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1.
Diagnosis and Management of Stable Angina: A Review.
Joshi, PH, de Lemos, JA
JAMA. 2021;(17):1765-1778
Abstract
IMPORTANCE Nearly 10 million US adults experience stable angina, which occurs when myocardial oxygen supply does not meet demand, resulting in myocardial ischemia. Stable angina is associated with an average annual risk of 3% to 4% for myocardial infarction or death. Diagnostic tests and medical therapies for stable angina have evolved over the last decade with a better understanding of the optimal use of coronary revascularization. OBSERVATIONS Coronary computed tomographic angiography is a first-line diagnostic test in the evaluation of patients with stable angina due to higher sensitivity and comparable specificity compared with imaging-based stress testing. Moreover, coronary computed tomographic angiography allows detection of nonobstructive atherosclerosis that would not be identified with other noninvasive imaging modalities, improving risk assessment and potentially triggering more appropriate allocation of preventive therapies. Novel therapies treating lipids (proprotein convertase subtilisin/kexin type 9 inhibitors, ezetimibe, and icosapent ethyl) and type 2 diabetes (sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists) have improved cardiovascular outcomes in patients with stable ischemic heart disease when added to usual care. Randomized clinical trials showed no improvement in the rates of mortality or myocardial infarction with revascularization (largely by percutaneous coronary intervention) compared with optimal medical therapy alone, even in the setting of moderate to severe ischemia. In contrast, revascularization provides a meaningful benefit on angina and quality of life compared with antianginal therapies. Measures of the effect of angina on a patient's quality of life should be integrated into the clinic encounter to assist with the decision to proceed with revascularization. CONCLUSIONS AND RELEVANCE For patients with stable angina, emphasis should be placed on optimizing lifestyle factors and preventive medications such as lipid-lowering and antiplatelet agents to reduce the risk for cardiovascular events and death. Antianginal medications, such as β-blockers, nitrates, or calcium channel blockers, should be initiated to improve angina symptoms. Revascularization with percutaneous coronary intervention should be reserved for patients in whom angina symptoms negatively influence quality of life, generally after a trial of antianginal medical therapy. Shared decision-making with an informed patient is important for effective treatment of stable angina.
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2.
CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction.
McDonald, M, Virani, S, Chan, M, Ducharme, A, Ezekowitz, JA, Giannetti, N, Heckman, GA, Howlett, JG, Koshman, SL, Lepage, S, et al
The Canadian journal of cardiology. 2021;(4):531-546
Abstract
In this update of the Canadian Cardiovascular Society heart failure (HF) guidelines, we provide comprehensive recommendations and practical tips for the pharmacologic management of patients with HF with reduced ejection fraction (HFrEF). Since the 2017 comprehensive update of the Canadian Cardiovascular Society guidelines for the management of HF, substantial new evidence has emerged that has informed the care of these patients. In particular, we focus on the role of novel pharmacologic therapies for HFrEF including angiotensin receptor-neprilysin inhibitors, sinus node inhibitors, sodium glucose transport 2 inhibitors, and soluble guanylate cyclase stimulators in conjunction with other long established HFrEF therapies. Updated recommendations are also provided in the context of the clinical setting for which each of these agents might be prescribed; the potential value of each therapy is reviewed, where relevant, for chronic HF, new onset HF, and for HF hospitalization. We define a new standard of pharmacologic care for HFrEF that incorporates 4 key therapeutic drug classes as standard therapy for most patients: an angiotensin receptor-neprilysin inhibitor (as first-line therapy or after angiotensin converting enzyme inhibitor/angiotensin receptor blocker titration); a β-blocker; a mineralocorticoid receptor antagonist; and a sodium glucose transport 2 inhibitor. Additionally, many patients with HFrEF will have clinical characteristics for which we recommended other key therapies to improve HF outcomes, including sinus node inhibitors, soluble guanylate cyclase stimulators, hydralazine/nitrates in combination, and/or digoxin. Finally, an approach to management that integrates prioritized pharmacologic with nonpharmacologic and invasive therapies after a diagnosis of HFrEF is highlighted.
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3.
A Novel Approach to Medical Management of Heart Failure With Reduced Ejection Fraction.
Miller, RJH, Howlett, JG, Fine, NM
The Canadian journal of cardiology. 2021;(4):632-643
Abstract
The advent of newly available medical therapies for heart failure with reduced ejection fraction (HFrEF) has resulted in many potential therapeutic combinations, increasing treatment complexity. Publication of expert consensus guidelines and initiatives aimed to improve implementation of treatment has emphasized sequential stepwise initiation and titration of medical therapy, which is labour intensive. Data taken from heart failure registries show suboptimal use of medications, prolonged titration times, and consequently little change in dose intensity, all of which indicate therapeutic inertia. Recently published evidence indicates that 4 medication classes-renin-angiotensin-neprilysin inhibitors, β-blockers, mineralocorticoid antagonists, and sodium-glucose cotransporter inhibitors-which we refer to as Foundational Therapy, confer rapid and robust reduction in both morbidity and mortality in most patients with HFrEF and that they work in additive fashion. Additional morbidity and mortality may be observed following addition of several personalized therapies in specific subgroups of patients. In this review, we discuss mechanisms of action of these therapies and propose a framework for their implementation, based on several principles. These include the critical importance of rapid initiation of all 4 Foundational Therapies followed by their titration to target doses, emphasis on multiple simultaneous drug changes with each patient encounter, attention to patient-specific factors in choice of medication class, leveraging inpatient care, use of the entire health care team, and alternative (ie, virtual visits) modes of care. We have incorporated these principles into a Cluster Scheme designed to facilitate timely and optimal medical treatment for patients with HFrEF.
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4.
The Potential Role of Creatine in Vascular Health.
Clarke, H, Hickner, RC, Ormsbee, MJ
Nutrients. 2021;(3)
Abstract
Creatine is an organic compound, consumed exogenously in the diet and synthesized endogenously via an intricate inter-organ process. Functioning in conjunction with creatine kinase, creatine has long been known for its pivotal role in cellular energy provision and energy shuttling. In addition to the abundance of evidence supporting the ergogenic benefits of creatine supplementation, recent evidence suggests a far broader application for creatine within various myopathies, neurodegenerative diseases, and other pathologies. Furthermore, creatine has been found to exhibit non-energy related properties, contributing as a possible direct and in-direct antioxidant and eliciting anti-inflammatory effects. In spite of the new clinical success of supplemental creatine, there is little scientific insight into the potential effects of creatine on cardiovascular disease (CVD), the leading cause of mortality. Taking into consideration the non-energy related actions of creatine, highlighted in this review, it can be speculated that creatine supplementation may serve as an adjuvant therapy for the management of vascular health in at-risk populations. This review, therefore, not only aims to summarize the current literature surrounding creatine and vascular health, but to also shed light onto the potential mechanisms in which creatine may be able to serve as a beneficial supplement capable of imparting vascular-protective properties and promoting vascular health.
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5.
Vascular Lesion-Specific Drug Delivery Systems: JACC State-of-the-Art Review.
Marlevi, D, Edelman, ER
Journal of the American College of Cardiology. 2021;(19):2413-2431
Abstract
Drug delivery is central to modern cardiovascular care, where drug-eluting stents, bioresorbable scaffolds, and drug-coated balloons all aim to restore perfusion while inhibiting exuberant healing. The promise and enthusiasm of these devices has in some cases exceeded demonstration of efficacy and even understanding of driving mechanisms. The authors review the means of drug delivery in each device, outlining how the technologies affect vascular behavior. They focus on how drug retention and response are governed by lesion morphology: lipid displacing drug-specific binding sites, calcium inhibiting diffusion, blocking thrombi or promoting luminal washout, and vascular healing steering hyperplastic developments. In this regard, the authors outline the fundamental impact of vascular structure on drug delivery and review the development of contemporary and future devices for coronary and peripheral intervention. They look toward a future where incorporating information on lesion distribution is central to therapeutic success and envision a transition toward lesion-specific treatment for improved interventional outcomes.
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6.
Integrating genomics with biomarkers and therapeutic targets to invigorate cardiovascular drug development.
Holmes, MV, Richardson, TG, Ference, BA, Davies, NM, Davey Smith, G
Nature reviews. Cardiology. 2021;(6):435-453
Abstract
Drug development in cardiovascular disease is stagnating, with lack of efficacy and adverse effects being barriers to innovation. Human genetics can provide compelling evidence of causation through approaches such as Mendelian randomization, with genetic support for causation increasing the probability of a clinical trial succeeding. Mendelian randomization applied to quantitative traits can identify risk factors for disease that are both causal and amenable to therapeutic modification. However, important differences exist between genetic investigations of a biomarker (such as HDL cholesterol) and a drug target aimed at modifying the same biomarker of interest (such as cholesteryl ester transfer protein), with implications for the methodology, interpretation and application of Mendelian randomization to drug development. Differences include the comparative nature of the genetic architecture - that is, biomarkers are typically polygenic, whereas protein drug targets are influenced by either cis-acting or trans-acting genetic variants - and the potential for drug targets to show disease associations that might differ from those of the biomarker that they are intended to modify (target-mediated pleiotropy). In this Review, we compare and contrast the use of Mendelian randomization to evaluate potential drug targets versus quantitative traits. We explain how genetic epidemiological studies can be used to assess the aetiological roles of biomarkers in disease and to prioritize drug targets, including designing their evaluation in clinical trials.
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7.
Timely and individualized heart failure management: need for implementation into the new guidelines.
Abdin, A, Bauersachs, J, Frey, N, Kindermann, I, Link, A, Marx, N, Lainscak, M, Slawik, J, Werner, C, Wintrich, J, et al
Clinical research in cardiology : official journal of the German Cardiac Society. 2021;(8):1150-1158
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Abstract
Due to remarkable improvements in heart failure (HF) management over the last 30 years, a significant reduction in mortality and hospitalization rates in HF patients with reduced ejection fraction (HFrEF) has been observed. Currently, the optimization of guideline-directed chronic HF therapy remains the mainstay to further improve outcomes for patients with HFrEF to reduce mortality and HF hospitalization. This includes established device therapies, such as implantable defibrillators and cardiac resynchronization therapies, which improved patients' symptoms and prognosis. Over the last 10 years, new HF drugs have merged targeting various pathways, such as those that simultaneously suppress the renin-angiotensin-aldosterone system and the breakdown of endogenous natriuretic peptides (e.g., sacubitril/valsartan), and those that inhibit the If channel and, thus, reduce heart rate (e.g., ivabradine). Furthermore, the treatment of patient comorbidities (e.g., iron deficiency) has shown to improve functional capacity and to reduce hospitalization rates, when added to standard therapy. More recently, other potential treatment mechanisms have been explored, such as the sodium/glucose co-transporter inhibitors, the guanylate cyclase stimulators and the cardiac myosin activators. In this review, we summarize the novel developments in HFrEF pharmacological and device therapy and discuss their implementation strategies into practice to further improve outcomes.
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8.
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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Diabetes without Manifest Cardiovascular Disease: A Novel Approach in Risk Stratification and Treatment Selection.
Andari, E, Arnaout, S, Azar, ST, Chammas, E, Jambart, S, Saleh, M, Nemr, R, Sarkis, A
Current diabetes reviews. 2020;(8):869-873
Abstract
BACKGROUND Cardiovascular disease (CVD), the main macro vascular complication of type 2 diabetes (T2D), increases the risk of death significantly in patients with T2D. INTRODUCTION Most of the patients with T2D do not have obvious CVD symptoms. Due to the paucity of data, CVD screening in asymptomatic patients with T2D remains highly controversial. METHODS This has driven a panel of experts to establish a novel consensus on how to approach patients with T2D at high CVD risk. The panel formulated a stepwise algorithm by which patients with T2D undergo initial risk stratification into low, intermediate and high risk using the ASCVD calculator. In patients with intermediate risk, coronary artery calcium measurement is used to further stratify those patients into new low and high-risk categories. RESULTS AND CONCLUSION The panel recommends using standard diabetes care in low risk patients and using SGLT2 inhibitors and GLP1 agonists with cardio protective effect, on top of standard care, in high risk individuals.
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10.
Ivabradine: a new frontier in the treatment of stable coronary artery disease and chronic heart failure.
Gammone, MA, Riccioni, G, D'Orazio, N
La Clinica terapeutica. 2020;(5):e449-e453
Abstract
Ivabradine (IVA) is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. This pure heart rate-lowering agent possesses well-documented antianginal and anti-ischemic properties comparable to well-established antianginal agents, such as β-blockers and calcium channel blockers. IVA lowers heart rate (HR) without affecting contractility or vascular tone and it is licensed for HR control in chronic heart diseases. The heart rate reduction is beneficial in patients with coronary artery disease (CAD), chronic stable angina pectoris, and chronic heart failure (CHF). Published trials documented not only pharmacodynamic and pharmacokinetic properties but also acceptable tolerance and safety profile of IVA, compared to other currently used cardiovascular drugs, including betablockers. The aim of this review is to describe recent evidences with IVA an interesting medicament, able to lower HR by selective inhibition of the If current, and to describe its applications.