Effectiveness of two‐drug therapy versus monotherapy as initial regimen in hypertension: A propensity score‐matched cohort study in the UK Clinical Practice Research Datalink

ObjectivesTo compare population-based incidence rates of new-onset depression or self-harm in patients initiating incretin-based therapies with that of sulfonylureas (SU) and other glucose-lowering agents.DesignPopulation-based cohort study.SettingPatients attending primary care practices registered with the UK-based Clinical Practice Research Datalink (CPRD).ParticipantsUsing the UK-based CPRD, we identified two incretin-based therapies cohorts: (1) dipeptidyl peptidase-4 inhibitor (DPP-4i)-cohort, consisting of new users of DPP-4i and SU and (2) glucagon-like peptide-1 receptor agonists (GLP-1RA)-cohort, consisting of new users of GLP-1RA and SU, between January 2007 and January 2016. Patients with a prior history of depression, self-harm and other serious psychiatric conditions were excluded.Main outcome measuresThe primary study outcome comprised a composite of new-onset depression or self-harm. Unadjusted and adjusted Cox proportional hazards regression was used to quantify the association between incretin-based therapies and depression or self-harm. Deciles of High-Dimensional Propensity Scores and concurrent number of glucose-lowering agents were used to adjust for potential confounding.ResultsWe identified new users of 6206 DPP-4i and 22 128 SU in the DPP-4i-cohort, and 501 GLP-1RA and 16 409 SU new users in the GLP-1RA-cohort. The incidence of depression or self-harm was 8.2 vs 11.7 events/1000 person-years in the DPP-4i-cohort and 18.2 vs 13.6 events/1000 person-years in the GLP-1RA-cohort for incretin-based therapies versus SU, respectively. Incretin-based therapies were not associated with an increased or decreased incidence of depression or self-harm compared with SU (DPP-4i-cohort: unadjusted HR 0.70, 95% CI 0.51 to 0.96; adjusted HR 0.80, 95% CI 0.57 to 1.13; GLP-1RA-cohort: unadjusted HR 1.36, 95% CI 0.72 to 2.58; adjusted HR 1.25, 95% CI 0.63 to 2.50). Consistent results were observed for other glucose-lowering comparators including insulin and thiazolidinediones.ConclusionsOur findings suggest that the two incretin-based therapies are not associated with an increased or decreased risk of depression or self-harm.

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Estimating the risk of acute kidney injury associated with use of diuretics and renin angiotensin aldosterone system inhibitors: A population based cohort study using the clinical practice research datalink

BMC Nephrology ◽

10.1186/s12882-019-1633-2 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Jemima Scott ◽

Tim Jones ◽

Maria Theresa Redaniel ◽

Margaret T. May ◽

Yoav Ben-Shlomo ◽

...

Keyword(s):

Acute Kidney Injury ◽

Cohort Study ◽

Clinical Practice ◽

Propensity Score ◽

Cox Regression ◽

Kidney Injury ◽

Exposed Group ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Raas Inhibitors

Abstract Background The risk of acute kidney injury (AKI) attributable to renin angiotensin aldosterone (RAAS) inhibitors and diuretics remains unclear. Methods We conducted a prospective cohort study using the Clinical Practice Research Datalink (2008–2015) linked to Hospital Episode Statistics – Admitted Patient Care and Office for National Statistics mortality data. Patients were included if they had one or more chronic diagnoses requiring medication. Exposed patients had a first ever prescription for RAAS inhibitors/diuretics during the study period. AKI risk associated with exposure was determined by multivariable Cox regression, propensity score-adjusted Cox regression and a prior event rate ratio (PERR) analysis. Results One hundred forty thousand nine hundred fifty-two individuals were included. Increased AKI risk in the exposed group was demonstrated in both the multivariable and propensity score-adjusted cox regressions (HR 1.23 (95% CI 1.04–1.45) and HR 1.24 (1.05–1.47) respectively). The PERR analysis provided a similar overall hazard ratio with a wider confidence interval (HR 1.29 (0.94–1.63)). The increased AKI risk in the exposed group was present only in those receiving two or more antihypertensives. Absolute AKI risk was small. Conclusions RAAS inhibitors/diuretics result in an increased risk of AKI. The absolute increase in AKI risk is small, however, and needs to be considered in the context of any potential benefits.

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