Optimizing the use of β-blockers in the effective treatment and management of heart failure: a case study approach

Lackland

J of Clinical Hypertension

et al. 2004

Patients with multiple cardiovascular risk factors benefit from having them all controlled, but this rarely occurs. Fifty-seven primary care providers were enrolled in a program to monitor cardiovascular risk factor control. Data were obtained on 7315 hypertensives. This analysis focuses on 3460 high-risk hypertensives including 2199 with diabetes and 1261 with clinical cardiovascular disease. Blood pressures were <140/90 mm Hg and <130/80 mm Hg in only 44.3% and 20.4% of diabetics and 49.6% and 26.6% nondiabetics, respectively, despite the use of an average of 2.7+/-1.8 antihypertensive medications. Among high-risk dyslipidemic hypertensives, the low-density lipoprotein cholesterol level was <100 mg/dL in only 34% of diabetic and 33% of nondiabetic patients. Among 1696 diabetic hypertensives, the most recent glycosylated hemoglobin value averaged 7.5%, with 46.6% less than 7%. Among 805 diabetic, dyslipidemic hypertensives, all three risk factors were controlled to goal in only 6.6% with higher rates in whites than in African Americans (14.8% vs. 1.6%, p<0.001). An angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or both were prescribed in 89.9% of diabetic and 70.8% of nondiabetic patients, p<0.05. Primary care providers use evidence-based combination therapy in high-risk hypertensive patients with and without diabetes. These findings confirm the low rates of multiple risk factor control and highlight challenges of reaching evidence-based goals in primary care.

Section: Discussionsupporting

confidence: 76%

A Statewide Primary Care Approach to Cardiovascular Risk Factor Control in High‐Risk Diabetic and Nondiabetic Patients With Hypertension

Lackland

J of Clinical Hypertension

et al. 2004

“…Initially, 17 b-adrenergic ligands currently used in various clinical indications (Castle et al, 1993;Cruickshank, 1993;Eichhorn and Young, 2001;Javed and Deedwania, 2009;Ram, 2010) and 2 endogenous ligands were selected to assess their functional selectivity toward 4 signaling pathways: cAMP production, calcium mobilization, ERK1/2 activation, and receptor endocytosis (Tables 1 and 2). For reference purposes, the compounds, structures, binding affinities (from published radioligand binding studies), relative efficacies (previously reported for cAMP production), receptor subtype selectivity profile, and clinical uses are 1 Because model parameter redundancy, it is usually not possible to estimate separate t or K A values for full agonists from direct fitting of the operational model to a full agonist concentration-response curve unless additional experimental manipulations are performed to provide information about other model parameters (e.g., receptor alkylation studies to reduce system maximum responsiveness and thus allow estimation of E m ) or parameter values are constrained to prior known values.…”

Section: Resultsmentioning

confidence: 99%

“…As such, we investigated 19 clinically relevant compounds that are used for treating diseases such as asthma, chronic obstructive pulmonary disease, cardiovascular disease, migraine, and glaucoma and determined their signaling efficacy toward four functional outcomes, namely, the cAMP, ERK1/2, and calcium signaling pathways, as well as b 2 AR endocytosis. Importantly, both formal clinical studies and anecdotal observations suggest that some of these compounds may be more efficacious and/or safer than others for certain clinical indications, despite having the same relative efficacy toward the cAMP pathway (Castle et al, 1993;Cruickshank, 1993;Eichhorn and Young, 2001;Javed and Deedwania, 2009;Ram, 2010). Although these differences may be attributed to other properties of the drugs (polypharmacology, pharmacokinetics, etc.…”

Section: Introductionmentioning

confidence: 99%

Quantification of Ligand Bias for Clinically Relevant β₂-Adrenergic Receptor Ligands: Implications for Drug Taxonomy

et al. 2013

The concepts of functional selectivity and ligand bias are becoming increasingly appreciated in modern drug discovery programs, necessitating more informed approaches to compound classification and, ultimately, therapeutic candidate selection. Using the b2-adrenergic receptor as a model, we present a proof of concept study that assessed the bias of 19 b-adrenergic ligands, including many clinically used compounds, across four pathways [cAMP production, extracellular signal-regulated kinase 1/2 (ERK1/2) activation, calcium mobilization, and receptor endocytosis] in the same cell background (human embryonic kidney 293S cells). Efficacy-based clustering placed the ligands into five distinct groups with respect to signaling signatures. In some cases, apparent functional selectivity originated from offtarget effects on other endogenously expressed adrenergic receptors, highlighting the importance of thoroughly assessing selectivity of the responses before concluding receptor-specific ligand-biased signaling. Eliminating the nonselective compounds did not change the clustering of the 10 remaining compounds. Some ligands exhibited large differences in potency for the different pathways, suggesting that the nature of the receptoreffector complexes influences the relative affinity of the compounds for specific receptor conformations. Calculation of relative effectiveness (within pathway) and bias factors (between pathways) for each of the compounds, using an operational model of agonism, revealed a global signaling signature for all of the compounds relative to isoproterenol. Most compounds were biased toward ERK1/2 activation over the other pathways, consistent with the notion that many proximal effectors converge on this pathway. Overall, we demonstrate a higher level of ligand texture than previously anticipated, opening perspectives for the establishment of pluridimensional correlations between signaling profiles, drug classification, therapeutic efficacy, and safety.

“…CAD is a chronic disease, and the long-term compliance with EBMs requires complicated medication dose adjustment and maintenance [ 13 ]. (4) Elderly patients often suffered from multiple diseases and therefore bear high medication costs [ 31 ]. (5) Elderly patients had decreased memory and limited social support, negatively affecting long-term medication compliance [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

The impact of age on the implementation of evidence-based medications in patients with coronary artery disease and its prognostic significance: a retrospective cohort study

Xia

Huang

et al. 2018

BMC Public Health

BackgroundElderly patients with coronary artery disease (CAD) frequently complicated with more cardiovascular risk factors, but received fewer evidence-based medications (EBMs). This study explored the association of EBMs compliance in different age groups and the risk of long-term death.MethodsA retrospective analysis was conducted from a single registered database. 2830 consecutive patients with CAD were enrolled and grouped into 3 categories by age. The primary end point was all-cause mortality and secondary endpoint is cardiovascular mortality.ResultsThe mean follow-up time was 30.25 ± 11.89 months and death occurred in 270 cases,including 150 cases of cardiac death. Cumulative survival curves indicated that the incidence rates of all-cause death and cardiovascular death increased with age (older than 75 years old vs. 60 to 75 years old vs. younger than 60 years old, mortality: 18.7% vs. 9.6% vs. 4.1%, p < 0.001; cardiovascular mortality: 10.3% vs. 5.1% vs. 2.7%, p < 0.001). The percentage of elderly patients using no EBMs was significantly higher than the percentages in the other age group (7.7% vs. 4.6% vs. 2.2%,p < 0.05). Cox regression analysis revealed the benefit of combination EBMs (all-cause mortality: hazard ratio [HR] 0.15, 95% CI 0.08–0.27; cardiac mortality: HR 0.08, 95% CI 0.04–0.19) for older CAD patients. Similar trends were found about different kinds of EBMs in elderly patients.ConclusionsElderly patients with CAD had higher risk of death but a lower degree of compliance with EBMs usage. Elderly CAD patients could receive more clinical benefits by using EBMs.Electronic supplementary materialThe online version of this article (10.1186/s12889-018-5049-x) contains supplementary material, which is available to authorized users.