scholarly journals Low Dose Rivaroxaban for Atherosclerotic Cardiovascular Diseases: A Systematic Review and Meta-analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Can Chen ◽  
Yuanqing Kan ◽  
Zhenyu Shi ◽  
Daqiao Guo ◽  
Weiguo Fu ◽  
...  

Background: This study aims to explore the role of low-dose rivaroxaban (≤10 mg daily) for the treatment of atherosclerotic cardiovascular disease (ASCVD).Methods: PubMed, Embase and the Cochrane Library were searched for randomized controlled trials (RCTs) of low-dose rivaroxaban in patients with ASCVD including coronary artery disease (CAD) and peripheral artery disease (PAD). Literature screening, data extraction, and risk of bias assessment were carried out independently by two researchers. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using random-effect models to determine risks of outcomes in ASCVD patients treated with rivaroxaban and comparators, and meta-analysis was conducted via Review Manager 5.3.5 software.Results: 3,768 records were obtained through literature search, and 9 articles representing 6 RCTs ultimately qualified for this study. The meta-analysis indicated that for patients with CAD, the addition of rivaroxaban (5 mg daily) to aspirin could significantly reduce the risk of major adverse cardiovascular events (MACEs) compared with aspirin alone (HR 0.81, 95% CI, 0.72 to 0.91, p = 0.0004, I2 = 60%, 4 studies). For PAD patients receiving rivaroxaban (5 mg daily) plus aspirin, there was no significant reduction in the risk of MACEs (HR 0.84, 95% CI, 0.63 to 1.13, p = 0.25, I2 = 74%, 2 studies); however, there was significant reduction in major adverse limb events (MALEs) (HR 0.54, 95% CI, 0.35 to 0.83, p = 0.005, one studies) and in the composite of MACEs or MALEs (HR 0.78, 95% CI, 0.64 to 0.95, p = 0.02, I2 = 66%, 2 studies) when compared with patients receiving aspirin alone. Meanwhile, rivaroxaban combined with aspirin significantly increased the risk of International Society on Thrombosis and Haemostasis (ISTH) major bleeding compared with aspirin alone in patients with CAD (HR 1.74, 95% CI, 1.43 to 2.13, p < 0.00001, I2 = 0%, 2 studies) and PAD (HR 1.47, 95% CI, 1.19 to 1.83, p = 0.0004, I2 = 0%, 2 studies).Conclusions: Compared with standard antiplatelet therapy, the addition of a 5 mg daily dose of rivaroxaban to standard antiplatelet therapy may improve cardiovascular or limb outcomes of patients with ASCVD, with an increase in major bleeding. Patients who would benefit from the addition of low-dose rivaroxaban to antiplatelet agents and appropriate dual-pathway antithrombotic strategies should be identified in clinical practice to individualize antithrombotic therapy.

Author(s):  
Donna Rahmatian ◽  
Arden R Barry

Abstract Purpose To identify randomized controlled trials that compared antiplatelet monotherapy to combination antiplatelet plus anticoagulant therapy and evaluated major adverse cardiovascular events (MACE) or major adverse limb events (MALE), death, or bleeding in patients with lower extremity peripheral artery disease (PAD). Summary A systematic search of MEDLINE, Embase, and CENTRAL databases revealed 5 trials. Two trials consisted of patients with stable PAD, while 3 trials examined patients with PAD post revascularization. Antiplatelet therapy was mostly aspirin (81-325 mg daily), and anticoagulation included rivaroxaban 2.5 mg twice daily or warfarin. Duration of follow-up ranged from 12 to 38 months. Two trials had low risk of bias, whereas 3 trials had high/unclear risk of bias. For patients with stable PAD, one trial showed that use of warfarin (or acenocoumarol) with antiplatelet therapy did not reduce MACE, MALE, or cardiovascular or all-cause death but increased the risk of life-threatening bleeding. A second trial demonstrated that low-dose rivaroxaban plus antiplatelet therapy lowered the risk of MACE and MALE, with no effect in preventing cardiovascular or all-cause death, but increased the risk of major bleeding. For patients with PAD post revascularization receiving warfarin and antiplatelet therapy, 2 trials showed no benefit in MACE or MALE but increased or similar rates of all-cause death and major bleeding. In a third trial, low-dose rivaroxaban plus aspirin reduced occurrence of the composite of MACE and MALE but increased major bleeding, with no effect on cardiovascular or all-cause death. Conclusion Dual-pathway inhibition with low-dose rivaroxaban and aspirin reduced MACE and MALE in patients with stable or revascularized PAD, but net clinical benefit is questionable.


2020 ◽  
Vol 26 (44) ◽  
pp. 5739-5745
Author(s):  
Jieqiong Guan ◽  
Wenjing Song ◽  
Pan He ◽  
Siyu Fan ◽  
Hong Zhi ◽  
...  

Objective: The aim was to evaluate the efficacy and safety of duration of dual antiplatelet therapy (DAPT) for patients who received percutaneous coronary intervention (PCI) with a drug-eluting stent. Background: The optimal duration of DAPT to balance the risk of ischemia and bleeding in CAD patients undergoing drug-eluting stent (DES) implantation remains controversial. Methods: PubMed, Cochrane Library, Web of Science, Clinicaltrials.gov, CNKI and Wanfang Databases were searched for randomized controlled trials of comparing different durations of DAPT after DES implantation. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), and major bleeding, and were pooled by Bayes network meta-analysis. Net adverse clinical and cerebral events were used to estimate the surface under the cumulative ranking (SUCRA) curves. The subgroup analysis based on clinical status, follow-up and area was conducted using traditional pairwise meta-analysis. Results: A total of nineteen trials (n=51,035) were included, involving six duration strategies. The network metaanalysis showed that T2 (<6-month DAPT followed by aspirin, HR:1.51, 95%CI:1.02-2.22), T3 (standard 6-month DAPT, HR:1.47, 95%CI:1.14-1.91), T4 (standard 12-month DAPT, HR:1.41, 95%CI:1.15-1.75) and T5 (18-24 months DAPT, HR:1.47, 95%CI:1.09-1.97) was associated with significantly increased risk of MACCE compared to T6 (>24-month DAPT). However, no significant difference was found in MACCE risk between T1 (<6-month DAPT followed by P2Y12 monotherapy) and T6. Moreover, T5 was associated with significantly increased risk of bleeding compared to T1(RR:3.94, 95%CI:1.66-10.60), T2(RR:3.65, 95%CI:1.32-9.97), T3(RR:1.93, 95%CI:1.21-3.50) and T4(RR:1.89, 95%CI:1.15-3.30). The cumulative probabilities showed that T6(85.0%), T1(78.3%) and T4(44.5%) were the most efficacious treatment compared to the other durations. In the ACS (<50%) subgroup, T1 was observed to significantly reduce the risk of major bleeding compared to T4, but not in the ACS (≥50%) subgroup. Conclusions: Compared with other durations, short DAPT followed by P2Y12 inhibitor monotherapy showed non-inferiority, with a lower risk of bleeding and not associated with an increased MACCE. In addition, the risk of major bleeding increased significantly, starting with DAPT for 18-month. Compared with the short-term treatment, patients with ACS with the standard 12-month treatment have a better prognosis, including lower bleeding rate and the decreased risk of MACCE. Due to study's limitations, the results should be verified in different risk populations.


Author(s):  
Marco Valvano ◽  
Stefano Fabiani ◽  
Marco Magistroni ◽  
Antonio Mancusi ◽  
Salvatore Longo ◽  
...  

Abstract Background It was not yet fully established whether the use of antiplatelet agents (APAs) is associated with an increased risk of colorectal post-polypectomy bleeding (PPB). Temporarily, discontinuation of APAs could reduce the risk of PPB, but at the same time, it could increase the risk of cardiovascular disease recurrence. This study aimed to assess the PPB risk in patients using APAs compared to patients without APAs or anticoagulant therapy who had undergone colonoscopy with polypectomy. Methods A systematic electronic search of the literature was performed using PubMed/MEDLINE, Scopus, and CENTRAL, to assess the risk of bleeding in patients who do not interrupt single antiplatelet therapy (P2Y12 inhibitors or aspirin) and undergone colonoscopy with polypectomy. Results Of 2417 identified articles, 8 articles (all of them were non-randomized studies of interventions (NRSI); no randomized controlled trials (RCT) were available on this topic) were selected for the meta-analysis, including 1620 patients on antiplatelet therapy and 13,321 controls. Uninterrupted APAs single therapy was associated with an increased risk of PPB compared to the control group (OR 2.31; CI 1.37–3.91). Patients on P2Y12i single therapy had a higher risk of both immediate (OR 4.43; CI 1.40–14.00) and delayed PPB (OR 10.80; CI 4.63–25.16) compared to the control group, while patients on aspirin single therapy may have a little to no difference increase in the number of both immediate and delayed PPB events. Conclusions Uninterrupted single antiplatelet therapy may increase the risk of PPB, but the evidence is very uncertain. The risk may be higher in delayed PPB. However, in deciding to discontinue APAs before colonoscopy with polypectomy, the potential higher risk of major adverse cardiovascular events should always be assessed.


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
A Benz ◽  
I Johansson ◽  
W Dewilde ◽  
RD Lopes ◽  
R Mehran ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr. Benz reports a personal research grant from the German Heart Foundation (Deutsche Herzstiftung e.V.). Dr. Johansson reports personal unrestricted research grants from Swedish Heart-Lung Foundation (Hjärt-Lungfonden) and from Stockholm County Council (Region Stockholm). Dr. McIntyre holds a fellowship award from the Canadian Institutes for Health Research (CIHR). Dr. Shoamanesh reports funding support from the Marta and Owen Boris Foundation and the Heart and Stroke Foundation of Canada. Background/Introduction: There is an ongoing controversy surrounding the efficacy and safety of antiplatelet agents in patients with atrial fibrillation (AF). Purpose We aimed to systematically assess the effects of antiplatelets on stroke and other outcomes in patients with AF, both receiving oral anticoagulation or not. Methods We searched MEDLINE, Embase and CENTRAL up until September 2020 to identify randomized trials allocating patients with AF to aspirin or a P2Y12 inhibitor, versus control. Where applicable, we obtained unpublished data from study authors. Random-effects models were applied for meta-analysis. Results Based on 21,518 patients from 18 randomized trials, there was no reduction in stroke with antiplatelet therapy (risk ratio [RR] 0.89, 95% confidence interval [CI] 0.76-1.04). There was a significant qualitative interaction according to whether patients were receiving concomitant oral anticoagulation or not (p &lt; 0.001). Without concomitant anticoagulation, antiplatelets reduced stroke (RR 0.77, 95% CI 0.69-0.86), while they appeared to increase stroke with it (RR 1.33, 95% CI 0.98-1.79). A similar pattern emerged for ischaemic stroke. Antiplatelets increased major bleeding (RR 1.54, 95% CI 1.35-1.77) and intracranial haemorrhage (RR 1.64, 95% CI 1.20-2.24), and reduced myocardial infarction (RR 0.79, 95% CI 0.65-0.94), consistently and irrespective of concomitant anticoagulation. Antiplatelets had a neutral effect on mortality (RR 1.02, 95% CI 0.89-1.17). Conclusions Antiplatelet therapy did not reduce stroke and increased major bleeding in patients with AF. Antiplatelets did not affect mortality. Subgroup analysis suggests a reduction in stroke with antiplatelets in patients without concomitant oral anticoagulation, and a corresponding signal for harm in those with it. Abstract Figure.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Ashkan Shoamanesh ◽  
Chun Shing Kwok ◽  
Phyo K Myint ◽  
Yoon K Loke ◽  
Hannah Copley ◽  
...  

INTRODUCTION: The predominant underlying mechanism of lacunar stroke differs from that of other ischemic stroke subtypes. Accordingly, so may the ideal stroke prevention regimen. We aimed to evaluate the efficacy of different antiplatelet agents in lacunar stroke patients. Method: We searched MEDLINE, EMBASE and the Cochrane library for RCTs that evaluated antiplatelet therapy in patients with ischemic stroke. Trials which provided stroke recurrence rates in patients presenting with lacunar stroke, or where the data was obtainable from manuscript authors were included. In addition, we included the novel SPS3 trial’s antiplatelet arm data presented at the 2011 ISC. We performed pooled analysis to assess the crude frequency of recurrent stroke and a random effects meta-analysis. Results: Lacunar stroke data was available for 12 trials encompassing 35, 218 participants (mean age 65, 65% male). The pooled crude recurrent stroke rate was least for cilostazol monotherapy (6.2%), followed by ASA monotherapy (7.4%), clopidogrel monotherapy (8.6%), ASA/dipyridamole (8.6%) and greatest for ASA/clopidogrel therapy (9.1%). Rate ratios of lacunar stroke patients suggest no significant efficacy advantage for ASA [ASA vs placebo (RR 0.72, 95% CI 0.34-1.50; p=0.38)], ASA/clopidogrel [ASA/clopidogrel vs ASA (RR 0.80, 95% CI 0.62-1.03; p=0.08), ASA/clopidogrel vs clopidogrel (RR 0.95, 95% CI 0.79-1.15; p=0.63)], sarpogrelate [sarpogrelate vs ASA (RR 1.31, 95% CI 0.84-2.04; p=0.23)] and ASA/dipyridamole [ASA/dipyridamole vs ASA (RR 0.90, 95% CI 0.70-1.16; p=0.042)] for recurrent stroke. The results from Japanese trials evaluating the efficacy of cilostazol found that it is significantly better than both placebo (RR 0.51, 95% CI 0.30-0.85; p=0.01) and ASA (RR 0.70, 95% CI 0.51-0.96; p=0.03) in the secondary prevention of stroke. Conclusions: There seems to be no significant advantage among the various antiplatelet agents studied in lacunar stroke patients apart for cilostazol. However, this requires confirmation within large randomized trials outside of Japanese populations.


2019 ◽  
Author(s):  
Mingxia Li ◽  
Hong Lin ◽  
Jiankuan Shi ◽  
Qianru Yang ◽  
Jianjun Li ◽  
...  

Abstract Background Anticoagulation and antiplatelet therapy were adopted respectively for the prevention ofcardio-embolic stroke or arterial origin stroke. while it’s difficult to make decisions for individual with Atrial fibrillation(AF)and arterial origin stroke as comorbidities, so we attempted to evaluate the efficacy and safety ofanticoagulants and antiplatelet forthe prevention of stroke in AF with arterial origin stroke and make an optimal treatment for these comorbidities. Methods Databases included PubMed, Cochrane Library and ClinicalTrials.gov were searched up to 31 Aug 2019. Eight RCTs with 77048 participants were enrolled. Results Direct oral anticoagulants(DOACs) reduced the relative risk of stroke and systemic embolism by 15% (95%CI 0.75-0.97, I2=65.6%) and the major bleeding by 23%(95%CI 0.63-0.95, I2=92.3%,). DOACs or warfarin plus aspirin compared with DOACs or warfarin alone did not show the benefit on stroke and systemic embolism prevent in AF patients, but increase the risk of major bleeding with RR 1.40 (95%CI 1.13-1.75,) and 1.33(95%CI 1.09-1.63)respectively. No differences in preventionof ischemic stroke were detected between OACs versus aspirin in arterial origin stroke. The major bleeding was significantly higher in the OACs group (RR,2.40,1.46-3.94, I2=62.2%). However, compared with aspirin, rivaroxabandid not increase the risk of major bleeding in Branch atheromatous stroke (RR,1.54,95%CI 0.26-9.12). Conclusions We speculatedthat DOACs alone may be enough to prevent stroke recurrence and not to increase the risk of bleeding in AF patients with arterial origin stroke. The well designed RCTs with the direct comparison would be needed in future.


2020 ◽  
Vol 18 ◽  
Author(s):  
Marco De Carlo ◽  
Giovanni Di Minno ◽  
Tobias Sayre ◽  
Mir Sohail Fazeli ◽  
Gaye Siliman ◽  
...  

Background: Clopidogrel monotherapy is guideline-recommended in symptomatic peripheral artery disease (PAD). The advent of new antithrombotic strategies prompts an updated analysis of available evidence on antiplatelet therapy for PAD. Methods: We searched MEDLINE, Embase and CENTRAL through January 2019 for randomised controlled trials and observational studies comparing antiplatelet therapies as monotherapy, dual therapy, or combination with anticoagulants. Efficacy (major adverse cardiovascular events, acute or chronic limb ischaemia, vascular amputation, peripheral revascularisation) and safety (all-cause mortality and overall bleeding) outcomes were evaluated via Bayesian network meta-analyses. Results: We analysed 26 randomised controlled trials. Clopidogrel (hazard ratio, HR, 0.78; 95% credible interval [CrI] 0.65- 0.93) and ticagrelor (HR 0.80; 95%CrI 0.65-0.98) significantly reduced major adverse cardiovascular events risk compared with aspirin. No significant difference was observed for dual antiplatelet therapy with clopidogrel and aspirin. Vorapaxar significantly reduced limb ischaemia and revascularisation compared with placebo, while dual antiplatelet therapy with clopidogrel and aspirin showed a trend for reduced risk of amputation compared with aspirin (risk ratio 0.68; 95%CrI 0.43- 1.04). For all-cause mortality, picotamide, vorapaxar, dipyridamole with aspirin, and ticlopidine showed significantly lower risk of all-cause mortality vs aspirin. Clopidogrel and ticagrelor showed similar overall bleeding risk vs aspirin, while dual antiplatelet therapy with clopidogrel and aspirin significantly increased bleeding risk. Conclusion: This updated network meta-analysis confirms that clopidogrel significantly decreases the risk of major adverse cardiovascular events compared with aspirin, without increasing bleeding risk. Clopidogrel should remain a mainstay of PAD treatment, at least in patients at higher bleeding risk.


2019 ◽  
Vol 24 (2) ◽  
pp. 132-140 ◽  
Author(s):  
Eric Kaplovitch ◽  
Luke Rannelli ◽  
Sonia S Anand

Patients with peripheral artery disease (PAD) are at high risk for ischemic cardiovascular complications. While single antiplatelet therapy (SAPT), predominantly aspirin, has long been the standard antithrombotic treatment in stable PAD, there have now been greater than 40,000 PAD patients randomized to varying antiplatelet and/or anticoagulant regimens. In this review, we provide a summary of the current evidence for antithrombotics in stable PAD, focusing on the rates of major adverse cardiovascular events (MACE), major adverse limb events (MALE), and major bleeding. SAPT has a limited role in the treatment of asymptomatic PAD, particularly in the absence of concomitant coronary artery disease. In symptomatic PAD, SAPT is effective in preventing MACE, though treatment with a thienopyridine appears marginally superior to aspirin. Dual antiplatelet therapy (DAPT) suggests benefit over SAPT in reducing MACE and MALE, though studies to date are not conclusive and/or are associated with excess major bleeding. Combining moderate to high intensity vitamin K antagonists with antiplatelet therapy does not reduce MACE or MALE and increases life-threatening bleeding. Rivaroxaban 2.5 mg BID in addition to aspirin reduces the incidence of both MACE and MALE as compared to aspirin alone, without increasing life-threatening bleeding. This regimen is associated with a reduced severity of MALE when it does occur. Comparisons across antithrombotic trials in PAD are challenging given the heterogeneity of patient populations and the differing assessment of outcomes. The vascular medicine practitioner can reduce ischemic cardiac and limb events, as well as minimize life-threatening bleeding, by choosing the optimal antithrombotic regimen in their PAD patients.


Thorax ◽  
2017 ◽  
Vol 73 (5) ◽  
pp. 464-471 ◽  
Author(s):  
David Jimenez ◽  
Carlos Martin-Saborido ◽  
Alfonso Muriel ◽  
Javier Zamora ◽  
Raquel Morillo ◽  
...  

BackgroundWe aimed to review the efficacy and safety of recanalisation procedures for the treatment of PE.MethodsWe searched PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science and CINAHL databases from inception through 31 July 2015 and included randomised clinical trials that compared the effect of a recanalisation procedure versus each other or anticoagulant therapy in patients diagnosed with PE. We used network meta-analysis and multivariate random-effects meta-regression to estimate pooled differences between each intervention and meta-regression to assess the association between trial characteristics and the reported effects of recanalisation procedures versus anticoagulation.ResultsFor all-cause mortality, there were no significant differences in event rates between any of the recanalisation procedures and anticoagulant treatment (full-dose thrombolysis: OR 0.60; 95% CI0.36 to 1.01; low-dose thrombolysis: 0.47; 95% CI 0.14 to 1.59; and catheter-associated thrombolysis: 0.31; 95% CI 0.01 to 7.96). Full-dose thrombolysis increased the risk of major bleeding (2.00; 95% CI 1.06 to 3.78) compared with anticoagulation. Catheter-directed thrombolysis was associated with the lowest probability of dying (surface under the cumulative ranking curve (SUCRA), 0.67), followed by low-dose thrombolysis (SUCRA, 0.66) and full-dose thrombolysis (SUCRA, 0.55). Similarly, low-dose thrombolysis was associated with the lowest probability of major bleeding (SUCRA, 0.61), followed by catheter-directed thrombolysis (SUCRA, 0.54) and full-dose thrombolysis (SUCRA, 0.17). The results were similar in sensitivity analyses based on restricting only to studies in haemodynamically stable patients with PE.ConclusionsIn the treatment of PE, recanalisation procedures do not seem to offer a clear advantage compared with standard anticoagulation. Low-dose thrombolysis was associated with the lowest probability of dying and bleeding.Trial registration numberPROSPERO CRD42015024670.


2020 ◽  
Vol 31 (3) ◽  
pp. 354-363 ◽  
Author(s):  
Saurabh Gupta ◽  
Emilie P Belley-Cote ◽  
Puru Panchal ◽  
Arjun Pandey ◽  
Ameen Basha ◽  
...  

Abstract OBJECTIVES Acetylsalicylic acid (ASA) monotherapy is the standard of care after coronary artery bypass grafting (CABG), but the benefits of more intense antiplatelet therapy, specifically dual antiplatelet therapy (DAPT), require further exploration in CABG patients. We performed a network meta-analysis to compare the effects of various antiplatelet regimens on saphenous vein graft patency, mortality, major adverse cardiovascular events and bleeding among CABG patients. METHODS We searched Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval Systems Online, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, American College of Physicians Journal Club and conference proceedings for randomized controlled trials. Screening, data extraction, risk of bias assessment and Grading of Recommendations Assessment, Development and Evaluation were performed in duplicate. We conducted a random effect Bayesian network meta-analysis including both direct and indirect comparisons. RESULTS We included 43 randomized controlled trials studying 15 511 patients. DAPT with low-dose ASA and ticagrelor [odds ratio (OR) 2.53, 95% credible interval (CrI) 1.35–4.72; I2 = 55; low certainty] or clopidogrel (OR 1.56, 95% CrI 1.02–2.39; I2 = 55; very low certainty) improved saphenous vein graft patency when compared to low-dose ASA monotherapy. DAPT with low-dose ASA and ticagrelor was associated with lower mortality (OR 0.52, 95% CrI 0.30–0.87; I2 = 14; high certainty) and lower major adverse cardiovascular events (OR 0.63, 95% CrI 0.44–0.91; I2 = 0; high certainty) when compared to low-dose ASA monotherapy. Based on moderate certainty evidence, DAPT was associated with an increase in major bleeding. CONCLUSIONS Our results suggest that DAPT improves saphenous vein graft patency, mortality and major adverse cardiovascular event. As such, surgeons and physicians should consider re-initiating DAPT for acute coronary syndrome patients after their CABG, at the expense of an increased risk for major bleeding. Clinical trial registration International Prospective Register of Systematic Reviews ID Number CRD42019127695


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