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Polypill for cardiovascular disease prevention: Systematic review and meta-analysis of randomized controlled trials.
Mohamed, MG, Osman, M, Kheiri, B, Saleem, M, Lacasse, A, Alkhouli, M
International journal of cardiology. 2022;:91-98
Abstract
BACKGROUND Cardiovascular disease is the leading cause of death worldwide. Although many pharmacological agents exist, drug compliance and therapeutic goal achievement continue to be suboptimal. This meta-analysis aims to study the effectiveness of polypills in controlling blood pressure, dyslipidemia and in reducing future cardiovascular events. METHODS We conducted a systematic search of electronic databases using pre-specified terms. Randomized clinical trials (RCT) comparing polypills (statin, antihypertensive agents, with or without aspirin) with the standard of care were included. Outcomes of interest were changes in [systolic blood pressure (SBP), diastolic blood pressure (DBP)] mmHg, [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C)] mg/dl, cardiovascular (CVD) mortality, and major adverse cardiovascular events (MACE). RESULTS A total of 18 RCTs with 26,483 participants were included. The population had 55% males, with a mean age of 61.8 ± 7 years, and a mean BMI of 26.7 ± 4.2 kg/m2. The mean follow-up was 15.0 ± 20 months. Compared with standard of care, polypill use was associated with a significant reduction of SBP (Mean Difference [MD] -6.39; [95%CI -9.21, -3.56] p < 0.001), DBP (MD -4.19, [95%CI -5.48, -2.89; p < 0.001], TC (MD -24.95, [95%CI -33.86, -16.04]; p < 0.001), and LDL-C (MD -27.92, [95%CI -35.39, -20.44]; p < 0.001). Polypill use was also associated with a significant reduction of CVD mortality (RR = 0.78; 95% CI (0.61, 0.99); P = 0.04) and MACE [RR = 0.76;95% CI (0.64, 0.91); P = 0.002]. CONCLUSION This meta-analysis showed that compared to standard of care, polypill use was associated with a significant reduction of SBP, DBP, TC, LDL-C, and a significant reduction in fatal and non-fatal cardiovascular events.
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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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Treatment of thrombotic antiphospholipid syndrome in adults and children.
Madison, JA, Duarte-García, A, Zuo, Y, Knight, JS
Current opinion in rheumatology. 2020;(3):215-227
Abstract
PURPOSE OF REVIEW Antiphospholipid syndrome (APS), more common than once believed, is an autoimmune disease best known for its high risk of incident and recurrent thrombotic events. The approach to treatment potentially differs from treatment of thrombosis in the general population, and this article endeavors to review the latest updates on this topic. RECENT FINDINGS The epidemiology of APS is being increasingly elucidated by large population-based studies, with APS perhaps affecting as many as 1 in 2000 individuals. Vitamin K antagonists, aspirin, and heparinoids continue to have obvious roles in the management of patients with APS. There has recently been intensive study of direct oral anticoagulants in APS, with the most recent randomized studies raising concerns about their inferiority to vitamin K antagonists, at least in some subgroups. Other approaches to treating APS beyond anticoagulants and antiaggregants are also receiving increased attention in mechanistic and preclinical studies with an eye toward future roles in patients with refractory and/or microvascular disease. Pediatric APS is identified as an area in desperate need of additional prospective research. SUMMARY Progress continues to be made in pursuit of improving the lives of individuals afflicted with APS. The most important future directions would seem to involve leveraging modern molecular technologies in order to improve subphenotyping of antiphospholipid antibody-positive individuals. This will help personalize risk profiles and ideally define the optimal approach to therapy based on future risk, rather than past morbid events.
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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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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.
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Long-Term Management of Venous Thromboembolism: Lessons from EINSTEIN CHOICE and Other Extension Trials.
Weitz, JI, Chan, NC
Thrombosis and haemostasis. 2019;(5):689-694
Abstract
Many patients with venous thromboembolism (VTE) are at risk of recurrence if anticoagulant therapy is stopped. Whereas 3 months of anticoagulation treatment is sufficient for patients with VTE provoked by major surgery or trauma, in many cases a longer course is needed. Extended therapy with vitamin K antagonists (VKAs) requires frequent coagulation monitoring and dose adjustments to ensure that the international normalized ratio (INR) remains within the therapeutic range; furthermore, there is a risk of major bleeding even if a therapeutic INR is maintained. Therefore, more convenient and safer anticoagulants are needed.The non-VKA oral anticoagulants (NOACs)-apixaban, dabigatran, edoxaban and rivaroxaban-simplify extended therapy because they can be given in fixed doses without routine coagulation monitoring. Randomized clinical trials have demonstrated the efficacy and safety of NOACs for extended VTE treatment, but bleeding remains a concern. Patients and physicians may, therefore, be reluctant to continue anticoagulation beyond 3 to 6 months except in patients at high risk of recurrence. Acetylsalicylic acid (ASA) is often prescribed instead of an anticoagulant because of its perceived lower risk of bleeding; however, the recent EINSTEIN CHOICE trial demonstrated that once-daily rivaroxaban at a dose of either 20 or 10 mg reduced the risk of recurrent VTE by 70% compared with ASA without significantly increasing the risk of bleeding. In this review, we discuss the EINSTEIN CHOICE trial in the context of previous trials for extended VTE treatment and examine some of the lessons that can be applied to clinical practice.
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Prescription of Aspirin and Statins in Primary Prevention.
Hennekens, CH, Schuttenberg, N, Pfeffer, MA
Primary care. 2019;(1):13-25
Abstract
The increasing burden of cardiovascular disease worldwide, including the United States, underscores the need for the more widespread use of adjunctive drug therapies of proven net benefit in the primary prevention of cardiovascular disease. These include aspirin to reduce mortality from cardiovascular disease, statins to lower LDL-cholesterol levels, appropriate use of multiple antihypertensive drug therapies to lower blood pressure, and aggressive multifactorial management of diabetes. This article reviews randomized evidence to provide guidance to primary care providers regarding the use of adjunctive drug therapies.
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Clinical updates in aspirin-exacerbated respiratory disease.
Laidlaw, TM
Allergy and asthma proceedings. 2019;(1):4-6
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Abstract
Background: Aspirin-exacerbated respiratory disease (AERD), a syndrome that includes asthma, recurrent nasal polyps, and pathognomonic reactions to aspirin and other nonselective cyclooxygenase inhibitors, is still not fully understood and lacks specific disease-modifying therapeutic options. Objective: To review the most recent clinical updates in the evaluation and treatment of patients with AERD. Methods: Recent clinical research studies relevant to patients with AERD were reviewed. Results: Multiple new biologics are available for the treatment of severe asthma, several of which have been specifically studied and determined to be efficacious in the subset of patients with asthma who are also aspirin sensitive. Zileuton continues to be underprescribed for AERD and is considered to be very effective by many patients with AERD. Dietary modifications toward a diet that is high in omega-3 fatty acids and low in omega-6 fatty acids can reduce the production of the inflammatory leukotriene and prostaglandin D₂ lipids and help improve symptoms for patients with AERD. Conclusion: A lack of definitive understanding of the causative mechanisms of AERD and the absence of an AERD-specific patient-reported outcome measure are obstacles that remain in this field, but much progress has been made over the past decade.
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Integrative Medicine on Optimizing Clopidogrel and Aspirin Therapy.
Chen, H
Chinese journal of integrative medicine. 2019;(5):395-400
Abstract
This article reviews the available published data on optimizing clopidogrel and aspirin therapy using translational and integrative medicine. Translational and evidence-based medical studies show that the CYP2C19 gene mutation (CYP2C19*2 and CYP2C19*3) could affect > 50% of the Chinese population, and that this mutation is closely associated with clopidogrel resistance and an increased risk of major adverse cardiovascular events, particularly stent thrombosis in patients following percutaneous coronary intervention (PCI). Adjusted-dose warfarin and aspirin reduce stroke in patients with atrial fibrillation (AF), and warfarin is substantially more efficacious than aspirin. However, a poor compliance is a big problem in warfarin use especially in China. The genetic variants of vitamin K expoxide reductase might account for the universally lower warfarin dosage used in Chinese population. The available evidence indicates that the integrating mainstream treatments (e.g., clopidogrel, CYP2C19 genotyping) and non-mainstream medicines [e.g., Chinese medicines, Naoxintong Capsule (, NXT)] to treat CYP2C19 gene mutation patients following PCI can be effective. Aspirin combined NXT and the adjusted-dose warfarin was equally effective in elderly patients with non-valvular AF in prevention of ischemic stroke.
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Effects of six types of aspirin combination medications for treatment of acute cerebral infarction in China: A network meta-analysis.
Jin, L, Zhou, J, Shi, W, Xu, L, Sheng, J, Fan, J, Yuan, Y, Yuan, H
Journal of clinical pharmacy and therapeutics. 2019;(1):91-101
Abstract
WHAT IS KNOWN AND OBJECTIVE Previous studies have shown that various aspirin combinations might be beneficial for the treatment of acute cerebral infarction (ACI). The aim of this study was to evaluate the efficacy of six aspirin combinations in the treatment of ACI using network meta-analysis (NMA). The performance of these combinations is then ranked according to results of this analysis. METHODS Multiple databases were consulted to find randomized controlled trials (RCT) of six different aspirin combinations for the treatment of ACI. NMA was conducted on the data using stata (13.0) software. The odds ratio (OR) was calculated. The studies included in this paper were divided into a control group (aspirin alone) and an observation group (one of six aspirin combinations). RESULTS A total of 103 eligible RCTs were identified. A total of 13 317 cases were included in the study, and the results showed that the six types of aspirin combinations (aspirin with atorvastatin, ozagrel sodium, low molecular weight heparin [LMWH], clopidogrel, cilostazol and ginkgo damo) were all significantly superior (P < 0.05) to aspirin alone. The combination of aspirin with LMWH had the highest probability of being the most clinically efficacious intervention, with a surface under the cumulative ranking (SUCRA) curve of 79.1. The combination of aspirin with ozagrel sodium was the worst, with a SUCRA value of 29.7. WHAT IS NEW AND CONCLUSION A combination of aspirin with LMWH is the best option among the six aspirin combinations considered for the treatment of ACI. The combination of aspirin with ozagrel sodium was ranked the last.