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Contemporary Treatment Patterns and Clinical Outcomes of Comorbid Diabetes Mellitus and HFrEF: The CHAMP-HF Registry.
Vaduganathan, M, Fonarow, GC, Greene, SJ, DeVore, AD, Kavati, A, Sikirica, S, Albert, NM, Duffy, CI, Hill, CL, Patterson, JH, et al
JACC. Heart failure. 2020;(6):469-480
Abstract
OBJECTIVES The purpose of this study was to characterize the clinical profile, treatment patterns, and clinical outcomes of patients with comorbid diabetes mellitus (DM) and heart failure with reduced ejection fraction (HFrEF) in a contemporary, real-world U.S. outpatient registry in the context of evolving treatment strategies. BACKGROUND Specific antihyperglycemic classes have differential risks and benefits with respect to HF. Limited data are available evaluating contemporary treatment patterns and outcomes of patients with comorbid DM and HFrEF. METHODS Among 4,970 patients with chronic HFrEF (≤40%) across 152 U.S. sites in the CHAMP-HF prospective, observational registry (2015 to 2017), we examined therapies and clinical outcomes by DM status. RESULTS Median age was 68 (58 to 75) years of age; 29% were women; 73.5% were white; and 64% had coronary artery disease. Overall, 42% (n = 2,085) had comorbid DM with a median hemoglobin A1c (HbA1c) level of 7.2% (interquartile range [IQR]: 6.4% to 8.3%). One-fourth of DM patients (24%) were not treated with an antihyperglycemic therapy. Most patients with DM were taking 1 (46%) or 2 (23%) antihyperglycemic therapies: metformin (40%); insulin (33%); sulfonylureas (24%); dipeptidyl peptidase-4 inhibitors (10%); glucagon-like peptide (GLP)-1 receptor agonists (4%); sodium-glucose cotransporter (SGLT)-2 inhibitors (2%); and thiazolidinediones (2%). Among patients with DM, 62%, 16%, 80%, and 33.5% were receiving any angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitor (ARNI), β-blockers, or mineralocorticoid receptor antagonists (MRAs) at baseline, respectively. Among patients without DM, corresponding baseline rates were 65%, 15%, 80%, and 37%, respectively. Patients with or without DM were infrequently treated with guideline-directed HFrEF therapies at target doses (≤27% across classes). During median 15-month follow-up, patients with DM experienced higher rates of all-cause mortality or HF hospitalization (30% vs. 23%, respectively), independent of 11 pre-specified covariates (adjusted hazard ratio: 1.35 (95% confidence interval: 1.21 to 1.52); p < 0.001). CONCLUSIONS Despite higher risk-adjusted clinical event rates in patients with comorbid HFrEF and DM, guideline-directed medical therapies for both disease states are incomplete and represent an important target for quality improvement through multidisciplinary care pathways.
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Beta-Blockers, Calcium Channel Blockers, and Mortality in Stable Coronary Artery Disease.
Cruz Rodriguez, JB, Alkhateeb, H
Current cardiology reports. 2020;(3):12
Abstract
PURPOSE OF REVIEW To examine the current clinical evidence behind the use of calcium channel blockers (CCB) and beta-blockers (BB) for the treatment of patients with stable coronary artery disease (SCAD) and their effect on mortality. RECENT FINDINGS Current evidence suggests that BB use as a first line antianginal medication is associated with lower 5-year all-cause mortality only in patients who had MI within a year. This could be driven due to their effects reducing the sympathetic neuro-hormonal activation of more acutely ill patients. The use of CCB as an antianginal therapy, although proven effective in multiple trials both as monotherapy and combined with other agents, has not shown mortality benefit. Both BB and CCB are effective antianginals, and the selection among them depends on the patient clinical presentation and comorbidities. BB are the only ones that have shown survival benefit in SCAD, particularly the first year post-MI.
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Beta blockers versus calcium channel blockers for provocation of vasospastic angina after drug-eluting stent implantation: a multicentre prospective randomised trial.
Sawano, M, Katsuki, T, Kitai, T, Tamita, K, Obunai, K, Ikegami, Y, Yamane, T, Ueda, I, Endo, A, Maekawa, Y, et al
Open heart. 2020;(2)
Abstract
BACKGROUND Drug-eluting stent-induced vasospastic angina (DES-VSA) has emerged as a novel complication in the modern era of percutaneous coronary intervention (PCI). Although beta blockers (BBs) are generally recommended for coronary heart disease, they may promote incidence of DES-VSA. This study aimed to compare the effects of calcium channel blockers (CCBs) perceived to be protective against DES-VSA and BBs on subsequent coronary events after second-generation drug-eluting stent implantation. METHODS In this multicentre prospective, randomised study, 52 patients with coronary artery disease who underwent PCI for a single-vessel lesion with everolimus-eluting stent placement were randomised into post-stenting BB (N=26) and CCB (N=26) groups and followed for 24 months to detect any major cardiovascular events (MACE). A positive result on acetylcholine provocation testing during diagnostic coronary angiography (CAG) at 9 months was the primary endpoint for equivalence. MACE included all-cause death, non-fatal myocardial infarction, unstable angina, cerebrovascular disease or coronary revascularisation for stable coronary artery disease after index PCI. RESULTS At 9 months, 42 patients (80.8%) underwent diagnostic coronary angiography and acetylcholine provocation testing. Among them, seven patients in each group were diagnosed with definite vasospasm (intention-to-treat analysis 26.9% vs 26.9%, risk difference 0 (-0.241, 0.241)). Meanwhile, the secondary endpoint, 24-month MACE, was higher in the CCB group (19.2%) than in the BB group (3.8%) (p=0.01). In detail, coronary revascularisation for stable coronary artery disease was the predominant endpoint that contributed to the greater proportion of MACE in the CCB group (CCB (19.2%) vs BB (3.8%), p=0.03). CONCLUSIONS The incidence of acetylcholine-induced coronary artery spasms did not differ between patients receiving BBs or CCBs at 9 months after PCI. However, a higher incidence of 2-year MACE was observed in the CCB group, suggesting the importance of BB administration. TRIAL REGISTRATION NUMBER This study was registered at the Japanese University Hospital Medical Information Network (UMIN) Clinical Trial Registry (The Prospective Randomized Trial for Optimizing Medical Therapy After Stenting: Calcium-Beta Trial; UMIN000008321, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009536).
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Hemodynamic Effects of Adding Simvastatin to Carvedilol for Primary Prophylaxis of Variceal Bleeding: A Randomized Controlled Trial.
Vijayaraghavan, R, Jindal, A, Arora, V, Choudhary, A, Kumar, G, Sarin, SK
The American journal of gastroenterology. 2020;(5):729-737
Abstract
INTRODUCTION Beta-blockers are the mainstay agents for portal pressure reduction and to modestly reduce hepatic venous pressure gradient (HVPG). We studied whether addition of simvastatin to carvedilol in cirrhotic patients for primary prophylaxis improves the hemodynamic response. METHODS Cirrhotic patients with esophageal varices and with baseline HVPG > 12 mm Hg were prospectively randomized for primary prophylaxis to receive either carvedilol (group A, n = 110) or carvedilol plus simvastatin (group B, n = 110). Primary objective was to compare hemodynamic response (HVPG reduction of ≥20% or <12 mm Hg) at 3 months, and secondary objectives were to compare first bleed episodes, death, and adverse events. RESULTS The groups were comparable at baseline. The proportion of patients achieving HVPG response at 3 months was comparable between groups (group A-36/62 [58.1%], group B-36/59 [61%], P = 0.85). The degree of mean HVPG reduction (17.3% and 17.8%, respectively, P = 0.98) and hemodynamic response (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.43-1.83, P = 0.74) was also not different between the groups. Patients who achieved target heart rate with no hypotensive episodes in either group showed better hemodynamic response (77.8% vs 59.2%, P = 0.04). Failure to achieve target heart rate (OR: 0.48; 95% CI: 0.22-1.06) and Child C cirrhosis (OR: 4.49; 95% CI: 1.20-16.8) predicted nonresponse. Three (3.7%) patients on simvastatin developed transient transaminitis and elevated creatine phosphokinase and improved with drug withdrawal. Two patients in each group bled (P = 0.99). Three patients and 1 patient, respectively, in group A and B died (P = 0.32), with sepsis being the cause of death. DISCUSSION Addition of simvastatin to carvedilol for 3 months for primary prophylaxis of variceal bleeding does not improve hemodynamic response over carvedilol monotherapy. Simvastatin usage should be closely monitored for adverse effects in Child C cirrhotic patients.
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Influence of timolol, benzalkonium-preserved timolol, and benzalkonium-preserved brimonidine on oxidative stress biomarkers in the tear film.
Sedlak, L, Wojnar, W, Zych, M, Wyględowska-Promieńska, D
Cutaneous and ocular toxicology. 2020;(3):260-268
Abstract
PURPOSE The objective of this study was to investigate the influence of topical preservative-free timolol, benzalkonium chloride(BAC)-preserved timolol, BAC-preserved timolol, and BAC-preserved brimonidine on total protein concentration, advanced oxidation protein products (AOPP) content, total sulfhydryl groups content, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as Total Oxidant Status (TOS), Total Antioxidant Response, and Oxidative Stress Index (OSI) in the tear film. METHODS The patients were divided into four groups: group C (n = 25)-control group-subjects who did not use topical antiglaucoma medications, group T (n = 17)-patients using topical preservative-free timolol, group T + BAC (n = 24)-patients using topical BAC-preserved timolol, and group BR + BAC (n = 19)-patients using topical BAC-preserved brimonidine. RESULTS The SOD, CAT, and GPx activities as well as AOPP, TOS, and OSI were found to be higher in the tear film of patients treated with BAC-preserved topical timolol or brimonidine in comparison with patients treated with preservative-free timolol or patients who did not use antiglaucoma topical medications. CONCLUSIONS This indicates that using BAC-preserved topical medications increases oxidative stress in the tear film and may, in the long-term, contribute to the clinical presentation of dry eye disease.
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[Treatment of coronary artery disease in renal insufficiency].
Lopau, K, Wanner, C
Der Internist. 2020;(4):362-367
Abstract
The treatment of chronic but stable coronary artery disease is based on the stages of chronic kidney disease (CKD) stages G1-2 and stages G3-G5, distinguishing between advanced kidney disease (stages G3-G5) and end-stage kidney disease (G5D) treated by dialysis. In Germany, national guidelines are followed for patients with normal kidney function in addition to the recommendations of Kidney Disease - Improving Global Outcomes (KDIGO) for CKD patients. These guidelines focus on standard of care and include treatment with aspirin, statins, beta-blockers, inhibitors of the renin-angiotensin system, and sodium glucose cotransporters for patients with cardiovascular disease. Revascularization strategies follow a more pragmatic approach for the fragile, comorbid, and aging patient population. Younger patients appear to benefit from surgical interventions. Treatment of acute events is currently administered independent of the patient's kidney function, but there is no consensus yet on the best strategy. The focus of our efforts should be, via more controlled studies, to avoid "navigating through the darkness" to reach the end of the tunnel.
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Managing Hypertension Using Combination Therapy.
Smith, DK, Lennon, RP, Carlsgaard, PB
American family physician. 2020;(6):341-349
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Abstract
More than 70% of adults treated for primary hypertension will eventually require at least two antihypertensive agents, either initially as combination therapy or as add-on therapy if monotherapy and lifestyle modifications do not achieve adequate blood pressure control. Four main classes of medications are used in combination therapy for the treatment of hypertension: thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). ACEIs and ARBs should not be used simultaneously. In black patients, at least one agent should be a thiazide diuretic or a calcium channel blocker. Patients with heart failure with reduced ejection fraction should be treated initially with a beta blocker and an ACEI or ARB (or an angiotensin receptor-neprilysin inhibitor), followed by add-on therapy with a mineralocorticoid receptor antagonist and a diuretic based on volume status. Treatment for patients with chronic kidney disease and proteinuria should include an ACEI or ARB plus a thiazide diuretic or a calcium channel blocker. Patients with diabetes mellitus should be treated similarly to those without diabetes unless proteinuria is present, in which case combination therapy should include an ACEI or ARB.
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Association of Weight-Adjusted Caffeine and β-Blocker Use With Ophthalmology Fellow Performance During Simulated Vitreoretinal Microsurgery.
Roizenblatt, M, Dias Gomes Barrios Marin, V, Grupenmacher, AT, Muralha, F, Faber, J, Jiramongkolchai, K, Gehlbach, PL, Farah, ME, Belfort, R, Maia, M
JAMA ophthalmology. 2020;(8):819-825
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Abstract
IMPORTANCE Vitreoretinal surgery can be technically challenging and is limited by physiologic characteristics of the surgeon. Factors that improve accuracy and precision of the vitreoretinal surgeon are invaluable to surgical performance. OBJECTIVES To establish weight-adjusted cutoffs for caffeine and β-blocker (propranolol) intake and to determine their interactions in association with the performance of novice vitreoretinal microsurgeons. DESIGN, SETTINGS, AND PARTICIPANTS This single-blind cross-sectional study of 15 vitreoretinal surgeons who had less than 2 years of surgical experience was conducted from September 19, 2018, to September 25, 2019, at a dry-laboratory setting. Five simulations were performed daily for 2 days. On day 1, performance was assessed after sequential exposure to placebo, low-dose caffeine (2.5 mg/kg), high-dose caffeine (5.0 mg/kg), and high-dose propranolol (0.6 mg/kg). On day 2, performance was assessed after sequential exposure to placebo, low-dose propranolol (0.2 mg/kg), high-dose propranolol (0.6 mg/kg), and high-dose caffeine (5.0 mg/kg). INTERVENTIONS Surgical simulation tasks were repeated 30 minutes after masked ingestion of placebo, caffeine, or propranolol pills during the 2 days. MAIN OUTCOMES AND MEASURES An Eyesi surgical simulator was used to assess surgical performance, which included surgical score (range, 0 [worst] to 700 [best]), task completion time, intraocular trajectory, and tremor rate (range, 0 [worst] to 100 [best]). The nonparametric Friedman test followed by Dunn-Bonferroni post hoc test was applied for multiple comparisons. RESULTS Of 15 vitreoretinal surgeons, 9 (60%) were male, with a mean (SD) age of 29.6 (1.4) years and mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 23.15 (2.9). Compared with low-dose propranolol, low-dose caffeine was associated with a worse total surgical score (557.0 vs 617.0; difference, -53.0; 95% CI, -99.3 to -6.7; P = .009), a lower antitremor maneuver score (55.0 vs 75.0; difference, -12.0; 95% CI, -21.2 to -2.8; P = .009), longer intraocular trajectory (2298.6 vs 2080.7 mm; difference, 179.3 mm; 95% CI, 1.2-357.3 mm; P = .048), and increased task completion time (14.9 minutes vs 12.7 minutes; difference, 2.3 minutes; 95% CI, 0.8-3.8 minutes; P = .048). Postcaffeine treatment with propranolol was associated with performance improvement; however, surgical performance remained inferior compared with low-dose propranolol alone for total surgical score (570.0 vs 617.0; difference, -51.0; 95% CI, -77.6 to -24.4; P = .01), tremor-specific score (50.0 vs 75.0; difference, -16.0; 95% CI, -31.8 to -0.2; P = .03), and intraocular trajectory (2265.9 mm vs 2080.7 mm; difference, 166.8 mm; 95% CI, 64.1-269.6 mm; P = .03). CONCLUSIONS AND RELEVANCE The findings suggest that performance of novice vitreoretinal surgeons was worse after receiving low-dose caffeine alone but improved after receiving low-dose propranolol alone. Their performance after receiving propranolol alone was better than after the combination of propranolol and caffeine. These results may be helpful for novice vitreoretinal surgeons to improve microsurgical performance.
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Medical Management of Heart Failure With Reduced Ejection Fraction in Patients With Advanced Renal Disease.
Hein, AM, Scialla, JJ, Edmonston, D, Cooper, LB, DeVore, AD, Mentz, RJ
JACC. Heart failure. 2019;(5):371-382
Abstract
Large randomized clinical trials (RCT) supporting guidelines for the management of heart failure with reduced ejection fraction (HFrEF) have typically excluded patients with advanced chronic kidney disease (CKD). Patients with concomitant advanced CKD and HFrEF experience poor cardiovascular outcomes and mortality relative to either disease in isolation and have been shown to consistently receive lower rates of HFrEF guideline-directed medical therapy (GDMT). This review evaluated recent evidence for the use of GDMT in patients with HFrEF and advanced CKD approaching dialysis from RCTs and observational cohorts. The authors also discuss the limitations and challenges inherent in the evidence for GDMT in this population, and offer guidance to clinicians for proper clinical use and future research directions.
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Improving outcomes in chronic obstructive pulmonary disease by taking beta-blockers after acute myocardial infarction: a nationwide observational study.
Wang, WH, Cheng, CC, Mar, GY, Wei, KC, Huang, WC, Liu, CP
Heart and vessels. 2019;(7):1158-1167
Abstract
β-Blockers are a standard therapy for acute myocardial infarction (AMI) due to their better short-term and long-term outcomes. However, β-blockers are often under-prescribed in chronic obstructive pulmonary disease (COPD) patients with AMI, since they are thought be related to bronchospasm. The aim of this study was to investigate the association between the usage of β-blockers and the risk of mortality in COPD patients after first AMI via a nationwide, population-based cohort study. In this retrospective study, we identified 186,326 patients with AMI diagnosed between January 2000 and December 2012, 23,116 of whom had COPD, from the National Health Insurance Research Database. A total of 7609 patients (32.92%) were prescribed β-blockers, while 15,507 were not. The β-blocker patients were stratified into selective and non-selective β-blocker groups. Multivariate Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) with 95% confidence intervals (95% CI). Selective β-blocker use showed a reduced risk of mortality, as compared with patients without β-blockers (HR 0.93; 95% CI 0.89-0.98; p < 0.01) while non-selective β-blocker groups did not increase the risk of mortality compared to the patients without β-blockers (HR 0.98; 95% CI 0.94-1.02; p = 0.38). In addition, the use of β-blockers was found to be associated with a reduced risk of mortality in most stratified analyses which was seen particularly in males, patients aged 65 years and above, and in individuals with an array of comorbidities. These findings suggest that β-blockers improve overall survival among COPD patients after first AMI.