Impact of Sex on Comparative Outcomes of Radial Versus ... · presenting with non–ST-segment elevation ACS (NSTE-ACS) were eligible if they had a history consistent with new or
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J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 1 , N O . 1 , 2 0 1 8
ª 2 0 1 8 B Y T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y F O U N D A T I O N
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Impact of Sex on Comparative Outcomesof Radial Versus Femoral Access inPatients With Acute Coronary SyndromesUndergoing Invasive ManagementData From the Randomized MATRIX-Access Trial
Giuseppe Gargiulo, MD,a,b Sara Ariotti, MD,a Pascal Vranckx, MD, PHD,c,d Sergio Leonardi, MD,e Enrico Frigoli, MD,a
Nestor Ciociano, PHARMD,f Carlo Tumscitz, MD,g Francesco Tomassini, MD,h Paolo Calabrò, MD,i
J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 1 , N O . 1 , 2 0 1 8 Gargiulo et al.J A N U A R Y 8 , 2 0 1 8 : 3 6 – 5 0 MATRIX-Access Trial and Sex
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T he advent of combined antithrombotic thera-pies and early invasive management hasreduced the ischemic burden but increased
bleeding risk in patients with acute coronary syn-drome (ACS) (1–3). The use of radial instead of femoralaccess mitigates bleeding while preserving ischemicrisks, thereby providing consistent mortality benefitacross trials (4).
Female patients have increased periproceduralbleeding risk as compared with men (1,5). However,female patients have smaller radial arteries that aremore prone to spasm as well as shorter aortic rootsthan men, which adds to the operative difficulty andmay undermine the efficacy of radial access in thispopulation. Previous studies have shown contrastingevidence about potential sex disparities for the safetyand efficacy of transradial access (TRA) versus trans-femoral access (TFA) (6,7).
SEE PAGE 51RR = rate ratio
TFA = transfemoral access
TRA = transradial access
We sought to investigate the comparative efficacy
and safety outcomes across sex of radial versus femoralaccess in ACS patients participating in the MATRIX-Access (Minimizing Adverse Haemorrhagic Events byTRansradial Access Site and Systemic Implementationof angioX) trial.
From the aDepartment of Cardiology, Bern University Hospital, Bern, Switzer
Federico II University of Naples, Naples, Italy; cDepartment of Cardiology an
Ziekenhuis, Hasselt, Belgium; dFaculty of Medicine and Life Sciences, Has
Dipartimento CardioToracoVascolare, Fondazione IRCCS Policlinico San Ma
Italy; gCardiology Unit, Azienda Ospedaliero Universitaria di Ferrara, Cona, It
Torino 3, Turin, Italy; iDivision of Cardiology, Department of Cardiothoracic
Naples, Italy; jStruttura complessa di Cardiologia ASST di Vimercate, Desio, I
Gabriele Monasterio, Pisa, Italy; pASST Bergamo Ovest, Ospedale di Trevigli
pital “Maggiore della Carità,” Novara, Italy; rCardiovascular Interventional U
Italy; sInterventional Cardiology Unit, Ospedale San Giovanni Bosco, TuruHumanitas Research Hospital, IRCCS, Rozzano, Italy; vDepartment of Cardi
and Geriatric Sciences, Policlinico Umberto I, “Sapienza” University of Rome
Hospital, Rimini, Italy; xCardiology Unit, A.O. Ospedale di Desio, Desio, Ital
lanini, Rome, Italy; zInterventional Cardiology Unit, IRCCS AOU San M
Cardiothoracic and Vascular Department, University of Pisa, Pisa, Italy; an
University of Bern, Bern, Switzerland. The trial was sponsored by the Socie
zation),which receivedgrant support fromTheMedicinesCompanyandTerum
funding. Dr. Gargiulo has received research grant support from the Cardiopa
diologia supported byMSD Italia-Merck Sharp and Dohme Corporation. Dr. Vr
and Bayer Healthcare. Dr. Leonardi has received personal fees from The M
submittedwork; and grant support fromAstraZeneca outside the submittedw
Terumo and Volcano-Phillips; and personal fees from Abbott, Bayer Healthcar
Dr. Cortese has received research grants from AB Medica, Abbott, St. Jude M
AstraZeneca, Daiichi-Sankyo and Eli-Lilly, Stentys, all outside the submitted w
Scientific, and Abbott. Dr Windecker has received research grants to the instit
Valgimigli has received research grant support from The Medicines Compan
Terumo, St. JudeVascular, andAbbottVascular. Dr. Soniahas served as a consu
Windecker has received institutional research grants from Abbott, Boston Sc
andSt. JudeMedical.All other authorshave reported that theyhaveno relation
Manuscript received July 17, 2017; revised manuscript received September 1
METHODS
STUDY DESIGN. The MATRIX-Access was arandomized, multicenter, superiority trialcomparing radial with femoral access in pa-tients with ACS with or without ST-segmentelevation undergoing coronary angiographyand percutaneous coronary intervention(PCI), if indicated (4,8). This was the first of 3trials of the MATRIX program (Clinical-Trials.gov; NCT01433627) and was performedin all patients with an ACS consenting toparticipate in the program. The institutionalreview board at each participating centerapproved the trial, and all patients gavewritten informed consent to participate.
STUDY PATIENTS. Patients were eligible ifthey had an ACS with or without ST-segmentelevation, were scheduled to undergo aninvasive approach, and the interventionalcardiologist was willing to proceed with
either radial or femoral access with expertise forboth, including at least 75 coronary interventionsperformed and at least 50% of interventions in ACSvia the radial route during the previous year. Patients
land; bDepartment of Advanced Biomedical Sciences,
d Critical Care Medicine, Hartcentrum Hasselt, Jessa
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presenting with non–ST-segment elevation ACS(NSTE-ACS) were eligible if they had a historyconsistent with new or worsening ischemia, occur-ring at rest or with minimal activity within 7 daysbefore randomization, and fulfilled at least 2 high-risk criteria (4,8). Patients with ST-segment eleva-tion myocardial infarction were eligible if theypresented within 12 h of the onset of symptoms orbetween 12 and 24 h after symptom onset if there wasevidence of continued ischemia or previous fibrino-lytic treatment and if they had ST-segment elevationof at least 1 mm in 2 or more contiguous leads, newleft bundle branch block, or true posterior MI. Themain inclusion and exclusion criteria were previouslyreported (4,8).
STUDY PROTOCOL AND RANDOMIZATION. Beforethe start of angiography, patients were randomlyassigned 1:1 to radial or femoral access for diagnosticangiography and PCI, if indicated, using a web-based system to ensure adequate concealment of
allocation. The randomization sequence was com-puter generated, blocked, and stratified by site,intended new or ongoing use of ticagrelor orprasugrel, type of ACS (ST-segment elevationmyocardial infarction or troponin-positive ortroponin-negative NSTE-ACS), and anticipated useof immediate PCI. Access site management duringand after the diagnostic or therapeutic procedurewas left to the discretion of the treating physician,and closure devices were allowed as per local prac-tice. The use of anticoagulant agents outside theprotocol of the MATRIX program was not allowed.Bivalirudin administration was consistent with theapproved product labeling, whereas unfractionatedheparin was dosed at 70 to 100 U/kg in patients notreceiving glycoprotein IIb or IIIa inhibitors and at50 to 70 U/kg in patients receiving glycoprotein IIbor IIIa inhibitors. Use of all other antithromboticmedications, including oral antiplatelet agentsand nonantithrombotic medications, such as beta-blockers, angiotensin-converting enzyme inhibitors,
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and other antihypertensive agents, were allowed asper guidelines (9).
STUDY OUTCOMES. Two coprimary 30-day compos-ite outcomes were pre-specified: major adverse car-diovascular and cerebrovascular events (MACCE),defined as the composite of all-cause mortality, MI, orstroke; and net adverse clinical events (NACE),defined as the composite of MACCE or noncoronaryartery bypass grafting–related major bleeding(Bleeding Academic Research Consortium [BARC]type 3 or 5) (10). Secondary outcomes includedeach component of the composite outcomes,
cardiovascular mortality, and stent thrombosis.Bleeding was also assessed and adjudicated on thebasis of the Thrombolysis In Myocardial Infarctionand GUSTO (Global Utilization of Streptokinase andTissue Plasminogen Activator for Occluded CoronaryArteries) scales (11,12). Stent thrombosis was definedas the definite or probable occurrence of a stent-related thrombotic event according to the AcademicResearch Consortium classification (13). All outcomeswere pre-specified (4,8). An independent clinicalevents committee blinded to treatment allocationadjudicated all suspected outcome events byreviewing relevant medical records after site
TABLE 2 Procedural Characteristics According to Access Site and Sex
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monitoring by Trial Form Support (Lund, Sweden) inItaly and the Netherlands, FLS-Research Support(Barcelona, Spain) in Spain, and Gothia Forum (VästraGötaland) in Sweden.
STATISTICAL ANALYSIS. Statistical analyses wereperformed by an academic statistical group led by 1 ofthe authors (B.R.d.C.), who had access to the fulldeidentified data set.
The trial was powered for superiority on the 2coprimary composite outcomes at 30 days expecting a
rate reduction of 30%, corresponding to rate ratio(RR) of 0.70.
All analyses were performed per intention-to-treatprinciple, including all patients in the analysis basedon the allocated access. Events up to 30 days post-randomization were considered. We analyzed pri-mary and secondary outcomes separately for maleand female patients as time to first event using theMantel-Cox method, accompanied by log-ranktests to calculate corresponding 2-sided p values.We did not perform any adjustments for multiple
TABLE 2 Continued
Male Patients Female PatientsMale
Patients(n ¼ 6,172)
FemalePatients
(n ¼ 2,232) p ValueRadial
(n ¼ 3,126)Femoral
(n ¼ 3,046) p ValueRadial
(n ¼ 1,071)Femoral
(n ¼ 1,161) p Value
Fluoroscopic time, min 11.0 (6.7–17.1) 9.7 (5.5–15.2) 0.88 9.2 (5.0–15.0) 8.1 (4.2–14.4) 0.43 10.2 (6.0–16.2) 9.0 (4.5–14.6) 0.27
Treated vessel(s) per patient
Left main coronary artery 107 (4.1) 88 (3.5) 0.26 45 (6.1) 31 (3.8) 0.033 195 (3.8) 76 (4.9) 0.039
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comparisons but set the alpha error at 2.5% to cor-rect for the 2 coprimary outcomes. We analyzedsecondary outcomes with a 2-sided alpha value setat 5% to allow conventional interpretation of results.Survival curves were constructed using Kaplan-Meier estimates. We performed stratified analysesaccording to the pre-specified subgroup of random-ization to heparin or bivalirudin, and estimated
possible interaction terms across ordered groupsseparately for the male and female study pop-ulations. We also analyzed clinical outcomes in theoverall population irrespective of randomized accessto compare male and female patients, but due to thesignificant differences in baseline and proceduralcharacteristics, multivariable adjustment was per-formed including the following variables: age, type
TABLE 3 Clinical Outcomes at 30 Days in Male and Female Patients
BARC ¼ Bleeding Academic Research Consortium; CI ¼ confidence interval; GUSTO ¼ Global Utilization of Streptokinase and Tissue Plasminogen Activator for OccludedCoronary Arteries; ST ¼ stent thrombosis; TVR ¼ other abbreviations as in Tables 1 and 2.
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of ACS, body mass index, diabetes, smoking,hypercholesterolemia, hypertension, previous MI,previous CABG, previous stroke or transientischemic attack, Killip class, renal function,
crossover, glycoprotein IIb or IIIa, and intra-aorticballoon pump. All analyses were performed usingthe statistical package Stata 13.1 (StataCorp, CollegeStation, Texas).
FIGURE 1 Main Outcomes of Radial Versus Femoral Access in Male and Female
Patients
Radial and femoral access were compared on the basis of sex subgroups, with rate ratios
and 95% confidence intervals (CIs), for the coprimary endpoints and their components
(death, myocardial infarction [MI], stroke, Bleeding Academic Research Consortium
[BARC] type 3 or 5).
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RESULTS
PATIENTS. The MATRIX-Access trial enrolled 8,404patients with ACS from 78 centers in Italy, theNetherlands, Spain, and Sweden between October2011 and November 2014. Of these patients, 6,172(73.4%) were men, of whom 3,126 (37.2%) were allo-cated to radial and 3,046 (36.2%) to femoral access;and 2,232 (26.6%) were women, of whom 1,071 (12.8%)were assigned to radial and 1,161 (13.8%) to femoralaccess.
Baseline and procedural characteristics werelargely imbalanced between sexes (Tables 1 and 2).Compared with men, women were older; had lowerbody weight and body mass index; presented morefrequently with NSTE-ACS and advanced Killip class;and had a higher prevalence of diabetes, hypercho-lesterolemia, hypertension, renal dysfunction, andprior cerebrovascular events. However, women lessfrequently were smokers or had prior MI, PCI, orCABG. Crossover rates, use of intra-aortic balloonpump, left main treatment, and bare-metal stent im-plantation occurred more often in women, whileattempted PCI, use of glycoprotein IIb/IIIa inhibitors,and bypass graft treatment were less frequent inwomen and stent diameter and length were lower(Table 1). Before arrival in the catheterization labo-ratory, female patients received aspirin and newP2Y12 inhibitors less frequently as compared withmen (Table 1).
On the contrary, female and male subgroups allo-cated to radial versus femoral access were generallywell matched in terms of demographics, medicalhistory, clinical presentation, and procedural aspects(Tables 1 and 2). Medications at discharge are shownin Online Table 1. Crossover rate from radial tofemoral was numerically higher in women ascompared with men (Table 2), however interactiontesting did not confirm heterogeneity across sexes(interaction p ¼ 0.051).
CLINICAL OUTCOMES OF MALE VERSUS FEMALE
PATIENTS. MACCE and NACE were significantlylower in men compared with women at unadjustedanalysis but they no longer differed after adjustmentfor the multiple imbalances identified across patients’characteristics (Table 3). Similarly, after adjustment,neither of the single components of both coprimaryendpoints differed significantly in male comparedwith female patients (Table 3). There was however atrend toward higher risk of BARC type 3 or 5 accesssite bleeding and a 36% increase of BARC type 2, 3, or
5 access site bleeding rates in women compared withmen after adjustment (Table 3). The need for trans-fusion and the composite of surgical access site repairand blood transfusion were also increased afteradjustment in female compared with male patients(Table 3).
CLINICAL OUTCOMES OF RADIAL VERSUS FEMORAL
ACCESS ACCORDING TO SEX. Overall crossoverrates were higher in women as compared with men(4.7% vs. 3.8%; p ¼ 0.037), however this differencedisappeared after adjustment (p ¼ 0.42).
No significant interaction was noted between ac-cess site and sex with respect to both coprimaryendpoints of 30-day MACCE and NACE (interactionp ¼ 0.15 and 0.18, respectively) (Figures 1 and 2,Table 4). MACCE and NACE were significantlyreduced with radial as compared with femoral in fe-male patients (MACCE: 9.1% vs. 12.2%; RR: 0.73; 95%confidence interval [CI]: 0.56 to 0.95; p ¼ 0.019;NACE: 10.4% vs. 13.9%; RR: 0.73; 95% CI: 0.56 to 0.93;
FIGURE 2 Coprimary Composite Outcomes at 30 Days in Male and Female Patients
(A, B) Cumulative incidence of the coprimary outcome of major adverse cardiac or ce-
rebrovascular events and net adverse clinical events, respectively. Blue indicates radial
access (transradial access [TRA]), red indicates femoral access (transfemoral access
[TFA]), continuous line indicates male patient, dashed line indicates female patient.
Abbreviations as in Figure 1.
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p ¼ 0.012) (Figure 1, Table 4) and trended in favor ofradial, albeit nonsignificantly in men (MACCE: 8.7%vs. 9.5%; RR: 0.92; 95% CI: 0.77 to 1.09; p ¼ 0.31;NACE: 9.6% vs. 10.8%; RR: 0.89; 95% CI: 0.76 to 1.05;p ¼ 0.16) (Figure 1, Table 4). Radial access wasconsistently (interaction p ¼ 0.79) associated to lowerall-cause fatalities in both sex groups (women: 2.4%vs. 3.5%; RR: 0.70; 95% CI: 0.43 to 1.15; men: 1.3% vs.1.7%; RR: 0.76; 95% CI: 0.50 to 1.15) (Figure 3, Table 4).At further analysis, no signal of interaction was noted
between access site and sex for stroke (interactionp ¼ 0.18), myocardial infarction (interaction p ¼ 0.25)and for other secondary endpoints includingcardiovascular mortality (interaction p ¼ 0.92), stentthrombosis (interaction p ¼ 0.18), target vesselrevascularization (interaction p ¼ 0.18), or the com-posite of access site surgery or blood transfusion(interaction p ¼ 0.18) (Figure 3, Table 4).
The key safety endpoint of BARC type 3 or 5bleeding was similarly reduced (interactionp ¼ 0.45) in the radial groups across sex, even ifformal statistical significance was achieved in fe-male (2.0% vs. 3.4%; RR: 0.58; 95% CI: 0.34 to0.98; p ¼ 0.040) but not in male patients (1.4% vs.1.9%; RR: 0.74; 95% CI: 0.50 to 1.11; p ¼ 0.14)(Table 4). Access site BARC type 3 or 5 bleedingwas consistently (interaction p ¼ 0.45) reduced inboth female and male patients whereas non–accesssite BARC type 3 or 5 bleeding did not differ withradial in both sexes (Table 4). Results remainedconsistent across any BARC, TIMI, or GUSTObleeding scales.
ADDITIONAL ANALYSES. Figures 4 and 5 show theconsistency of randomized treatment effect (radialvs. femoral) on MACCE, NACE, all-cause death andBARC bleeds in female and male patients stratified byrandomly allocated antithrombin type (bivalirudin orunfractionated heparin).
DISCUSSION
We assessed the role of sex disparities on clinicaloutcomes in largely unselected ACS patients recruitedin the MATRIX-Access trial and undergoing invasivemanagement via either radial or femoral access. Themain findings are the following.
First, male and female patients differed consid-erably for multiple baseline characteristics, proce-dural features, and choice of medications. Althoughunadjusted analyses apparently yielded greater riskof main efficacy and safety endpoints in femalepatients as compared with men, they no longerdiffered after adjustment. Only access sitebleeding, but not overall bleeding, along withtransfusion rates alone or in combination withsurgical repair for the instrumented access site,remained higher in female as compared with malepatients.
Second, there was no clear signal of heterogeneityacross sex with respect to any of the investigated
TABLE 4 Clinical Outcomes at 30 Days in Radial Versus Femoral Access According to Sex
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outcome measures, including the 2 coprimary com-posite endpoints or each of the individual compo-nents. Women but not men showed a significantreduction of both coprimary endpoints (fulfilling thepre-specified level of significance at an alpha error
of 2.5%) with radial access, indicating that the well-known sex-specific procedural challenges of trans-radial coronary catheterization and intervention donot mitigate the expected benefits in femalepatients.
FIGURE 3 Components of Coprimary Composite Outcomes at 30 Days in Male and Female Patients
Panels show the cumulative incidence of the coprimary outcome of (A) all-cause death, (B) myocardial infarction, (C) stroke, and (D) BARC type 3 or 5 bleeding.
Blue indicates radial access (TRA), red indicates femoral access (TFA), continuous line indicates male patient, dashed line indicates female patient. Abbreviations as
in Figures 1 and 2.
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Advances in PCI procedures and optimization ofconcomitant antithrombotic agents have improvedoutcomes of patients with ACS by reducing ischemicevents, but at the cost of greater bleeding risk. Thelatter remains a matter of concerns especially forpatients at increased procedural hemorrhagic risksuch as female patients. Although the spontaneous(i.e., out of hospital) bleeding risk appears not todiffer among sexes (14–17), female patients havebeen consistently shown to suffer the greatest fromaccess site hemorrhagic complications as comparedwith male counterparts (1,5) Access site bleedsrepresent a large part of periprocedural bleeding andTRA has emerged as the most appealing and cost-saving treatment strategy to mitigate those
complications. However, sex-specific proceduralchallenges of transradial coronary catheterizationand intervention, possibly leading to a delayed orless effective percutaneous treatment especially inACS female patients, remain a matter of concern.Previous studies have reported that female sex is anindependent predictor of failure of transradial PCI(18) and an independent predictor of radial spasm(19), limiting the success of the transradialprocedure.
The MATRIX-Access trial is the largest (n ¼ 8,404)randomized trial to compare radial and femoral ac-cess, including unselected patients at high baselineand procedural risk. Our current findings are inagreement with those of previous observational
FIGURE 4 Main Outcomes of Radial Versus Femoral Access Stratified by Antithrombin Type in Female Patients
Radial and femoral access were compared on the basis of the randomly assigned antithrombin type (bivalirudin or unfractionated heparin
[UFH]), with rate ratios and 95% CIs, for the coprimary endpoints, death, and BARC type 3 or 5. Abbreviations as in Figure 1.
FIGURE 5 Main Outcomes of Radial Versus Femoral Access Stratified by Antithrombin Type in Male Patients
Radial and femoral access were compared on the basis of the randomly assigned antithrombin type (bivalirudin or unfractionated heparin),
with rate ratios and 95% CIs, for the coprimary endpoints, death, and BARC type 3 or 5. Abbreviations as in Figure 1.
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studies (20,21), and those reported in the RIVAL(Radial Vs femorAL access for coronary intervention)trial. A pre-specified subgroup analysis of RIVALcompared outcomes in women (n ¼ 1,861) and men(n ¼ 5,160) who were randomized to radial versusfemoral access and showed that women undergoingcoronary angiography and PCI had a higher risk ofvascular access site complications compared withmen, but radial access was an effective method toreduce these complications (7). In the RIVAL trial thetype of antithrombotic medications during coronaryintervention was not protocol-mandated. As a result,the majority of patients were treated with heparinrather than bivalirudin (approximately 2.6%).Therefore, it was not possible to exclude that usingbivalirudin would have reduced the benefits ofradial access especially in female patients (22). In theMATRIX-Access trial, heparin and bivalirudin wererandomly and evenly assigned to patients at thetime of coronary intervention. No signal of hetero-geneity was noted for type of anticoagulant agentand access site for both men and women across thecoprimary endpoints, mortality, or the key safetybleeding endpoint. This novel and unique observa-tion that the benefits of radial access remainconsistent in both sexes irrespective of the choice ofparenteral anticoagulation during PCI has notableimplications for current practice. Against the wide-spread belief that radial access and use of bivalir-udin represent competing treatment strategies tominimize bleeding risks, our findings support theircomplementary role to mitigate both access site andnon–access site bleeding risks, both in male and fe-male patients.
The SAFE-PCI for Women (Study of Access Site forEnhancement of PCI for Women) trial was unique forselecting exquisitely women to undergo radial orfemoral access (6). The trial was stopped prematurelydue to lower than expected event rate and no signif-icant difference was found in the primary efficacyendpoint (BARC 2, 3, or 5 bleeding or vascular com-plications requiring intervention) between TRA andTFA in patients undergoing PCI (n ¼ 691; primaryendpoint cohort). However, in a secondary analysisalso including female patients who underwent car-diac catheterization (n ¼ 1,787), radial access signifi-cantly reduced bleeding and vascular complications(6). Hence, the apparent lack of benefit of radialover femoral access in this study likely reflects
limited study power more than lack of treatment ef-fect in women.
We observed that women randomized to TRAmore frequently needed crossovers to TFA comparedwith men (7.6% vs. 5.2%). This likely reflects greaterchallenges in women to obtain vascular access whenattempting TRA, likely because of smaller and moreprone to spasm radial arteries. Yet, the duration ofthe procedure was overall shorter in women ascompared with men, and in the former group TRAdid not require longer procedural or fluoroscopictime as compared with TFA. This observation sug-gests that female patients who are intervened uponvia the radial access do not pose specific furthertechnical challenges once vascular access has beenestablished.
Overall, present findings contribute to support theconcept that radial access should be preferred overthe femoral access, adding to the current knowledgefirm evidence that this approach is applicable to bothmale and female patients, and that probably it is evenmore beneficial in women who are characterized byincreased risk of bleeding and access site relatedcomplications. Therefore, efforts should be done toincrease the adoption of radial access, but at the sametime improving the operators’ training, which isfundamental to reach the most appropriate skills,particularly in women where radial access might bemore challenging due to anatomical reasons.
STUDY LIMITATIONS. Although a sex subgroupanalysis was pre-specified, the MATRIX-Access trialwas not powered to explore differences betweensexes, and randomization was not stratified by sex. Assuch, the current analyses may be subject to type IIerror. As expected in an exploratory analysis of effectmodification, an ad hoc power analysis indicates a30% power for the analysis of our primary outcome.Female study population was smaller compared withthe male group, as observed in most trials investi-gating patients with CAD. Yet, the benefits of TRAover TFA were consistent across sexes and if anythingseemed to be slightly more pronounced amongwomen. We did not adjust for multiple comparisons,increasing the risk of type I error. Radial artery oc-clusion was not systematically looked for in thecontext of the MATRIX study. Results apply to thecontext of this trial in which most centers partici-pating were highly experienced in the radial
PERSPECTIVES
WHAT IS KNOWN? There are limited and contrasting data
about sex disparities for the safety and efficacy of TRA versus
TFA for coronary intervention.
WHAT IS NEW? The MATRIX-Access trial results showing su-
periority of TRA versus TFA were consistent across sexes. Women
experienced a higher risk of severe bleeding and access site
complications, and radial access was an effective method to
reduce these complications, as well as composite ischemic and
ischemic or bleeding endpoints.
WHAT IS NEXT? Radial access should become the default ac-
cess for patients with ACS undergoing invasive management,
irrespective of sex.
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technique; therefore, similar outcomes may notapply in centers performing lower volumes of radialaccess.
CONCLUSIONS
This sex-specific analysis of the largest trial comparingradial versus femoral access in ACS patients invasivelymanaged suggests that women experienced a higherrisk of severe bleeding and access site complications,and radial access was an effective method to reducethese complications, as well as composite ischemicand ischemic or bleeding endpoints.
ADDRESS FOR CORRESPONDENCE: Dr. MarcoValgimigli, Bern University Hospital, Freiburgstrasse 4,CH-3010, Bern, Switzerland. E-mail: [email protected].
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KEY WORDS acute coronary syndrome(s),female, femoral access, male, MATRIX,radial access
APPENDIX For a supplemental table, pleasesee the online version of this paper.