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Aims: Liquid chromatography-mass spectrometry (LC-MS/MS) is an objective new technique to assess non-adherence to medications. We used this method to study the prevalence, predictors and outcomes of non-adherence in patients with heart failure with reduced left ventricular ejection fraction (HFrEF).
Methods and results: This study included 1296 patients with HFrEF from BIOSTAT-CHF, a study that aimed to optimise guideline-recommended therapies. Angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists, β-blockers and loop diuretics were measured in a single spot urine sample at 9 months using LC-MS/MS. The relationship between medication non-adherence and the composite endpoint of all-cause death or heart failure hospitalisation, over a median follow-up of 21 months, was evaluated. Non-adherence to at least one prescribed medication was observed in 45.9% of patients. The strongest predictor of non-adherence was non-adherence to any of the other medication classes (P < 0.0005). Regional differences within Europe were observed. On multivariable analyses, non-adherence to ACEi/ARBs and β-blockers was associated with an increased risk of the composite endpoint [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.09–1.95, P = 0.008 and HR 1.48, 95% CI 1.12–1.96, P = 0.006, respectively). Non-adherence to β-blockers was also associated with an increased risk of death (HR 2.48, 95% CI 1.67–3.68, P < 0.0005). Patients who were non-adherent to loop diuretics were healthier and had a decreased risk of the composite endpoint (HR 0.69, 95% CI 0.51–0.93, P = 0.014). Non-adherence to mineralocorticoid receptor antagonists was not related to any clinical outcome.
Conclusion: Non-adherence to medications, assessed by a single urine test, is common and predicts clinical outcomes in patients with HFrEF.
- All-cause mortality
- Angiotensin receptor blockers
- Angiotensin-converting enzyme inhibitors
- Biochemical adherence screening
- Heart failure