scholarly journals Efficacy and Safety of Long‐Term Antithrombotic Strategies in Patients With Chronic Coronary Syndrome: A Network Meta‐analysis of Randomized Controlled Trials

Author(s):  
Houyong Zhu ◽  
Xiaoqun Xu ◽  
Xiaojiang Fang ◽  
Fei Ying ◽  
Liuguang Song ◽  
...  

Background Long‐term antithrombotic strategies for patients with chronic coronary syndrome with high‐risk factors represent an important treatment dilemma in clinical practice. Our aim was to conduct a network meta‐analysis to evaluate the efficacy and safety of long‐term antithrombotic strategies in patients with chronic coronary syndrome. Methods and Results Four randomized studies were included (n=75167; THEMIS [Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study], COMPASS [Cardiovascular Outcomes for People Using Anticoagulation Strategies], PEGASUS‐TIMI 54 [Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54], and DAPT [Dual Anti‐platelet Therapy]). The odds ratios (ORs) and 95% CIs) were calculated as the measure of effect size. The results of the network meta‐analysis showed that, compared with aspirin monotherapy, the ORs for trial‐defined major adverse cardiovascular and cerebrovascular events were 0.86; (95% CI, 0.80–0.93) for ticagrelor plus aspirin, 0.89 (95% CI, 0.78–1.02) for rivaroxaban monotherapy, 0.74 (95% CI, 0.64–0.85) for rivaroxaban plus aspirin, and 0.72 (95% CI, 0.60,–0.86) for thienopyridine plus aspirin. Compared with aspirin monotherapy, the ORs for trial‐defined major bleeding were 2.15 (95% CI, 1.78–2.59]) for ticagrelor plus aspirin, 1.51 (95% CI, 1.23–1.85) for rivaroxaban monotherapy, and 1.68 (95% CI, 1.37–2.05) for rivaroxaban plus aspirin. For death from any cause, the improvement effect of rivaroxaban plus aspirin was detected versus aspirin monotherapy (OR, 0.76; 95% CI, 0.65–0.90), ticagrelor plus aspirin (OR, 0.79; 95% CI, 0.66–0.95), rivaroxaban monotherapy (OR, 0.82; 95% CI, 0.69–0.97), and thienopyridine plus aspirin (OR, 0.58; 95% CI, 0.41–0.82) regimens. Conclusions All antithrombotic strategies combined with aspirin significantly reduced the incidence of major adverse cardiovascular and cerebrovascular events and increased the risk of major bleeding compared with aspirin monotherapy. Considering the outcomes of all ischemic and bleeding events and all‐cause mortality, rivaroxaban plus aspirin appears to be the preferred long‐term antithrombotic regimen for patients with chronic coronary syndrome and high‐risk factors.

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
A Abdul Razzack ◽  
S Pothuru ◽  
N Hussain ◽  
S Adeel Hassan ◽  
P Panday ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background The current guidelines of the European Society of Cardiology recommends dual antiplatelet treatment (DAPT) including a  new-generation P2Y12-inhibitor ticagrelor and aspirin for patients with acute coronary syndrome (ACS) with or without ST segment elevation (STEMI). However, the efficacy and safety profile of standard DAPT regimen clopidogrel and aspirin (CDAPT) vs. new DAPT regiment ticagrelor and aspirin (TDAPT) is controversial in geriatric population with age >70 years given this population is a high risk for bleeding due to frailty and recurrent of ACS. Objective   To assess the efficacy and safety of DAPT regimens including CDAPT or TDAPT  for elderly patients >70 years presenting with ACS with or without ST-segment elevation.  Methods Electronic databases (PubMed, Embase, Scopus, Cochrane) were searched from inception to November 28th, 2020. Using a generic invariance weighted fixed effects model, Hazard ratios (HRs) and their 95% confidence intervals (CIs) from individual studies were converted to Log HRs and corresponding standard errors, which were then pooled. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE)and was defined as a composite of death, myocardial reinfarction and stroke. The secondary outcome was any major bleeding events.  Results- A total of four studies with 18365 participants was included in our analysis.Mean age was 79.4 and 79.2 in the CDAPT and TDAPT groups respectively.  Average follow up period was 12 months. There is no difference in MACCE among CDAPT and TDAPT( HR 0.93, 95%CI 0.86-1.01;P = 0.10). However, TDAPT is associated with high risk of major bleeding as compared to CDAPT (HR 1.15, 95%CI 1.02-1.29; P = 0.02) (Figure 1). We had no publication bias in our results (Egger’s regression p > 0.05). Conclusion- Amongst geriatric patients aged 70 years or older with ACS with or without STEMI, TDAPT has the same MACCE as compared to CDAPT while TDAPT can have high major bleeding. Abstract Figure. A)MACCE B)Major Bleeding events


2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
HY Wang ◽  
R Zhang ◽  
ZX Cai ◽  
KF Dou

Abstract Funding Acknowledgements Type of funding sources: None. Background Recent emphasis on reduced duration and/or intensity of antiplatelet therapy following PCI irrespective of indication for PCI may fail to account for the substantial risk of subsequent nontarget lesion events in acute coronary syndrome (ACS) patients. This study sought to investigate the benefits and risks of extended-term (>12-month) DAPT as compared with short-term DAPT in high-risk "TWILIGHT-like" ACS patients undergoing PCI. Methods All consecutive patients fulfilling the "TWILIGHT-like" criteria undergoing PCI from January 2013 to December 2013 were identified from the prospective Fuwai PCI Registry. High-risk "TWILIGHT-like" patients were defined by at least 1 clinical and 1 angiographic feature based on TWILIGHT trial selection criteria. The present analysis evaluated 4,875 high-risk "TWILIGHT-like" patients with ACS who were event-free at 12 months after PCI. The primary outcome was the composite of all-cause death, myocardial infarction (MI), or stroke at 30 months while BARC type 2, 3, or 5 bleeding was key secondary outcome. Results Extended DAPT compared with shorter DAPT reduced the composite outcome of all-cause death, MI, or stroke by 63% (1.5% vs. 3.8%; HRadj: 0.374, 95% CI: 0.256 to 0.548; HRmatched: 0.361, 95% CI: 0.221-0.590). The HR for cardiovascular death was 0.049 (0.007 to 0.362) and that for MI 0.45 (0.153 to 1.320) and definite/probable stent thrombosis 0.296 (0.080-1.095) in propensity-matched analyses. Rates of BARC type 2, 3, or 5 bleeding (0.9% vs. 1.3%; HRadj: 0.668 [0.379 to 1.178]; HRmatched: 0.721 [0.369-1.410]) did not differ significantly in patients treated with DAPT > 12-month or DAPT ≤ 12-month. The effect of long-term DAPT on primary and key secondary outcome across the proportion of ACS patients with 1-3, 4-5, or 6-9 risk factors showed a consistent manner (Pinteraction > 0.05). Conclusion Among high-risk "TWILIGHT-like" patients with ACS after PCI, long-term DAPT reduced ischemic events without increasing clinically meaningful bleeding events as compared with short-term DAPT, suggesting that extended DAPT might be considered in the treatment of ACS patients who present with a particularly higher risk for thrombotic complications. Abstract Figure.


2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Faizan Khan ◽  
Miriam Kimpton ◽  
Tobias Tritschler ◽  
Grégoire Le Gal ◽  
Brian Hutton ◽  
...  

Abstract Background The optimal duration of anticoagulation after a first unprovoked venous thromboembolism (VTE) remains controversial. Deciding to stop or continue anticoagulant therapy indefinitely after completing 3 to 6 months of initial treatment requires balancing the long-term risk of recurrent VTE if anticoagulation is stopped against the long-term risk of major bleeding if anticoagulation is continued. However, knowledge of the long-term risk for major bleeding events during extended anticoagulation in this patient population is limited. We plan to conduct a systematic review and meta-analysis to quantify the risk for major bleeding events during extended oral anticoagulation in patients with first unprovoked VTE. Methods Electronic databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials will be systematically searched with the assistance of an information specialist (from inception to March 1, 2019) to identify randomized controlled trials and prospective cohort studies reporting major bleeding during extended oral anticoagulation in patients with first unprovoked VTE, who have completed at least 3 months of initial anticoagulant therapy. Study selection, risk of bias assessment, and data extraction will be performed independently by at least two investigators. The number of major bleeding events and person-years of follow-up will be used to calculate the rate (events per 100 person-years) with its 95% confidence interval for each study cohort, during clinically relevant time periods of extended anticoagulant therapy. Results will be pooled using random effect meta-analysis. Discussion The planned systematic review and meta-analysis will provide reliable estimates of the risk for major bleeding events during extended anticoagulation. This information will help inform patient prognosis and assist clinicians with balancing the risks and benefits of treatment to guide management of unprovoked VTE. Systematic review registration PROSPERO CRD42019128597.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 592-592
Author(s):  
Walter Ageno ◽  
Nicoletta Riva ◽  
Sam Schulman ◽  
Jan Beyer-Westendorf ◽  
Soo-Mee Bang ◽  
...  

Abstract Background: Little information is available on the long-term clinical outcome of patients with splanchnic vein thrombosis (SVT). We aimed to assess incidence rates of bleeding, recurrence, and mortality in a large prospective cohort of SVT patients after a 2-year follow-up. Methods: Consecutive SVT patients were enrolled in a multicenter international registry, from 2008 to 2012. Information was gathered on baseline characteristics, risk factors and therapeutic strategies. Clinical outcomes (major bleeding; vascular events, defined as venous or arterial thrombosis, and mortality) during follow-up were collected and reviewed by a Central Adjudication Committee. Major bleeding was defined using the ISTH definition plus the need for hospitalization. The primary analysis was performed up to the first adjudicated major bleeding or thrombotic event. Results: 604 patients from 31 centers were enrolled in this study, 21 (3.5%) were lost to follow-up. Median follow-up duration was 2 years (IQR 1-2). Median age was 54 years (range 16-85); 62.6% were males. Most common risk factors were liver cirrhosis in 27.8% of patients and solid cancer in 22.3%. Portal vein was the most common site of thrombosis. 139 patients were not anticoagulated; 175 received parenteral anticoagulants only (median duration 5.8 months, IQR 3-12) and 290 were started on vitamin K antagonists (median duration 24 months, IQR 7-24). According to the primary analysis, 103 events occurred during follow-up: 35 major bleeding events (3.8/100 patient-years [pt-y]; 95%CI, 2.7-5.2), 2 of which were fatal bleeding, and 68 thrombotic events (7.3/100 pt-y; 95%CI 5.8-9.3), 9 of which were vascular deaths. All-cause mortality occurred in 106 patients (10.3/100 pt-y; 95% CI 8.5-12.5). The incidence of major bleeding events was 4.0/100 pt-y in patients on anticoagulant drugs and 3.4/100 pt-y in patients not receiving anticoagulants. The incidence of vascular events was 5.6/100 pt-y and 9.7/100 pt-y, respectively. Major bleeding and vascular event rates were highest in cirrhotic patients (10.0/100 pt-y and 11.3/100 pt-y, respectively), and lowest in the subgroup of non-malignant non-cirrhotic patients (1.8/100 pt-y and 5.6/100 pt-y, respectively). Conclusions: SVT patients have a non-negligible long-term risk of both bleeding and thrombotic events, but this risk varies according to the pathogenesis of SVT. Anticoagulant treatment is associated with a reduced incidence of thrombotic events without apparently resulting in an increased risk of bleeding. Funding: The study was funded by a grant from Pfizer Canada to ISTH Disclosures Ageno: Bayer Healthcare: Research Funding. Schulman:Bayer HealthCare: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding. Beyer-Westendorf:Bayer: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Boehringer: Honoraria, Research Funding.


2021 ◽  
Author(s):  
Yuttana Wonngsalap ◽  
Supakorn Ungsriwong ◽  
Wanalee Kumtepm ◽  
Surasak Saokaew ◽  
Vichai Senthong ◽  
...  

Abstract Purpose To assess the efficacy and safety of prasugrel at low doses compared to clopidogrel by looking at the occurrence of major adverse cardiac events (MACE) and major bleeding in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Methods We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for eligible randomized controlled trials (RCTs) and observational studies assessing efficacy and safety of low-dose prasugrel versus clopidogrel in patients with ACS or undergoing PCI up to May 22, 2020. We did a meta-analysis using a random-effects model to estimate relative risks (RRs). The primary efficacy and safety endpoints were MACE and major bleeding, respectively. Results Six RCTs (n = 6,131) and six observational studies (n = 31,426) were included. There was no MACE reduction in patients receiving low-dose prasugrel compared with those receiving clopidogrel (RR 1.02, 95%CI 0.91 to 1.14), but there was an increased risk of major bleeding (RR 1.35, 95%CI 1.10 to 1.67). Conclusions Low-dose prasugrel yields no increase in efficacy when compared with clopidogrel, but it does expose patients to an increased risk of bleeding. Most studies considered here were conducted in Japan. Studies conducted with non-Asian patients may find that low-dose prasugrel offers a more favorable efficacy and risk profile. Considering the results of this analysis we believe low-dose prasugrel should be prescribed with extreme caution as it may result in bleeding events without any additional benefit over clopidogrel.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Y Minematsu ◽  
M Natsuaki ◽  
G Yoshioka ◽  
K Shinzato ◽  
Y Nishimura ◽  
...  

Abstract Background/Introduction CREDO-Kyoto bleeding risk score was developed to predict the post-discharge bleeding events in patients with percutaneous coronary intervention. However, there were limited reports of the effectiveness of this score to predict the in-hospital bleeding events in patients with acute coronary syndrome (ACS). Methods We evaluated 562 consecutive ACS patients in Saga university hospital between 2014 and 2019. Primary outcome was major bleeding during hospitalization. Major bleeding was defined as the GUSTO moderate/severe bleeding. Patients were classified into three groups according to the CREDO-Kyoto bleeding risk score (low, intermediate and high). Results Major bleeding events occurred in 12.1% of all patients during hospitalization. Patients in the high risk group (n=22) had significantly higher incidence of major bleeding than those in the intermediate (n=113) and the low risk groups (n=427) (22.7%, 18.6%, versus 9.8%, respectively, p=0.018, see figure). Multivariate analysis showed that intermediate and high risk groups were independent predictors for the in-hospital major bleeding. Conclusions CREDO-Kyoto risk score successfully identified high risk ACS patients for the major bleeding during hospitalization. FUNDunding Acknowledgement Type of funding sources: None. Results


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
F Mendonca ◽  
M I Mendonca ◽  
M Temtem ◽  
M Santos ◽  
J A Sousa ◽  
...  

Abstract Introduction Coronary Heart Disease (CAD) is a multifactorial disease, including environmental and genetic risk factors. Current smoking, dyslipidemia and diabetes have a significant impact in long- term mortality and morbidity. However, several genetic variants associated with CAD but not with traditional risk factors (TRFs) has been reported to improve prediction of events and extended mortality, in younger CAD people. Aim To evaluate the clinical utility of a GRS composed by variants from GWAS associated to CAD but not with TRF to predict life-long residual risk in patients under 55 years old and a low level of TRFs. Methods We conducted a prospective study with 573 consecutive patients aged <55 years presenting with AMI and a low level of TRFs (without diabetes and with LDL cholesterol >150 mg/ml). We analysed several biochemical markers and performed a GRS with variants not associated with TRFs (TCF21 rs12190287, CDKN2B-AS1 rs1333049, CDKN2B rs4977574, PHACTR1 rs1332844, MIA3 rs17465637, ADAMTS7 rs3825807, ZC3HC1 rs11556924, SMAD3 rs17228212 and GJA4 rs618675). We studied the GRS association with a primary composite endpoint of all-cause vascular morbidity and mortality including recurrent acute coronary syndrome (myocardial infarct and unstable angina), coronary revascularization (coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), re-hospitalization for heart failure, ischemic stroke and cardiovascular dead. Results A total of 573 patients were studied and followed up for a mean of 4.7±4.0 years. There were 169 recurrent cardiovascular events. The GRS was sub-divided into terciles, verifying that patients in the third tercile (high risk) had a higher number of risk alleles. Compared with the low-risk GRS tercile, the multivariate-adjusted HR for recurrences was 1.520 (95% CI 1.011–2.286); p=0.044 for the intermediate-risk group and was 2.051 (95% CI 1.382–3.044); p<0.0001 for the high-risk group. Inclusion of the GRS in the model with TRFs alone (low risk) improved the C-statistic analysis (C-statistic = 0.030; p=0.004), cNRI (continuous net reclassification improvement) (30.8%), and the IDI (integrated discrimination improvement index) (0.022). Conclusions A multilocus GRS may identify young coronary disease patients with a low level of TRFs but at significant risk of long-term events recurrence. The genetic information may improve prediction discrimination, and reclassification over the conventional risk factors alone, providing better cost-effective therapeutic strategies. FUNDunding Acknowledgement Type of funding sources: None. Figure 1


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247782
Author(s):  
Rachel Van Doorn ◽  
Narmin Mukhtarova ◽  
Ian P. Flyke ◽  
Michael Lasarev ◽  
KyungMann Kim ◽  
...  

Objective To evaluate the effect of aspirin dose on the incidence of all gestational age preeclampsia and preterm preeclampsia. Data sources Electronic databases (Cochrane, PubMed, Scopus, ClinicalTrials.gov and the Web of Science) were searched for articles published between January 1985 and March 2019 with no language restrictions. Methods We followed the PRIMSA guidelines and utilized Covidence software. Articles were screened by 2 independent reviewers, with discrepancies settled by an independent 3rd party. Study selection criteria were randomized trials comparing aspirin for prevention of all gestational age and preterm preeclampsia to placebo or no antiplatelet treatment in women aged 15–55 years with moderate or high-risk factors according to the list of risk factors from American College of Obstetricians and Gynecologists and United States Preventive Services Task Force guidelines. The quality of trials was assessed using the Cochrane risk of bias tool. The data were pooled using a random-effects meta-analysis comparing aspirin at doses of <81, 81, 100, and 150 mg. Pre-specified outcomes were all gestational age and preterm preeclampsia. Results Of 1,609 articles screened, 23 randomized trials, which included 32,370 women, fulfilled the inclusion criteria. In preterm preeclampsia, women assigned at random to 150 mg experienced a significant 62% reduction in risk of preterm preeclampsia (RR = 0.38; 95% CI: 0.20–0.72; P = 0.011). Aspirin doses <150 mg produced no significant reductions. The number needed to treat with 150 mg of aspirin was 39 (95% CI: 23–100). There was a maximum 30% reduction in risk of all gestational age preeclampsia at all aspirin doses. Conclusions In this meta-analysis, based on indirect comparisons, aspirin at a dose greater than the current, recommended 81 mg was associated with the highest reduction in preterm preeclampsia. Our meta-analysis is limited due to the deficiency of homogeneous high evidence data available in the literature to date; however, it may be prudent for clinicians to consider that the optimal aspirin dose may be higher than the current guidelines advise. Future research to compare the efficacy aspirin doses greater than 81 mg is recommended. Study registration PROSPERO, CRD42019127951 (University of York, UK; http://www.crd.york.ac.uk/PROSPERO/).


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