Urinary drug metabolite testing in chronic heart failure patients indicates high levels of adherence with life-prolonging therapies

Aims Despite medical therapy for heart failure (HF) having proven benefits of improving quality of life and survival, many patients remain under-treated. This may be due to a combination of under-prescription by medical professionals and poor adherence from patients. In HF, as with many other chronic diseases, adherence to medication can deteriorate over time particularly when symptoms are well controlled. Therefore, detecting and addressing non-adherence has a crucial role in the management of HF. Significant flaws and inaccuracies exist in the methods currently used to assess adherence such as patient reporting, pill counts, and pharmacy fill records. We aim to use high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS) to detect metabolites of HF medications in the urine samples of chronic HF patients. Methods and results Urine samples were collected from 35 patients in a specialist HF clinic. Patients were included if they had an ejection fraction <45% and were taking at least two disease-modifying HF medications. They were excluded if they had been admitted to hospital for HF in the 3 months preceding clinic attendance. These samples were sent for HPLC-MS and tested for all HF medications prescribed for that patient. A high rate of complete adherence of 89% was detected in these patients, with 94% being partially adherent (at least one HF medication detected) to therapy (at least one HF medication detected). This analysis also highlighted that mineralocorticoid antagonists represent both the most under-prescribed (67%) and poorly adhered (75%) medication class. Conclusions This analysis revealed a surprisingly high level of adherence to disease-modifying therapy in chronic HF patients and highlights that most of our ‘total’ under-treatment is likely to be from a failure to prescribe rather than a failure to adhere. Testing for metabolites of disease-modifying HF drugs in urine using HPLC-MS is feasible and is a useful adjunct to a specialist HF service. At present, the distinction between treatment failure and failure to take treatment is not always clear, which is important because the investigation and potential solutions are different. The former needs initiation of additional therapies and consideration of additional diagnoses, whereas the latter requires strategies to understand reasons underlying poor adherence and collaborative working to improve this: the wrong strategy will be ineffective

Cholesterol-lowering agents. Statins - for everyone?

Cardiovascular disease (CVD) remains the leading cause of death worldwide. To date, decades of research has established LDL-C (low-density lipoprotein cholesterol) as a causal factor in the development of atherosclerotic CVD. Statin therapy, supported by a broad evidence base, has demonstrated its superior efficacy in reducing LDL-C and subsequent cardiovascular risk. It therefore currently forms the mainstay of lipid-lowering therapy as recommended by international guidelines. Statin therapy is indicated in the secondary prevention of atherosclerotic CVD, as well as genetic causes of dyslipidemia (such as familial hypercholesterolemia). Although this strategy targets those most at risk, it merely addresses those most susceptible and does not account for the fact that most cardiovascular events occur in those at moderate to low risk. In addition, there is evidence for use in primary prevention such as in those with diabetes mellitus, chronic kidney disease, and high risk of future atherosclerotic CVD as determined by risk prediction calculators. Risk prediction tools, however, are far from perfect and do not accurately account for those at low short-term but high lifelong risk. Considering the log-linear relationship between LDL-C reductions and reductions in risk of atherosclerotic CVD, even in those at very low risk of future events, a clinical question posed is can we and should we shift the entire risk distribution by treating everyone? The present review discusses these issues in more detail outlining arguments for and against each approach

Urinary drug metabolite testing in chronic heart failure patients indicates high levels of adherence with life‐prolonging therapies

Aims Despite medical therapy for heart failure (HF) having proven benefits of improving quality of life and survival, many patients remain under-treated. This may be due to a combination of under-prescription by medical professionals and poor adherence from patients. In HF, as with many other chronic diseases, adherence to medication can deteriorate over time particularly when symptoms are well controlled. Therefore, detecting and addressing non-adherence has a crucial role in the management of HF. Significant flaws and inaccuracies exist in the methods currently used to assess adherence such as patient reporting, pill counts, and pharmacy fill records. We aim to use high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS) to detect metabolites of HF medications in the urine samples of chronic HF patients. Methods and results Urine samples were collected from 35 patients in a specialist HF clinic. Patients were included if they had an ejection fraction <45% and were taking at least two disease-modifying HF medications. They were excluded if they had been admitted to hospital for HF in the 3 months preceding clinic attendance. These samples were sent for HPLC-MS and tested for all HF medications prescribed for that patient. A high rate of complete adherence of 89% was detected in these patients, with 94% being partially adherent (at least one HF medication detected) to therapy (at least one HF medication detected). This analysis also highlighted that mineralocorticoid antagonists represent both the most under-prescribed (67%) and poorly adhered (75%) medication class. Conclusions This analysis revealed a surprisingly high level of adherence to disease-modifying therapy in chronic HF patients and highlights that most of our ‘total’ under-treatment is likely to be from a failure to prescribe rather than a failure to adhere. Testing for metabolites of disease-modifying HF drugs in urine using HPLC-MS is feasible and is a useful adjunct to a specialist HF service. At present, the distinction between treatment failure and failure to take treatment is not always clear, which is important because the investigation and potential solutions are different. The former needs initiation of additional therapies and consideration of additional diagnoses, whereas the latter requires strategies to understand reasons underlying poor adherence and collaborative working to improve this: the wrong strategy will be ineffective