COVID-19. However, the prevalence of these prognostic factors is unknown in many countries. We aimed to describe the burden and prevalence of prognostic factors of severe COVID-19 at national and county level in Sweden. We calculated the burden and prevalence of prognostic factors for severe COVID-19 based on records from the Swedish national health care and population registers for 3 years before 1st January 2016. 9,624,428 individuals were included in the study population. 22.1% had at least one prognostic factor for severe COVID-19 (2,131,319 individuals), and 1.6% had at least three factors (154,746 individuals). The prevalence of underlying medical conditions ranged from 0.8% with chronic obstructive pulmonary disease (78,516 individuals) to 7.4% with cardiovascular disease (708,090 individuals), and the county specific prevalence of at least one prognostic factor ranged from 19.2% in Stockholm (416,988 individuals) to 25.9% in Kalmar (60,005 individuals). We show that one in five individuals in Sweden is at increased risk of severe COVID-19. When compared with the critical care capacity at a local and national level, these results can aid authorities in optimally planning healthcare resources during the current pandemic. Findings can also be applied to underlying assumptions of disease burden in modelling efforts to support COVID-19 planning.