Electronic Letters to Improve Patient Activation in IHD: The NUDGE-IHD Trial

This study is a nationwide, pragmatic, registry-based, nested factorial randomized trial conducted in Denmark. The trial evaluates whether simple electronic information letters ("nudges") can increase patient activation and support guideline-directed risk-factor monitoring among persons with ischemic heart disease (IHD) who have LDL cholesterol levels above guideline-recommended treatment targets in routine clinical care.

The primary study population consists of adults with documented ischemic heart disease and LDL cholesterol above the recommended target level. Eligible participants are identified using Danish nationwide health registries and randomized 1:1 to receive either an electronic information letter addressing elevated LDL cholesterol (the "LDL letter") or no letter. The LDL letter provides general, non-technical information about LDL cholesterol as a cardiovascular risk factor in ischemic heart disease and encourages recipients to consult their physician if relevant.

A secondary study population is defined as a subset of the primary population with elevated lipoprotein(a) [Lp(a)] levels identified from laboratory registry data. Participants in this subgroup are independently randomized 1:1 to receive or not receive an additional electronic information letter addressing elevated Lp(a) (the "Lp(a) letter"). The Lp(a) letter provides information on Lp(a) as a genetically determined and independent cardiovascular risk factor and emphasizes the importance of optimizing other modifiable risk factors. The two randomizations are conducted independently, with the LDL letter randomization stratified by elevated Lp(a) status, resulting in a nested factorial design in which participants with elevated Lp(a) may receive no letter, the LDL letter only, the Lp(a) letter only, or both letters.

All intervention letters are delivered through Denmark's mandatory national digital mailbox system (Digital Post). The interventions are informational and non-invasive. The study does not involve any in-person visits, clinical procedures, or changes to usual medical care.

The trial has dual primary endpoints, evaluated within each of the two independently randomized comparisons: (1) disease-related patient activation, defined as the proportion of participants with at least one LDL cholesterol measurement recorded within 6 months after randomization; and (2) major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, myocardial infarction, or stroke, within 5 years after randomization. The trial meets its objective if either primary endpoint reaches statistical significance at its prespecified alpha level; each addresses a distinct question and is interpreted on its own merits.

Secondary outcomes are general patient activation, assessed by the number of healthcare contacts in general practice or outpatient hospital settings, and cardiometabolic risk-factor monitoring, defined as the proportion of participants with at least one cardiometabolic blood test (lipid profile, hemoglobin A1c, or creatinine) within 6 months after randomization. Additional exploratory outcomes related to laboratory testing, healthcare utilization, medication use, and clinical events are assessed during longer-term follow-up.

All baseline characteristics, outcomes, and follow-up data are obtained from Danish nationwide health and administrative registries. Due to the registry-based and informational nature of the interventions, informed consent is not required. Data for the first primary endpoint and for the secondary endpoints are retrieved 6 months after randomization; data for the second primary endpoint are retrieved 5 years after randomization.