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Renin-angiotensin system inhibitors and risk of fractures: a prospective cohort study and meta-analysis of published observational cohort studies.

ABSTRACT: The renin-angiotensin system (RAS) represents an important target of antihypertensive medications. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), which are widely-used RAS inhibiting drugs, have been suggested to have beneficial effects on bone tissue. We aimed to assess the associations of use of ACEIs and/or ARBs with the risk of fractures using a population-based prospective cohort and a meta-analysis of published prospective cohort studies. Information on antihypertensive medication use (including both ACEIs and ARBs) were assessed in 1743 men and women of the Kuopio Ischemic Heart Disease prospective cohort study. Hazard ratios (HRs) [95% confidence intervals (CI)] of ACEIs or ARBs use with incident fractures were calculated. A total of 203 composite (hip, humeral, and wrist) fractures occurred during a median follow-up of 14.8 years. In multivariate adjusted analysis, the HR for composite fractures comparing users of ACEIs or ARBs with non-users was 1.00 (0.59-1.69). The corresponding adjusted HR for hip fractures comparing users versus non-users of ACEIs or ARBs was 0.89 (0.32-2.47). Including the current study, a total of 11 observational cohort studies involving 3526,319 participants and >323,355 fractures were included in a meta-analysis. Comparing ACEI users with non-users and ARB users with non-users, the HRs for composite fractures were 1.09 (0.89-1.33) and 0.87 (0.76-1.01) respectively. The corresponding HRs for hip fractures were 0.91 (0.86-0.95) and 0.80 (0.75-0.85) respectively. Use of RAS inhibitors was not associated with long-term risk of composite fractures in both primary and pooled analyses. Pooled evidence however suggests a beneficial effect of RAS blockers on hip fracture risk.

SUBMITTER: Kunutsor SK

PROVIDER: S-EPMC5684291 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Renin-angiotensin system inhibitors and risk of fractures: a prospective cohort study and meta-analysis of published observational cohort studies.

Kunutsor Setor K SK Blom Ashley W AW Whitehouse Michael R MR Kehoe Patrick G PG Laukkanen Jari A JA

European journal of epidemiology 20170727 11

The renin-angiotensin system (RAS) represents an important target of antihypertensive medications. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), which are widely-used RAS inhibiting drugs, have been suggested to have beneficial effects on bone tissue. We aimed to assess the associations of use of ACEIs and/or ARBs with the risk of fractures using a population-based prospective cohort and a meta-analysis of published prospective cohort studies. Inform ...[more]

PMID: 28752198

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Project description:Background and objectivesThe risk-benefit ratio of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy after AKI may be altered due to concerns regarding recurrent AKI. We evaluated, in a prospective cohort, the association between use (versus nonuse) of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and the subsequent risk of AKI and other adverse outcomes after hospitalizations with and without AKI.Design, setting, participants, & measurementsWe studied 1538 patients recently discharged from the hospital who enrolled in the multicenter, prospective ASSESS-AKI study, with approximately half of patients experiencing AKI during the index hospitalization. All participants were seen at a baseline visit 3 months after their index hospitalization and were categorized at that time on whether they were using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or not. We used multivariable Cox regression, adjusting for demographics, comorbidities, eGFR, urine protein-creatinine ratio, and use of other medications, to examine the association between angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and subsequent risks of AKI, death, kidney disease progression, and adjudicated heart-failure events.ResultsThe use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 50% (386/769) among those with AKI during the index hospitalization and 47% (362/769) among those without. Among those with AKI during the index hospitalization, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use was not associated with a higher risk of recurrent hospitalized AKI (adjusted hazard ratio, 0.88; 95% confidence interval, 0.69 to 1.13). Associations between angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and death, kidney disease progression, and adjudicated heart-failure events appeared similar in study participants who did and did not experience AKI during the index hospitalization (all interaction P values >0.05).ConclusionsThe risk-benefit ratio of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy after hospital discharge appears to be similar regardless of whether AKI occurred during the hospitalization.

Project description:AIMS:To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease. To assess the association between renin-angiotensin system inhibitors (RASIs) and disease progression and critical outcomes. METHODS AND RESULTS:All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study. The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission. Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint. Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2. Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32-54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61-84)]. A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU. Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age. After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02-2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents. CONCLUSIONS:We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome. Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.

Dataset Information

Renin-angiotensin system inhibitors and risk of fractures: a prospective cohort study and meta-analysis of published observational cohort studies.

Publications

Renin-angiotensin system inhibitors and risk of fractures: a prospective cohort study and meta-analysis of published observational cohort studies.

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