***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND Transcatheter aortic valve replacement ( TAVR ) is an option in certain high-risk surgical patients with severe aortic valve stenosis . It is unknown whether TAVR can be safely introduced to lower-risk patients . OBJECTIVES The NOTION ( Nordic Aortic Valve Intervention Trial ) r and omized clinical trial compared TAVR with surgical aortic valve replacement ( SAVR ) in an all-comers patient cohort . METHODS Patients ≥ 70 years old with severe aortic valve stenosis and no significant coronary artery disease were r and omized 1:1 to TAVR using a self-exp and ing bioprosthesis versus SAVR . The primary outcome was the composite rate of death from any cause , stroke , or myocardial infa rct ion ( MI ) at 1 year . RESULTS A total of 280 patients were r and omized at 3 Nordic centers . Mean age was 79.1 years , and 81.8 % were considered low-risk patients . In the intention-to-treat population , no significant difference in the primary endpoint was found ( 13.1 % vs. 16.3 % ; p = 0.43 for superiority ) . The result did not change in the as-treated population . No difference in the rate of cardiovascular death or prosthesis reintervention was found . Compared with SAVR-treated patients , TAVR-treated patients had more conduction abnormalities requiring pacemaker implantation , larger improvement in effective orifice area , more total aortic valve regurgitation , and higher New York Heart Association functional class at 1 year . SAVR-treated patients had more major or life-threatening bleeding , cardiogenic shock , acute kidney injury ( stage II or III ) , and new-onset or worsening atrial fibrillation at 30 days than did TAVR-treated patients . CONCLUSIONS In the NOTION trial , no significant difference between TAVR and SAVR was found for the composite rate of death from any cause , stroke , or MI after 1 year . ( Nordic Aortic Valve Intervention Trial [ NOTION ] ; NCT01057173 ) Context Whether female sex is associated with an increased risk for adverse events among patients having transcatheter aortic valve replacement ( TAVR )  is unclear . Contribution In this secondary analysis of data from the Placement of Aortic Transcatheter Valves trial , women who had TAVR  had more postprocedural major bleeding and vascular complications and improved 1-year survival than men . Caution Other factors , such as paravalvular leak or patientprosthesis mismatch , may have confounded the results . Implication The sex-specific risk associated with TAVR is the reverse of that for surgical aortic valve replacement , for which female sex is associated with an increased risk for adverse events . During the past 50 years , the st and ard of care for patients with severe , symptomatic aortic stenosis ( AS ) has been surgical aortic valve replacement ( SAVR ) , which has been shown to prolong survival and alleviate symptoms compared with medical therapy alone ( 1 , 2 ) . However , at least one third of patients with AS are deemed to be high-risk or inoperable for SAVR due to comorbidities or unfavorable anatomy ( 3 ) . For these patients , transcatheter aortic valve replacement ( TAVR ) has emerged as an alternative ( 1 , 2 , 411 ) . The PARTNER ( Placement of Aortic Transcatheter Valves ) trial was the first to show the safety and efficacy of TAVR compared with accepted st and ard therapies in high-risk and inoperable patients with AS ( 49 ) . The results of this trial ultimately led to the approval of the SAPIEN transcatheter valve ( Edwards Lifesciences ) by the U.S. Food and Drug Administration . Since the PARTNER trial , many other trials and international registries have shown the benefits of TAVR in higher-risk patients ( 1012 ) . Female sex has been shown to be associated with increased risk for adverse events after SAVR ( 1317 ) but has been shown to be a potentially favorable characteristic for patients having TAVR ( 1823 ) . However , prior trials examining sex-based differences in patients having  TAVR  have been limited in size or have involved only single- or dual-center experiences . Furthermore , not all studies agree that TAVR may be more beneficial in women , with some finding no difference in outcomes or increased adverse events in women ( 2428 ) . Given the conflicting data in the literature , we sought to perform a comprehensive analysis of sex-based differences in patients having TAVR  by using the clinical trial structure of the PARTNER experience ( encompassing all  TAVR patients treated in not only the r and omized PARTNER trials but also the r and omized and nonr and omized continued access registries ) . We report the baseline demographic characteristics and core laboratoryassessed echocardiographic parameters of women and men treated with TAVR  , as well as adjudicated 30-day and 1-year outcomes stratified by sex . Methods Study Design and Patients The PARTNER trial incorporated 2 parallel prospect i ve , multicenter , r and omized , active treatmentcontrolled clinical trials . Patients were divided into 2 cohorts . Cohort A comprised patients who were considered to be high-risk c and i date s for surgery , as defined by a  Society of Thoracic Surgeons Predicted Risk of Mortality ( STS-PROM ) score of at least 8 % ( on a scale of 0 % to 100 % , with higher scores indicating greater risk for death within 30 days after surgery ) ( 13 ) and /or by the presence of coexisting conditions associated with a 15 % or greater risk for death at 30 days . Cohort B comprised those who were not considered to be suitable c and i date s for surgery because they had coexisting conditions associated with a 50 % or greater probability of death or serious irreversible morbidity after surgery based on a multidisciplinary heart team assessment . In cohort A , patients were r and omly assigned to TAVR or SAVR ;  in cohort B , patients were r and omly assigned to TAVR or medical therapy . Patients in cohort A were enrolled from 11 May 2007 to 28 August 2009 , and those in cohort B were enrolled from 11 May 2007 to 16 March 2009 . After enrollment in the r and omized PARTNER trial , sites were able to continue to consecutively enroll patients in a continued access registry using the same inclusion and exclusion criteria . The purpose of the continued access registry was to accumulate greater real-world experience with regard to the safety and efficacy of TAVR while approval by the U.S. Food and Drug Administration was pending . At the time of initiation of the registry , TAVR could not be performed in the United States unless the patient was formally enrolled in the registry or a comparable clinical trial . Because enrollment in the inoperable trial ( cohort B ) was completed 6 months before enrollment in the high-risk trial ( cohort A ) was completed , investigators decided to extend r and omization of cohort B into the continued access registry to prevent enrollment bias in the ongoing high-risk trial . Once enrollment in the high-risk trial was completed , both cohorts were enrolled in a nonr and omized continued access registry . Enrollment in this registry concluded on 9 January 2012 . The same data collection procedures and follow-up used for the r and omized PARTNER trial were used for the continued access registry . The same clinical events committee , adjudication process , and core laboratory interpretation of echocardiographic data were also used for both the r and omized and continued access portions of the PARTNER trial . The institutional review board at each site approved the study , and all patients provided written informed consent . End Points The 30-day and 1-year frequencies of all-cause mortality , cardiovascular mortality , rehospitalization , stroke , major vascular complications , major bleeding , myocardial infa rct ion , acute kidney injury , and need for a permanent pacemaker were recorded per the PARTNER trial protocol ( 4 , 5 ) . Major vascular complications were defined as any thoracic aortic dissection ; access site or access-related vascular injury leading to death , need for significant blood transfusions , or unplanned percutaneous or surgical intervention ; or distal embolization from a vascular source . Major bleeding was defined as a bleeding event that caused death or permanent disability , caused or prolonged a hospitalization , or required an open or endovascular procedure or a transfusion . All adverse events were fully adjudicated by an independent clinical events committee .  Echocardiograms  were obtained at baseline ; at discharge or 7 days , whichever came first ; and at 30 days , 6 months , and 1 year after the procedure . All echocardiograms were analyzed at an independent core laboratory that followed the American Society of Echocardiography st and ards for echocardiography core laboratories ( 29 ) . Statistical Analysis The current analysis was an as-treated analysis , which included all TAVR patients from cohort A , cohort B , and the continued access registry . Patients were stratified on the basis of sex . Continuous variables are presented as means and SDs and were compared using the t test ; categorical variables were compared by using the chi-square test or the Fisher exact test , as appropriate . KaplanMeier techniques were used for outcomes that contained all-cause death . All nonmortality outcomes were modeled by using a proportional subdistribution hazards regression to account for the competing risk for death ; the corresponding hazard ratios ( HRs ) and P values are reported from this model . For each sex , the cumulative incidence for 30-day and 1-year outcomes is summarized in the presence of all-cause death . A 2-sided level of 0.05 was used to indicate statistical significance . To assess the association between sex and all-cause mortality at 1 year , Cox multivariable regression analyses were performed . The multivariable model was created by forcing sex into a stepwise model selection procedure with clinical ly relevant c and i date variables using an entry/stay criterion of a P value less than 0.10 . Variables of clinical interest were included if the variable was significant ( P < 0.10 ) in the univariate Cox model . A supplemental model included moderate or severe paravalvular regurgitation at discharge and any major vascular complication as a time-dependent covariate along with variables selected in the final model . Using the same variables as those selected for the multivariable model for mortality , we tested for an association between sex and rehospitalization while accounting for the competing risk for death . We also tested for an interaction between sex and treatment approach ( transfemoral vs. transapical TAVR ) on 1-year all-cause mortality . Analyses were done using the FREQ , TTEST , UNIVARIATE , PHREG , and LIFETEST procedures in SAS , version 9.2 ( SAS Institute ) . Clinical Trial Registration The PARTNER trial was registered at Clinical Trials.gov on 14 September 2007 , slightly more than 4 months after the first patient was enrolled on 11 May 2007 . Only 41 ( 1.3 % ) of the 3216 total patients were enrolled before registration of the trial , and no interval analysis was conducted between enrollment of the first patient and registration of the trial . Role of the Funding Source The PARTNER trial was funded by Edwards Lifesciences , and the protocol was developed collaboratively by the sponsor and the steering committee . The funding source had no involvement in the design , analysis , or interpretation of this sub study or the decision to publish the manuscript . Results Baseline Characteristics All 2559 patients who had TAVR in the PARTNER trial were analyzed on the basis of their sex ( Table 1 ) . Of these , 2000 were in the nonr and omized continued access registry , 40 were in the r and omized continued access registry , and 519 were in the r and omized trial . Five patients in cohort A , 1 in cohort B , and none in the continued access registries were lost to follow-up . A total of 47.7 % of all patients were women , and 52.3 % were men . Table 1 . Study Population The baseline presenting characteristics varied between sexes in terms of demographic variables and AIMS In a prospect i ve r and omised trial we aim ed to compare transapical transcatheter aortic valve implantation ( a-TAVI ) with surgical aortic valve replacement ( SAVR ) in operable elderly patients . METHODS AND RESULTS The study was design ed as a r and omised controlled trial of a-TAVI ( Edwards SAPIEN heart valve system ; Edwards Lifesciences , Irvine , CA , USA ) vs. SAVR .  Operable patients with isolated aortic valve stenosis and an age ≥75 years were included . The primary endpoint was the composite of all-cause mortality , cerebral stroke and /or renal failure requiring haemodialysis at 30 days . After advice from the Data Safety Monitoring Board , the study was prematurely terminated after the inclusion of 70 patients because of an excess of events in the a-TAVI  group . The primary endpoint was met in five a-TAVI patients ( two deaths , two strokes , and one case of renal failure requiring dialysis ) vs. one stroke in the SAVR group ( p=0.07 ) . In the a-TAVI group , one patient was converted to SAVR because of an abnormally positioned heart , and four patients were re-operated with open heart surgery because of annulus rupture ( n=1 ) , severe paravalvular leakage ( n=2 ) , and blockage of the left coronary artery ( n=1 ) . In the SAVR group , one patient was converted to TAVI because of a large intra-thoracic goitre . CONCLUSIONS Given the limitations of a small 
    Output:
    
Secondary outcomes of kidney injury , new-onset atrial fibrillation , and major bleeding favoured TAVI , while major vascular complications , incidence of permanent pacemaker implantation , and paravalvular regurgitation favoured SAVR .
CONCLUSION Compared with SAVR , TAVI is associated with a significant survival benefit throughout 2 years of follow-up .
Importantly , this superiority is observed irrespective of the TAVI device across the spectrum of intermediate and high-risk patients , and is particularly pronounced among patients undergoing transfemoral TAVI and in females