You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial
Abstract 1:
Aims We investigated clinical characteristics and outcomes of patients with significant valvular disease ( SVD ) in the Rivaroxaban  Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation ( ROCKET AF ) trial . Methods and results ROCKET AF excluded patients with mitral stenosis or artificial valve prostheses . We used Cox regression to adjust comparisons for potential confounders . Among 14 171 patients , 2003 ( 14.1 % ) had SVD ; they were older and had more comorbidities than patients without SVD .  The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [ 2.01 vs. 2.43 % ; hazard ratio ( HR ) 0.83 , 95 % confidence interval ( CI ) 0.55–1.27 ] and without SVD ( 1.96 vs. 2.22 % ; HR 0.89 , 95 % CI 0.75–1.07 ; interaction P = 0.76 ) . However , rates of major and non-major clinical ly relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD ( 19.8 % rivaroxaban vs. 16.8 % warfarin ; HR 1.25 , 95 % CI 1.05–1.49 ) vs. those without ( 14.2 % rivaroxaban vs. 14.1 % warfarin ; HR 1.01 , 95 % CI 0.94–1.10 ; interaction P = 0.034 ) , even when controlling for risk factors and potential confounders . In intracranial haemorrhage , there was no interaction between patients with and without SVD where the overall rate was lower among those r and omized to rivaroxaban . Conclusions Many patients with ‘ non-valvular atrial fibrillation ’ have significant valve lesions . Their risk of stroke is similar to that of patients without SVD after controlling for stroke risk factors . Efficacy of rivaroxaban vs. warfarin was similar in patients with and without SVD ; however , the observed risk of bleeding was higher with rivaroxaban in patients with SVD but was the same among those without SVD . Atrial fibrillation patients with and without SVD experience the same stroke-preventive benefit of oral anticoagulants


Title 2:
Comparison of unfractionated heparin, low-molecular-weight heparin, low-dose and high-dose rivaroxaban in preventing thrombus formation on mechanical heart valves: results of an in vitro study
Abstract 2:
Thromboembolism and bleeding after mechanical heart valve replacement are still unsolved problems , particularly for patients requiring anticoagulative bridging therapy . The aim of this study was to investigate whether rivaroxaban , a new oral selective and direct coagulation factor Xa inhibitor , is as effective as enoxaparin and unfractionated heparin ( UFH ) in preventing thrombus formation on mechanical heart valves using an in vitro system . Blood from healthy male donors was anticoagulated with either UFH , enoxaparin , rivaroxaban at 300 ng/ml , ( n = 10 each ) , or rivaroxaban at 30 ng/ml ( n = 3 ) . Mechanical aortic valve prostheses were placed into the in vitro testing system THIA II and exposed to the anticoagulant blood mixtures at a pulsatile flow for 60 min . Overall thrombus weight , coagulation parameters , and electron microscopic features of thrombus formation on the valve surface were quantified as endpoints . The mean thrombus weights were 163 ± 64 mg for group 1 ( UFH ) , 341 ± 63 mg for the group 2 ( enoxaparin ) , 238 ± 83 mg for group 3 ( rivaroxaban 300 ng/ml ) and 1.739 ± 16 mg for group 4 ( rivaroxaban 30 ng/ml ) . Whereas high-dosed rivaroxaban showed no significant differences compared to UFH or enoxaparin , low-dosed rivaroxaban generated a massive thrombus generation , thus differing significantly from all other treatment groups regarding the thrombus weight . We hypothesize that high-dose rivaroxaban is a competitive oral available alternative to UFH and LMWH ’s , that might be a worthwhile alternative for patients in need of anticoagulative bridging therapy . Prospect i ve studies have to evaluate if rivaroxaban might even overcome the limitations of OAC in patients after implantation of artificial heart valves


Title 3:
Dabigatran Versus Warfarin After Bioprosthesis Valve Replacement for the Management of Atrial Fibrillation Postoperatively: DAWA Pilot Study
Abstract 3:
Objectives Dabigatran is a direct thrombin inhibitor shown to be an effective alternative to warfarin in patients with non-valvular atrial fibrillation ( AF ) . We evaluated the use of dabigatran in patients with bioprosthetic mitral and /or aortic valve replacement and AF . Methods We selected 34 and r and omized 27 patients in a 1:1 ratio to receive dabigatran or warfarin . The primary endpoint was the presence of a new intracardiac thrombus at 90 days , by transesophageal echocardiogram ( TEE ) . Secondary endpoints included the development of dense spontaneous echo contrast ( SEC ) and incidence of stroke ( ischemic or hemorrhagic ) , myocardium infa rct ion , valve thrombosis and peripheral embolic events . Results The trial was terminated prematurely because of low enrollment . There were 27 patients in total : 15 patients placed in the dabigatran group and 12 in the warfarin group . After 90 days , one patient ( 8.3 % ) in the warfarin group and none in the dabigatran group had developed a new intracardiac thrombus . In the dabigatran group , two patients ( 13.3 % ) developed dense SEC versus one patient ( 8.3 % ) in the warfarin group . In the warfarin group , one patient ( 8.3 % ) presented ischemic stroke , and none did in the dabigatran group . We observed no cases of hemorrhagic stroke , valve thrombosis , embolic events or myocardial infa rct ion in either group throughout the study . However , one patient ( 6.7 % ) in the dabigatran group had a fully recovered transient ischemic attack and one patient in the warfarin group died of heart failure . Conclusions The use of dabigatran appears to be similar to warfarin in preventing the formation of intracardiac thrombus . Trial Registration Clinical trials.gov NCT01868243


Title 4:
Effectiveness of rivaroxaban for thromboprophylaxis of prosthetic heart valves in a porcine heterotopic valve model.
Abstract 4:
OBJECTIVES Warfarin is used to reduce the risk of stroke and thromboembolic complications in patients with mechanical heart valves . Yet , despite frequent blood testing , its poor pharmacokinetic and pharmacodynamic profiles often result in variable therapeutic levels . Rivaroxaban is a direct competitive factor Xa inhibitor that is taken orally . It inhibits the active site of factor Xa without the need for the cofactor antithrombin , and thus , its mechanism of action is differentiated from that of the fractionated heparins and indirect factor Xa inhibitors . No in vivo data exist regarding the effectiveness of rivaroxaban in preventing thromboembolic complications of mechanical heart valves . We tested the hypothesis that rivaroxaban is as effective as enoxaparin for thromboprophylaxis of mechanical valves that use a previously described heterotopic aortic valve porcine model . METHODS A modified bileaflet mechanical valved conduit that bypassed the native , ligated descending thoracic aorta was implanted into 30 swine . Postoperatively , the animals were r and omly assigned to groups receiving no anticoagulation ( n = 10 ) , enoxaparin at 2 mg/kg subcutaneously twice daily ( n = 10 ) or rivaroxaban at 2 mg/kg orally twice daily ( n = 10 ) . The amount of valve thrombus was measured on post-implantation day 30 as the primary end point . Quantitative evaluation of radiolabelled platelet deposition on the valve prostheses was done and embolic and haemorrhagic events were measured as secondary end points . RESULTS Animals with no anticoagulation had a thrombus mean of 759.9 mg compared with 716.8 mg with enoxaparin treatment and 209.6 mg with rivaroxaban treatment ( P = 0.05 for enoxaparin vs rivaroxaban ) . Similarly , the mean number of platelets deposited on the valve prosthesis was lower in the rivaroxaban group ( 6.13 × 10(9 ) ) than in the enoxaparin group ( 3.03 × 10(10 ) ) ( P = 0.03 ) . CONCLUSIONS In this study , rivaroxaban was more effective than enoxaparin for short-term thromboprophylaxis of mechanical valve prosthetics in the heterotopic aortic position . It reduced valve thrombus and platelet deposition on day 30 following implantation without increased adverse events . Future studies would provide additional support for clinical trials evaluating rivaroxaban as an alternative to warfarin for appropriately selected patients with prosthetic aortic valves


Title 5:
Burden of valvular heart diseases: a population-based study
Abstract 5:
BACKGROUND Valvular heart diseases are not usually regarded as a major public-health problem . Our aim was to assess their prevalence and effect on overall survival in the general population . METHODS We pooled population -based studies to obtain data for 11 911 r and omly selected adults from the general population who had been assessed prospect ively with echocardiography .  We also analysed data from a community study of 16 501 adults who had been assessed by clinical ly indicated echocardiography .  FINDINGS In the general population group , moderate or severe valve disease was identified in 615 adults . There was no difference in the frequency of such diseases between men and women ( p=0.90 ) . Prevalence increased with age , from 0.7 % ( 95 % CI 0.5 - 1.0 ) in 18 - 44 year olds to 13.3 % ( 11.7 - 15.0 ) in the 75 years and older group ( p<0.0001 ) . The national prevalence of valve disease , corrected for age and sex distribution from the US 2000 population , is 2.5 % ( 2.2 - 2.7 ) . In the community group , valve disease was diagnosed in 1505 ( 1.8 % adjusted ) adults and frequency increased considerably with age , from 0.3 % ( 0.2 - 0.3 ) of the 18 - 44 year olds to 11.7 % ( 11.0 - 12.5 ) of those aged 75 years and older , but was diagnosed less often in women than in men ( odds ratio 0.90 , 0.81 - 1.01 ; p=0.07 ) . The adjusted mortality risk ratio associated with valve disease was 1.36 ( 1.15 - 1.62 ; p=0.0005 ) in the population and 1.75 ( 1.61 - 1.90 ; p<0.0001 ) in the community . INTERPRETATION Moderate or severe valvular diseases are notably common in this population and increase with age . In the community , women are less often diagnosed than are men , which could indicate an important imbalance in view of the associated lower survival . Valve diseases thus represent an important public-health problem


Title 6:
Usefulness and Safety of Rivaroxaban in Patients Following Isolated Mitral Valve Replacement With a Mechanical Prosthesis.
Abstract 6:
Rivaroxaban has previously been tested in experimental and animal models with encouraging results . We prospect ively selected seven patients between May 2017 and January 2018 who underwent isolated mitral valve replacement with a mechanical prosthesis and had unstable INR control at least 3 months after surgery . An intervention of rivaroxaban 15 mg was then administered twice daily for a period of 90days . No patient presented intracardiac thrombus , reversible ischemic neurological deficit , ischemic or hemorrhagic stroke , and hospitalization or death during 3 months of follow-up . Two patients eradicated the presence of spontaneous echo contrast . Mean and peak pressure gradients , peak velocity , effective orifice area , and PHT were similar before and after the intervention . In conclusion , the use of rivaroxaban for 90days in seven patients after replacement of mitral valve with the mechanical prosthesis did not present thromboembolic or bleeding events ( NCT02894307 )


Title 7:
Outcomes of Direct Oral Anticoagulants in Patients With Mitral Stenosis.
Abstract 7:
BACKGROUND Patients with mitral stenosis and atrial fibrillation ( AF ) require anticoagulation for stroke prevention . Thus far , all studies on direct oral anticoagulants ( DOACs ) have excluded patients with moderate to severe mitral stenosis . OBJECTIVES The aim of this study was to vali date the efficacy of DOACs in patients with mitral stenosis . METHODS The study population was enrolled from the Health Insurance Review and Assessment Service ( HIRA ) data base in the Republic of Korea , and it included patients who were diagnosed with mitral stenosis and AF and either were prescribed DOACs for off-label use or received conventional treatment with warfarin .  The primary efficacy endpoint was ischemic strokes or systemic embolisms , and the safety outcome was intracranial hemorrhage . RESULTS A total of 2,230 patients ( mean age 69.7 ± 10.5 years ; 682 [ 30.6 % ] males ) were included in the present study . Thromboembolic events occurred at a rate of 2.22%/year in the DOAC group , and 4.19%/year in the warfarin group ( adjusted hazard ratio for DOAC : 0.28 ; 95 % confidence interval : 0.18 to 0.45 ) . Intracranial hemorrhage occurred in 0.49 % of the DOAC group and 0.93 % of the warfarin group ( adjusted hazard ratio for DOAC : 0.53 ; 95 % confidence interval : 0.22 to 1.26 ) . CONCLUSIONS In patients with AF accompanied with mitral stenosis , DOAC use is promising and hypothesis generating in preventing thromboembolism . Our results need to be replicated in a r and omized trial
Conclusions The efficacy and safety of NOACs as thromboprophylaxis for AF and VHD are similar to those of warfarin