-
1.
Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial.
Kasner, SE, Swaminathan, B, Lavados, P, Sharma, M, Muir, K, Veltkamp, R, Ameriso, SF, Endres, M, Lutsep, H, Messé, SR, et al
The Lancet. Neurology. 2018;(12):1053-1060
-
-
Free full text
-
Abstract
BACKGROUND Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. METHODS NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. FINDINGS Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22-1·36), and the risk was similar for those without known PFO (1·06; 0·84-1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51-8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69-4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24-0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. INTERPRETATION Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. FUNDING Bayer and Janssen.
-
2.
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.
-
3.
Effects of Ramadan fasting on aspirin resistance in type 2 diabetic patients.
Bouida, W, Beltaief, K, Baccouche, H, Sassi, M, Dridi, Z, Trabelsi, I, Laaouiti, K, Chakroun, T, Hellara, I, Boukef, R, et al
PloS one. 2018;(3):e0192590
Abstract
AIMS: Ramadan fasting (RF) may affect aspirin resistance. We conducted this study in patients with cardiovascular risk (CVR) factors to assess the effect of RF on aspirin resistance and explore whether type 2 diabetes mellitus (DM) would influence this effect. METHODS A total of 177 stable patients with ≥2 CVR factors were recruited. All patients observed RF and were taking aspirin. Physical exam and standard biological tests including glycaemia and serum lipids data were performed before Ramadan (Pre-R), at the last week of Ramadan (R) and four weeks after the end of Ramadan (Post-R). In the same visits caloric intake was calculated and platelet reactivity to aspirin was assessed using Verify Now point-of-care assay. RESULTS In the overall population, there was no significant change in absolute aspirin reaction unit (ARU) values and in metabolic parameters. In DM patients (n = 127), ARU change from Pre-R values was+19.7 (p = 0.01) and +14.4 (p = 0.02) respectively at R and Post-R. During Ramadan, glycaemia, triglycerides, and cholesterol levels increased significantly and returned to Pre-R values thereafter. These changes were not observed in non-DM patients. CONCLUSIONS During RF aspirin resistance increased only in DM patients. This effect persisted one month after Ramadan. Simultaneous alteration of glycemic control and increase of serum lipids levels could potentially be a favorable factor. STUDY REGISTRATION The protocol was registered at clinicaltrials.gov under: NCT02720133.
-
4.
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.
-
5.
The Incidence of Myocardial Injury after Loading Doses of Clopidogrel versus Prasugrel in the Candidates for Percutaneous Coronary Intervention: A Randomized Controlled Trial.
Rahmani, R, Jiriaee, L, Jiriaee, Z, Shafiee, A, Zand Parsa, AF
Critical pathways in cardiology. 2018;(2):69-72
Abstract
INTRODUCTION Prevention of myocardial injury is an essential issue in percutaneous coronary intervention (PCI). We compared the incidence of myocardial injury after loading doses of clopidogrel versus prasugrel in the candidates for PCI. METHODS In this randomized-controlled clinical trial, we enrolled 88 stable angina patients, candidate for PCI. Patients received either prasugrel (60 mg orally) (n = 42) or clopidogrel (600 mg orally) (n = 46). Serum levels of creatine phosphokinase muscle-brain type, cardiac troponin I, and high sensitive C-reactive protein were measured at baseline and 6 and 12 hours postprocedural. Primary endpoint was periprocedural myocardial infarction (MI), defined as elevation of cTn values (>5 times) in patients with normal baseline values or a rise of cTn values >20% if the baseline values are elevated. RESULTS Based on the levels of cTnI 6 hours after PCI, 1 patient (2.4%) had MI in the prasugrel group, whereas 4 patients (8.7%) had MI in the clopidogrel group. After 12 hours, 4 patients (9.5%) had MI in the prasugrel group versus 5 patients (10.9%) in the clopidogrel arm. There was no significant difference between the groups regarding the changes in cardiac specific enzyme levels. However, serum levels of cTnI were significantly lower in patients with myocardial injury in the prasugrel arm (P < 0.001). CONCLUSIONS Prasugrel is an effective antiplatelet drug in preventing periprocedural MI.
-
6.
Lipid Effects of Icosapent Ethyl in Women with Diabetes Mellitus and Persistent High Triglycerides on Statin Treatment: ANCHOR Trial Subanalysis.
Brinton, EA, Ballantyne, CM, Guyton, JR, Philip, S, Doyle, RT, Juliano, RA, Mosca, L
Journal of women's health (2002). 2018;(9):1170-1176
-
-
Free full text
-
Abstract
BACKGROUND High triglycerides (TG) and diabetes mellitus type 2 (DM2) are stronger predictors of cardiovascular disease (CVD) in women than in men, but few randomized, controlled clinical trials have investigated lipid-lowering interventions in women and none have reported results specifically in women with high TG and DM2. Icosapent ethyl (Vascepa) is pure prescription eicosapentaenoic acid (EPA) ethyl ester approved at 4 g/day as an adjunct to diet to reduce TG ≥500 mg/dL. METHODS The 12-week ANCHOR trial randomized 702 statin-treated patients (73% with DM; 39% women) at increased CVD risk with TG 200-499 mg/dL despite controlled low-density lipoprotein cholesterol (LDL-C; 40-99 mg/dL) to receive icosapent ethyl 2 g/day, 4 g/day, or placebo. This post hoc analysis included 146 women with DM2 (97% white, mean age 62 years) randomized to icosapent ethyl 4 g/day (n = 74) or placebo (n = 72). RESULTS Icosapent ethyl significantly reduced TG (-21.5%; p < 0.0001) without increasing LDL-C and lowered other potentially atherogenic lipid/lipoprotein, apolipoprotein, and inflammatory parameters versus placebo. Icosapent ethyl increased EPA levels in plasma (+639%; p < 0.0001; n = 49) and red blood cells (+599%; p < 0.0001; n = 47) versus placebo. Safety and tolerability of icosapent ethyl were generally similar to placebo. CONCLUSION In women with DM2 at high CVD risk with persistently high TG on statins, icosapent ethyl 4 g/day reduced potentially atherogenic parameters with safety and tolerability comparable to placebo. Potential CVD benefits of icosapent ethyl are being tested in ∼8000 men and women at high CVD risk with high TG on statins in the ongoing Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial (REDUCE-IT) cardiovascular (CV) outcome trial.
-
7.
A randomized multicentre trial to compare revascularization with optimal medical therapy for the treatment of chronic total coronary occlusions.
Werner, GS, Martin-Yuste, V, Hildick-Smith, D, Boudou, N, Sianos, G, Gelev, V, Rumoroso, JR, Erglis, A, Christiansen, EH, Escaned, J, et al
European heart journal. 2018;(26):2484-2493
Abstract
AIMS: The clinical value of percutaneous coronary intervention (PCI) for chronic coronary total occlusions (CTOs) is not established by randomized trials. This study should compare the benefit of PCI vs. optimal medical therapy (OMT) on the health status in patients with at least one CTO. METHOD AND RESULTS Three hundred and ninety-six patients were enrolled in a prospective randomized, multicentre, open-label, and controlled clinical trial to compare the treatment by PCI with OMT with a 2:1 randomization ratio. The primary endpoint was the change in health status assessed by the Seattle angina questionnaire (SAQ) between baseline and 12 months follow-up. Fifty-two percent of patients have multi-vessel disease in whom all significant non-occlusive lesions were treated before randomization. An intention-to-treat analysis was performed including 13.4% failed procedures in the PCI group and 7.3% cross-overs in the OMT group. At 12 months, a greater improvement of SAQ subscales was observed with PCI as compared with OMT for angina frequency [5.23, 95% confidence interval (CI) 1.75; 8.71; P = 0.003], and quality of life (6.62, 95% CI 1.78-11.46; P = 0.007), reaching the prespecified significance level of 0.01 for the primary endpoint. Physical limitation (P = 0.02) was also improved in the PCI group. Complete freedom from angina was more frequent with PCI 71.6% than OMT 57.8% (P = 0.008). There was no periprocedural death or myocardial infarction. At 12 months, major adverse cardiac events were comparable between the two groups. CONCLUSION Percutaneous coronary intervention leads to a significant improvement of the health status in patients with stable angina and a CTO as compared with OMT alone. TRIAL REGISTRATION NCT01760083.
-
8.
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
-
-
Free full text
-
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.
-
9.
[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.
-
10.
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.