Abstract

BACKGROUND In some randomized controlled trials (RCTs), transradial (TRA) compared with transfemoral access (TFA) was associated with lower mortality in coronary artery disease patients undergoing invasive management. We analyzed the effects of TRA versus TFA across multicenter RCTs and whether these associations are modified by patient or operator characteristics. METHODS We performed an individual patient data meta-analysis of multicenter RCTs comparing TRA versus TFA among patients undergoing coronary angiography with or without percutaneous coronary intervention (PCI) (PROSPERO; CRD42018109664). The primary outcome was all-cause mortality and the co-primary outcome was major bleeding at 30 days. The primary analysis was conducted by one-stage mixed-effects models based on the intention-to-treat cohort. The impact of access-site on mortality and major bleeding was further assessed by multivariable analysis. The relationship among access-site, bleeding, and mortality was investigated by natural effect model mediation analysis with multivariable adjustment. RESULTS A total of 21,600 patients (TRA=10,775 vs. TFA=10,825) from 7 RCTs were included. Median age was 63.9 years, 31.9% were female, 95% presented with acute coronary syndrome (ACS), and 75.2% underwent PCI. All-cause mortality (1.6% vs. 2.1%; HR 0.77, 95% CI 0.63-0.95, p=0.012) and major bleeding (1.5% vs. 2.7%; OR 0.55, 95% CI 0.45- 0.67, p<0.001) were lower with TRA. Subgroup analyses for mortality showed consistent results, except for baseline hemoglobin ((pinteraction)=0.033), indicating that the benefit of TRA was substantial in patients with significant anemia, while it was not significant in patients with milder or no baseline anemia. After adjustment, TRA remained associated with 24% and 51% relative risk reduction of all-cause mortality and major bleeding. A mediation analysis showed that the benefit of TRA on mortality was only partially driven by major bleeding prevention, and ancillary mechanisms are required to fully explain the causal association. CONCLUSIONS TRA is associated with lower all-cause mortality and major bleeding at 30 days, compared with TFA. The effect on mortality was driven by patients with anemia. The reduction in major bleeding only partially explains the mortality benefit.

Abstract

BACKGROUND The comparative effectiveness of transradial (TRA) compared with transfemoral access (TFA) in acute coronary syndrome (ACS) patients undergoing complex percutaneous coronary intervention (PCI) remains unclear. METHODS Among 8,404 ACS patients in the Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX (MATRIX)-Access trial, 5,233 underwent noncomplex (TRA, n=2,590 and TFA, n=2,643) and 1,491 complex PCI (TRA, n=777 and TFA, n=714). Co-primary outcomes were major adverse cardiovascular events (MACE, the composite of all-cause mortality, myocardial infarction, or stroke) and the composite of MACE and BARC type 3-5 bleeding (net adverse cardiovascular events, NACE) at 30 days. RESULTS Rates of 30-day MACE (hazard ratio [HR]:0.94; 95% confidence interval [CI]:0.72-1.22) or NACE (HR:0.89; 95% CI:0.69-1.14) did not significantly differ between groups in the complex PCI group, whereas both primary endpoints were lower (HR:0.84; 95% CI:0.70-1.00, HR:0.83; 95% CI:0.70-0.98, respectively) with TRA among noncomplex PCI patients, with negative interaction testing (P(int) 0.473 and 0.666, respectively). Access-site BARC type 3 or 5 bleeding was lower with TRA, consistently among complex (HR:0.18; 95% CI:0.05-0.63) and noncomplex (HR:0.41; 95% CI:0.20-0.85) PCI patients, whereas the former group had a greater absolute risk reduction of 1.7% (number needed to treat: 59) due to their higher absolute risk. CONCLUSIONS Among ACS patients, PCI complexity does not affect the comparative efficacy and safety of TRA versus TFA, whereas the absolute risk reduction of access-site major bleeding was greater with TRA compared with TFA in complex as opposed to noncomplex PCI.

Abstract

BACKGROUND Bleeding is the principal safety concern of antithrombotic therapy and occurs frequently among patients with coronary artery disease (CAD). AIMS We aim to evaluate the prognostic impact of bleeding on mortality compared with that of myocardial infarction (MI) in patients with CAD. METHODS We searched Medline and Embase for studies that included patients with CAD and that reported both, the association between the occurrence of bleeding and mortality, and between the occurrence of MI and mortality within the same population. Adjusted hazard ratios (HRs) for mortality associated with bleeding and MI were extracted and ratio of hazard ratios (rHRs) were pooled by using inverse variance weighted random effects meta-analyses. Early events included periprocedural or within 30-day events after revascularization or acute coronary syndrome (ACS). Late events included spontaneous or beyond 30-day events after revascularization or ACS. RESULTS 141,059 patients were included across 16 studies and 128,660 (91%) underwent percutaneous coronary intervention. Major bleeding, increased the risk of mortality to the same extent of MI (rHRbleedingvs.MI 1.10, 95%CI, 0.71-1.71, P=0.668). Early bleeding was associated with a higher risk of mortality than early MI (rHRbleedingvs.MI 1.46, 95%CI, 1.13-1.89, P=0.004), although this finding was not present when only randomized trials were included. Late bleeding was prognostically comparable to late MI (rHRbleedingvs.MI 1.14, 95%CI, 0.87-1.49, P=0.358). CONCLUSIONS Compared with MI, major and late bleeding is associated with a similar increase in mortality, whereas early bleeding might have a stronger association with mortality.

Abstract

Aims: In the Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX (MATRIX) trial, adults with acute coronary syndrome undergoing coronary intervention who were allocated to radial access had a lower risk of bleeding, acute kidney injury (AKI), and all-cause mortality, as compared with those allocated to femoral access. The mechanism of the mortality benefit of radial access remained unclear. Methods and results: We used multistate and competing risk models to determine the effects of radial and femoral access on bleeding, AKI and all-cause mortality in the MATRIX trial and to disentangle the relationship between these different types of events. There were large relative risk reductions in mortality for radial compared with femoral access for the transition from AKI to death [hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.31-0.97] and for the pathway from coronary intervention to AKI to death (HR 0.49, 95% CI 0.26-0.92). Conversely, there was little evidence for a difference between radial and femoral groups for the transition from bleeding to death (HR 1.05, 95% CI 0.42-2.64) and the pathway from coronary intervention to bleeding to death (HR 0.84, 95% CI 0.28-2.49). Conclusion: The prevention of AKI appeared predominantly responsible for the mortality benefit of radial as compared with femoral access in the MATRIX trial. There was little evidence for an equally important, independent role of bleeding.

Abstract

Aims: To assess whether radial compared with femoral access is associated with consistent outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods and results: In the Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX (MATRIX) programme patients were randomized to radial or femoral access, stratified by STEMI (2001 radial, 2009 femoral) and NSTE-ACS (2196 radial, 2198 femoral). The 30-day co-primary outcomes were major adverse cardiovascular events (MACE), defined as death, myocardial infarction, or stroke, and net adverse clinical events (NACE), defined as MACE or major bleeding In the overall study population, radial access reduced the NACE but not MACE endpoint at the prespecified 0.025 alpha. MACE occurred in 121 (6.1%) STEMI patients with radial access vs. 126 (6.3%) patients with femoral access [rate ratio (RR) = 0.96, 95% CI = 0.75-1.24; P = 0.76] and in 248 (11.3%) NSTE-ACS patients with radial access vs. 303 (13.9%) with femoral access (RR = 0.80, 95% CI = 0.67-0.96; P = 0.016) (Pint = 0.25). NACE occurred in 142 (7.2%) STEMI patients with radial access and in 165 (8.3%) patients with femoral access (RR = 0.86, 95% CI = 0.68-1.08; P = 0.18) and in 268 (12.2%) NSTE-ACS patients with radial access compared with 321 (14.7%) with femoral access (RR = 0.82, 95% CI = 0.69-0.97; P = 0.023) (Pint = 0.76). All-cause mortality and access site-actionable bleeding favoured radial access irrespective of ACS type (Pint = 0.11 and Pint = 0.36, respectively). Conclusion: Radial as compared with femoral access provided consistent benefit across the whole spectrum of patients with ACS, without evidence that type of presenting syndrome affected the results of the random access allocation.