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Dual therapy with an oral non-vitamin K antagonist and a P2Y12 inhibitor vs triple therapy with aspirin, a P2Y12 inhibitor and a vitamin K antagonist for the treatment of diabetes mellitus patients with co-existing atrial fibrillation following percutaneous coronary intervention: A meta-analysis.
Wang, Q, Yang, K
Medicine. 2021;(15):e25546
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Abstract
BACKGROUND In this analysis, we aimed to compare the efficacy and safety of dual therapy (DT) with a non-vitamin K oral anticoagulant (NOAC) and an adenosine diphosphate receptor antagonist (P2Y12 inhibitor) vs triple therapy (TT) with aspirin, a P2Y12 inhibitor and a vitamin K antagonist for the treatment of diabetes mellitus (DM) patients with co-existing atrial fibrillation (AF) following percutaneous coronary intervention (PCI). METHODS Medical Literature Analysis and Retrieval System Online (MEDLINE), http://www.ClinicalTrials.gov, Excerpta Medical data BASE (EMBASE), Web of Science, Cochrane Central and Google Scholar were the searched databases. Studies that were randomized trials or observational studies comparing DT vs TT for the treatment of DM patients with co-existing AF following PCI were included in this analysis. The adverse cardiovascular outcomes and bleeding events were the endpoints. This meta-analysis was carried out by the RevMan version 5.4 software. Risk ratios (RR) with 95% confidence intervals (CI) were used to represent data and interpret the analysis. RESULTS A total number of 4970 participants were included whereby 2456 participants were assigned to the DT group and 2514 participants were assigned to the TT group. The enrollment period varied from year 2006 to year 2018. Our current results showed that major adverse cardiac events (RR: 1.00, 95% CI: 0.84-1.20; P = .98), mortality (RR: 1.08, 95% CI: 0.78-1.48; P = .66), myocardial infarction (RR: 1.02, 95% CI: 0.74-1.42; P = .90), stroke (RR: 0.94, 95% CI: 0.53-1.67; P = .84) and stent thrombosis (RR: 1.09, 95% CI: 0.56-2.10; P = .80) were similar with DT versus TT in these patients. However, the risks for total major bleeding (RR: 0.66, 95% CI: 0.54-0.82; P = .0001), total minor bleeding (RR: 0.74, 95% CI: 0.64-0.85; P = .0001), Thrombolysis in Myocardial Infarction (TIMI) defined major bleeding (RR: 0.58, 95% CI: 0.35-0.95; P = .03), TIMI defined minor bleeding (RR: 0.62, 95% CI: 0.42-0.92; P = .02), intra-cranial bleeding (RR: 0.34, 95% CI: 0.13-0.95; P = .04) and major bleeding defined by the International Society on Thrombosis and Hemostasis (RR: 0.68, 95% CI: 0.51-0.90; P = .008) were significantly higher with TT. CONCLUSIONS DT with a NOAC and a P2Y12 inhibitor was associated with significantly less bleeding events without increasing the adverse cardiovascular outcomes when compared to TT with aspirin, a P2Y12 inhibitor and a Vitamin K antagonist for the treatment of DM patients with co-existing AF following PCI. Hence, DT is comparable in efficacy, but safer compared to TT. This interesting hypothesis will have to be confirmed in future studies.
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Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD): an open-label, randomised, non-inferiority trial.
Engelter, ST, Traenka, C, Gensicke, H, Schaedelin, SA, Luft, AR, Simonetti, BG, Fischer, U, Michel, P, Sirimarco, G, Kägi, G, et al
The Lancet. Neurology. 2021;(5):341-350
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Abstract
BACKGROUND Cervical artery dissection is a major cause of stroke in young people (aged <50 years). Historically, clinicians have preferred using oral anticoagulation with vitamin K antagonists for patients with cervical artery dissection, although some current guidelines-based on available evidence from mostly observational studies-suggest using aspirin. If proven to be non-inferior to vitamin K antagonists, aspirin might be preferable, due to its ease of use and lower cost. We aimed to test the non-inferiority of aspirin to vitamin K antagonists in patients with cervical artery dissection. METHODS We did a multicentre, randomised, open-label, non-inferiority trial in ten stroke centres across Switzerland, Germany, and Denmark. We randomly assigned (1:1) patients aged older than 18 years who had symptomatic, MRI-verified, cervical artery dissection within 2 weeks before enrolment, to receive either aspirin 300 mg once daily or a vitamin K antagonist (phenprocoumon, acenocoumarol, or warfarin; target international normalised ratio [INR] 2·0-3·0) for 90 days. Randomisation was computer-generated using an interactive web response system, with stratification according to participating site. Independent imaging core laboratory adjudicators were masked to treatment allocation, but investigators, patients, and clinical event adjudicators were aware of treatment allocation. The primary endpoint was a composite of clinical outcomes (stroke, major haemorrhage, or death) and MRI outcomes (new ischaemic or haemorrhagic brain lesions) in the per-protocol population, assessed at 14 days (clinical and MRI outcomes) and 90 days (clinical outcomes only) after commencing treatment. Non-inferiority of aspirin would be shown if the upper limit of the two-sided 95% CI of the absolute risk difference between groups was less than 12% (non-inferiority margin). This trial is registered with ClinicalTrials.gov, NCT02046460. FINDINGS Between Sept 11, 2013, and Dec 21, 2018, we enrolled 194 patients; 100 (52%) were assigned to the aspirin group and 94 (48%) were assigned to the vitamin K antagonist group. The per-protocol population included 173 patients; 91 (53%) in the aspirin group and 82 (47%) in the vitamin K antagonist group. The primary endpoint occurred in 21 (23%) of 91 patients in the aspirin group and in 12 (15%) of 82 patients in the vitamin K antagonist group (absolute difference 8% [95% CI -4 to 21], non-inferiority p=0·55). Thus, non-inferiority of aspirin was not shown. Seven patients (8%) in the aspirin group and none in the vitamin K antagonist group had ischaemic strokes. One patient (1%) in the vitamin K antagonist group and none in the aspirin group had major extracranial haemorrhage. There were no deaths. Subclinical MRI outcomes were recorded in 14 patients (15%) in the aspirin group and in 11 patients (13%) in the vitamin K antagonist group. There were 19 adverse events in the aspirin group, and 26 in the vitamin K antagonist group. INTERPRETATION Our findings did not show that aspirin was non-inferior to vitamin K antagonists in the treatment of cervical artery dissection. FUNDING Swiss National Science Foundation, Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, Academic Society Basel.
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Comparison of Ticagrelor Versus Clopidogrel on Cerebrovascular Microembolic Events and Platelet Inhibition during Transcatheter Aortic Valve Implantation.
Vavuranakis, MA, Kalantzis, C, Voudris, V, Kosmas, E, Kalogeras, K, Katsianos, E, Oikonomou, E, Siasos, G, Aznaouridis, K, Toutouzas, K, et al
The American journal of cardiology. 2021;:78-85
Abstract
The impact of the antiplatelet regimen and the extent of associated platelet inhibition on cerebrovascular microembolic events during transcatheter aortic valve implantation (TAVI) are unknown. Our aim was to evaluate the effects of ticagrelor versus clopidogrel and of platelet inhibition on the number of cerebrovascular microembolic events in patients undergoing TAVI. Patients scheduled for TAVI were randomized previous to the procedure to either aspirin and ticagrelor or to aspirin and clopidogrel. Platelet inhibition was expressed in P2Y12 reaction units (PRU) and percentage of inhibition. High intensity transient signals (HITS) were assessed with transcranial Doppler (TCD). Safety outcomes were recorded according to the VARC-2 definitions. Among 90 patients randomized, 6 had an inadequate TCD signal. The total number of procedural HITS was lower in the ticagrelor group (416.5 [324.8, 484.2]) (42 patients) than in the clopidogrel group (723.5 [471.5, 875.0]) (42 patients), p <0.001. After adjusting for the duration of the procedure, diabetes, extra-cardiac arteriopathy, BMI, hypertension, aortic valve calcium content, procedural ACT, and pre-implantation balloon valvuloplasty, patients on ticagrelor had on average 256.8 (95% CI: [-335.7, -176.5]) fewer total procedural HITS than patients on clopidogrel. Platelet inhibition was greater with ticagrelor 26 [10, 74.5] PRU than with clopidogrel 207.5 (120 to 236.2) PRU, p <0.001, and correlated significantly with procedural HITS (r = 0.5, p <0.05). In conclusion, ticagrelor resulted in fewer procedural HITS, compared with clopidogrel, in patients undergoing TAVI, while achieving greater platelet inhibition.
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Cilostazol Versus Aspirin in Ischemic Stroke Patients With High-Risk Cerebral Hemorrhage: Subgroup Analysis of the PICASSO Trial.
Kim, BJ, Kwon, SU, Park, JH, Kim, YJ, Hong, KS, Wong, LKS, Yu, S, Hwang, YH, Lee, JS, Lee, J, et al
Stroke. 2020;(3):931-937
Abstract
Background and Purpose- Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods- Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results- Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke (P for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01-0.61]; P=0.01). A marginal interaction between treatment group and white matter change on any stroke (P for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13-0.97]; P=0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29-0.92]; P=0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions- Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.
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Platelet Apoptotic Response May Be Associated With the Capacity of Aspirin to Inhibit Platelets.
Zamorano-León, JJ, Gascón, M, Martínez, CH, Freixer, G, Guerra, R, Zekri-Nechar, K, Bernardo, E, Serna-Soto, M, Segura, A, Giner, M, et al
Journal of cardiovascular pharmacology. 2020;(5):584-591
Abstract
An inadequate platelet response to aspirin (ASA) has been identified in some patients under chronic ASA treatment. The aim of this study was to analyze if ASA-sensitive and ASA-resistant platelets have differences in their apoptotic capability. Clinically stable ischemic coronary patients who had been taking ASA (100 mg/d) for at least 9 months before inclusion were divided into ASA-resistant (n = 11) and ASA-sensitive (n = 13) groups as defined by the PFA-100 test. Platelets from ASA-sensitive patients showed higher expression of the proapoptotic proteins Bak and Bax than those from ASA-resistant patients, although only Bak protein remained different when the results were adjusted by age. In resting platelets, neither caspase-3 activity nor cytosolic cytochrome C levels were different between both experimental groups. Stimulation of platelets with calcium ionophore (10 nmol/L, A23187) increased caspase-3 activity (1.91-fold higher; P < 0.05) and cytosolic cytochrome C levels (1.84-fold higher; P < 0.05) to a higher degree in ASA-sensitive than in ASA-resistant platelets. In conclusion, ASA-sensitive platelets seem to be better prepared to undergo apoptosis during robust platelet activation.
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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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Hospitalization Among Patients With Atrial Fibrillation and a Recent Acute Coronary Syndrome or Percutaneous Coronary Intervention Treated With Apixaban or Aspirin: Insights From the AUGUSTUS Trial.
Vora, AN, Alexander, JH, Wojdyla, DM, Aronson, R, Granger, CB, Darius, H, Windecker, S, Mehran, R, Averkov, O, Budaj, A, et al
Circulation. 2019;(23):1960-1963
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Antithrombotic Therapy in Patients With Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or With Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial.
Windecker, S, Lopes, RD, Massaro, T, Jones-Burton, C, Granger, CB, Aronson, R, Heizer, G, Goodman, SG, Darius, H, Jones, WS, et al
Circulation. 2019;(23):1921-1932
Abstract
BACKGROUND The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. METHODS Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. RESULTS Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). CONCLUSIONS An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.
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Frequency of silent brain lesions and aspirin protection evaluation over 3 years follow-up in beta thalassemia patients.
Karimi, M, Haghpanah, S, Pishdad, P, Zahedi, Z, Parand, S, Safaei, S
Annals of hematology. 2019;(10):2267-2271
Abstract
Silent brain lesions might be associated with overt cerebrovascular accident over time in beta thalassemia major (BTM) and intermediate (BTI). Aspirin may be protective in these patients. We evaluated brain magnetic resonance imaging (MRI) in thalassemia patients to see whether aspirin is protective or not. A historical cohort study was conducted on 35 thalassemia patients, 22 BTI, and 13 BTM patients at Shiraz Hematology Research Center in 2018. Median age of the patients was 32 years and ranged from 8 to 42 years. Twenty-four patients (68.6%) were females. Overall frequency of white matter lesions (WMLs) in the first MRI was 10 patients (28.6%). After 3 years, 3 patients developed new lesions and the frequency of WMLs was 13 patients (37.1%) in the second MRI. Moreover, in 3 patients, number of WMLs increased. Patients with new lesions or more lesions compared to the baseline were significantly older than the other group (median age 36.5 years vs. 31 years, P = 0.046). Regarding aspirin consumption, only 1 patient (16.7%) of patients with new lesions was using aspirin compared to 10 (34.5%) of the other group (P = 0.640). The high-risk patients with thrombocytosis, splenectomy, severe iron overload, and older age (> 30 years) should be under close follow-up and evaluated on a regular periodic basis as well as brain MRI at least once every 3 years. Aspirin could be protective against new or progressive brain lesions so that low-dose aspirin is recommended in high-risk thalassemia patients.
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Comparison of Aspirin and Naoxintong Capsule () with Adjusted-Dose Warfarin in Elderly Patients with High-Risk of Non-Valvular Atrial Fibrillation and Genetic Variants of Vitamin K Epoxide Reductase.
Wang, H, Zhou, XK, Zheng, LF, Wu, XY, Chen, H
Chinese journal of integrative medicine. 2018;(4):247-253
Abstract
OBJECTIVE To compared the therapeutic effect of a Chinese patent medicine Naoxintong Capsule (, NXT) and aspirin with adjusted-dose warfarin in Chinese elderly patients (over 65 years) with nonvalvular atrial fibrillation (NVAF) and genetic variants of vitamin K epoxide reductase (VKORC1), who are at high-risk of thromboembolism. METHODS A total of 151 patients, with NVAF and AA genotype of VKORC1-1639 (a sensitive genotype to warfarin) and a CHA2DS2-VASc clinical risk score of 2 or above, were chosen for this study. Patients were randomized into two groups and orally treated with a combination of aspirin (100 mg/day) and NXT (1.6 g thrice a day) or adjusted-dose warfarin [international normalized ratio 2.0-3.0). The primary end points including ischemic stroke and death as well as the secondary end points including hemorrhage events were followed up for at least 1 year. RESULTS Baseline clinical data and the rates of primary end points were similar between groups. However, the rate of serious bleeding (secondary event) in the combination therapy group was lower than that in the adjusted-dose warfarin group (0% vs. 7.9%, odds ratio: 0.921, 95% confidence interval: 0.862-0.984, P=0.028). CONCLUSIONS Aspirin combined with NXT and warfarin displayed comparable rates of primary end point including ischemic stroke and all-cause death during the 1-year follow-up. However, as compared with warfarin, the combination therapy reduced the rate of serious bleeding. Therefore, aspirin combined with NXT might provide an alternative pharmacotherapy in preventing ischemic stroke for elderly patients with NAVF who cannot tolerate warfarin. (No. ChiCTR-TRC-13003596).