Implementation and Adherence-Supporting Strategies to Improve Healthcare 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 Trials (Preprint)

BACKGROUND In patients with atherosclerotic occlusive diseases, systematic reviews and meta-analyses of randomized controlled trials (RCTs) report that antiplatelets, statins, and antihypertensives reduce risk of major adverse cardiac events, need for revascularization procedures, cardiovascular and all-cause mortality, and healthcare resource use. However, evidence suggests that patients with these diseases are not prescribed these medications adequately or do not adhere to them when prescribed. OBJECTIVE To systematically review and meta-analyze RCTs examining the effectiveness of implementation or adherence-supporting strategies for improving healthcare 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 Preferred Reporting Items for Systematic review and Meta-Analysis-Protocols statement. We will use a peer-reviewed search strategy created with the assistance of an information-specialist to search MEDLINE, EMBASE, CENTRAL, 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 (CVD), coronary artery disease (CAD), peripheral artery disease (PAD), 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 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 healthcare 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 DerSimonian and Laird random-effects models. Subgroup analyses and meta-regressions will assess if strategy effectiveness varies by recruited patient populations, prescriber types, clinical practice settings, and study design characteristics. GRADE will be used to communicate evidence certainty. RESULTS Protocols for both systematic reviews were registered separately on PROSPERO. The search was completed on June 6th, 2023. We are currently screening titles/abstracts. We hope to complete data analyses by December 2024. CONCLUSIONS These studies will identify which implementation and adherence-supporting strategies are being used (and in which combinations) across published RCTs for improving 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 according to patient, prescriber, and/or clinical practice setting traits. CLINICALTRIAL PROSPERO Protocol Registration Numbers: Underprescription: CRD42023461317 Nonadherence: CRD42023461299