Impact of medication nonadherence and drug-drug interaction testing on the management of primary care patients with polypharmacy: a randomized controlled trial.

Background: Clinical management of patients with chronic cardiometabolic disease is complicated by polypharmacy. Consequently, when patients clinically deteriorate, physicians are challenged to distinguish both medication nonadherence and drug-drug interactions (DDI) from chronic disease progression.

Methods: In this randomized controlled trial, we enrolled U.S. board-certified Primary Care Physicians (PCPs) serving patients with cardiometabolic disease. PCPs were randomized and managed their patients with (intervention), or without (control), a novel chronic disease management test (CDMT) that can detect medication nonadherence and DDIs. Patients' medical records were abstracted at baseline and 3-month follow-up. Primary outcomes were the CDMT's impact on both the PCPs' detection of medication nonadherence and DDI, and the frequency of performing medication nonadherence- and DDI-related clinical actions. Secondary outcomes examined the types of clinical actions performed. Primary and secondary outcomes were analyzed by logistic regression using single variable and clustered multivariable modeling to adjust for similarities in patient characteristics, by PCP practice.

Results: Sixteen intervention and 20 control PCPs shared de-identified records for 126 and 207 patients, respectively. There were no significant demographic differences between the two study arms, among PCPs or patients. At baseline, there was no significant difference between the intervention and control PCPs in the percentage of clinical actions performed for medication nonadherence (P = 0.98) and DDI (P = 0.41). At 3-month follow-up (after CDMT), 69.1% of intervention compared to 20.3% of control patients with medication nonadherence had a related clinical action performed (P < 0.001). Regarding DDI, 37.3% of intervention compared to 0.5% of control patients had a relevant clinical action performed in follow-up (P < 0.001). Across the range of medication nonadherence- and DDI-related actions, the intervention compared to the control PCPs were more likely to adjust the medication regimen (24.1% vs. 9.5%) and document medication nonadherence in the patient chart (31.0% vs. 14.3%) at follow-up (P = 0.04).

Conclusions: Although intervention and control PCPs similarly detected and acted upon medication nonadherence and DDI at baseline, intervention PCPs' detection increased significantly after using the CDMT. Also, the clinical actions performed with CDMT support were more clinically rigorous. These outcomes support the clinical utility of CDMT in the management of symptomatic patients with cardiometabolic disease and polypharmacy.

Trial registration: https://clinicaltrials.gov/study/NCT05910684 .