Dataset Information

Use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers and cancer risk: a meta-analysis of observational studies.

ABSTRACT:

Background

Epidemiologic studies have reported inconsistent findings regarding the association between the use of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers and the risk of cancer. We performed a meta-analysis of observational studies to assess the association.

Methods

We searched MEDLINE, EMBASE and the Cochrane Library to identify studies through January 2011. Two evaluators independently reviewed and selected articles of cohort and case-control studies on the basis of predetermined selection criteria.

Results

Of 3970 screened articles, 12 cohort studies and 16 case-control studies were selected for analysis. We found no significant association between the use of ACE inhibitors or angiotensin-receptor blockers and the overall risk of cancer (relative risk [RR] 0.96, 95% confidence interval [CI] 0.90-1.03). We found a decreased risk of cancer associated with use of either medication when we restricted the analyses to cohort and nested case-control studies (RR 0.90, 95% CI 0.83-0.97) or to studies with long-term follow-up of more than five years (RR 0.89, 95% CI 0.83-0.96). In the subgroup meta-analyses by cancer site, a decreased risk was identified for esophageal cancer, whereas an increased risk was found for melanoma and kidney cancer.

Interpretation

No significant association was found between the use of ACE inhibitors or angiotensin-receptor blockers and overall risk of cancer. A possible beneficial effect associated with use of either medication was suggested in sensitivity analyses, including those of studies with long-term follow-up. Large randomized controlled trials with long-term follow-up are needed to specifically test the effect of each of these medications on the risk of cancer.

SUBMITTER: Yoon C

PROVIDER: S-EPMC3185099 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThe renin-angiotensin system has been implicated in mood disorders. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are among the most commonly used medications, yet their effects on mental health outcomes, particularly suicide, are poorly understood. This study examined the association between suicide and exposure to ACEIs and ARBs. Because of differences in their mode of action, it was speculated that ARBs would be associated with a higher risk of suicide than ACEIs.ObjectiveTo examine the association between suicide and exposure to ARBs compared with ACEIs.Design, setting, and participantsThis population-based nested case-control study of individuals aged 66 years and older used administrative claims databases in Ontario, Canada, from January 1, 1995, to December 31, 2015. Data analysis was performed from January to April 2019. Cases were individuals who died by suicide within 100 days of receiving an ACEI or ARB. The date of death served as the index date. For each case, 4 controls were identified and matched by age (within 1 year), sex, and presence of hypertension and diabetes. All individuals received an ACEI or ARB within 100 days before the index date.ExposuresUse of an ACEI or ARB.Main outcomes and measuresConditional logistic regression was used to estimate odds ratios for the association between suicide and exposure to ARBs compared with ACEIs.ResultsNine hundred sixty-four cases were matched to 3856 controls. The median (interquartile range) age of cases and controls was 76 (70-82) years. Most cases (768 [79.7%]) and controls (3068 [79.6%]) were men. Among cases, 260 (26.0%) were exposed to ARBs, and 704 (18.4%) were exposed to ACEIs. Among controls, 741 (74.0%) were exposed to ARBs, and 3115 (81.6%) were exposed to ACEIs. Compared with ACEI exposure, ARB exposure was associated with higher risk of death by suicide (adjusted odds ratio, 1.63; 95% CI, 1.33-2.00). The findings were consistent in a sensitivity analysis excluding individuals with a history of self-harm (odds ratio, 1.60; 95% CI, 1.29-1.98).Conclusions and relevanceThe use of ARBs may be associated with an increased risk of suicide compared with ACEIs. Preferential use of ACEIs over ARBs should be considered whenever possible, particularly in patients with severe mental health illness.

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.