Expert Comment: Is Medication Titration in Heart Failure too Complex?
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ABSTRACT:
SUBMITTER: Atherton JJ
PROVIDER: S-EPMC5494159 | biostudies-other | 2017 Apr
REPOSITORIES: biostudies-other
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Project description:BackgroundGuideline-directed medical therapy (GDMT), optimized to target doses, improves health outcomes in patients with heart failure. However, GDMT remains underused, with <25% of patients receiving target doses in clinical practice. A randomized controlled trial was conducted at the Peter Munk Cardiac Centre in Toronto to compare a remote GDMT titration intervention with standard in-office titration. This randomized controlled trial found that remote titration increased the proportion of patients who achieved optimal GDMT doses, decreased the time to dose optimization, and reduced the number of essential clinic visits. This paper presents findings from the qualitative component of the mixed methods study, which evaluated the implementation of the remote titration intervention.ObjectiveThe objective of the qualitative component is to assess the perceptions and experiences of clinicians and patients with heart failure who participated in the remote titration intervention to identify factors that affected the implementation of the intervention.MethodsWe conducted semistructured interviews with clinicians (n=5) and patients (n=11) who participated in the remote titration intervention. Questions probed the experiences of the participants to identify factors that can serve as barriers and facilitators to its implementation. Conventional content analysis was first used to analyze the interviews and gain direct information based on the participants' unique perspectives. Subsequently, the generated themes were delineated and mapped following a multilevel framework.ResultsPatients and clinicians indicated that the intervention was easy to use, integrated well into their routines, and removed practical barriers to titration. Key implementation facilitators from the patients' perspective included the reduction in clinic visits and daily monitoring of their condition, whereas clinicians emphasized the benefits of rapid drug titration and efficient patient management. Key implementation barriers included the resources necessary to support the intervention and lack of physician remuneration.ConclusionsThis study presents results from a real-world implementation assessment of remote titration facilitated by telemonitoring. It is among the first to provide insight into the perception of the remote titration process by clinicians and patients. Our findings indicate that the relative advantages that remote titration presents over standard care strongly appeal to both clinicians and patients. However, to ensure uptake and adherence, it is important to ensure that suitable patients are enrolled and the impact on the physicians' workload is minimized. The implementation of remote titration is now more critical than ever, as it can help provide access to care for patients during times when physical distancing is required.Trial registrationClinicalTrials.gov NCT04205513; https://clinicaltrials.gov/ct2/show/NCT04205513.International registered report identifier (irrid)RR2-10.2196/19705.
| S-EPMC8663515 | biostudies-literature
Project description:BACKGROUND:Guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) have medical therapy titrated to target doses derived from clinical trials, as tolerated. The degree to which titration occurs in contemporary U.S. practice is unknown. OBJECTIVES:This study sought to characterize longitudinal titration of HFrEF medical therapy in clinical practice and to identify associated factors and reasons for medication changes. METHODS:Among 2,588 U.S. outpatients with chronic HFrEF in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry with complete medication data and no contraindications to medical therapy, use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and mineralocorticoid receptor antagonist (MRA) were examined at baseline and at 12-month follow-up. RESULTS:At baseline, 658 (25%), 525 (20%), 287 (11%), and 45 (2%) patients were receiving target doses of MRA, beta-blocker, ACEI/ARB, and ARNI therapy, respectively. At 12 months, proportions of patients with medication initiation or dose increase were 6% for MRA, 10% for beta-blocker, 7% for ACEI/ARB, and 10% for ARNI; corresponding proportions with discontinuation or dose decrease were 4%, 7%, 11%, and 3%, respectively. Over 12 months, <1% of patients were simultaneously treated with target doses of ACEI/ARB/ARNI, beta-blocker, and MRA. In multivariate analysis, across the classes of medications, multiple patient characteristics were associated with a higher likelihood of initiation or dose increase (e.g., previous HF hospitalization, higher blood pressure, lower ejection fraction) and discontinuation or dose decrease (e.g., previous HF hospitalization, impaired quality of life, more severe functional class). Medical reasons were the most common reasons for discontinuations and dose decreases of each therapy, but the relative contributions from patient preference, health team, and systems-based reasons varied by medication. CONCLUSIONS:In this contemporary U.S. registry, most eligible HFrEF patients did not receive target doses of medical therapy at any point during follow-up, and few patients had doses increased over time. Although most patients had no alterations in medical therapy, multiple clinical factors were independently associated with medication changes. Further quality improvement efforts are urgently needed to improve guideline-directed medication titration for HFrEF.
| S-EPMC7197490 | biostudies-literature
Project description:BackgroundInitiation and up-titration of guideline-directed medical therapies (GDMTs) for heart failure with reduced ejection fraction (HFrEF) remains suboptimal, in part because of concerns regarding tolerability and adverse events (AEs).ObjectivesThe authors sought to compare rates of AE in patients randomized to GDMT medication vs placebo in a meta-analysis of landmark cardiovascular outcomes trials.MethodsThe authors assessed rates of reported AE in 17 landmark HFrEF clinical trials across each class of GDMT in the placebo and intervention arms. The overall rates of AE for each drug class, the absolute difference in frequency in AEs between the placebo and intervention arms, and the odds of each AE according based on randomization strata were calculated.ResultsAE were reported commonly in trials across each class of GDMT, with 75% to 85% of participants reporting at least 1 AE. There was no significant difference in the frequency of AE between the intervention and placebo arms, except for angiotensin-converting enzyme inhibitors (87.0% [95% CI: 85.0%-88.8%] vs 82.0% [95% CI: 79.8%-84.0%], absolute difference: +5% with intervention; P < 0.001). There was no significant difference in drug discontinuation because of AE between placebo and intervention arms in angiotensin-converting enzyme inhibitors, mineralocorticoid receptor antagonists, sodium glucose cotransporter 2 inhibitors, or angiotensin receptor neprilysin inhibitor/angiotensin II receptor blocker trials. Patients randomized to beta-blocker were significantly less likely to stop study drug because of AE than placebo (11.3% [95% CI: 10.3%-12.3%] vs 13.7% [95% CI: 12.5%-14.9%], absolute difference: -1.1%; P = 0.015). When individual types of AE were assessed, the initiation of an intervention vs placebo resulted in small differences in absolute frequency of AE that were largely not statistically significant.ConclusionsIn clinical trials of GDMT for HFrEF, AEs are observed frequently. However, rates of AE are similar between active medication and control, suggesting these may reflect the high risk nature of the heart failure disease state rather than be attributive to a specific therapy.
| S-EPMC10084875 | biostudies-literature
Project description:To determine medication use and adherence among community-dwelling patients with heart failure (HF).Residents of Olmsted County, Minnesota, with HF were recruited from October 10, 2007, through February 25, 2009. Pharmacy records were obtained for the 6 months after enrollment. Medication adherence was measured by the proportion of days covered (PDC). A PDC of less than 80% was classified as poor adherence. Factors associated with medication adherence were investigated.Among the 209 study patients with HF, 123 (59%) were male, and the mean ± SD age was 73.7 ± 13.5 years. The median (interquartile range) number of unique medications filled during the 6-month study period was 11 (8-17). Patients with a documented medication allergy were excluded from eligibility for medication use within that medication class. Most patients received conventional HF therapy: 70% (147/209) were treated with ?-blockers and 75% (149/200) with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Most patients (62%; 127/205) also took statins. After exclusion of patients with missing dosage information, the proportion of those with poor adherence was 19% (27/140), 19% (28/144), and 13% (16/121) for ?-blockers, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and statins, respectively. Self-reported data indicated that those with poor adherence experienced more cost-related medication issues. For example, those who adhered poorly to statin therapy more frequently reported stopping a prescription because of cost than those with good adherence (46% vs 6%; P < .001), skipping doses to save money (23% vs 3%; P = .03), and not filling a new prescription because of cost (46% vs 6%; P < .001).Community-dwelling patients with HF take a large number of medications. Medication adherence was suboptimal in many patients, often because of cost.
| S-EPMC3068886 | biostudies-other
Project description:Cognitive decline is a prevalent condition and independent prognostic marker of unfavourable outcomes in patients with heart failure. The highest prevalence, up to 80 %, is reported in patients hospitalised due to acute decompensation. Numerous factors contribute to cognitive dysfunction in heart failure patients, with hypertension, atrial fibrillation, stroke and impaired haemodynamics being the most relevant. Cerebral hypoperfusion, disruption of blood-brain barrier, oxidative damage and brain-derived cytokines are pathogenic links between heart failure and alteration of cognitive functioning. White matter hyperintensities, lacunar infarcts and generalised volume loss are common features revealed by neuroimaging. Typically affected cognitive domains are presented. Assessment of cognitive functioning, even by simple screening tests, should be part of routine clinical examination of heart failure patients.
| S-EPMC5490972 | biostudies-literature
Project description:Depression is a major issue in heart failure (HF). Depression is present in about one in five HF patients, with about 48 % of these individuals having significant depression. There is a wide variation in reported prevalences because of differences in the cohorts studied and methodologies. There are shared pathophysiological mechanisms between HF and depression. The adverse effects of depression on the outcomes in HF include reduced quality of life, reduced healthcare use, rehospitalisation and increased mortality. Results from metaanalysis suggest a twofold increase in mortality in HF patients with compared to those without depression. Pharmacological management of depression in HF has not been shown to improve major outcomes. No demonstrable benefits over cognitive behavioural therapy and psychotherapy have been demonstrated.
| S-EPMC5490872 | biostudies-other
Project description:BACKGROUND:Heart failure (HF) is associated with poor prognosis, high morbidity and mortality. The prognosis can be optimised by guideline adherence, which also can be used as a benchmark of quality of care. The purpose of this study was to evaluate differences in use of HF medication between Dutch HF clinics. METHODS:The current analysis was part of a cross-sectional registry of 10,910 chronic HF patients at 34 Dutch outpatient clinics in the period of 2013 until 2016 (CHECK-HF), and focused on the differences in prescription rates between the participating clinics in patients with heart failure with reduced ejection fraction (HFrEF). RESULTS:A total of 8,360 HFrEF patients were included with a mean age of 72.3 ± 11.8 years (ranging between 69.1 ± 11.9 and 76.6 ± 10.0 between the clinics), 63.9% were men (ranging between 54.3 and 78.1%), 27.3% were in New York Heart Association (NYHA) class III/IV (ranging between 8.8 and 62.1%) and the average estimated glomerular filtration rate (eGFR) was 59.6 ± 24.6 ml/min (ranging between 45.7 ± 23.5 and 97.1 ± 16.5). The prescription rates ranged from 58.9-97.4% for beta blockers (p < 0.01), 61.9-97.1% for renin-angiotensin system (RAS) inhibitors (p < 0.01), 29.9-86.8% for mineralocorticoid receptor antagonists (MRAs) (p < 0.01), 0.0-31.3% for ivabradine (p < 0.01) and 64.9-100.0% for diuretics (p < 0.01). Also, the percentage of patients who received the target dose differed significantly, 5.9-29.1% for beta blockers (p < 0.01), 18.4-56.1% for RAS inhibitors (p < 0.01) and 13.2-60.6% for MRAs (p < 0.01). CONCLUSIONS:The prescription rates and prescribed dosages of guideline-recommended medication differed significantly between HF outpatient clinics in the Netherlands, not fully explained by differences in patient profiles.
| S-EPMC7270463 | biostudies-literature
Project description:ObjectivesTo determine whether the number of medications taken by adults with heart failure (HF) and impairment in activities of daily living (ADL)-a subpopulation in whom the risks of a high medication burden may outweigh the benefits-differs from the number taken by those without impairment in ADLs.DesignCross-sectional.SettingNational Health and Nutrition Examination Survey (NHANES; 2003-2014), a cross-sectional survey that produces national estimates of adults in the United States.ParticipantsAdults aged 50 and older (mean 70) with self-reported HF (N= 947; representing 4.6 million adults with HF in the United States.MeasurmentsWe assessed ADL impairment and medication count based on self-report. ADL impairment was defined as having difficulty with or being unable to dress, feed oneself, or get in and out of bed. To determine the independent association between ADL impairment and medication count, we performed sequential Poisson multivariable regression analyses. All analyses were cross-sectional in nature and accounted for the complex survey design of NHANES.ResultsMean medication count was 7.2, and 74% of participants were taking 5 or more medications (polypharmacy). In a multivariable model, ADL impairment was not independently associated with medication count. These findings were similar for those with 3 or more hospitalizations in the prior year, declining health status, and cognitive impairment.ConclusionAfter adjusting for confounders including comorbidity, we found that adults with HF and ADL impairment take as many medications as those without ADL impairment. This suggests that providers may not sufficiently consider functional impairment when prescribing medications to adults with HF and thus may unnecessarily expose individuals to risk of adverse outcomes. J Am Geriatr Soc 67:284-291, 2019.
| S-EPMC6790071 | biostudies-literature
Project description:Heart failure (HF) following myocardial infarction (MI) is associated with high incidence of cardiac arrhythmias. Development of therapeutic strategy requires detailed understanding of electrophysiological remodeling. However, changes of ionic currents in ischemic HF remain incompletely understood, especially in translational large-animal models. Here, we systematically measure the major ionic currents in ventricular myocytes from the infarct border and remote zones in a porcine model of post-MI HF. We recorded eight ionic currents during the cell's action potential (AP) under physiologically relevant conditions using selfAP-clamp sequential dissection. Compared with healthy controls, HF-remote zone myocytes exhibited increased late Na+ current, Ca2+-activated K+ current, Ca2+-activated Cl- current, decreased rapid delayed rectifier K+ current, and altered Na+/Ca2+ exchange current profile. In HF-border zone myocytes, the above changes also occurred but with additional decrease of L-type Ca2+ current, decrease of inward rectifier K+ current, and Ca2+ release-dependent delayed after-depolarizations. Our data reveal that the changes in any individual current are relatively small, but the integrated impacts shift the balance between the inward and outward currents to shorten AP in the border zone but prolong AP in the remote zone. This differential remodeling in post-MI HF increases the inhomogeneity of AP repolarization, which may enhance the arrhythmogenic substrate. Our comprehensive findings provide a mechanistic framework for understanding why single-channel blockers may fail to suppress arrhythmias, and highlight the need to consider the rich tableau and integration of many ionic currents in designing therapeutic strategies for treating arrhythmias in HF.
| S-EPMC5879679 | biostudies-literature
Project description:BackgroundThis study assessed the association between heart failure (HF) medication (angiotensin-converting-enzyme inhibitors (ACEI)/angiotensin-receptor blockers (ARB), beta-blockers (BB), mineralocorticoid-receptor antagonists (MRA) and diuretics) and HF readmissions in a real-world unselected group of patients after a first hospital admission for HF. Furthermore we analysed readmission rates for ACEI versus ARB and for carvedilol versus β1-selective BB and we investigated the effect of HF medication in relation to time since discharge.Methods and findingsMedication at discharge was determined with dispensing data from the Dutch PHARMO Database Network including 22,476 patients with HF between 2001 and 2015. After adjustment for age, gender, number of medications and year of admission no associations were found for users versus non-users of ACEI/ARB (hazard ratio, HR = 1.01; 95%CI 0.96-1.06), BB (HR = 1.00; 95%CI 0.95-1.05) and readmissions. The risk of readmission for patients prescribed MRA (HR = 1.11; 95%CI 1.05-1.16) or diuretics (HR = 1.17; 95%CI 1.09-1.25) was higher than for non-users. The HR for ARB relative to ACEI was 1.04 (95%CI 0.97-1.12) and for carvedilol relative to β1-selective BB 1.33 (95%CI 1.20-1.46). Post-hoc analyses showed a protective effect shortly after discharge for most medications. For example one month post discharge the HR for ACEI/ARB was 0.77 (95%CI 0.69-0.86). Although we did try to adjust for confounding by indication, probably residual confounding is still present.ConclusionsPatients who were prescribed carvedilol have a higher or at least a similar risk of HF readmission compared to β1-selective BB. This study showed that all groups of HF medication -some more pronounced than others- were more effective immediately following discharge.
| S-EPMC7755181 | biostudies-literature