Long-term exposure to antihypertensive drugs and the risk of cancer occurrence: evidence from a large population-based study.

OBJECTIVE: Available data on the association between antihypertensive drugs and cancer are characterized by a few years follow-up. Our aim has been to evaluate the association between long-term exposure to antihypertensive drugs and the risk of cancer occurrence. METHODS: Using the healthcare utilization databases of the Lombardy region (Italy), individuals aged 40-85 years who had no previous history of cancer and were newly dispensed with at least one antihypertensive drug from the major drug classes between 2009 and 2011 were followed from the first drug dispensation to December 31, 2020. Data were analyzed according to the first drug used and the intention to treat principle, but also via an "as treated" approach, that is, by considering changes of and exposure to drugs during follow-up. The association between the duration of exposure to each drug class and the risk of cancer occurrence was evaluated using the adjusted Cox regression models. RESULTS: The study cohort included 338 910 new drug users (median age, 59 years; 49.5% males). During a median follow-up of 10.2 years, 36 556 cancers occurred. There was no consistent significant association between the risk of cancer occurrence and angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, or thiazides. A progressive, weak increase in cancer occurrence was associated with progressive exposure to calcium channel blockers and, limited to long-term exposure, to beta-blockers. A modest progressive increase in risk was observed also for thiazide-like and loop diuretics in the as treated, although not in the intention to treat approach. CONCLUSIONS: Long-term evaluation of exposure to antihypertensive drugs did not show consistent associations between thiazides, angiotensin-receptor blockers, or angiotensin-converting-enzyme inhibitors and the risk of cancer occurrence. A weak association was observed between cancer and the duration of exposure to calcium channel blockers and beta-blockers.

Incidence and risk of arterial and venous thrombotic events in Systemic Lupus Erythematosus patients: a population-based study.

OBJECTIVES: Current data on arterial and venous thrombotic events (ATE & VTE) and cardiovascular (CV) risk management in European systemic lupus erythematosus (SLE) population are limited. This study aimed to investigate the incidence and risk of thrombotic events and all-cause death in an Italian SLE cohort over the past decade, along with its pharmacotherapy. METHODS: Incident SLE cases between 2010 and 2019 were identified using administrative health databases of the Lombardy Region. The association between SLE and outcomes, compared with age- and sex-matched controls, was reported as incidence rate per 1000 person-years and as adjusted hazard ratios with 95% confidence intervals. RESULTS: Overall, 2133 SLE patients and 21 283 no-SLE individuals were included. A higher incidence rate of ATE (4.22 vs 2.26 1000 PY), VTE (1.85 vs 0.67 1000 PY,) and all-cause death (15.18 vs 6.22 1000 PY) was reported in SLE patients than in those without (p< 0.0001) as well as an increased risk of ATE (HR, 1.65; 95% CI, 1.20-2.26), VTE (HR, 2.25; 95% CI, 1.35-3.74), and all-cause death (HR, 1.81; 95% CI, 1.52-2.15). After SLE diagnoses, hydroxychloroquine and glucocorticoids were prescribed for at least 60% of patients. Additionally, a higher exposure to cardiovascular medications was also seen in SLE patients. CONCLUSION: Our findings confirmed higher risks of ATE, VTE and all-cause death in SLE patients. While increased CV medications use after SLE diagnoses suggests heightened awareness to CV risk profile, more attention is required to balance SLE disease activity with minimizing exposure to drugs associated with exacerbating CV risk.

Risk of incident atrial fibrillation after COVID-19 infection: A systematic review and meta-analysis.

BACKGROUND: Data regarding the risk of atrial fibrillation (AF) during the post-acute phase of COVID-19 are lacking. OBJECTIVE: We assessed the risk of incident AF in COVID-19 recovered patients by performing a systematic review and meta-analysis of the available data. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched Medline and Scopus to locate all articles published up to December 1, 2023, reporting the risk of AF in patients recovered from COVID-19 infection compared with noninfected patients in whom the arrhythmia developed during the same follow-up period. AF risk was evaluated by the Mantel-Haenszel random effects model with hazard ratio as the effect measure with 95% confidence interval (CI); heterogeneity was assessed by Higgins I2 statistic. RESULTS: Overall, 19,478,173 patients (mean age, 56.5 years; 63.0% male) enrolled in 5 observational studies were included in the analysis. Of these, 5,692,510 recovered from severe acute respiratory syndrome coronavirus 2 infection. During a mean follow-up of 14.5 ± 3.2 months, a random effects model revealed a pooled incidence of new-onset AF in 2.6% of cases (95% CI, 1.8%-6.18%). Recovered COVID-19 patients presented with a higher risk of incident AF (hazard ratio, 1.57; 95% CI, 1.24-1.99; P < .0001; I2 = 77.9%) compared with noninfected patients during the same follow-up period. Sensitivity analyses confirmed the yielded results. A multivariable metaregression including age, male sex, history of hypertension, coronary artery disease, and length of follow-up was able to explain a significant part of the heterogeneity (R2 = 54.3%; P = .01). CONCLUSION: Recovered COVID-19 patients have a higher risk of AF events compared with individuals from the general population.

Proton Pump Inhibitor Use and the Risk of Cardiovascular Complications and Death in Older Adults with Diabetes: A Population-Based Cohort Study.

BACKGROUND: The unfavorable effect of proton pump inhibitors (PPIs) on cardiovascular (CV) outcomes and mortality was reported in the general population. We investigated the impact of PPIs on CV outcomes and total mortality in older people with diabetes mellitus (DM) for whom evidence is missing. METHODS: Using administrative health databases of the Lombardy Region, we analyzed the risk of myocardial infarction (MI), ischemic stroke and total mortality in individuals with DM (≥65 years of age) exposed to PPIs in 2015 and followed up to 2021. The outcomes were analyzed using a multivariable-adjusted Cox proportional hazards model to compute hazard ratios (HRs) with 95% confidence intervals (CIs). HRs between PPI users and non-users were also estimated in selected subgroups. A sensitivity analysis was also performed in a 1:1 propensity score matching population. RESULTS: A total of 284,068 patients were included in the analysis (49.4% PPI users, 50.6% non-PPI users). A higher prevalence of comorbidities and medications was reported in PPI users as compared with non-users. During a median follow-up of 6.7 years, the use of PPIs was associated with a higher risk for ischemic stroke (HR 1.14, 95% CI 95% 1.08-1.20), MI (HR 1.36, 95% CI 1.31-1.41) and total mortality (HR 1.24, 95% CI 1.22-1.26). These risks were higher in PPI users regardless of the PPI type. Among sexes, previous CV diseases, and insulin subgroups, the use of PPIs was correlated with a statistically significant increased risk of ischemic stroke in men, in individuals without a history of CV disease, and in those who were not treated with insulin. A significantly higher risk of MI was associated with PPIs for all subgroups, as well as for total mortality, with the exception of patients with a previous history of CV diseases. The sensitivity analysis confirmed the results of the unmatched cohort. CONCLUSIONS: Our findings confirmed an increased risk of CV events and all-cause mortality in a large population of older adults with DM exposed to PPIs. This could have an important impact on public health and costs for National Health Service, therefore a regular assessment of PPI appropriateness is recommended, particularly in this population.