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Long-term use of angiotensin receptor blockers and the risk of cancer.

ABSTRACT: The association between angiotensin receptor blockers (ARBs) and cancer is controversial with meta-analyses of randomized controlled trials and observational studies reporting conflicting results. Thus, the objective of this study was to determine whether ARBs are associated with an overall increased risk of the four most common cancers, namely, lung, colorectal, breast and prostate cancers, and to explore these effects separately for each cancer type. We conducted a retrospective cohort study using a nested case-control analysis within the United Kingdom (UK) General Practice Research Database. We assembled a cohort of patients prescribed antihypertensive agents between 1995, the year the first ARB (losartan) entered the UK market, and 2008, with follow-up until December 31, 2010. Cases were patients newly-diagnosed with lung, colorectal, breast and prostate cancer during follow-up. We used conditional logistic regression to estimate adjusted rate ratios (RRs) and 95% confidence intervals (CIs) of cancer incidence, comparing ever use of ARBs with ever use of diuretics and/or beta-blockers. The cohort included 1,165,781 patients, during which 41,059 patients were diagnosed with one of the cancers under study (rate 554/100,000 person-years). When compared to diuretics and/or beta-blockers, ever use of ARBs was not associated with an increased rate of cancer overall (RR: 1.00; 95% CI: 0.96-1.03) or with each cancer site separately. The use of angiotensin-converting enzyme inhibitors and calcium channel blockers was associated with an increased rate of lung cancer (RR: 1.13; 95% CI: 1.06-1.20 and RR: 1.19; 95% CI: 1.12-1.27, respectively). This study provides additional evidence that the use of ARBs does not increase the risk of cancer overall or any of the four major cancer sites. Additional research is needed to further investigate a potentially increased risk of lung cancer with angiotensin-converting enzyme inhibitors and calcium channel blockers.

SUBMITTER: Azoulay L

PROVIDER: S-EPMC3521027 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Long-term use of angiotensin receptor blockers and the risk of cancer.

Azoulay Laurent L Assimes Themistocles L TL Yin Hui H Bartels Dorothee B DB Schiffrin Ernesto L EL Suissa Samy S

PloS one 20121212 12

The association between angiotensin receptor blockers (ARBs) and cancer is controversial with meta-analyses of randomized controlled trials and observational studies reporting conflicting results. Thus, the objective of this study was to determine whether ARBs are associated with an overall increased risk of the four most common cancers, namely, lung, colorectal, breast and prostate cancers, and to explore these effects separately for each cancer type. We conducted a retrospective cohort study u ...[more]

PMID: 23251399

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Project description:ImportanceAnimal and human studies have suggested that the use of angiotensin receptor blockers (ARBs) may be associated with a lower risk of incident epilepsy compared with other antihypertensive medications. However, observational data from the US are lacking.ObjectiveTo evaluate the association between ARB use and epilepsy incidence in subgroups of US patients with hypertension.Design, setting, and participantsThis retrospective cohort study used data from a national health administrative database from January 2010 to December 2017 with propensity score (PS) matching. The eligible cohort included privately insured individuals aged 18 years or older with diagnosis of primary hypertension and dispensed at least 1 ARB, angiotensin-converting enzyme inhibitor (ACEI), β-blocker, or calcium channel blocker (CCB) from 2010 to 2017. Patients with a diagnosis of epilepsy at or before the index date or dispensed an antiseizure medication 12 months before or 90 days after initiating the study medications were excluded. The data analysis for this project was conducted from April 2022 to April 2024.ExposuresPropensity scores were generated based on baseline covariates and used to match patients who received ARBs with those who received either ACEIs, β-blockers, CCBs, or a combination of these antihypertensive medications.Main outcomes and measuresCox regression analyses were used to evaluate epilepsy incidence during follow-up comparing the ARB cohort with other antihypertensive classes. Subgroup and sensitivity analyses were conducted to examine the association between ARB use and epilepsy incidence in various subgroups.ResultsOf 2 261 964 patients (mean [SD] age, 61.7 [13.9] years; 1 120 630 [49.5%] female) included, 309 978 received ARBs, 807 510 received ACEIs, 695 887 received β-blockers, and 448 589 received CCBs. Demographic and clinical characteristics differed across the 4 comparison groups prior to PS matching. Compared with ARB users, patients receiving ACEIs were predominantly male and had diabetes, CCB users were generally older (eg, >65 years), and β-blocker users had more comorbidities and concurrent medications. The 1:1 PS-matched subgroups included 619 858 patients for ARB vs ACEI, 619 828 patients for ARB vs β-blocker, and 601 002 patients for ARB vs CCB. Baseline characteristics were equally distributed between comparison groups after matching with propensity scores. Use of ARBs was associated with a decreased incidence of epilepsy compared with ACEIs (adjusted hazard ratio [aHR], 0.75; 95% CI, 0.58-0.96), β-blockers (aHR, 0.70; 95% CI, 0.54-0.90), and a combination of other antihypertensive classes (aHR, 0.72; 95% CI, 0.56-0.95). Subgroup analyses revealed a significant association between ARB use (primarily losartan) and epilepsy incidence in patients with no preexisting history of stroke or cardiovascular disease.Conclusions and relevanceThis cohort study found that ARBs, mainly losartan, were associated with a lower incidence of epilepsy compared with other antihypertensive agents in hypertensive patients with no preexisting stroke or cardiovascular disease. Further studies, such as randomized clinical trials, are warranted to confirm the comparative antiepileptogenic properties of antihypertensive medications.

Project description:ObjectiveTo systematically review longitudinal studies evaluating use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and risk of pneumonia.DesignSystematic review and meta-analysis.Data sourcesMedline through PubMed, Web of Science with conference proceedings (inception to June 2011), and US Food and Drug Administration website (June 2011). Systematic reviews and references of retrieved articles were also searched.Study selectionTwo reviewers independently selected randomised controlled trials and cohort and case-control studies evaluating the use of ACE inhibitors or ARBs and risk of pneumonia and retrieved characteristics of the studies and data estimates.Data synthesisThe primary outcome was incidence of pneumonia and the secondary outcome was pneumonia related mortality. Subgroup analyses were carried according to baseline morbidities (stroke, heart failure, and chronic kidney disease) and patients' characteristics (Asian and non-Asian). Pooled estimates of odds ratios and 95% confidence intervals were derived by random effects meta-analysis. Adjusted frequentist indirect comparisons between ACE inhibitors and ARBs were estimated and combined with direct evidence whenever available. Heterogeneity was assessed using the I(2) test.Results37 eligible studies were included. ACE inhibitors were associated with a significantly reduced risk of pneumonia compared with control treatment (19 studies: odds ratio 0.66, 95% confidence interval 0.55 to 0.80; I(2) = 79%) and ARBs (combined direct and indirect odds ratio estimate 0.69, 0.56 to 0.85). In patients with stroke, the risk of pneumonia was also lower in those treated with ACE inhibitors compared with control treatment (odds ratio 0.46, 0.34 to 0.62) and ARBs (0.42, 0.22 to 0.80). ACE inhibitors were associated with a significantly reduced risk of pneumonia among Asian patients (0.43, 0.34 to 0.54) compared with non-Asian patients (0.82, 0.67 to 1.00; P<0.001). Compared with control treatments, both ACE inhibitors (seven studies: odds ratio 0.73, 0.58 to 0.92; I(2)=51%) and ARBs (one randomised controlled trial: 0.63, 0.40 to 1.00) were associated with a decrease in pneumonia related mortality, without differences between interventions.ConclusionsThe best evidence available points towards a putative protective role of ACE inhibitors but not ARBs in risk of pneumonia. Patient populations that may benefit most are those with previous stroke and Asian patients. ACE inhibitors were also associated with a decrease in pneumonia related mortality, but the data lacked strength.

Project description:BackgroundUse of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) has been hypothesized to affect COVID-19 risk.ObjectiveTo examine the association between use of ACEI/ARB and household transmission of COVID-19.MethodsWe conducted a modified cohort study of household contacts of patients who tested positive for COVID-19 between March 4 and May 17, 2020 in a large Northeast US health system. Household members were identified by geocoding and full address matching with exclusion of addresses with >10 matched residents or known congregate living functions. Medication use, clinical conditions and sociodemographic characteristics were obtained from electronic medical record (EMR) data on cohort entry. Cohort members were followed for at least one month after exposure to determine who tested positive for SARS-CoV-2. Mixed effects logistic regression and propensity score analyses were used to assess adjusted associations between medication use and testing positive.Results1,499 of the 9,101 household contacts were taking an ACEI or an ARB. Probability of COVID-19 diagnosis during the study period was slightly higher among ACEI/ARB users in unadjusted analyses. However, ACEI/ARB users were older and more likely to have clinical comorbidities so that use of ACEI/ARB was associated with a decreased risk of being diagnosed with COVID-19 in mixed effect models (OR 0.60, 95% CI 0.44-0.81) or propensity score analyses (predicted probability 18.6% in ACEI/ARB users vs. 24.5% in non-users, p = 0.03). These associations were similar within age and comorbidity subgroups, including patients with documented hypertension, diabetes or cardiovascular disease, as well as when including other medications in the models.ConclusionsIn this observational study of household transmission, use of ACEIs or ARBs was associated with a decreased risk of being diagnosed with COVID-19. While causality cannot be inferred from these observational data, our results support current recommendations to continue ACEI/ARB in individuals at risk of COVID-19 exposure.

Project description:ObjectiveTo investigate whether angiotensin receptor blockers protect against Alzheimer's disease and dementia or reduce the progression of both diseases.DesignProspective cohort analysis.SettingAdministrative database of the US Veteran Affairs, 2002-6. Population 819 491 predominantly male participants (98%) aged 65 or more with cardiovascular disease.Main outcome measuresTime to incident Alzheimer's disease or dementia in three cohorts (angiotensin receptor blockers, lisinopril, and other cardiovascular drugs, the "cardiovascular comparator") over a four year period (fiscal years 2003-6) using Cox proportional hazard models with adjustments for age, diabetes, stroke, and cardiovascular disease. Disease progression was the time to admission to a nursing home or death among participants with pre-existing Alzheimer's disease or dementia.ResultsHazard rates for incident dementia in the angiotensin receptor blocker group were 0.76 (95% confidence interval 0.69 to 0.84) compared with the cardiovascular comparator and 0.81 (0.73 to 0.90) compared with the lisinopril group. Compared with the cardiovascular comparator, angiotensin receptor blockers in patients with pre-existing Alzheimer's disease were associated with a significantly lower risk of admission to a nursing home (0.51, 0.36 to 0.72) and death (0.83, 0.71 to 0.97). Angiotensin receptor blockers exhibited a dose-response as well as additive effects in combination with angiotensin converting enzyme inhibitors. This combination compared with angiotensin converting enzyme inhibitors alone was associated with a reduced risk of incident dementia (0.54, 0.51 to 0.57) and admission to a nursing home (0.33, 0.22 to 0.49). Minor differences were shown in mean systolic and diastolic blood pressures between the groups. Similar results were observed for Alzheimer's disease.ConclusionsAngiotensin receptor blockers are associated with a significant reduction in the incidence and progression of Alzheimer's disease and dementia compared with angiotensin converting enzyme inhibitors or other cardiovascular drugs in a predominantly male population.

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Long-term use of angiotensin receptor blockers and the risk of cancer.

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Long-term use of angiotensin receptor blockers and the risk of cancer.

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