Strategies to Improve Health Care Provider Prescription of and Patient Adherence to Guideline-Recommended Cardiovascular Medications for Atherosclerotic Occlusive Disease: Protocol for Two Systematic Reviews and Meta-Analyses of Randomized Controlled Trials
Authors: Kirkham Aidan M , Fergusson Dean A , Presseau Justin , McIsaac Daniel I , Shorr Risa , Roberts Derek J 
Published: November 2024

Background
In patients with atherosclerotic occlusive diseases, systematic reviews and meta-analyses of randomized controlled trials (RCTs) report that antiplatelets, statins, and antihypertensives reduce the risk of major adverse cardiac events, need for revascularization procedures, mortality, and health care resource use. However, evidence suggests that these patients are not prescribed these medications adequately or do not adhere to them once prescribed.

Objective
We aim to systematically review and meta-analyze RCTs examining the effectiveness of implementation or adherence-supporting strategies for improving health care provider prescription of, or patient adherence to, guideline-recommended cardiovascular medications in patients with atherosclerotic occlusive disease.

Methods
We designed and reported the protocol according to the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis-Protocols) statement. We will search MEDLINE, Embase, The Cochrane Central Register of Controlled Trials, PsycINFO, and CINAHL from their inception. RCTs examining implementation or adherence-supporting strategies for improving prescription of, or adherence to, guideline-recommended cardiovascular medications in adults with cerebrovascular disease, coronary artery disease, peripheral artery disease, or polyvascular disease (>1 of these diseases) will be included. Two investigators will independently review identified titles/abstracts and full-text studies, extract data, assess the risk of bias (using the Cochrane tool), and classify implementation or adherence-supporting strategies using the refined Cochrane Effective Practice and Organization of Care (EPOC) taxonomy (for strategies aimed at improving prescription) and Behavior Change Wheel (BCW; for adherence-supporting strategies). We will narratively synthesize data describing which implementation or adherence-supporting strategies have been evaluated across RCTs, and their reported effectiveness at improving prescription of, or adherence to, guideline-recommended cardiovascular medications (primary outcomes) and patient-important outcomes and health care resource use (secondary outcomes) within refined EPOC taxonomy levels and BCW interventions and policies. Where limited clinical heterogeneity exists between RCTs, estimates describing the effectiveness of implementation or adherence-supporting strategies within different refined EPOC taxonomy levels and BCW interventions and policies will be pooled using random-effects models. Stratified meta-analyses and meta-regressions will assess if strategy effectiveness varies by recruited patient populations, prescriber types, clinical practice settings, and study design characteristics. GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) will be used to communicate evidence certainty.

Results
The search was completed on June 6, 2023. Database searches and the PubMed “related articles” feature identified 4319 unique citations for title/abstract screening. We are currently screening titles/abstracts.

Conclusions
These studies will identify which implementation and adherence-supporting strategies are being used (and in which combinations) across RCTs for improving the prescription of, or adherence to, guideline-recommended cardiovascular medications in adults with atherosclerotic occlusive diseases. They will also determine the effectiveness of currently trialed implementation and adherence-supporting strategies, and whether effectiveness varies by patient, prescriber, or clinical practice setting traits.

Trial Registration
PROSPERO CRD42023461317; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=461317; PROSPERO CRD42023461299; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=461299