Novel Oral Anticoagulants In Prevention Of Major Adverse Cardiovascular Events In Patients With Heart Failure And Coronary Artery Disease:a Meta-analysis

Aims:To evaluate the effectiveness and safety of novel oral anticoagulants(NOACs)in preventing major adverse cardiovascular events(MACE)in patients with heart failure(HF)and coronary artery disease(CAD).Methods:Literature databases included Pubmed,the Cochrane Library,Embase,CNKI,Wan Fang,CBM,VIP.The search time was from the establishment of the database to July 1,2019.Randomized controlled trials(RCT)of NOACs(dabigatran,rivaroxaban,apixaban,edoxaban)in HF and CAD patients compared with placebo were included through researching medical literature databases.We included HF patients complicated with CAD.The primary endpoint was MACE(stroke,myocardial infarction,death).Secondary end points were stroke,myocardial infarction,cardiovascular death,all-cause death.And safety end points were major bleeding,intracranial hemorrhage.In our study,two participants independently completed the quality evaluation and data extraction of the included articles.Stata software,Version 12.0 was used for statistical analysis,and the Hazard ratios(HR)and 95%confidence interval(95%CI)were calculated to compare the differences between groups.Results:Our meta-analysis included 4 RCTs of HF with CAD and 12160 patients.Our meta-analysis found that NOACs did not reduce the risk of MACE(HR:0.80,95%CI 0.64-1.00,P=0.052,I~2=75.4%).Compared with the control group,our results suggest that NOACs can significantly reduce the incidence of stroke(HR:0.61,95%CI 0.46-0.81,P=0.001,I~2=0.0%),and NOACs obviously reduced the incidence of myocardial infarction(HR:0.82,95%CI0.69-0.97,P=0.022,I~2=0.0%).However,NOACs did not reduce cardiovascular death(HR:0.81,95%CI 0.59-1.10,P=0.171,I~2=62.9%)and all-cause death(HR:0.69,95%CI 0.45-1.06,P=0.088,I~2=86.9%)in patients with HF complicated with CAD.In terms of safety endpoint events,it is worth noting that NOACs obviously increased the incidence of major bleeding in HF and CAD(HR:1.54,95%CI 1.19-1.98,P=0.001,I~2=0.0%),but not increased the incidence of intracranial hemorrhage(HR:1.14,95%CI 0.44-2.92,P=0.792,I~2=27.1%).Subgroup analysis showed that low-dose rivaroxaban can significantly reduce myocardial infarction(HR:0.78,95%CI 0.64-0.95,P=0.015,I~2=0.0%).However,it does not reduce the MACE events(HR:0.74,95%CI 0.55-1.00,p=0.051,I~2=82.0%)and the risk of cardiovascular death(HR:0.73,95%CI 0.45-1.19,P=0.211,I~2=75.0%).And low-dose rivaroxaban increased the risk of major bleeding events(HR:1.51,95%CI1.16-1.98,P=0.003,I~2=0.0%).Conclusion:Our meta-analysis concluded that NOACs has an advantage in reducing stroke and myocardial infarction.However,it does not reduce the risk of death in people with HF combined with CAD.NOACs can significantly increase the incidence of major bleeding in HF patients complicated with CAD.The use of NOACs in patients with HF combined with CAD has failed to reduce the mortality of HF by reducing ischemic event,and because of its increased bleeding risk,it has not achieved clinical net benefit.The risk of ischemia and bleeding needs to be weighed when using NOACs.