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1.
Asymptomatic peripheral artery disease: Silent but deadly.
Behroozian, AA, Beckman, JA
Progress in cardiovascular diseases. 2021;:2-8
Abstract
Peripheral Artery Disease (PAD) is a manifestation of atherosclerosis characterized by diminished perfusion of the limb and a state of dysmetabolism. The asymptomatic PAD phenotype is a relatively recent classification. It is unknown how many people currently live with asymptomatic PAD because there are no universal screening recommendations for patients at risk for PAD. Patients with asymptomatic PAD suffer from a similar risk profile of morbidity and mortality as their counterparts with claudication. Despite this increased risk, there is a dearth of clinical investigations into therapies that specifically benefit the asymptomatic PAD population. At present, current pharmacotherapies that have been studied in PAD patient populations do not stratify by symptom status. We believe that further investigation of the impact of existing therapies in this unique population presents an opportunity to reduce morbidity and mortality due to PAD. This can only be achieved in combination with wide-spread adoption of screening for asymptomatic PAD.
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2.
Dietary Antiplatelets: A New Perspective on the Health Benefits of the Water-Soluble Tomato Concentrate Fruitflow®.
O'Kennedy, N, Duss, R, Duttaroy, AK
Nutrients. 2021;(7)
Abstract
Our understanding of platelet functionality has undergone a sea change in the last decade. No longer are platelets viewed simply as regulators of haemostasis; they are now acknowledged to be pivotal in coordinating the inflammatory and immune responses. This expanded role for platelets brings new opportunities for controlling a range of health conditions, targeting platelet activation and their interactions with other vascular cells. Antiplatelet drugs may be of wider utility than ever expected but often cause platelet suppression too strong to be used out of clinical settings. Dietary antiplatelets represent a nutritional approach that can be efficacious while safe for general use. In this review, we discuss potential new uses for dietary antiplatelets outside the field of cardiovascular health, with specific reference to the water-soluble tomato extract Fruitflow®. Its uses in different aspects of inflammation and immune function are discussed, highlighting exercise-induced inflammation, mediating the effects of air pollution, and controlling thrombotic aspects of the immune response. Potential future developments in women's health, erectile dysfunction, and the allergic response indicate how broad the utility of dietary antiplatelets can be.
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3.
Aspirin in Primary Prevention: What Changed? A Critical Appraisal of Current Evidence.
Dasa, O, Pepine, CJ, Pearson, TA
The American journal of cardiology. 2021;:38-48
Abstract
Aspirin has been the mainstay of both secondary and primary prevention of cardiovascular disease for half a century. In 2018, 3 trials showed a modest reduction in cardiovascular outcomes that appeared counterbalanced by the risk of clinically significant bleeding. The latest ACC/AHA primary prevention guidelines downgraded their recommendation for aspirin use in primary prevention to that of physician preference. Despite the consistent and robust evidence previously supporting the use of aspirin in cardiovascular disease prevention, little discussion has been given to mechanisms or analytic explanations for this revision of recommendations. In this review, we explore 3 possible mechanisms that may have contributed to the alteration of our perception of aspirin's role in primary prevention. These include changes in the population potentially using aspirin in primary prevention, changes in cardiovascular disease and its presentation, and changes in aspirin itself. Here we present a translational look at knowledge gaps that should be addressed to better guide contemporary aspirin use in primary prevention. In conclusion, based on these considerations, the current recommendations might be improved by recalibration of the cardiovascular risk threshold above which aspirin should be recommended for primary prevention, including the incorporation of newer risk assessment modalities such as calcium scoring. A second enhancement would be developing a bleeding risk calculator to support clinicians' assessment of risk vs benefit. The use of enteric-coated aspirin vs noncoated aspirin should also be reassessed.
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4.
Management of anticoagulant-refractory thrombotic antiphospholipid syndrome.
Cohen, H, Sayar, Z, Efthymiou, M, Gaspar, P, Richards, T, Isenberg, D
The Lancet. Haematology. 2020;(8):e613-e623
Abstract
Lifelong anticoagulation with warfarin or alternative vitamin K antagonist is the standard anticoagulant treatment for thrombotic antiphospholipid syndrome. Anticoagulant-refractory thrombotic antiphospholipid syndrome can be broadly defined as breakthrough thrombosis while on standard oral anticoagulation treatment and its management is a major challenge given the serious nature of the thrombotic disease observed, which has become refractory to oral anticoagulation. The factors (genetic and cellular) that cause anticoagulant-refractory thrombotic antiphospholipid syndrome are now better understood. However, efforts to use this greater understanding have not yet transformed the capacity to treat it successfully in many patients. In this Viewpoint, we review the factors that are likely to be contributing to the cause of this syndrome and consider how they might be modified or inhibited. We also discuss management, including general strategies to minimise thrombotic risk, intensification of anticoagulation, addition of an antiplatelet agent, adjunctive treatment for thrombosis, immunomodulatory therapy, complement inhibition, vascular options, and future potential therapeutic targets.
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5.
Tackling Elevated Risk in PAD: Focus on Antithrombotic and Lipid Therapy for PAD.
Govsyeyev, N, Nehler, MR, Hiatt, WR, Bonaca, MP
Current cardiology reports. 2020;(3):13
Abstract
The PAD population is at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Risk factor modification, symptom control, antithrombotic, and lipid therapies are the mainstays of PAD medical therapy. Recent data has challenged prior recommendations regarding the optimal secondary prevention strategies in PAD. PURPOSE OF REVIEW To review clinical evidence from large randomized controlled trials showing the benefit of antithrombotic and lipid therapy in the PAD population. RECENT FINDINGS The COMPASS trial challenged prior recommendations regarding anticoagulation in PAD. Among the PAD subgroup, rivaroxaban 2.5 mg plus aspirin reduced MACE (HR 0.72, 95% CI 0.57-0.90, p = 0.0047), MALE (HR 0.54, 95% CI 0.35-0.82, p = 0.0037), and major amputation (HR 0.30, 95% CI 0.11-0.80, p = 0.011) compared with aspirin monotherapy. The THEMIS trial showed a 55% risk reduction for MALE with ticagrelor DAPT compared with aspirin monotherapy (HR 0.45, 95% CI 0.23-0.86). The FOURIER trial revealed that lowering LDL cholesterol below current targets with a PCSK9 inhibitor reduced MACE (HR 0.73, 95% CI 0.59-0.91, p = 0.0040) and MALE (HR 0.43, 95% CI 0.19-0.99, p = 0.042) in subjects with symptomatic PAD. Recent high-quality evidence shows the benefit of antiplatelet therapy, anticoagulation therapy, and lipid therapy in reducing MACE and MALE in PAD. Despite these findings, implementation remains a challenge and focus should now shift towards adopting evidence-based recommendations in clinical practice.
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6.
Honey and Its Phenolic Compounds as an Effective Natural Medicine for Cardiovascular Diseases in Humans?
Olas, B
Nutrients. 2020;(2)
Abstract
Honey is a sweet, viscous syrup produced by the honey bee (Apis mellifera). It is probably the first natural sweetener ever discovered, and is currently used as a nutritious food supplement and medicinal agent. The aim of the present mini-review is to summarize and update the current knowledge regarding the role of honey in CVDs based on various experimental models. It also describes the role of its phenolic compounds in treating CVDs. Many such phenolic and flavonoid compounds, including quercetin, kaempferol, apigenin, and caffeic acid, have antioxidant and anti-platelet potential, and hence may ameliorate cardiovascular diseases (CVDs) through various mechanisms, such as by decreasing oxidative stress and inhibiting blood platelet activation. However, as the phenolic content of a particular type of honey is not always known, it can be difficult to determine whether any observed effects on the human cardiovascular system may be associated with the consumption of honey or its constituents. Therefore, further experiments in this area are needed.
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7.
Benefit-Risk Tradeoffs in Assessment of New Drugs and Devices.
Kaul, S, Stockbridge, N, Butler, J
Circulation. 2020;(20):1974-1988
Abstract
Balancing benefits and risks is a complex task that poses a major challenge, both to the approval of new medicines and devices by regulatory authorities and in therapeutic decision-making in practice. Several analysis methods and visualization tools have been developed to help evaluate and communicate whether the benefit-risk profile is favorable or unfavorable. In this White Paper, we describe approaches to benefit-risk assessment using qualitative approaches such as the Benefit Risk Action Team framework developed by the Pharmaceutical Research and Manufacturers of America, and the Benefit-Risk Framework developed by the United States Food and Drug Administration; and quantitative approaches such as the numbers needed to treat for benefit and harm, the benefit-risk ratio, and Incremental Net Benefit. We give illustrative examples of benefit-risk evaluations using 4 treatment interventions including sodium glucose cotransporter 2 inhibitors in patients with type 2 diabetes; a direct antithrombin agent, dabigatran, for reducing stroke and systemic embolism in patients with nonvalvular atrial fibrillation; transcatheter aortic valve replacement in patients with symptomatic severe aortic valve stenosis; and antiplatelet agents vorapaxar and prasugrel for reducing cardiovascular events in patients at high cardiovascular risk. Regular applications of structured benefit-risk assessment, whether qualitative, quantitative, or both, enabled by easy-to-understand graphical presentations that capture uncertainties around the benefit-risk metric, may aid shared decision-making and enhance transparency of those decisions.
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8.
Stroke Prevention in Older Adults: Recent Advances.
Spence, JD, Azarpazhooh, MR, Larsson, SC, Bogiatzi, C, Hankey, GJ
Stroke. 2020;(12):3770-3777
Abstract
The risks of stroke and dementia increase steeply with age, and both are preventable. At present, the best way to preserve cognitive function is to prevent stroke. Therapeutic nihilism based on age is common and unwarranted. We address recent advances in stroke prevention that could contribute greatly to prevention of stroke and dementia at a time when the aging of the population threatens to markedly increase the incidence of both. Issues discussed: (1) old patients benefit even more from lipid-lowering therapy than do younger patients; (2) patients with stiff arteries are at risk from a target systolic blood pressure <120 mm Hg; (3) the interaction of the intestinal microbiome, age, and renal function has important dietary implications for older adults; (4) anticoagulation with direct-acting oral anticoagulants should be prescribed more to old patients with atrial fibrillation; (5) B vitamins to lower homocysteine prevent stroke; and (6) most old patients in whom intervention is warranted for carotid stenosis would benefit more from endarterectomy than from stenting. An 80-year-old person has much to lose from a stroke and should not have effective therapy withheld on account of age. Lipid-lowering therapy, a more plant-based diet, appropriate anticoagulation or antiplatelet therapy, appropriate blood pressure control, B vitamins to lower homocysteine, and judicious intervention for carotid stenosis could do much to reduce the growing burden of stroke and dementia.
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9.
Platelet Responses in Cardiovascular Disease: Sex-Related Differences in Nutritional and Pharmacological Interventions.
Gasperi, V, Catani, MV, Savini, I
Cardiovascular therapeutics. 2020;:2342837
Abstract
Cardiovascular diseases (CVD) represent one of the biggest causes of death globally, and their prevalence, aetiology, and outcome are related to genetic, metabolic, and environmental factors, among which sex- and age-dependent differences may play a key role. Among CVD risk factors, platelet hyperactivity deserves particular mention, as it is involved in the pathophysiology of main cardiovascular events (including stroke, myocardial infarction, and peripheral vascular injury) and is closely related to sex/age differences. Several determinants (e.g., hormonal status and traditional cardiovascular risk factors), together with platelet-related factors (e.g., plasma membrane composition, receptor signaling, and platelet-derived microparticles) can elucidate sex-related disparity in platelet functionality and CVD onset and outcome, especially in relation to efficacy of current primary and secondary interventional strategies. Here, we examined the state of the art concerning sex differences in platelet biology and their relationship with specific cardiovascular events and responses to common antiplatelet therapies. Moreover, as healthy nutrition is widely recognized to play a key role in CVD, we also focused our attention on specific dietary components (especially polyunsaturated fatty acids and flavonoids) and patterns (such as Mediterranean diet), which also emerged to impact platelet functions in a sex-dependent manner. These results highlight that full understanding of gender-related differences will be useful for designing personalized strategies, in order to prevent and/or treat platelet-mediated vascular damage.
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10.
Indications and Evidence for Dual Antiplatelet Therapy After Acute Ischemic Stroke.
Ringler, J, Steck, M, Shah, SP, Chester, KW
Critical care nursing quarterly. 2020;(2):122-137
Abstract
The antiplatelet landscape for the secondary prevention of ischemic stroke has changed significantly over the past decade. Poststroke dual antiplatelet regimens are becoming increasingly routine as supported by recent literature and guideline recommendations. Dual antiplatelet therapy after stroke generally consists of aspirin and clopidogrel and is considered in the short term after stroke in select populations including those with mild stroke or transient ischemic attack and in patients with severe intracranial atherosclerosis. When initiating dual antiplatelet therapy, factors that may increase a patient's risk of bleeding must be weighed against the patient's risk of future ischemic events. This review focuses on antiplatelet medications available in the United States with the aim to provide a summary of the available literature on poststroke dual antiplatelet therapy, pharmacological nuances of the agents, and reversal of antiplatelets in the setting of intracerebral hemorrhage.