Non-adherence to heart failure medications predicts clinical outcomes: Assessment in a single spot urine sample by liquid chromatography - tandem mass spectrometry (results of a prospective multicentre study)

TY - JOUR

T1 - Non-adherence to heart failure medications predicts clinical outcomes

T2 - Assessment in a single spot urine sample by liquid chromatography - tandem mass spectrometry (results of a prospective multicentre study)

AU - Gupta, Pankaj

AU - Voors, Adriaan A.

AU - Patel, Prashanth

AU - Lane, Dan

AU - Anker, Stefan D.

AU - Cleland, John G. F.

AU - Dickstein, Kenneth

AU - Filippatos, Gerasimos

AU - Lang, C. C.

AU - van Veldhuisen, Dirk J.

AU - Metra, Marco

AU - Zannad, Faiez

AU - Samani, Nilesh J.

AU - Jones, Don J. L.

AU - Squire, Iain B.

AU - Ng, Leong L.

N1 - Funded by the European Commission [FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29] and the John and Lucille Van Geest Foundation.

PY - 2021/7

Y1 - 2021/7

N2 - 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.

AB - 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.

KW - All-cause mortality

KW - Angiotensin receptor blockers

KW - Angiotensin-converting enzyme inhibitors

KW - BIOSTAT-CHF

KW - Biochemical adherence screening

KW - Heart failure

KW - Non-adherence

KW - β-blockers

UR - https://www.scopus.com/pages/publications/85104256159

U2 - 10.1002/ejhf.2160

DO - 10.1002/ejhf.2160

M3 - Article

C2 - 33759308

SN - 1388-9842

VL - 23

SP - 1182

EP - 1190

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

IS - 7

ER -