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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.
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Development of New Antithrombotic Regimens for Patients with Acute Coronary Syndrome.
George, S, Onwordi, ENC, Gamal, A, Zaman, A
Clinical drug investigation. 2019;(6):495-502
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Abstract
Patients with acute coronary syndrome (ACS) require long-term antithrombotic intervention to reduce the risk of further ischemic events; dual antiplatelet therapy with a P2Y12 inhibitor and acetylsalicylic acid (ASA) is the current standard of care. However, pivotal clinical trials report that patients receiving this treatment have a residual risk of approximately 10% for further ischemic events. The development of non-vitamin K antagonist oral anticoagulants (NOACs) has renewed interest in a 'dual pathway' strategy, targeting both the coagulation cascade and platelet component of thrombus formation. In the phase III ATLAS ACS 2 TIMI 51 trial, a 'triple therapy' approach (NOAC plus dual antiplatelet therapy) showed reduced ischemic events with rivaroxaban 2.5 mg twice daily, albeit at an increased risk of bleeding. Two studies have investigated the role of NOACs in combination with a P2Y12 inhibitor, with or without ASA, in reducing bleeding risk in patients with atrial fibrillation undergoing percutaneous coronary intervention; two further studies are underway. Although these trials will help to inform optimal treatment protocols for secondary prevention of ACS, an individualized approach to treatment will be needed, taking account of the high frequency of co-morbid conditions found in this patient population.
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Anti-Aggregatory Potential of Selected Vegetables-Promising Dietary Components for the Prevention and Treatment of Cardiovascular Disease.
Olas, B
Advances in nutrition (Bethesda, Md.). 2019;(2):280-290
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Abstract
Increased blood platelet activation, especially platelet aggregation, plays an important function in cardiovascular disease; however, various dietary components may inhibit platelet activation. Recent clinical and epidemiologic studies indicate that both fruits and vegetables, and their products, contain various phytoprotective substances possessing biological properties such as antiplatelet and antioxidant effects that may work synergistically to ameliorate the effect of cardiovascular disease. In addition, the consumption of vegetables and their products may also play an important role in prevention. However, the mechanisms involved have not been clearly defined. Various studies clearly indicate that certain vegetables (e.g., onions, garlic, and tomatoes) have beneficial effects on blood platelet hyperactivity, an important cardiovascular risk factor, and hence may offer new prophylactic and therapeutic possibilities for the treatment of blood platelet hyperactivation and cardiovascular disease. This mini-review evaluates the current literature on the relationship between the consumption of onion (Allium cepa L.), garlic (Allium sativum L.), tomato (Solanum lycopersicum L.), and beetroot (Beta vulgaris L.), and blood platelet activation, which may have important implications for the prophylaxis and treatment of cardiovascular disease.
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Economic evaluation of the use of non-vitamin K oral anticoagulants in patients with atrial fibrillation on antiplatelet therapy: a modelling analysis using the healthcare system in the Netherlands.
Bennaghmouch, N, de Veer, AJWM, Mahmoodi, BK, Jofre-Bonet, M, Lip, GYH, Bode, K, Ten Berg, JM
European heart journal. Quality of care & clinical outcomes. 2019;(2):127-135
Abstract
AIMS: Non-vitamin K oral anticoagulants (NOACs) have consistently demonstrated superior efficacy in terms of stroke prevention and safety in terms of bleeding over vitamin K antagonist (VKA) in patients with non-valvular atrial fibrillation (AF). The potential use of NOACs in AF patients requiring antiplatelet therapy (APT) has only been assessed in small meta-analyses reporting consistent benefits of NOACs over VKAs. However, the prescription costs of NOACs are higher than those of VKAs. The aim of his study was to estimate the cost-effectiveness (CE) of NOACs compared to VKAs in patients with non-valvular AF also requiring APT with the Dutch healthcare system used as a surrogate of many European healthcare systems. METHODS AND RESULTS A decision tree was constructed to analyse the CE of NOACs compared to VKAs in patients with non-valvular AF with an indication for APT over a horizon of 1 year. Beside the base-case analysis, univariate probabilistic sensitivity and two sensitivity analyses were performed: first, we assessed the impact of VKA home monitoring; second, we varied the NOACs price assuming patent expiration. Use of NOACs instead of VKA is associated with a health gain of 0.0171 quality-adjusted life years (QALYs) and with an incremental cost of €357, resulting in an incremental cost-effectiveness ratio of €20 919, which is almost equal to the generally accepted CE threshold of €20 000 used in the Netherlands. The probability that NOACs are cost-effective at a conservative willingness-to-pay threshold of €20 000 per QALY was 50%. Introducing home monitoring increased VKAs costs so much that NOACs became the dominant option (less costly and more effective). Price drops associated to patent expiration of NOACs increased its CE. CONCLUSION This analysis suggests that the use of NOACs is a cost-effective alternative of VKAs in patients with AF needing APT. Our findings in the Netherlands healthcare system are probably consistent with other European populations.
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Benefits and Risks of Anticoagulation in Acute Coronary Syndrome.
Pop, C, Matei, C
American journal of therapeutics. 2019;(2):e198-e207
Abstract
BACKGROUND Both antiplatelets and anticoagulants are necessary in the management of acute coronary syndrome (ACS), although the exact proportion of antithrombotic effect that each drug and class should ideally provide remains a matter of ongoing study. AREA OF UNCERTAINTY Defining the best combination between the antiplatelet agents and oral anticoagulants (OACs) can be challenging. The choice is particularly important for special categories of patients with ACS who have an indication of a long-term OAC. DATA SOURCES A literature search regarding benefits and risks of anticoagulation in ACS was conducted through MEDLINE and EMBASE (past 20 years until September 2018). THERAPEUTIC ADVANCES Many patients with ACS have an indication for long-term OACs. Those receiving dual antiplatelet therapy and anticoagulants are considered to be at a high bleeding risk. The addition of a vitamin K antagonist (VKA) imposes a target international normalized ratio of 2.0-3.0. When non-VKA oral anticoagulants are used, the lowest effective tested dose for stroke prevention should be applied. For most patients, triple therapy in the form of an OAC plus dual antiplatelet therapy [aspirin and P2Y12 inhibitors (usually clopidogrel)] should be considered for 3-6 months. Later, dual therapy (OAC plus aspirin or clopidogrel) should be considered for an additional 6 months. After 1 year, it is recommended that only the OAC is maintained. In cases of very high bleeding risk, triple therapy can be reduced to 1 month after ACS, continuing on dual therapy up to 1 year, and thereafter only anticoagulation. In general, the bleeding risk seems to be lower with non-VKA oral anticoagulants than VKA plus antiplatelet combination. CONCLUSIONS Many risk factors for ischemic events and bleeding overlap. The clinician's challenges include monitoring patients' adherence and global assessment of the antithrombotic effect that incorporates antiplatelet and anticoagulant effects.
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Dual (Anticoagulant Plus Single Antiplatelet) vs Triple (Anticoagulant Plus Dual Antiplatelet) Antithrombotic Therapy - "Real World" Experience.
Effron, MB, Gibson, CM
Progress in cardiovascular diseases. 2018;(4-5):531-536
Abstract
Atrial fibrillation (AF) is a common arrhythmia that increases in prevalence with advancing age and in patients with coronary artery disease, revascularization, particularly with percutaneous coronary intervention (PCI), is also common. Both disease states have thrombosis as a core pathophysiologic process which requires treatment - low sheer stress thrombi in AF and intracoronary high sheer stress thrombi in PCI. For the 10-20% of patients who have both AF and undergo PCI, preventing thrombotic complications will require inhibition of both processes requiring simultaneous use of anticoagulation and antiplatelet therapy. There is a broad experience of combining oral anticoagulation therapy, used to prevent stroke and systemic embolization, in AF with dual antiplatelet therapy, used to prevent stent thrombosis and thrombotic coronary events. This "triple antithrombotic therapy" (TT) has been evaluated through many observation studies, both small and large. TT has more frequently been associated with a significant increase in bleeding events with non-significant reduction in thrombotic events. Current guidelines recommend shorter duration of TT, especially in patients with high risk of bleeding.
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Duration of Dual Antiplatelet Therapy Following Drug-Eluting Stent Implantation in Diabetic and Non-Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Sharma, A, Garg, A, Elmariah, S, Drachman, D, Obiagwu, C, Vallakati, A, Sharma, SK, Lavie, CJ, Mukherjee, D, Waksman, R, et al
Progress in cardiovascular diseases. 2018;(4-5):500-507
Abstract
BACKGROUND Diabetic patients account for an increasing number of patients undergoing percutaneous coronary intervention (PCI). However, diabetes mellitus (DM) is associated with increased residual platelet activity during dual antiplatelet treatment (DAPT) and DM patients have worse clinical outcomes after PCI as compared to non-DM. OBJECTIVE To evaluate efficacy and safety of short duration DAPT (S-DAPT) and long duration DAPT (L-DAPT) after drug eluting stent (DES) implantation in DM and non-DM patients. METHODS We searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials (RCTs) assessing the effect of S-DAPT versus L-DAPT after DES implantation in DM and non-DM patients. Efficacy endpoints were all-cause mortality, cardiac mortality, myocardial infarction (MI), stent thrombosis (ST), target vessel revascularization (TVR), and composite end point of net adverse clinical events (NACE) (all-cause mortality, cardiac mortality, MI, ST, TVR, stroke, major bleeding). Safety endpoints were major bleeding and stroke. Event rates were compared using a forest plot of relative risk using a random effects model. RESULTS We included eight RCTs that randomized 28,318 patients to S-DAPT versus L-DAPT (8234 DM and 20,084 non-DM). S-DAPT was associated with an increased rate of ST in non-DM patients [3.67 (2.04, 6.59)]. There was no significant difference in the rate of all-cause mortality, cardiac mortality, ST, MI, TVR, major bleeding, stroke and NACE with S-DAPT and L-DAPT in DM patients [1.19 (0.72-1.95); 1.25 (0.69, 2.25); 1.52 (0.70, 3.29); 1.33 (0.88, 2.01); 1.39 (0.89, 2.17); 0.92 (0.19, 4.42); 0.98 (0.29, 3.28); and 0.94 (0.57, 1.54) respectively]. Further, there was no significant difference in the rate of all-cause mortality, cardiac mortality, MI, TVR, major bleeding, stroke and NACE with S-DAPT and L-DAPT in non-DM patients [0.93 (0.58, 1.48); 0.75 (0.42, 1.35); 1.52 (0.81, 2.83); 0.99 (0.71, 1.39); 0.72 (0.28, 1.84); 1.01 (0.40, 2.56); and 1.01 (0.77, 1.32) respectively]. CONCLUSION Compared to L-DAPT, S-DAPT was associated with significant increase in rate of ST in non-DM patients. Duration of DAPT had no significant impact on rates of all-cause mortality, cardiac mortality, MI, ST and TVR among DM patients.
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Antiplatelet and anticoagulant agents for primary prevention of thrombosis in individuals with antiphospholipid antibodies.
Bala, MM, Paszek, E, Lesniak, W, Wloch-Kopec, D, Jasinska, K, Undas, A
The Cochrane database of systematic reviews. 2018;(7):CD012534
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Abstract
BACKGROUND Antiphospholipid syndrome (APS) is an autoimmune disease characterised by the presence of antiphospholipid (aPL) antibodies that have prothrombotic activity. Antiphospholipid antibodies are associated with an increased risk of pregnancy complications (recurrent miscarriage, premature birth, intrauterine growth retardation) and thrombotic events (both arterial and venous). The most common thrombotic events include brain ischaemia (stroke or transient ischaemic attack) and deep vein thrombosis. To diagnose APS, the presence of aPL antibodies in two measurements and at least one thrombotic event or pregnancy complication are required. It is unclear if people with positive aPL antibodies but without any previous thrombotic events should receive primary antithrombotic prophylaxis. OBJECTIVES To assess the effects of antiplatelet or anticoagulant agents versus placebo or no intervention or other intervention on the development of thrombosis in people with aPL antibodies who have not had a thrombotic event. We did not address obstetric outcomes in this review as these have been thoroughly addressed by other Cochrane Reviews. SEARCH METHODS We searched the Cochrane Vascular Specialised Register (4 December 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (last search 29 November 2017), MEDLINE Ovid, Embase Ovid, CINAHL, and AMED (searched 4 December 2017), and trials registries (searched 29 November 2017). We also checked reference lists of included studies, systematic reviews, and practice guidelines, and contacted experts in the field. SELECTION CRITERIA We included randomised controlled trials (RCTs) that compared any antiplatelet or anticoagulant agents, or their combinations, at any dose and mode of delivery with placebo, no intervention, or other intervention. We also included RCTs that compared antiplatelet or anticoagulant agents with each other or that compared two different doses of the same drug. We included studies performed in people of any age and with no history of thrombosis (as defined by APS Sapporo classification criteria or updated Sydney classification criteria), but with aPL antibodies confirmed on at last two separate measurements. The studies included both pregnant women who tested positive for aPL antibodies and had a history of recurrent obstetric complications, as well as non-pregnancy related cases with positive screening for antibodies, in accordance with the criteria mentioned above. DATA COLLECTION AND ANALYSIS Pairs of authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies and quality of evidence using GRADE. Any discrepancies were resolved through discussion or by consulting a third review author when necessary. In addition, one review author checked all the extracted numerical data. MAIN RESULTS We included nine studies involving 1044 randomised participants. The studies took place in several countries and had different funding sources. No study was at low risk of bias in all domains. We classified all included studies as at unclear or high risk of bias in two or more domains. Seven included studies focused mainly on obstetric outcomes. One study included non-pregnancy-related cases, and one study included both pregnancy-related cases and other patients with positive results for aPL antibodies. The remaining studies concerned women with aPL antibodies and a history of pregnancy failure. Four studies compared anticoagulant with or without acetylsalicylic acid (ASA) versus ASA only and observed no clear difference in thrombosis risk (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.25 to 3.77; 4 studies; 493 participants; low-quality evidence). No major bleeding was reported, but minor bleeding risk (nasal bleeding, menorrhagia) was higher in the anticoagulant with ASA group as compared with ASA alone in one study (RR 22.45, 95% CI 1.34 to 374.81; 1 study; 164 participants; low-quality evidence). In one study ASA was compared with placebo, and there were no clear differences in thrombosis (RR 5.21, 95% CI 0.63 to 42.97; 1 study; 98 participants; low-quality evidence) or minor bleeding risk between the groups (RR 3.13, 95% CI 0.34 to 29.01; 1 study; 98 participants; low-quality evidence), and no major bleeding was observed. Two studies compared ASA with low molecular weight heparin (LMWH) versus placebo or intravenous immunoglobulin (IVIG), and no thrombotic events were observed in any of the groups. Moreover, there were no clear differences in the risk of bleeding requiring transfusion (RR 9.0, 95% CI 0.49 to 164.76; 1 study; 180 participants; moderate-quality evidence) or postpartum bleeding (RR 1.30, 95% CI 0.60 to 2.81; 1 study; 180 participants; moderate-quality evidence) between the groups. Two studies compared ASA with high-dose LMWH versus ASA with low-dose LMWF or unfractionated heparin (UFH); no thrombotic events or major bleeding was reported. Mortality and quality of life data were not reported for any of the comparisons. AUTHORS' CONCLUSIONS There is insufficient evidence to demonstrate benefit or harm of using anticoagulants with or without ASA versus ASA alone in people with aPL antibodies and a history of recurrent pregnancy loss and with no such history; ASA versus placebo in people with aPL antibodies; and ASA with LMWH versus placebo or IVIG, and ASA with high-dose LMWH versus ASA with low-dose LMWH or UFH, in women with aPL antibodies and a history of recurrent pregnancy loss, for the primary prevention of thrombotic events. In a mixed population of people with a history of previous pregnancy loss and without such a history treated with anticoagulant combined with ASA, the incidence of minor bleeding (nasal bleeding, menorrhagia) was increased when compared with ASA alone. Studies that are adequately powered and that focus mainly on thrombotic events are needed to draw any firm conclusions on the primary prevention of thrombotic events in people with antiphospholipid antibodies.
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[Oral anticoagulants in elderly patients with coronary artery disease and atrial fibrillation].
Gallet, R, Teiger, E
Annales de cardiologie et d'angeiologie. 2018;(6):404-410
Abstract
Anti-thrombotic management of percutaneous coronary intervention and atrial fibrillation relies on dual antiplatelet therapy and anticoagulation respectively. Because of people ageing, the coexistence of coronary artery disease and atrial fibrillation is increasing. This coexistence raises concerns about the anti-thrombotic strategy, particularly about the association of dual antiplatelet therapy and anticoagulation, known as triple therapy. This triple therapy is responsible for a dramatic increase in bleeding risk (3-4 fold) especially in elderlies. However, older patients are also at increased risk of ischemic events. In this setting, dual anti-thrombotic strategies combining non-vitamin K oral anticoagulants and a P2Y12 inhibitor have been developed. These strategies provide a net benefit by reducing bleeding events. Therefore, they are becoming an attractive alternative, especially for frailer patient. This article reviews the rational, risks and strategies of anti-thrombotic therapy in elderly people with coronary artery disease and atrial fibrillation.
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Concomitant Use of Antiplatelets and Anticoagulants in Patients with Coronary Heart Disease and Atrial Fibrillation: What Do Recent Clinical Trials Teach Us?
Lam, DH, Bell, SM, Hira, RS
Current atherosclerosis reports. 2018;(1):4
Abstract
PURPOSE OF REVIEW Coronary heart disease (CHD) and atrial fibrillation (AF) are among the most common cardiovascular diseases. A significant proportion of patients have both CHD and AF and are at increased risk for thrombotic complications. Current therapy for CHD and AF includes antiplatelet and anticoagulant medications, respectively. Patients with concurrent CHD and AF may be prescribed dual antiplatelet therapy (DAPT) in addition to anticoagulation, which increases their bleeding risk. Controversy remains on how to balance risks and benefits in patients with CHD and AF in which multiple antithrombotic therapies may be indicated. RECENT FINDINGS We review clinical trials and current guidelines for antiplatelet and anticoagulant therapy in CHD and AF. Aspirin and P2Y12 inhibitors are the mainstay of antiplatelet therapy. Vitamin K antagonists (VKAs) are the most commonly used anticoagulant, although the use of non-VKA oral anticoagulants (NOACs) in patients with AF is increasing. Recent studies provide guidance on how to address antithrombotic therapies in patients with concomitant CHD and AF. To date, we have evidence that in patients with AF who undergo percutaneous coronary intervention (PCI), clopidogrel with VKA may be used safely without aspirin. Also, low-dose rivaroxaban in combination with either clopidogrel only or DAPT is as effective as the traditional regimen of triple therapy with VKA and DAPT with lower bleeding risk. Dabigatran with a P2Y12 inhibitor was also found to be safe with less bleeding compared to triple therapy with VKA and DAPT. Use of a single antiplatelet agent with anticoagulation has become a viable choice in patients with CHD and AF, but more clinical trial data is needed to confirm therapy and duration regimens.