Bivalirudin or Heparin in Patients Undergoing Invasive Management of Acute Coronary Syndromes

Background: Contrasting evidence exists on the comparative efficacy and safety of bivalirudin and unfractionated heparin (UFH) in relation to the planned use of glycoprotein IIb/IIIa inhibitors (GPIs). Objectives: This study assessed the efficacy and safety of bivalirudin compared with UFH with or without GPIs in patients with acute coronary syndrome (ACS) who underwent invasive management. Methods: In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX) program, 7,213 patients were randomly assigned to receive either bivalirudin or UFH with or without GPIs at discretion of the operator. The 30-day coprimary outcomes were major adverse cardiovascular events (MACEs) (a composite of death, myocardial infarction, or stroke), and net adverse clinical events (NACEs) (a composite of MACEs or major bleeding). Results: Among 3,603 patients assigned to receive UFH, 781 (21.7%) underwent planned treatment with GPI before coronary intervention. Bailout use of GPIs was similar between the bivalirudin and UFH groups (4.5% and 5.4%) (p = 0.11). At 30 days, the 2 coprimary endpoints of MACEs and NACEs, as well as individual endpoints of mortality, myocardial infarction, stent thrombosis or stroke did not differ among the 3 groups after adjustment. Compared with the UFH and UFH+GPI groups, bivalirudin reduced bleeding, mainly the most severe bleeds, including fatal and nonaccess site−related events, as well as transfusion rates and the need for surgical access site repair. These findings were not influenced by the administered intraprocedural dose of UFH and were confirmed at multiple sensitivity analyses, including the randomly allocated access site. Conclusions: In patients with ACS, the rates of MACEs and NACEs were not significantly lower with bivalirudin than with UFH, irrespective of planned GPI use. However, bivalirudin significantly reduced bleeding complications, mainly those not related to access site, irrespective of planned use of GPIs. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX [MATRIX]; NCT01433627

Impact of Sex on Comparative Outcomes of Radial Versus Femoral Access in Patients With Acute Coronary Syndromes Undergoing Invasive Management: Data From the Randomized MATRIX-Access Trial

Objectives This study sought to assess whether transradial access (TRA) compared with transfemoral access (TFA) is associated with consistent outcomes in male and female patients with acute coronary syndrome undergoing invasive management. Background There are limited and contrasting data about sex disparities for the safety and efficacy of TRA versus TFA for coronary intervention. Methods In the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) program, 8,404 patients were randomized to TRA or TFA. The 30-day coprimary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE), defined as death, myocardial infarction, or stroke, and net adverse clinical events (NACE), defined as MACCE or major bleeding. Results Among 8,404 patients, 2,232 (26.6%) were women and 6,172 (73.4%) were men. MACCE and NACE were not significantly different between men and women after adjustment, but women had higher risk of access site bleeding (male vs. female rate ratio [RR]: 0.64; p = 0.0016), severe bleeding (RR: 0.17; p = 0.0012), and transfusion (RR: 0.56; p = 0.0089). When comparing radial versus femoral, there was no significant interaction for MACCE and NACE stratified by sex (p int = 0.15 and 0.18, respectively), although for both coprimary endpoints the benefit with TRA was relatively greater in women (RR: 0.73; p = 0.019; and RR: 0.73; p = 0.012, respectively). Similarly, there was no significant interaction between male and female patients for the individual endpoints of all-cause death (p int = 0.79), myocardial infarction (p int = 0.25), stroke (p int = 0.18), and Bleeding Academic Research Consortium type 3 or 5 (p int = 0.45). Conclusions Women showed 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

Effects of Ticagrelor, Prasugrel, or Clopidogrel on Endothelial Function and Other Vascular Biomarkers: A Randomized Crossover Study

Objectives: The study sought to assess whether treatment with ticagrelor, as compared with prasugrel and clopidogrel, improves endothelium-dependent dilation throughout the course of the treatment and other vascular biomarkers, including systemic adenosine plasma levels. Background: The in vivo off-target effects of ticagrelor in post–acute coronary syndrome (ACS) patients remain poorly characterized. Methods: Fifty-four stable post-ACS patients were sequentially exposed to each of the 3 oral P2Y12 inhibitors following a 3-period balanced Latin square crossover design with 4 weeks per treatment in 5 European centers. The primary endpoint was the assessment of endothelial function with pulse amplitude tonometry and expressed as reactive hyperemia index at treatment steady state. Secondary endpoints included reactive hyperemia index after loading or before maintenance regimen, systemic adenosine plasma levels, a wide set of vascular biomarkers, and ticagrelor or AR-C124910XX plasma levels throughout each ticagrelor period. In 9 patients, the evaluation of endothelial function was performed simultaneously by pulse amplitude tonometry and flow-mediated dilation. Results: Reactive hyperemia index did not differ after ticagrelor (1.970 ± 0.535) as compared with prasugrel (2.007 ± 0.640; p = 0.557) or clopidogrel (2.072 ± 0.646; p = 0.685), nor did systemic adenosine plasma levels or vascular biomarkers at any time points. P2Y12 platelet reactivity units were lower after ticagrelor as compared with clopidogrel at all time points and after maintenance dose as compared with prasugrel. Flow-mediated dilation did not differ after the maintenance dose of ticagrelor as compared with clopidogrel and prasugrel. Conclusions: Ticagrelor did not improve endothelial function or increased systemic adenosine plasma levels as compared with prasugrel and clopidogrel in stabilized patients who suffered from an ACS. (Hunting for the Off-Target Properties of Ticagrelor on Endothelial Function in Humans [HI-TECH]; NCT02587260)

Acute Kidney Injury After Radial or Femoral Access for Invasive Acute Coronary Syndrome Management: AKI-MATRIX

Background It remains unclear whether radial access (RA), compared with femoral access (FA), mitigates the risk of acute kidney injury (AKI). Objectives The authors assessed the incidence of AKI in patients with acute coronary syndrome (ACS) enrolled in the MATRIX-Access (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial. Methods Among 8,404 patients, 194 (2.3%) were excluded due to missing creatinine values, no or an incomplete coronary angiogram, or previous dialysis. The primary AKI-MATRIX endpoint was AKI, defined as an absolute (>0.5 mg/dl) or a relative (>25%) increase in serum creatinine (sCr). Results AKI occurred in 634 patients (15.4%) with RA and 712 patients (17.4%) with FA (odds ratio [OR]: 0.87; 95% confidence interval [CI]: 0.77 to 0.98; p = 0.0181). A >25% sCr increase was noted in 633 patients (15.4%) with RA and 710 patients (17.3%) with FA (OR: 0.87; 95% CI: 0.77 to 0.98; p = 0.0195), whereas a >0.5 mg/dl absolute sCr increase occurred in 175 patients (4.3%) with RA versus 223 patients (5.4%) with FA (OR: 0.77; 95% CI: 0.63 to 0.95; p = 0.0131). By implementing the Kidney Disease Improving Global Outcomes criteria, AKI was 3-fold less prevalent and trended lower with RA (OR: 0.85; 95% CI: 0.70 to 1.03; p = 0.090), with stage 3 AKI occurring in 28 patients (0.68%) with RA versus 46 patients (1.12%) with FA (p = 0.0367). Post-intervention dialysis was needed in 6 patients (0.15%) with RA and 14 patients (0.34%) with FA (p = 0.0814). Stratified analyses suggested greater benefit with RA than FA in patients at greater risk for AKI. Conclusions In ACS patients who underwent invasive management, RA was associated with a reduced risk of AKI compared with FA. (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX [MATRIX]; NCT01433627