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1.
Drug Testing in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes From a Patient With Short QT Syndrome Type 1.
Zhao, Z, Li, X, El-Battrawy, I, Lan, H, Zhong, R, Xu, Q, Huang, M, Liao, Z, Lang, S, Zimmermann, WH, et al
Clinical pharmacology and therapeutics. 2019;(3):642-651
Abstract
Short QT syndrome (SQTS) predisposes afflicted patients to sudden cardiac death. Until now, only one drug-quinidine-has been shown to be effective in patients with SQTS type 1(SQTS1). The objective of this study was to use human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with SQTS1 to search for potentially effective drugs for the treatment of SQTS1 patients. Patch clamp and single-cell contraction measurements were employed to assess drug effects. Ivabradine, mexiletine, and ajmaline but not flecainide, ranolazine, or amiodarone prolonged the action potential duration (APD) in hiPSC-CMs from an SQTS1 patient. Ivabradine, ajmaline, and mexiletine inhibited KCNH2 channel currents significantly, which may underlie their APD-prolonging effects. Under proarrhythmic epinephrine stimulation in spontaneously beating SQTS1 hiPSC-CMs, ivabradine, mexiletine, and ajmaline but not flecainide reduced the epinephrine-induced arrhythmic events. The results demonstrate that ivabradine, ajmaline, and mexiletine may be candidate drugs for preventing tachyarrhythmias in SQTS1 patients.
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2.
Effects of Heart Rate Reduction With Either Pyridostigmine or Ivabradine in Patients With Heart Failure: A Randomized, Double-Blind Study.
Villacorta, AS, Villacorta, H, Caldas, JA, Precht, BC, Porto, PB, Rodrigues, LU, Neves, M, Xavier, AR, Kanaan, S, Mesquita, CT, et al
Journal of cardiovascular pharmacology and therapeutics. 2019;(2):139-145
Abstract
BACKGROUND Heart rate (HR) reduction with ivabradine has been proved to reduce hospitalization and death from heart failure (HF). We sought to investigate whether pyridostigmine would effectively reduce HR in patients with chronic HF as compared with ivabradine. METHODS Twenty-one patients with HF who were in sinus rhythm with a resting HR over 70 bpm, despite optimal medical treatment, were included in a randomized, double-blind study comparing pyridostigmine versus ivabradine. The initial dose of ivabradine was 5 mg twice daily to reach a target HR between 50 and 60 bpm and could be titrated to a maximum of 7.5 mg twice daily. Pyridostigmine was used in a fixed dose of 30 mg 3 times daily. RESULTS The baseline HR for ivabradine and pyridostigmine groups was 89.1 (13.5) and 80.1 (7.2) bpm, respectively (P = .083). After 6 months of treatment, HR was significantly reduced to 64.8 (8.3) bpm in the ivabradine group (P = .0014) and 63.6 (5.9) bpm in the pyridostigmine group (P = .0001). The N-terminal pro-B-type natriuretic peptide was reduced in the ivabradine group (median: 1308.4 [interquartile range: 731-1896] vs 755.8 [134.5-1014] pg/mL; P = .027) and in the pyridostigmine group (132.8 [89.9-829] vs 100.7 [38-360] pg/mL; P = .002). Inflammatory markers interleukin-1, interleukin-6, and tumor necrosis factor were reduced in both groups. Exercise capacity was improved in both groups, with increments in volume of oxygen utilization (V˙O2; ivabradine: 13.1 vs 15.6, P = .048; pyridostigmine: 13.3 vs 16.7, P = .032). Heart rate recovery in the first minute postexercise was improved with pyridostigmine (11.8 [3.9] vs 18 [6.5]; P = .046), but not with ivabradine (13.3 [6.9] vs 14.1 [8.2]; P = .70). No differences in either group were observed in the myocardial scintigraphy with 123-iodine-metaiodobenzylguanidine. CONCLUSION Both drugs significantly reduced HR, with improvements in exercise capacity and in neurohormonal and inflammatory profiles.
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3.
Strategies for Appropriate Selection of SGLT2-i vs. GLP1-RA in Persons with Diabetes and Cardiovascular Disease.
Dhindsa, DS, Mehta, A, Sandesara, PB, Thobani, A, Brandt, S, Sperling, LS
Current cardiology reports. 2019;(9):100
Abstract
PURPOSE OF REVIEW This review will serve to highlight the clinical rationale used in the selection of sodium-glucose cotransporter 2 inhibitors (SGLT2-i) or glucagon-like peptide 1 receptor agonists (GLP1-ra). RECENT FINDINGS SGLT2-i and GLP1-ra are the first anti-hyperglycemics to demonstrate significant cardiovascular benefit in multiple cardiovascular outcomes trials (CVOTs), with benefits that are consistent across class of medication. Diabetes is a major risk factor for morbidity and mortality from cardiovascular disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) and glucagon-like peptide 1 receptor agonists (GLP1-ra) are the first anti-hyperglycemics to demonstrate significant cardiovascular benefit. Given the unique side effect and benefit profiles, appropriate consideration of these agents with a focus on cardiovascular risk reduction requires an individualized approach.
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4.
Hospitalization Among Patients With Atrial Fibrillation and a Recent Acute Coronary Syndrome or Percutaneous Coronary Intervention Treated With Apixaban or Aspirin: Insights From the AUGUSTUS Trial.
Vora, AN, Alexander, JH, Wojdyla, DM, Aronson, R, Granger, CB, Darius, H, Windecker, S, Mehran, R, Averkov, O, Budaj, A, et al
Circulation. 2019;(23):1960-1963
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5.
Cardiovascular Disease in Type 2 Diabetes: A Review of Sex-Related Differences in Predisposition and Prevention.
Al-Salameh, A, Chanson, P, Bucher, S, Ringa, V, Becquemont, L
Mayo Clinic proceedings. 2019;(2):287-308
Abstract
Type 2 diabetes mellitus is a major risk factor for cardiovascular disease. However, compiled data suggest that type 2 diabetes affects the risk of cardiovascular disease differentially according to sex. In recent years, large meta-analyses have confirmed that women with type 2 diabetes have a higher relative risk of incident coronary heart disease, fatal coronary heart disease, and stroke compared with their male counterparts. The reasons for these disparities are not completely elucidated. A greater burden of cardiometabolic risk in women was proposed as a partial explanation. Indeed, several studies suggest that women experience a larger deterioration in major cardiovascular risk factors and put on more weight than do men during their transition from normoglycemia to overt type 2 diabetes. This excess weight is associated with higher levels of biomarkers of endothelial dysfunction, inflammation, and procoagulant state. Moreover, sex differences in the prescription and use of some cardiovascular drugs may compound an "existing" disparity. We searched PubMed for articles published in English and French, by using the following terms: ("cardiovascular diseases") AND ("diabetes mellitus") AND ("sex disparity" OR "sex differences" OR "sex related differences" OR "sex-related differences" OR "sex disparities"). In this article, we review the available literature on the sex aspects of primary and secondary prevention of cardiovascular disease in people with type 2 diabetes, in the predisposition to cardiovascular disease in those people, and in the control of diabetes and associated cardiovascular risk factors.
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6.
Antithrombotic Therapy in Patients With Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or With Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial.
Windecker, S, Lopes, RD, Massaro, T, Jones-Burton, C, Granger, CB, Aronson, R, Heizer, G, Goodman, SG, Darius, H, Jones, WS, et al
Circulation. 2019;(23):1921-1932
Abstract
BACKGROUND The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. METHODS Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. RESULTS Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). CONCLUSIONS An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.
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7.
Review of Cardiovascular Drugs in Pregnancy.
Kaye, AB, Bhakta, A, Moseley, AD, Rao, AK, Arif, S, Lichtenstein, SJ, Aggarwal, NT, Volgman, AS, Sanghani, RM
Journal of women's health (2002). 2019;(5):686-697
Abstract
Cardiovascular disease is now the leading cause of pregnancy-related deaths in the United States. Increasing maternal mortality in the United States underscores the importance of proper cardiovascular management. Significant physiological changes during pregnancy affect the heart's ability to respond to pathological processes such as hypertension and heart failure. These physiological changes further affect the pharmacokinetic and pharmacodynamic properties of cardiac medications. During pregnancy, these changes can significantly alter medication efficacy and metabolism. This article systematically reviews the literature on safety, efficacy, pharmacokinetics, and pharmacodynamics of cardiovascular drugs used for hypertension and heart failure during pregnancy and lactation. The 2017 American College of Cardiology/American Heart Association hypertension guidelines recommend transitioning pregnant patients to methyldopa, nifedipine, or labetalol. Heart failure medications, including beta-blockers, furosemide, and digoxin, are relatively safe and can be used effectively. Medications that block the renin angiotensin-aldosterone system have been shown to be beneficial in the general population; however, they are teratogenic and, therefore, contraindicated in pregnancy. Cardiovascular medications can also enter breast milk and, therefore, care must be taken when selecting drugs during the lactation period. A summary of the safety of drugs during pregnancy and lactation from an online resource, LactMed by the National Library of Medicine's TOXNET database, is included. High-risk pregnant patients with cardiovascular disease require a multispecialty team of doctors, including health care providers from obstetrics and gynecology, maternal fetal medicine, internal medicine, cardiovascular disease specialists, and specialized pharmacology expertise.
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8.
A review of interventions ≥ 6 months by pharmacists on adherence to medicines in cardiovascular disease: Characteristics of what works and what doesn't.
Doggrell, SA
Research in social & administrative pharmacy : RSAP. 2019;(2):119-129
Abstract
BACKGROUND Nonadherence to cardiovascular medicines occurs in 60% of subjects with chronic cardiovascular disease and leads to poor outcomes. In an attempt to improve adherence and cardiovascular outcomes, interventions are often used. Interventions may involve a pharmacist, but it is not always clear whether these are effective. OBJECTIVES The primary objective of this review is to determine whether interventions by pharmacists, alone, discussing adherence to medicines, improve adherence to medicines for cardiovascular disease. Subsequently, the review links the characteristics of the individual studies with effectiveness or lack of effect. The second objective of this review is to consider whether any improvement in adherence with interventions by pharmacist is associated with better clinical outcomes. METHODS A literature search of PubMed and CINAHL for 'pharmacist', 'medicine' with 'adherence' or 'compliance' or 'persistence' was undertaken. To be included in this review, papers had to be of a pharmacist working alone and in person in an intervention of subjects with hypertension, hyperlipidemia (prior to or after a coronary artery event) or heart failure. The paper had to be published in a peer review journal, with a measure of adherence to medicines. The effectiveness of the intervention had to be evaluated after ≥6 months. RESULTS Only 3 out of 8 interventions by pharmacists in hypertension, and 5 out of 12 interventions in subjects with hyperlipidemia led to improved adherence to medicines. In contrast, all 6 interventions by a pharmacist in subjects with heart failure were successful in improving adherence. One characteristic of successful interventions by pharmacists to improve adherence to cardiovascular medicines is that they must be more than brief/single interventions. A second characteristic is that the intervention should not involve subjects who are already highly adherent, as it is unlikely adherence can be improved in this population. Only 2 of 3 successful interventions in hypertension were associated with small reductions in blood pressure, and only one intervention in hyperlipidemia was shown to decrease LDL-cholesterol to a small extent. In subjects with heart failure, 5 of the 6 successful studies of the successful interventions by pharmacists to increase adherence also showed improved clinical outcomes. CONCLUSIONS When planning an intervention to improve adherence to medicines and cardiovascular outcomes in subjects with hypertension or hyperlipidemic, by a pharmacist alone, or as part of a multi-faceted interventions, it is essential to use an intervention that has been shown to be effective, as most interventions are not effective at improving adherence or only improve adherence and clinical outcomes to a small extent. In heart failure, there is well documented evidence of interventions by pharmacists that do improve clinical outcomes, which should be adopted widely.
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9.
Effects of the Antianginal Drugs Ranolazine, Nicorandil, and Ivabradine on Coronary Microvascular Function in Patients With Nonobstructive Coronary Artery Disease: A Meta-analysis of Randomized Controlled Trials.
Zhu, H, Xu, X, Fang, X, Zheng, J, Zhao, Q, Chen, T, Huang, J
Clinical therapeutics. 2019;(10):2137-2152.e12
Abstract
PURPOSE The goal of this study was to investigate the effects of the antianginal drugs ranolazine, nicorandil, and ivabradine on coronary microvascular function. METHODS Electronic scientific databases were searched for randomized trials investigating the effects of antianginal drugs on coronary microvascular function. Primary outcomes were changes in the coronary flow reserve (CFR), index of microvascular resistance (IMR), and myocardial perfusion reserve index (MPRI). The secondary outcome was the Seattle Angina Questionnaire scores. The standardized mean difference or weighted mean difference (WMD) (95% CI) served as a summary statistic. FINDINGS The antianginal drugs ranolazine, nicorandil, and ivabradine did not increase the CFR compared with the control drugs (standardized mean difference, 0.39; 95% CI, -0.08 to 0.85; P = 0.10). Ranolazine did not increase the global MPRI compared with the control drugs (weighted mean difference [WMD], 0.11; 95% CI, -0.06 to 0.29; P = 0.21). However, in the subgroups with a baseline CFR <2.5 or a global MPRI <2, ranolazine increased the global MPRI (WMD, 0.19; 95% CI, 0.10 to 0.27; P < 0.0001). In addition, the subendocardial midventricular MPRI (mid-subendocardial MPRI) was improved after ranolazine treatment (WMD, 0.12; 95% CI, 0.03 to 0.20; P = 0.007). Moreover, nicorandil significantly reduced the IMR compared with the control drugs (WMD, -7.63; 95% CI, -11.82 to -3.44; P = 0.0004). In addition, ranolazine and ivabradine improved 3 of the 5 Seattle Angina Questionnaire scores. IMPLICATIONS Ranolazine improved the global MPRI in patients with definite coronary microvascular dysfunction and the mid-subendocardial MPRI with suspicious coronary microvascular dysfunction, and nicorandil reduced the IMR. In addition, ranolazine and ivabradine reduced angina. Moreover, it is possible that the IMR and mid-subendocardial MPRI are more sensitive than the CFR and global MPRI for evaluating coronary microvascular function.
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10.
Beneficial effect of polaprezinc on cardiac function post-myocardial infarction: A prospective and randomized clinical trial.
Yoshikawa, F, Nakajima, T, Hanada, M, Hirata, K, Masuyama, T, Aikawa, R
Medicine. 2019;(10):e14637
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Abstract
BACKGROUND Polaprezinc is clinically used for the treatment of gastric ulcers. It induces the mobilization of mesenchymal stem cells and the mRNA expression of insulin-like growth factor-1 in vascular endothelial cells in order to protect injured gastric tissue or skin. METHODS The current study population included 50 patients with primary acute myocardial infarction (AMI). After percutaneous coronary intervention, the subjects were randomly divided into 2 groups, namely, the nonpolaprezinc and polaprezinc groups. Peripheral blood and urinary samples were collected in a specific time to analyze zinc concentration, cardiac enzymes, and the levels of the inflammation marker interleukin-6. To evaluate the cardiac function, echocardiography was performed upon admission to the hospital and at 9 months post-AMI. RESULTS The urine and blood zinc levels of the polaprezinc group were higher compared with those of the non-polaprezinc group at 8 days after percutaneous coronary intervention. The mean interleukin-6/maximal creatine phosphokinase level was significantly reduced in the polaprezinc group (0.024 [0.003-0.066] vs. 0.076 [0.015-0.212], respectively; P = .045). In addition, echocardiography revealed that the ejection fraction of the nonpolaprezinc group was not significantly increased between day 3 and 9 months post-AMI (53 [49-60.8] vs. 59.5 [52-69.3], respectively; P = .015). However, a significant increase was detected in the ejection fraction of the polaprezinc group at the 2 time points (54 [51-57] vs. 62 [55-71], respectively; P < .01). CONCLUSIONS The results of the present study suggest that polaprezinc has an anti-inflammatory effect and improves cardiac function after AMI.