Timing of multivessel revascularization in stable patients with STEMI: a systematic review and network meta-analysis.

INTRODUCTION AND OBJECTIVES: Multivessel percutaneous coronary intervention (MV-PCI) is recommended in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD) without cardiogenic shock. The present network meta-analysis investigated the optimal timing of MV-PCI in this context. METHODS: We pooled the aggregated data from randomized trials investigating stable STEMI patients with multivessel cad treated with a strategy of either MV-PCI or culprit vessel-only PCI. The primary outcome was all-cause death. The main secondary outcomes were cardiovascular death, myocardial infarction, and unplanned ischemia-driven revascularization. This study is registered at PROSPERO (CRD42023457794). RESULTS: Among 11 trials, a total of 10 507 patients were randomly assigned to MV-PCI (same sitting, n = 1683; staged during the index hospitalization, n = 3460; staged during a subsequent hospitalization within 45 days, n = 3275) or to culprit vessel-only PCI (n = 2089). The median follow-up was 18.6 months. In comparison with culprit vessel-only PCI, MV-PCI staged during the index hospitalization significantly reduced all-cause death (risk ratio, 0.73; 95%CI, 0.56-0.92; P = .008) and ranked as possibly the best treatment option for this outcome compared with all other strategies. In comparison with culprit vessel-only PCI, a MV-PCI reduced cardiovascular mortality without differences dependent on the timing of revascularization. MV-PCI within the index hospitalization, either in a single procedure or staged, significantly reduced myocardial infarction and unplanned ischemia-driven revascularization, with no significant difference between each other. CONCLUSIONS: In patients with STEMI and multivessel CAD without cardiogenic shock, multivessel PCI within the index hospitalization, either in a single procedure or staged, represents the safest and most efficacious approach. The different timings of multivessel PCI did not result in any significant differences in all-cause death.

Incidence and pattern of urgent revascularization in acute coronary syndromes treated with ticagrelor or prasugrel.

BACKGROUND: The ISAR-REACT 5 trial compared the efficacy and safety of ticagrelor and prasugrel in patients with ACS managed invasively. The present study sought to investigate the impact of ticagrelor and prasugrel on the incidence and pattern of urgent revascularization in acute coronary syndromes (ACS) patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: This post-hoc analysis of the ISAR-REACT 5 trial included all ACS patients who underwent PCI. The primary endpoint for this analysis was the incidence of urgent revascularization at 12-month follow-up. Secondary outcome was the pattern of urgent revascularization procedures (namely, urgent target vessel/non-target vessel revascularization - TVR/NTVR). Among 3,377 ACS patients who underwent PCI, 1,676 were assigned to ticagrelor and 1,701 to prasugrel before PCI. After 12 months, the incidence of urgent revascularization was higher among patients assigned to ticagrelor as compared to prasugrel (6.8% vs. 5.2%; hazard ratio [HR] = 1.32, 95% confidence interval [CI] 1.00-1.75; p = 0.051), mostly attributable to significantly more urgent NTVR in the ticagrelor group (3.8% vs. 2.4%; HR = 1.62 [1.09-2.41]; p = 0.017). The risk of urgent TVR did not differ between treatment groups (3.3% vs. 3.0%; HR = 1.13 [0.77-1.65]; p = 0.546). CONCLUSIONS: In ACS patients treated with PCI, the cumulative rate of urgent revascularizations after 12 months is higher with ticagrelor compared to prasugrel, due to a significant increase in urgent revascularizations involving remote coronary vessels.

A Ten-Year Follow-Up Study of the Association Between Uric Acid and Adverse Cardiovascular Events in Patients With Coronary Artery Disease.

The association between uric acid (UA) and long-term mortality in patients with coronary artery disease is poorly investigated. We assessed the association between UA and 10-year mortality after percutaneous coronary intervention (PCI) in 3,998 patients who underwent PCI. Patients were categorized in groups according to UA tertiles: tertile 1 (UA <5.80 mg/100 ml, n = 1,347), tertile 2 (UA 5.80 to 7.04 mg/100 ml, n = 1,340), and tertile 3 (UA >7.94 mg/100 ml, n = 1,311). The primary outcome was 10-year all-cause mortality. All-cause deaths occurred in 1,200 patients: 320 deaths (26.5%) in patients with UA in the first tertile, 325 deaths (26.9%) in patients with UA in the second tertile, and 555 deaths (46.0%) in patients with UA in the third tertile (adjusted hazard ratio 1.22, 95% confidence interval 1.17 to 1.27, p <0.001) for 1 mg/100 ml increment in UA level. Cardiac deaths occurred in 748 patients: 194 deaths (16.5%) in patients with UA in the first tertile, 202 deaths (17.0%) in patients with UA in the second tertile, and 352 deaths (29.7%) in patients with UA in the third tertile (adjusted hazard ratio 1.24 [1.17 to 1.32], p <0.001) for 1 mg/100 ml increment in the UA level. The 10-year rates of target lesion revascularization, target vessel revascularization, or nontarget vessel revascularization did not differ significantly according to the UA level. In conclusion, in patients with coronary artery disease treated with PCI, increased UA level was associated with higher 10-year mortality. Increased UA level was not associated with the progression of atherosclerosis in nontreated coronary vessels or progression of intimal hyperplasia in stented lesions requiring intervention.

Aspirin loading and coronary no-reflow after percutaneous coronary intervention in patients with acute myocardial infarction.

BACKGROUND: The association of aspirin loading with the risk of coronary no-reflow (CNR) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) has not been investigated. We assessed the association of aspirin loading before PCI with CNR in patients with AMI. MATERIALS AND METHODS: This study included 3100 patients with AMI undergoing PCI. Of them, 2812 patients received aspirin loading (a single oral [or chewed] or intravenous dose of 150-300 mg) and 288 patients did not receive aspirin loading before PCI. The primary endpoint was CNR, defined as Thrombolysis in Myocardial Infarction blood flow grade of <3 after the PCI. RESULTS: CNR occurred in 130 patients: 127 patients in the group with aspirin loading and 3 patients in the group without aspirin loading before PCI (4.5% vs. 1.0%; odds ratio [OR] = 4.50, 95% confidence interval, [1.42-14.21], p = 0.005). After adjustment, the association between aspirin loading and CNR was significant (adjusted OR = 4.49 [1.56-12.92]; p < 0.001). There was no aspirin loading-by-P2Y12 inhibitor (ticagrelor or prasugrel) interaction (pint = 0.465) or aspirin loading-by-chronic aspirin therapy on admission (pint = 0.977) interaction with respect to the occurrence of CNR after PCI. Chronic low-dose aspirin therapy on admission was not independently associated with higher risk of CNR after PCI (adjusted OR = 1.06 [0.65-1.72]; p = 0.824). CONCLUSION: In patients with AMI undergoing PCI, aspirin loading before the PCI procedure at the guideline-recommended doses was associated with higher odds of developing CNR. However, due to the limited number of events, the findings should be considered as hypothesis generating.

Plasma Soluble Glycoprotein VI, Platelet Function, Bleeding, and Ischemic Events in Patients Undergoing Elective Percutaneous Coronary Intervention.

BACKGROUND AND AIMS: Glycoprotein VI (GPVI) is the major platelet-specific collagen receptor. GPVI shedding with generation of soluble GPVI (sGPVI) is an endogenous feedback mechanism preventing platelet overstimulation. sGPVI has not been investigated in patients with chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI), especially regarding its potential value as a predictor of ischemic and bleeding risk. METHODS: Baseline plasma sGPVI levels were available in 318 patients with CCS undergoing PCI. Platelet function was assessed by measuring both adenosine diphosphate (ADP) and collagen-induced platelet aggregation. Co-primary endpoints were a composite of death or myocardial injury at 48 hours after PCI, and Bleeding Academic Research Consortium (BARC) type 1 to 5 bleeding at 30 days. RESULTS: There was no significant correlation between sGPVI and platelet function at baseline or at 48 hours after PCI and loading with antiplatelet drugs. Baseline plasma sGPVI levels were not associated with the ischemic risk: the incidence of the ischemic endpoint was 25.0% in the lower, 22.9% in the middle, and 26.7% in the upper sGPVI tertile (p = 0.82). There was a significant nonlinear relationship between sGPVI and the risk of bleeding: the incidence of the bleeding endpoint was 11.8% in the lower, 12.6% in the middle, and 26.4% in the upper sGPVI tertile (p = 0.006). CONCLUSION: In patients with CCS undergoing PCI, plasma levels of sGPVI did not correlate with ADP- or collagen-induced platelet aggregation. Patients with higher baseline levels of sGPVI may carry an increased risk of bleeding at 30 days after PCI but no excess risk of ischemic events.

Coronary no-reflow and adverse events in patients with acute myocardial infarction after percutaneous coronary intervention with current drug-eluting stents and third-generation P2Y12 inhibitors.

BACKGROUND: The frequency and prognostic value of coronary no-reflow (CNR) was investigated in studies that have used an outdated reperfusion therapy in terms of stent technology and antithrombotic drugs. We assessed the association of CNR with adverse outcomes in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and newer antithrombotic drugs, ticagrelor or prasugrel. METHODS: This study included 3100 patients with AMI who underwent PCI with current DES and third-generation P2Y12 inhibitors. CNR was defined as Thrombolysis in Myocardial Infarction (TIMI) blood flow grade ≤ 2 at the end of PCI. The primary end point was 1-year incidence of net adverse clinical and cerebral events-a composite end point of death of any cause, myocardial infarction, stroke or major bleeding. RESULTS: CNR was diagnosed in 130 patients (4.2%). The primary end point occurred in 28 patients in the CNR group and 354 patients in the reflow group (cumulative incidence 23.2% and 12.8%; adjusted hazard ratio = 1.53, 95% confidence interval 1.01-2.33; P = 0.049). The 1-year incidences of death or myocardial infarction (14.6% vs. 7.6%; P = 0.003), myocardial infarction (8.8% vs. 3.9%; P = 0.007) and major bleeding (10.9% vs. 5.6%; P = 0.008) were significantly higher in patients with CNR than patients with reflow. The risk of adverse events in patients with CNR was highest within the first 30 days after PCI. CONCLUSION: In patients with AMI undergoing PCI with current DES and third generation P2Y12 receptor inhibitors, CNR was associated with a higher risk of adverse outcomes at 1 year.

Modified balloons to prepare severely calcified coronary lesions before stent implantation: a systematic review and meta-analysis of randomized trials.

BACKGROUND: The performance of modified balloons (namely cutting or scoring balloons) to prepare severely calcified lesions in patients undergoing percutaneous coronary intervention (PCI) remains controversial. We investigated the clinical and imaging outcomes of patients undergoing PCI assigned to modified balloon therapy to prepare severely calcified coronary lesions before stent implantation. METHODS: In this meta-analysis, we aggregated the study-level data from trials enrolling invasively treated patients who were randomly assigned to modified balloon or control therapy to prepare severely calcified lesions before stenting. The primary outcome was major adverse cardiac events (MACE), including death, myocardial infarction (MI), and repeat revascularization. The secondary outcomes included the individual components of the primary outcome, coronary perforation and final minimal stent area (MSA) as measured by intracoronary imaging. RESULTS: A total of 648 participants in six trials were allocated to modified balloon therapy (n = 335) or control therapy (semi-compliant, non-compliant, or super high-pressure balloon, n = 313). The median follow-up was 11 months. Overall, MACE occurred in 8.96% of patients assigned to a modified balloon and 12.78% of patients assigned to control therapy [risk ratio = 0.70, 95% confidence interval (CI) 0.35-1.39; P = 0.24]. There was a significant treatment effect-by-modified balloon type interaction for the outcome MACE in patients assigned to cutting balloon compared with control therapy [RR = 0.40 (0.28-0.56), P for interaction (Pint) < 0.001]. Patients treated with a modified balloon compared with control therapy showed neither a significant difference for the other clinical outcomes nor for final MSA [standardized mean difference = 0.67 (- 0.71, 2.06); P = 0.26]. CONCLUSIONS: In patients treated with PCI for severely calcific coronary artery disease a strategy of lesion preparation with a modified balloon before stenting does not improve clinical or imaging outcomes compared with control therapy. The different performance of cutting and scoring balloons warrants further investigation.

Coronary No-Reflow after Primary Percutaneous Coronary Intervention-Current Knowledge on Pathophysiology, Diagnosis, Clinical Impact and Therapy.

Coronary no-reflow (CNR) is a frequent phenomenon that develops in patients with ST-segment elevation myocardial infarction (STEMI) following reperfusion therapy. CNR is highly dynamic, develops gradually (over hours) and persists for days to weeks after reperfusion. Microvascular obstruction (MVO) developing as a consequence of myocardial ischemia, distal embolization and reperfusion-related injury is the main pathophysiological mechanism of CNR. The frequency of CNR or MVO after primary PCI differs widely depending on the sensitivity of the tools used for diagnosis and timing of examination. Coronary angiography is readily available and most convenient to diagnose CNR but it is highly conservative and underestimates the true frequency of CNR. Cardiac magnetic resonance (CMR) imaging is the most sensitive method to diagnose MVO and CNR that provides information on the presence, localization and extent of MVO. CMR imaging detects intramyocardial hemorrhage and accurately estimates the infarct size. MVO and CNR markedly negate the benefits of reperfusion therapy and contribute to poor clinical outcomes including adverse remodeling of left ventricle, worsening or new congestive heart failure and reduced survival. Despite extensive research and the use of therapies that target almost all known pathophysiological mechanisms of CNR, no therapy has been found that prevents or reverses CNR and provides consistent clinical benefit in patients with STEMI undergoing reperfusion. Currently, the prevention or alleviation of MVO and CNR remain unmet goals in the therapy of STEMI that continue to be under intense research.

Association of De Ritis Ratio with Prognosis in Patients with Coronary Artery Disease and Aminotransferase Activity within and outside the Healthy Values of Reference Range.

BACKGROUND: The aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (De Ritis ratio), obtained from AST and ALT activities in the healthy range, has not been studied in association with mortality. METHODS: This study included 3392 patients with stable coronary heart disease and aminotransferase activity in the reference range. Patients are categorized into two groups: a group with AST and ALT activity in the healthy range (n = 1697), and a group with AST and/or ALT activity outside the healthy range but in the reference range (n = 1695). The primary endpoint was all-cause mortality at three years. RESULTS: The De Ritis ratio (median 5th-95th percentile] was 0.94 [0.61-1.41] in patients with AST and ALT in the healthy range and 0.93 [0.45-1.96] in patients with AST and/or ALT outside the healthy range (p = 0.700). At three years, there were 86 deaths in patients with AST and ALT in the healthy range: 27 deaths (3.9%) in patients with a De Ritis ratio ≤median, and 59 deaths (8.2%) in patients with the De Ritis ratio >median (adjusted hazard ratio [HR] = 1.16, 95% confidence interval [CI] 0.94 to 1.42; p = 0.159); in patients with AST and/or ALT outside the healthy range, there were 148 deaths: 49 deaths (6.6%) in patients with a De Ritis ratio ≤median, and 99 deaths (14.1%) in patients with De Ritis ratio >median (adjusted HR = 1.27 [1.09-1.48], p = 0.002), with both HRs calculated per unit higher values of the De Ritis ratio. CONCLUSIONS: The De Ritis ratio obtained from AST and ALT activity in the healthy range was not independently associated with higher risk of mortality. The De Ritis ratio obtained from aminotransferase activity outside the healthy range (but still in the reference range) was independently associated with the risk of mortality.

High on-aspirin treatment platelet reactivity and restenosis after percutaneous coronary intervention: results of the Intracoronary Stenting and Antithrombotic Regimen-ASpirin and Platelet Inhibition (ISAR-ASPI) Registry.

OBJECTIVE: The aim of this study was to assess the association between high on-aspirin treatment platelet reactivity (HAPR) and the subsequent risk of restenosis after percutaneous coronary intervention (PCI) with predominantly drug-eluting stents. BACKGROUND: The association between HAPR and subsequent risk of restenosis after PCI is unclear. METHODS: This study included 4839 patients undergoing PCI (02/2007-12/2011) in the setting of the Intracoronary Stenting and Antithrombotic Regimen-ASpirin and Platelet Inhibition (ISAR-ASPI) registry. Platelet function was assessed with impedance aggregometry using the multi-plate analyzer immediately before PCI and after intravenous administration of aspirin (500 mg). The primary outcome was clinical restenosis, defined as target lesion revascularization at 1 year. Secondary outcomes included binary angiographic restenosis and late lumen loss at 6- to 8-month angiography. RESULTS: The upper quintile cut-off of platelet reactivity measurements (191 AU × min) was used to categorize patients into a group with HAPR (platelet reactivity > 191 AU × min; n = 952) and a group without HAPR (platelet reactivity ≤ 191 AU × min; n = 3887). The primary outcome occurred in 94 patients in the HAPR group and 405 patients without HAPR (cumulative incidence, 9.9% and 10.4%; HR = 0.96, 95% CI 0.77-1.19; P = 0.70). Follow-up angiography was performed in 73.2% of patients. There was no difference in binary restenosis (15.2% vs. 14.9%; P = 0.79) or late lumen loss (0.32 ± 0.57 vs. 0.32 ± 0.59 mm; P = 0.93) between patients with HAPR versus those without HAPR. CONCLUSIONS: This study did not find an association between HAPR, measured at the time of PCI, and clinical restenosis at 1 year after PCI.

Ticagrelor or prasugrel in patients with acute coronary syndrome with off-hour versus on-hour presentation: a subgroup analysis of the ISAR-REACT 5 trial.

OBJECTIVES: To assess the efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome (ACS) presenting during off- and on-hours. BACKGROUND: The efficacy and safety of ticagrelor versus prasugrel in patients with ACS according to time of hospital presentation remain unknown. METHODS: This post hoc analysis of the ISAR-REACT 5 trial included 1565 patients with ACS presenting off-hours and 2453 patients presenting on-hours, randomized to ticagrelor or prasugrel. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium (BARC) type 3-5 bleeding, both at 12 months. RESULTS: The primary endpoint occurred in 80 patients (10.4%) in the ticagrelor group and 57 patients (7.3%) in the prasugrel group in patients presenting off-hours (hazard ratio [HR] = 1.45; 95% confidence interval [CI] 1.03-2.03; P = 0.033), and 104 patients (8.5%) in the ticagrelor group and 80 patients (6.7%) in the prasugrel group in patients presenting on-hours (HR = 1.29 [0.97-1.73]; P = 0.085), without significant treatment arm-by-presentation time interaction (Pint = 0.62). BARC type 3 to 5 bleeding occurred in 35 patients (5.1%) in the ticagrelor group and 37 patients (5.3%) in the prasugrel group (P = 0.84) in patients presenting off-hours, and 60 patients (5.9%) in the ticagrelor group and 43 patients (4.6%) in the prasugrel group in patients presenting on-hours (P = 0.17). CONCLUSIONS: In patients with ACS planned to undergo an invasive treatment strategy, time of presentation (off-hours vs. on-hours) does not interact significantly with the relative efficacy and safety of ticagrelor vs. prasugrel. CLINICAL TRIAL REGISTRATION: NCT01944800.

Association between Platelet Count and Treatment Effect of Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes.

BACKGROUND: The relative efficacy and safety of ticagrelor and prasugrel based dual antiplatelet therapy strategies according to the platelet count (PC) in patients with acute coronary syndromes (ACS) have not been defined. METHODS: This is a posthoc analysis of the ISAR-REACT 5 trial, in which patients presenting with ACS were randomized to treatment with ticagrelor versus prasugrel. Patients were divided into quartiles according to PC. The primary endpoint was incidence of death, myocardial infarction, or stroke, and the safety endpoint was incidence of BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 12 months. RESULTS: A total of 3,943 patients with known PC (997 patients in quartile 1 (Q1), 1,003 in quartile 2 (Q2) [205 ± 10.3 × 109/L], 961 patients in quartile 3 (Q3) [241 ± 11.7 × 109/L], and 982 patients in quartile 4 (Q4) [317 ± 68.6 × 109/L]). There was no significant interaction between treatment arm (ticagrelor vs. prasugrel) and PC group with respect to primary endpoint (Q1: 8.8 vs. 6.3%, hazard ratio [HR] =1.41, 95% confidence interval [CI]: 0.89-2.23; p = 0.148; Q2: 9.9 vs. 5.8%, HR = 1.68, 95% CI: 1.06-2.66; p = 0.027; Q3: 7.8 vs. 5.5%, HR = 1.43, 95% CI: 0.87-2.37; p = 0.159; Q4: 10.1 vs. 10.1%, HR = 1.05, 95% CI: 0.71-1.57; p = 0.799; p for interaction [p int] = 0.482) and with respect to bleeding endpoint (Q1: 5.8 vs. 4.2%, HR = 1.41, 95% CI: 0.76-2.63; p = 0.279; Q2: 6.4 vs. 3.7%, HR = 1.62, 95% CI: 0.85-2.06; p = 0.140; Q3: 4.4 vs. 3.0%, HR = 1.53, 95% CI: 0.73-3.18; p = 0.258; Q4: 5.6 vs. 8.5%, HR = 0.67, 95% CI: 0.40-1.14; p = 0.138, p int = 0.102). CONCLUSIONS: In this analysis, incidences of ischemic and bleeding events at 12 months are comparable across quartiles of platelet count.

De Ritis ratio and long-term major cardiovascular adverse events in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The association of aspartate aminotransferase to alanine aminotransferase ratio (De Ritis ratio) with clinical outcomes in patients with chronic coronary syndromes (CCS) remains unclear. This study aims to assess the association of De Ritis ratio with adverse cardiovascular events in patients with CCS. MATERIALS AND METHODS: The study included 5020 patients with CCS undergoing percutaneous coronary intervention. Patients were categorized into groups according to tertiles of the De Ritis ratio: tertile 1 (De Ritis ratio: <.75; n = 1688 patients), tertile 2 (De Ritis ratio: .75-1.08; n = 1666 patients) and tertile 3 (De Ritis ratio: >1.08; n = 1666 patients). The primary endpoint was 3-year mortality. RESULTS: At 3 years, there were 384 deaths, 176 myocardial infarctions and 61 strokes. In groups with De Ritis in the 1st, 2nd and 3rd tertiles, deaths occurred in 5.0%, 7.5% and 14.5% of the patients, respectively (adjusted hazard ratio = 1.09, 95% confidence interval [1.06-1.12], p < .001); myocardial infarctions occurred in 2.6%, 3.5% and 5.1% of the patients, respectively (p < .001); strokes occurred in 1.0%, 1.2% and 1.9% of the patients, respectively (p = .030); bleeding at 30 days (n = 112) occurred in 1.4%, 1.6% and 3.7% of the patients, respectively (p < .001). The C-statistic of the Cox proportional hazards model for all-cause mortality with baseline data without the De Ritis ratio was .815 [.794-.836] and .818 [.797-.838] after the inclusion of the De Ritis ratio (delta C-statistic = .003; p = .005). CONCLUSIONS: In patients with CCS undergoing percutaneous coronary intervention, an elevated De Ritis ratio was associated with long-term major adverse cardiovascular events.

The effect of a Prasugrel- vs. a Ticagrelor-based strategy on total ischaemic and bleeding events in patients with acute coronary syndromes.

AIMS: The effect of a prasugrel vs. a ticagrelor based strategy on total (including both first and recurrent) ischaemic and bleeding events in patients with acute coronary syndromes (ACS) has not been evaluated. The aim of this analysis was to investigate the treatment effect of a prasugrel vs. a ticagrelor based strategy in patients with ACS undergoing an invasive management strategy when both first and recurrent non-fatal ischaemic and bleeding events are taken into account. METHODS AND RESULTS: This is a post-hoc analysis of the ISAR-REACT 5 randomized control trial, including all 4018 patients in the trial. The main clinical endpoints of interest included ischaemic events [myocardial infarction (MI) and stroke] and bleeding events [Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding]. An additional endpoint of interest was definite/probable stent thrombosis. The effect of the prasugrel vs. ticagrelor based strategies on these endpoints was evaluated on both time-to-first event and total events analyses. Patients in the prasugrel group had a lower risk of MI in comparison to the ticagrelor group on both time-to-first event [hazard ratio (HR) = 0.61; 95% confidence interval 0.44-0.85] and total events [HR = 0.62 (0.45-0.86)] analysis. The risk of BARC type 3 to 5 bleeding was comparable between the prasugrel and ticagrelor groups on both time-to-first event [HR = 0.96 (0.75-1.25)] and total events [HR = 0.99 (0.76-1.31)] analysis. CONCLUSION: A prasugrel based strategy was associated with a reduction in total MI events in comparison to a ticagrelor based strategy in patients with ACS undergoing invasive assessment. Total BARC type 3 to 5 bleeding events were comparable between the two groups. Given the importance of this topic, future studies to confirm these findings would be welcome. ClinicalTrials.gov identifier: NCT01944800.

Prognostic value of De Ritis ratio with aspartate aminotransferase and alanine aminotransferase within the reference range.

BACKGROUND: Whether aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (De Ritis ratio) with AST and ALT activities within the reference range has prognostic value is unknown. METHODS: This study included 3392 patients with stable coronary artery disease and AST and ALT activities within the reference range. Patients are categorized in groups according to tertiles of the De Ritis ratio: a group with De Ritis ratio in the 1st tertile (De Ritis ratio: 0.22 to 0.81; n = 1131), a group with De Ritis ratio in the 2nd tertile (De Ritis ratio: >0.81 to 1.09; n = 1130) and a group with De Ritis ratio in the 3rd tertile (De Ritis ratio: >1.09 to 3.40; n = 1131). The primary endpoint was 3-year mortality. RESULTS: The mean value of De Ritis ratio was 1.00 ± 0.39 (range: 0.22-3.40). Overall, there were 234 deaths at 3 years: 43 deaths in patients of 1st tertile, 75 deaths in patients of 2nd tertile and 116 deaths in patients of 3rd tertile of De Ritis ratio (Kaplan-Meier estimates of 3-year mortality, 4.4 %, 7.8 % and 12.5 %, respectively; (adjusted hazard ratio = 1.24, 95 % confidence interval 1.12 to 1.38; P < 0.001 for 1 unit higher De Ritis ratio). The C-statistic of the risk prediction model for mortality with baseline demographical and clinical variables without De Ritis ratio was 0.803 [0.774-0.832] and it increased to 0.810 [0.782-0.839] after inclusion of De Ritis ratio into the model (P = 0.038). CONCLUSIONS: An elevated De Ritis ratio with aminotransferase levels within the reference range was associated with the increased risk of mortality.

Prior Myocardial Infarction and Treatment Effect of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndromes - A Post-hoc Analysis of the ISAR-REACT 5 Trial.

Background The efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome and prior myocardial infarction (MI) remain unstudied. We aimed to assess the treatment effect of ticagrelor versus prasugrel according to prior MI status in patients with ACS. Methods and Results Patients with acute coronary syndrome planned for an invasive strategy and randomized to ticagrelor or prasugrel in the ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) 5 trial were included. The primary end point was the composite of 1-year all-cause death, MI, or stroke; the secondary safety end point was the composite of 1-year Bleeding Academic Research Consortium type 3 to 5 bleeding. The study included 4015 patients (prior MI=631 patients; no prior MI=3384 patients). As compared with patients without prior MI, the primary end point occurred more frequently in patients with prior MI (12.6% versus 7.2%; hazard ratio [HR], 1.78 [95% CI, 1.38-2.29]); the secondary safety end point appears to differ little between patients with and without prior MI (5.8% versus 5.7%, respectively; HR, 1.02 [95% CI, 0.71-1.45]). With regard to the primary end point, ticagrelor versus prasugrel was associated with an HR of 1.62 (95% CI, 1.03-2.55) in patients with prior MI and an HR of 1.28 (95% CI, 0.99-1.65) in patients without prior MI (Pint=0.37). With regard to the secondary safety end point, ticagrelor versus prasugrel was associated with an HR of 1.28 (95% CI, 0.56-2.91) in patients with prior MI and an HR of 1.13 (95% CI, 0.82-1.55) in patients without prior MI (Pint=0.79). Conclusions Patients with acute coronary syndrome and prior MI are at higher risk for recurrent ischemic but not bleeding events. Prasugrel is superior to ticagrelor in reducing the risk of ischemic events without a tradeoff in bleeding regardless of prior MI status. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.