Comparison of different strategies to measure medication adherence via claims data in patients with chronic heart failure

Medication adherence correlates with morbidity and mortality in patients with chronic heart failure (CHF), but is difficult to assess. We conducted a retrospective methodological cohort study in 3,808 CHF patients, calculating adherence as proportion of days covered (PDC) utilizing claims data from 2010 to 2015. We aimed to compare different parameters’ influence on the PDC of elderly CHF patients exemplifying a complex chronic disease. Investigated parameters were the assumed prescribed daily dose (PDD), stockpiling, and periods of hospital stay. Thereby, we investigated a new approach using the PDD assigned to different percentiles. The different dose assumptions had the biggest influence on the PDC, with variations from 41.9% to 83.7%. Stockpiling and hospital stays increased the values slightly. These results queries that a reliable PDC can be calculated with an assumed PDD. Hence, results based on an assumed PDD have to be interpreted carefully and should be presented with sensitivity analyses to show the PDC's possible range

PCSK9 Inhibition: Insights From Clinical Trials and Future Prospects

In 2003, clinical observations led to the discovery of the involvement of proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipid metabolism. Functional studies demonstrated that PCSK9 binds to the low-density lipoprotein (LDL) receptor directing it to its lysosomal degradation. Therefore, carriers of gain-of-function mutations in PCSK9 exhibit decreased expression of LDL receptors on the hepatocyte surface and have higher LDL cholesterol (LDL-C) levels. On the contrary, loss-of-function mutations in PCSK9 are associated with low LDL-C concentrations and significantly reduced lifetime risk of cardiovascular disease. These insights motivated the search for strategies to pharmacologically inhibit PCSK9. In an exemplary rapid development, fully human monoclonal antibodies against PCSK9 were developed and found to effectively reduce LDL-C. Administered subcutaneously every 2–4 weeks, the PCSK9 antibodies evolocumab and alirocumab reduce LDL-C by up to 60% in a broad range of populations either as monotherapy or in addition to statins. Two large cardiovascular outcome trials involving a total of 46,000 cardiovascular high-risk patients on guideline-recommended lipid-lowering therapy showed that treatment with evolocumab and alirocumab led to a relative reduction of cardiovascular risk by 15% after 2.2 and 2.8 years of treatment, respectively. These findings expanded the armamentarium of pharmacological approaches to address residual cardiovascular risk associated with LDL-C. Furthermore, the unprecedented low LDL-C concentrations achieved (e.g., 30 mg/dL in the FOURIER study) suggest that the relationship between LDL-C and cardiovascular risk is without a lower threshold, and without associated adverse events during the timeframe of the studies. The side effect profile of PCSK9 antibodies is favorable with few patients exhibiting injection-site reactions. Currently, the access to PCSK9 antibodies is limited by high treatment costs. The development of novel approaches to inhibit PCSK9 such as the use of small interfering RNA to inhibit PCSK9 synthesis seems promising and may soon become available

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We thank Dr. Kalmanovich and colleagues for their comments on our randomized controlled trial on improving medication adherence and quality of life of heart failure (HF) patients by a pharmacist‐led interdisciplinary approach.1 This study showed that pharmacy care safely improved adherence to HF medications and quality of life. These data extend recent consensus statements of both the Canadian Cardiovascular Society guidelines for the management of HF2 and the German clinical practice guideline on chronic HF3 that acknowledge the available evidence of pharmacist care and interdisciplinary care.4, 5 Topics and tasks include prevention of HF, particularly by improving adherence to antihypertensives, providing medication reviews, assuring appropriate self‐medication, and improving both medication safety and adherence.4 We congratulate Kalmanovich et al. to their research plan. Their study will hopefully provide additional randomized evidence for the effects of interdisciplinary care in patients with HF

Use of fixed-dose combination antihypertensives in Germany between 2016 and 2020: an example of guideline inertia

Background The 2018 European Society of Cardiology (ESC)/European Society of Hypertension (ESH) guidelines for the management of hypertension highlight the importance of fxed-dose combinations (FDC) for the treatment of hypertension and recommend initial single-pill combination therapy in almost all patients. However, data on the implementation of these recommendations in clinical practice are scarce. Methods Data from the German Institute for Drug Use Evaluation (DAPI) were analyzed and extrapolated accounting for approximately 88% of Germany’s population (approximately 73.3 million subjects). All antihypertensive (AHT) FDC products available on the German market were included in the analyses. We examined the time course of dispensed packages between January 2016 and December 2020. Results FDCs accounted for 15.4% of all AHT in 2016 and for 10.9% in 2020. While dispensing of all AHT increased slightly from year to year (2016: 143.8 million, 2020: 153.2 million packs), dispensing of FDCs decreased from 22.2 million (2016) to 16.6 million (2020) packs. Dispensing of FDCs containing hydrochlorothiazide (HCT) declined considerably from 2016 to 2020 (Q1 2016: 4.65 million, Q4 2020: 3.13 million packs). Accordingly, the proportion of HCT-containing combinations in all FDCs decreased from 85.3 to 74.2% from Q1 2016 to Q4 2020. Patients younger than 80 years were prescribed FDCs more frequently (14.6% of all AHT, based on the entire evaluation period) than patients 80 years and older (10.0%). In both age groups, this proportion decreased continuously over time. Conclusions Almost 2 years following the release of the 2018 ESC/ESH guidelines, only 10.9% of the prescribed packs of antihypertensive drugs in 2020 were FDC products, documenting underutilization of current guideline recommendations on pharmacotherapy in hypertension. Structured programs to evidence-based decision support are required to improve guideline inertia and patient outcomes, eventually

Association of medication adherence and depression with the control of low-density lipoprotein cholesterol and blood pressure in patients at high cardiovascular risk

Background: Many patients at high cardiovascular risk do not reach targets for low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP). Depression is a frequent comorbidity in these patients and contributes to poor medication adherence. Objective: The aim of this study was to elucidate the associations between adherence to lipid- and BP-lowering drugs, the diagnosis of depression, and the control of LDL-C and BP. Patients and methods: This study was conducted as multicenter, single-visit cross-sectional study in Germany. Adherence was assessed by the Morisky Medication Adherence Scale-8 (MMAS-8), and depression was assessed as documented in the patient chart. Results: A total of 3,188 ambulatory patients with hypercholesterolemia (39.8%), stable coronary artery disease (CAD; 7.4%), or both (52.9%) were included. Patients had a history of myocardial infarction (30.8%), diabetes (42.0%), were smokers (19.7%), and 16.1% had the investigator-reported diagnosis of depression. High or moderate adherence to lipid-lowering medication compared to low adherence was associated with lower LDL-C levels (105.5±38.3 vs 120.8±42.4 mg/dL) and lower BP (systolic BP 133.4±14.5 vs 137.9±13.9 mmHg, diastolic BP 78.3±9.6 vs 81.8±9.6 mmHg) and with a higher proportion of patients achieving the guideline-recommended LDL-C (16.9% vs 10.1%) and BP target (52.2% vs 40.8%, all comparisons P<0.0001). Adherence was worse in patients with depression. Correspondingly, patients with depression showed higher LDL-C levels, higher BP, and a lower probability of achieving the LDL-C and BP goal. Medication adherence correlated between BP- and lipid-lowering medications. Conclusion: Self-reported medication adherence can be easily obtained in daily practice. A low adherence and the diagnosis of depression identify patients at risk for uncontrolled LDL-C and BP who likely benefit from intensified care

Medication knowledge of patients hospitalized for heart failure at admission and after discharge

Background: A substantial aspect of health literacy is the knowledge of prescribed medication. In chronic heart failure, incomplete intake of prescribed drugs (medication non-adherence) is inversely associated with clinical prognosis. Therefore, we assessed medication knowledge in a cohort of patients with decompensated heart failure at hospital admission and after discharge in a prospective, cross-sectional study. Methods: One hundred and eleven patients presenting at the emergency department with acute decompensated heart failure were included (mean age 78.4±9.2, 59% men) in the study. Patients’ medication knowledge was assessed during individual interviews at baseline, course of hospitalization, and 3 months after discharge. Individual responses were compared with the medical records of the referring general practitioner. Results: Median N-terminal prohormone of brain natriuretic peptide plasma concentration in the overall population at baseline was 4,208 pg/mL (2,023–7,101 pg/mL [interquartile range]), 20 patients died between the second and third interview. The number of prescribed drugs increased from 8±3 at baseline to 9±3 after 3 months. The majority of patients did not know the correct number of their drugs. Medication knowledge decreased continuously from baseline to the third interview. At baseline, 37% (n=41) of patients stated the correct number of drugs to be taken, whereas only 18% (n=16) knew the correct number 3 months after discharge (P=0.008). Knowledge was inversely related to N-terminal prohormone of brain natriuretic peptide levels. Conclusion: Medication knowledge of patients with acute decompensated heart failure is poor. Despite care in a university hospital, patients’ individual medication knowledge decreased after discharge. The study reveals an urgent need for better strategies to improve and promote the knowledge of prescribed medication in these very high-risk patients

Vascular Pathophysiology in Response to Increased Heart Rate

This review summarizes the current literature and the open questions regarding the physiology and pathophysiology of the mechanical effects of heart rate on the vessel wall and the associated molecular signaling that may have implications for patient care. Epidemiological evidence shows that resting heart rate is associated with cardiovascular morbidity and mortality in the general population and in patients with cardiovascular disease. As a consequence, increased resting heart rate has emerged as an independent risk factor both in primary prevention and in patients with hypertension, coronary artery disease, and myocardial infarction. Experimental and clinical data suggest that sustained elevation of heart rate—independent of the underlying trigger—contributes to the pathogenesis of vascular disease. In animal studies, accelerated heart rate is associated with cellular signaling events leading to vascular oxidative stress, endothelial dysfunction, and acceleration of atherogenesis. The underlying mechanisms are only partially understood and appear to involve alterations of mechanic properties such as reduction of vascular compliance. Clinical studies reported a positive correlation between increased resting heart rate and circulating markers of inflammation. In patients with coronary heart disease, increased resting heart rate may influence the clinical course of atherosclerotic disease by facilitation of plaque disruption and progression of coronary atherosclerosis. While a benefit of pharmacological or interventional heart rate reduction on different vascular outcomes was observed in experimental studies, prospective clinical data are limited, and prospective evidence determining whether modulation of heart rate can reduce cardiovascular events in different patient populations is needed

HDL - Quo vadis

Many epidemiological studies found low plasma levels of high-density lipoprotein (HDL) cholesterol (HDL-C) associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). In cell culture and animal models, HDL particles show many anti-atherogenic actions. However, until now, clinical trials did not find any prevention of ASCVD events by drugs elevating HDL-C levels, at least not beyond statins. Also, genetic studies show no associations of HDL-C levels altering variants with cardiovascular risk. Therefore, the causal role and clinical benefit of HDL-C elevation in ASCVD are questioned. However, the interpretation of previous data has important limitations: First, the inverse relationship of HDL-C with the risk of ASCVD is limited to concentrations < 60 mg/dl (< 1.5 mmol/l). Higher concentrations do not reduce the risk of ASCVD events and are even associated with increased mortality. Therefore, neither the higher-the-better strategies of earlier drug developments nor the assumption of linear cause-and-effect relationships in Mendelian randomization trials are justified. Second, most of the drugs tested so far do not act specifically on HDL metabolism. Therefore, the futile endpoint studies question the clinical benefit of the investigated drugs, but not the importance of HDL in ASCVD. Third, the vascular functions of HDL are not exerted by its cholesterol content (i.e. HDL-C), but by a variety of other molecules. Comprehensive knowledge of the structure-function-disease relationships of HDL particles and their molecules is a prerequisite for testing their physiological and pathogenic relevance and possibly for optimizing the diagnosis and treatment of persons with HDL-associated risk of ASCVD, but also for other diseases, such as diabetes, chronic kidney disease, infections, autoimmune and neurodegenerative diseases

An Agent based approach for Task Management System

In the current era, the hardware resources are getting improved each day. It can take more processing power, thus quick results from the given input. But most of the existing applications still rely on the analytical skills of human when that can be delegated to a computer system easily. The application ClickOnce Task is developed as a solution to manage the corporate tasks where the system takes the responsibility of making the trivial decision hence making the work of people much less and straight forward. This solution provides a comprehensive system for handling the dynamic nature of creating and assigning tasks and meeting. First the user can add new task and meetings using the system where there can be lots of conflict resolution needed. If the person does not know who can complete this task successfully, the system will search for a person with the best capabilities to do the task. According to the results system will suggest people who are capable of doing the same work. These procedures reduce the burden of the task assigner by delegating the responsibility of the task assigning to the system. Managing our resources such as time and money is important today. ClickOnce Task will take most of the decisions on behalf of the user and save the valuable time

Analysis of chronic aortic regurgitation by 2D and 3D echocardiography and cardiac MRI

Purpose: The study compares the feasibility of the quantitative volumetric and semi-quantitative approach for quantification of chronic aortic regurgitation (AR) using different imaging modalities. Methods: Left ventricular (LV) volumes, regurgitant volumes (RVol) and regurgitant fractions (RF) were assessed retrospectively by 2D, 3D echocardiography and cMRI in 55 chronic AR patients. Semi-quantitative parameters were assessed by 2D echocardiography. Results: 22 (40%) patients had mild, 25 (46%) moderate and 8 (14%) severe AR. The quantitative volumetric approach was feasible using 2D, 3D echocardiography and cMRI, whereas the feasibility of semi-quantitative parameters varied considerably. LV volume (LVEDV, LVESV, SVtot) analyses showed good correlations between the different imaging modalities, although significantly increased LV volumes were assessed by cMRI. RVol was significantly different between 2D/3D echocardiography and 2D echocardiography/cMRI but was not significantly different between 3D echocardiography/cMRI. RF was not statistically different between 2D echocardiography/cMRI and 3D echocardiography/cMRI showing poor correlations (r < 0.5) between the different imaging modalities. For AR grading by RF, moderate agreement was observed between 2D/3D echocardiography and 2D echocardiography/cMRI and good agreement was observed between 3D echocardiography/cMRI. Conclusion: Semi-quantitative parameters are difficult to determine by 2D echocardiography in clinical routine. The quantitative volumetric RF assessment seems to be feasible and can be discussed as an alternative approach in chronic AR. However, RVol and RF did not correlate well between the different imaging modalities. The best agreement for grading of AR severity by RF was observed between 3D echocardiography and cMRI. LV volumes can be verified by different approaches and different imaging modalities