#4951 NON-ADHERENCE TO CARDIOMETABOLIC DRUGS AS ASSESSED BY LS-MS/MS IN URINE AND ITS ASSOCIATION WITH RENAL AND CARDIOVASCULAR OUTCOMES IN T2DM
Authors: Denicolo Sara , Reinstadler Vera , Keller Felix , Thöni Stefanie , Eder Susanne , Heerspink Hiddo Lambers , Rosivall Laszlo , Wiecek Andrzej Jan , Mark Patrick , Perco Paul , Leierer Johannes , Kronbichler Andreas , Oberacher Herbert , Mayer Gert 
Published: June 2023

Abstract

Background and Aims
Cardiovascular and renal complications have a detrimental impact on the prognosis and quality of life of patients with type 2 diabetes mellitus (T2DM). Guidelines recommend combination drug therapy to prevent or delay these complications[1]. However, non-adherence to medication is common and a barrier to successful disease management[2]. Most previous studies on adherence and outcome used indirect methods to assess adherence[3]. In this study we used liquid chromatography-tandem mass spectrometry (LC-MS/MS), a direct and objective adherence measure, to asses adherence to cardiometabolic drugs in a large real-world cohort of individuals with T2DM and analyzed non-adherence in the context of cardiovascular and renal outcomes.

Method
1125 eligible PROVALID participants were included. PROVALID is a prospective observational cohort study of patients with T2DM followed annually at the primary health care level. Urine samples from the PROVALID biobank were screened for 79 cardiometabolic drugs and metabolites thereof by LC-MS/MS. An individual was classified as fully adherent when markers for all prescribed drugs were detected, partially non-adherent when at least a marker for one drug was detected and totally non-adherent when no marker for any prescribed drug was detectable. In order to assess outcome by adherence we defined a cardiovascular (myocardial infarction, stroke, and cardiovascular death) and a renal (ESKD, renal death, sustained 40% reduction in eGFR to &lt; 60 ml/min per 1.73 m², sustained progression of albuminuria) composite endpoint.

Results
The mean age was 64.2 (±8.9) years and 46.1% were female. The mean duration of T2DM was 11.4 (±7.9) years. The mean HbA1c was 7.1 (±1.1)%, the mean eGFR was 77.6 (±23.6) ml/min/1.73 m2 and mean albuminuria 67.3 (±287.9) mg/g creatinine. Participants were prescribed 5.4 (±2.0) cardiometabolic drugs on average. Based on the results of LC-MS/MS measurements, 56.3% were totally adherent, 42.0% were partially adherent, and 1.7% were totally non-adherent to screened cardiometabolic drugs. Adherence was highest to antiplatelet and glucose lowering drugs and lowest to lipid lowering drugs (totally adherent individuals 90.1%, 89.2% and 70.7%, respectively). Non-adherent patients had a longer history of T2DM (12.3 ± 8.5 vs. 10.7 ± 7.5, p = 0.003) and a higher number of prescribed drugs (5.8 ± 2.1 vs. 5.1 ± 1.9, p &lt; 0.001). Age per se had no influence on adherence, however the number of prescribed medications had more impact on adherence in younger patients (Fig. 1). Ex-smokers were more likely to be adherent than current or never-smokers (odds ratio 1.4, p-value = 0.014). Patients who were adherent to lipid lowering drugs had significantly lower LDL (82.4 ± 29.8 vs. 111.4 ± 39.7 mg/dl, p &lt; 0.001). A trend for lower HbA1c with adherence to glucose-lowering drugs and lower systolic blood pressure with adherence to antihypertensive drugs could be observed, however these differences were not statistically significant. In the longitudinal analysis, worse cardiovascular prognosis was especially seen with non-adherence to antiplatelet drugs and worse renal outcome especially with non-adherence to antihypertensive drugs (Fig. 2).

Conclusion
Our analysis confirms that non-adherence, especially partial non-adherence, to cardiometabolic drugs is common in T2DM. A higher incidence of cardiovascular events was observed with non-adherence to antiplatelet drugs, whereas non-adherence to antihypertensive drugs was associated with a higher renal event rate.