Comparative efficacy and safety of antihypertensive strategies for diabetic kidney disease: a systematic review and component network meta-analysis

Research Question: which blood pressure lowering therapies in adults with diabetes who have or are at risk of kidney disease are most efficacious in improving survival and reducing the risk of end-stage kidney disease (ESKD)?

Background: Diabetes and high blood pressure are the leading causes of chronic kidney disease (CKD), and are the most common causes of ESKD. Together they markedly increase the risk of both cardiovascular disease and mortality.

One of the most common modifiable factors to reduce these risks in people with diabetes and CKD is through the management of blood pressure.

However, in these individuals the pharmacology of blood pressure lowering therapies is increasingly complex, and the efficacy and safety of available drugs is unknown due to the lack of head-to-head trials.

Aims and Objectives: The research question is: which blood pressure lowering therapies in adults with diabetes who have or are at risk of kidney disease are most efficacious in improving survival and reducing the risk of ESKD. The research has four aims: 1.

To update a previous systematic review using the same search strategies and databases to the previously published review. 2.

To use the novel approach of component network meta-analysis with the updated dataset to compare the efficacy and acceptability of blood pressure lowering therapies in adults with diabetes who have or are at risk of CKD. 3.

To use the data generated from the component network meta-analysis to produce a clinically meaningful hierarchy of antihypertensive interventions according to their efficacy and safety. 4.

To feedback the results of this research to patients and patient groups (alongside other key stakholders) through an animated video which will be developed alongside our public co-applicant and our PPIE panel.

Methods: This project will conduct a systematic review and component network meta-analysis comparing blood pressure lowering therapies in adults with diabetic kidney disease.

Electronic databases will be searched systematically for trials in adults with diabetes and kidney disease comparing orally administered blood pressure drugs. Primary outcomes will be total mortality and progression to ESKD. We will initially perform a pairwise meta-analysis.

We will then perform component network meta-analysis using three models; additive effects model, pairwise interactions model, and standard network meta-analysis model. A clinically meaningful hierarchy of blood pressure lowering therapies will be produced.

Timelines for delivery: Months 1-8 formulate review protocol, perform searches, data extraction, data synthesis and interpretation. Months 9-12 development of animated video, and other knowledge mobilisation strategies.

Anticipated Impact and Dissemination: As well as having a direct impact upon patients, this research has the capacity to lead to a direct change and adoption within UK and global clinical practice.