Thrombolysis In Myocardial Infarction Minor Bleeding Research Articles

Bleeding characteristics and mortality outcomes following ST-elevation myocardial infarction thrombolysis: a 5-year analysis in an Asian population.

Bleeding outcomes are crucial primary safety endpoints in studies involving thrombolytic agents. This study aimed to determine the incidence, characteristics and mortality outcomes of bleeding following ST-elevation myocardial infarction (STEMI) thrombolysis in an Asian population. This single-centre retrospective study included all STEMI patients who received thrombolytic therapy from 2016 to 2020 in a Malaysian tertiary hospital. Total population sampling was used in this study. The primary outcome was bleeding events post-thrombolysis, categorised using the Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria. Inferential statistics were used to determine the associations between relevant variables. Data from 941 patients were analysed. A total of 156 (16.6%) STEMI patients bled post-thrombolysis. Major, minor, and minimal TIMI occurred in 7 (0.7%), 17 (1.8%), and 132 (14.0%) patients, respectively. Age 65 years (P=0.031) and Malaysian Chinese (P=0.008) were associated with a higher incidence of bleeding post-thrombolysis. Conversely, foreigners (P=0.032) and current smoker (P=0.007) were associated with a lower incidence of bleeding. Both TIMI major (P<0.001) and TIMI minor (P<0.001) were associated with a higher incidence of all-cause in-hospital mortality among STEMI patients. TIMI minor bleeding was significantly higher in the streptokinase recipients. The bleeding sites were comparable between streptokinase and tenecteplase recipients, except for a significantly higher incidence of gastrointestinal bleeding in the streptokinase recipients (P=0.027). In our Asian population, the incidence of total bleeding events following STEMI thrombolysis is comparable to that previously reported. The development of TIMI major and minor bleeding complications is associated with higher mortality.

Acute coronary syndrome in very elderly patients-a real-world experience.

Very elderly population constitutes an increasingly larger proportion of patients admitted for acute coronary syndromes (ACS). Notably, age represents both a proxy of frailty and an exclusion criterion in clinical randomized trials, which probably contributes to lack of data and undertreatment of real-world elderly patients. The aim of the study is to describe patterns of treatment and outcome of very elderly patients with ACS. All consecutive patients aged ≥ 80years old (yo) admitted between January 2017 and December 2019 with ACS were included. The primary endpoint was in-hospital occurrence of major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, new onset cardiogenic shock, definite/probable stent thrombosis, and ischemic stroke. The secondary endpoints were in-hospital incidence of Thrombolysis in Myocardial Infarction (TIMI) major/minor bleedings, contrast-induced nephropathy (CIN), six-month all-cause mortality, and unplanned readmission. One hundred ninety-three patients (mean age 84.1 ± 3.5 yo, 46% females) were included, of whom 86 (44.6%), 79 (40.9%), and 28 (14.5%) presented with ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina (UA), respectively. The vast majority of patients received an invasive strategy, with 92.7% undergoing coronary angiography and 84.4% to percutaneous coronary intervention (PCI). Aspirin was administered to 180 (93.3%) patients, clopidogrel to 89 (46.1%) patients, and ticagrelor to 85 (44%) patients. In-hospital MACE occurred in 29 patients (15.0%), whereas 3 (1.6%) and 12 patients (7.2%) experienced in-hospital TIMI major and TIMI minor bleeding, respectively. Of the overall population, 177 (91.7%) were discharged alive. After discharge, 11 patients (6.2%) died of all-cause death, whereas 42 patients (23.7%) required a new hospitalization within six months. Invasive strategy of ACS in elderly patients seems safe and effective. Six-month new hospitalization appears inevitably related to age.

Streptokinase-Based Pharmacoinvasive Strategy Versus Primary Percutaneous Coronary Intervention: A Propensity Score Matching Analysis from the Siriraj STEMI Network

Objective: To investigate the efficacy and safety of pharmacoinvasive (PI) strategy compared to primary percutaneous coronary intervention (PPCI) in the setting of a real-world ST-elevation myocardial infarction (STEMI) network where streptokinase (SK) is predominantly prescribed. Materials and Methods: The authors analyzed 325 STEMI patients who participated in The Siriraj STEMI network between July 2015 and October 2020. The primary efficacy endpoint was the incidence of cumulative major adverse cardiovascular and cerebrovascular events (MACCE) at one month, which were the composite of death, myocardial infarction, stroke, and non-coronary artery bypass graft (CABG)-related thrombolysis in myocardial infarction (TIMI) major or minor bleeding. The safety endpoint was non-CABG-related TIMI major or minor bleeding during the index hospitalization. Cox regression was performed for survival analysis. The authors applied propensity score matching to reduce the bias of the confounding variables. Results: Two hundred four patients received fibrinolytic therapy, 191 (93.6%) obtained SK, and 121 participants underwent PPCI. After propensity score matching analysis, the incidence of cumulative MACCE at one-month follow-up was not significantly different between the PI and the PPCI group (p=0.726) as well as the incidence of bleeding endpoint (p=0.446). In the subgroup analysis of the 191 patients who received SK (SK-PI), there was no statistical difference in the occurrence of cumulative MACCE compared to PPCI (p=0.136). Killip classification class III (hazard ratio [HR] 7.50, 95% confidence interval [CI] 3.25 to 17.31, p&lt;0.001), and class IV (HR 9.78, 95% CI 4.31 to 22.21, p&lt;0.001) were independent risk factors for developing MACCE. Conclusion: The streptokinase-based pharmacoinvasive strategy is non-statistically different in terms of efficacy and safety compared to PPCI. This evidence supports the utilization of the SK-PI approach in low- to middle-income countries where the availability of fibrin-specific fibrinolytic agents is often limited. Keywords: Revascularization strategy; Acute coronary syndrome; Fibrinolytic therapy

The Incidence and Impact of In-Hospital Bleeding in Patients with Acute Coronary Syndrome during the COVID-19 Pandemic.

Background: The COVID-19 pandemic increased the complexity of the clinical management and pharmacological treatment of patients presenting with an Acute Coronary Syndrome (ACS). Aim: to explore the incidence and prognostic impact of in-hospital bleeding in patients presenting with ACS before and during the COVID-19 pandemic. Methods: We evaluated in-hospital Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding among 2851 patients with ACS from 17 Italian centers during the first wave of the COVID-19 pandemic (i.e., March–April 2020) and in the same period in the previous two years. Results: The incidence of in-hospital TIMI major and minor bleeding was similar before and during the COVID-19 pandemic. TIMI major or minor bleeding was associated with a significant threefold increase in all-cause mortality, with a similar prognostic impact before and during the COVID-19 pandemic. Conclusions: the incidence and clinical impact of in-hospital bleeding in ACS patients was similar before and during the COVID-19 pandemic. We confirmed a significant and sizable negative prognostic impact of in-hospital bleeding in ACS patients.

Impact of preprocedural coronary flow grade on duration of dual antiplatelet therapy in acute myocardial infarction

We investigated the impact of pre-percutaneous coronary intervention (pre-PCI) thrombolysis in myocardial infarction (TIMI) flow grade (pre-TIMI) on 3-month (3-mo) and 12-mo of dual antiplatelet therapy (DAPT) in patients with acute myocardial infarction (AMI). This was a post hoc analysis of the TICO trial. A total of 2083 patients with AMI (pre-TIMI 0/1: n = 1143; pre-TIMI 2/3: n = 940) were evaluated. The primary outcome was the occurrence of net adverse clinical events (NACE), defined as a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events (MACCE) within 12-mo following PCI. The secondary outcomes were the occurrence of the individual components of TIMI bleedings and MACCE. In the pre-TIMI 0/1 group, the primary and second outcomes were not significantly different between the 3-mo and 12-mo DAPT groups. However, in the pre-TIMI 2/3 group, the occurrences of TIMI minor (adjusted hazard ratio [aHR]: 0.294; p = 0.016) and major or minor bleeding (aHR: 0.483; p = 0.014) on intention-to-treat analysis were significantly higher in the 12-mo than in the 3-mo DAPT group. The occurrence of MACCE was similar between the two groups. A higher bleeding tendency in 12-mo DAPT compared with 3-mo DAPT was more obvious in the pre-TIMI 2/3 group than in the pre-TIMI 0/1 group.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02494895.

Anticoagulation profile of staged-dose vs. single-dose enoxaparin for trans-radial percutaneous coronary intervention

Abstract Background Anticoagulation is indicated in patients undergoing trans-radial coronary angiography (CAG) with or without percutaneous coronary intervention (PCI). However, full-dose enoxaparin given before CAG to all patients may cause over-anticoagulation in those without indication for subsequent PCI. Purpose This study prospectively assessed the anticoagulation profile of staged-dose (0.5±0.25 mg/kg) vs. single-dose (0.75 mg/kg) enoxaparin in troponin-negative patients undergoing elective trans-radial PCI. Methods Eligible patients were randomly assigned to the Planned Staged-dose group or the Planned Single-dose group. In the Planned Staged-dose group, enoxaparin 0.5 mg/kg was administered to all patients before CAG and additional 0.25 mg/kg was given only to those undergoing subsequent PCI immediately before PCI. In the Planned Single-dose group, all patients received enoxaparin 0.75 mg/kg before CAG irrespective of their indication for subsequent PCI. Patients undergoing subsequent PCI in each group were defined as Staged-dose and Single-dose groups, respectively. Anti-Xa levels were assessed at 0 min (before) and 10 min after enoxaparin administration (CAG-0min and CAG-10min, respectively), and 0 min (before) and 10 min after the beginning of PCI (PCI-0min and PCI-10min, respectively), and at the end of PCI (PCI-end). Therapeutic anticoagulation was defined as anti-Xa levels of 0.5–1.2 IU/ml before PCI and 0.5–1.8 IU/ml during PCI, respectively. Bleeding was according to the thrombolysis in myocardial infarction (TIMI) criteria. Results In 170 randomized patients, 38 of 85 and 37 of 85 patients were included in the Staged-dose and the Single-dose groups, respectively. The baseline characteristics were well balanced between the two groups. The anti-Xa levels were lower before PCI (CAG-10min: 0.903±0.124 IU/ml vs. 1.303±0.207 IU/ml, p&amp;lt;0.001; PCI-0min: 0.874±0.149 IU/ml vs. 1.215±0.185 IU/ml, p&amp;lt;0.001) and higher during PCI (PCI-10min: 1.207±0.190 IU/ml vs. 1.083±0.157 IU/ml, p=0.004; PCI-end: 1.079±0.237 IU/ml vs. 1.050±0.255 IU/ml, p=0.62) in patients receiving staged-dose vs. single-dose enoxaparin (Figure 1). The percentages of patients with therapeutic anticoagulation were higher before PCI (CAG-10min: 100% [35/35] vs. 30.6% [11/36], p&amp;lt;0.001; PCI-0min: 96.8% [30/31] vs. 54.1% [20/37], p&amp;lt;0.001) and similar during PCI (PCI-10min: 100% [34/34] vs. 100% [36/36], p=1.000; PCI-end: 97.2% [35/36] vs. 100% [36/36], p=1.000) in the Staged-dose vs. the Single-dose group. No TIMI major or minor bleeding occurred within 24 h of randomization in both groups. Conclusions Although both regimens of enoxaparin achieved adequate anticoagulation during the entire course of PCI, the staged-dose compared to the single-dose regimen reduced over-anticoagulation before PCI. The staged-dose enoxaparin would be a superior anticoagulation regimen in patients undergoing trans-radial CAG, especially when the indication for subsequent PCI is unclear. Figure 1. Staged-dose vs. Single-dose Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): 2016 Peking Union Medical College Hospital (PUMCH) Science Fund for Junior Faculty

Anticoagulation profile of high-dose vs. standard-dose enoxaparin for percutaneous coronary intervention

Abstract Background Although enoxaparin 0.5 mg/kg is a recommended anticoagulation regimen for percutaneous coronary intervention (PCI), a randomized study demonstrated that more patients receiving enoxaparin 0.75 mg/kg compared to those receiving 0.5 mg/kg achieved therapeutic anticoagulation without increase of major bleeding. However, no detailed data regarding the anticoagulation profile of enoxaparin 0.75 mg/kg was reported in the study. Purpose This study prospectively assessed the anticoagulation profile of enoxaparin 0.75 mg/kg vs. 0.5 mg/kg in troponin-negative patients undergoing elective trans-radial coronary angiography (CAG). Methods Eligible patients were randomly assigned to the Planned Single-dose group (0.75 mg/kg) or the Planned Staged-dose group (0.5±0.25 mg/kg). In the Planned Single-dose group, all patients received enoxaparin 0.75 mg/kg before CAG irrespective of their indication for subsequent PCI. In the Planned Staged-dose group, enoxaparin 0.5 mg/kg was administered to all patients before CAG and additional 0.25 mg/kg was given only to those undergoing subsequent PCI immediately before PCI. Patients without indication for subsequent PCI in each group were defined as High-dose (0.75 mg/kg) and Standard-dose (0.5 mg/kg) groups, respectively. Anti-Xa levels were assessed at 0 min (immediately before), 10 min, and 90 min after enoxaparin administration. Therapeutic anticoagulation was defined as anti-Xa level of 0.5–1.8 IU/ml. Bleeding was according to the thrombolysis in myocardial infarction (TIMI) criteria. Results In 170 randomized patients, 48 of 85 patients in the Planned Single-dose group and 47 of 85 patients in the Planned Staged-dose group were included in the High-dose and Standard-dose groups, respectively. The baseline characteristics were well balanced between the two groups. The anti-Xa levels were higher in the High-dose vs. Standard-dose group both at 10 min (1.354±0.228 IU/ml vs. 0.976±0.213 IU/ml, p&amp;lt;0.001) and 90 min (0.827±0.195 IU/ml vs. 0.583±0.169 IU/ml, p&amp;lt;0.001) (Figure 1). The percentages of patients with therapeutic anticoagulation were similar at 10 min (100% [46/46] vs. 100% [46/46], p=1.000) but higher at 90 min (100% [41/41] vs. 75% [33/44], p=0.001) in the High-dose vs. Standard-dose group. No TIMI major or minor bleeding occurred within 24 h of randomization in both groups. Conclusions Enoxaparin 0.75 mg/kg compared to 0.5 mg/kg provided higher anticoagulation which was adequate for up to 90 min of administration. Enoxaparin 0.75 mg/kg would be a superior anticoagulation regimen for PCI, especially when the procedure duration is long. Figure 1. High-dose vs. Standard-dose Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): 2016 Peking Union Medical College Hospital (PUMCH) Science Fund for Junior Faculty

Efficacy and safety of newer P2Y12 inhibitors for acute coronary syndrome: a network meta-analysis

Whether newer P2Y12 inhibitors are more efficacious and safer than clopidogrel and whether there is a superior one remain uncertain. We compared the effect of P2Y12 inhibitors on clinical outcomes in patients with acute coronary syndrome (ACS). Randomized controlled trials comparing clopidogrel, prasugrel, ticagrelor, or cangrelor, in combination with aspirin were searched. Sixteen trials with altogether 77,896 patients were included. Compared to clopidogrel, cardiovascular mortality was reduced with prasugrel (OR 0.85, 95% CI 0.75–0.97) and ticagrelor (0.82, 0.73–0.93). Myocardial infarction (0.75, 0.63–0.89) and major adverse cardiovascular events (0.80, 0.69–0.94) were reduced by prasugrel. Stent thrombosis was reduced by prasugrel (0.49, 0.38–0.63), ticagrelor (0.72, 0.57–0.90), and cangrelor (0.59, 0.43–0.81). It was reduced more by prasugrel than ticagrelor (0.69, 0.51–0.93). There were more major bleeds with prasugrel (1.24, 1.05–1.48). Thrombolysis in Myocardial Infarction (TIMI) major bleeding was increased with prasugrel compared to clopidogrel (1.36, 1.11–1.66) and ticagrelor (1.33, 1.06–1.67). TIMI minor bleeding was increased with prasugrel (1.44, 1.16–1.77) and cangrelor (1.47, 1.01–2.16) compared to clopidogrel while it was increased with prasugrel compared to ticagrelor (1.32, 1.01–1.72). Prasugrel is preferable to those ACS patients at low bleeding risk to reduce cardiovascular events whereas ticagrelor is a relatively safe antiplatelet drug of choice for most patients.

Antithrombotic regimen for patients with cardiac indication for dual antiplatelet therapy and anticoagulation: a meta-analysis of randomized trials.

The optimal antithrombotic strategy for patients with a long-term indication for anticoagulation and acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remains controversial. This meta-analysis aims to compare randomised trials' outcomes of these patients, focussing on dual versus triple antithrombotic and non vitamin K oral anticoagulants (NOACs) versus vitamin K oral anticoagulants regimens. Medline, Embase and Cochrane databases were searched from January 1980 to March 2019 yielding 309 articles, and after careful screening, five randomized trials totalling 10 643 patients were included for analysis. Dual antithrombotic regimens were associated with significantly less thrombolysis in myocardial infarction (TIMI) major and minor bleeding [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.40-0.71], with no significant difference in major adverse cardiovascular events (OR 0.93, 95% CI 0.72-1.22) or all-cause mortality (OR 0.89, 95% CI 0.61-1.19). NOAC regimens had significantly lower TIMI major and minor bleeding (OR 0.58, 95% CI 0.43-0.78) and intracranial bleeding (OR 0.33, 95% CI 0.16-0.66), with similar rates of major adverse cardiovascular events (OR 1.00, 95% CI 0.86-1.16) and all-cause mortality (OR 1.01, 95% CI 0.81-1.26). Dual antithrombotic and NOAC regimens have reduced bleeding without compromising the risk of cardiovascular events or mortality, and should be preferred for patients with ACS or PCI also needing long-term anticoagulation.

Impact of bleeding events after percutaneous coronary intervention in patients on hemodialysis.

Coronary artery disease is common in patients on dialysis; there is a high rate of bleeding events after percutaneous coronary intervention (PCI) in such patients. We investigated the impact of bleeding events after PCI on mortality in patients on hemodialysis. We included 386 consecutive hemodialysis patients who underwent PCI using a drug-eluting stent (DES) between September 2004 and December 2017 in our hospital, and investigated the impact of bleeding events on all-cause mortality after PCI. Bleeding events were assessed by the Thrombolysis in Myocardial Infarction (TIMI) bleeding definition within 24months after PCI. A total of 42 patients experienced bleeding events. Of these, 30 patients (71.4%) had TIMI major bleeding events and 12 patients (28.6%) had TIMI minor bleeding events. Patients with bleeding events had significantly higher mortality than patients without bleeding events (survival rate, 55.1% vs 81.5%, log-rank: p < 0.001). These results suggest that bleeding events after PCI with a DES are notably associated with all-cause mortality among patients on hemodialysis. This is the first report about relationship between bleeding events and mortality to focus on patients on hemodialysis.

Prasugrel for Japanese Patients With Ischemic Heart Disease in Long-Term Clinical Practice (PRASFIT-Practice II) - 1-Year Follow-up Results of a Postmarketing Observational Study.

Although the effectiveness and safety of prasugrel for the prevention of cardiovascular events in patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) have been demonstrated, long-term real-world data of Japanese unique doses are insufficient. Therefore, we report the results of an analysis of 1-year follow-up data from a postmarketing observational study (PRASFIT-Practice II).Methods and Results:The safety and effectiveness analysis sets included 4,155 IHD patients receiving prasugrel (loading dose/maintenance dose, 20/3.75 mg) as dual antiplatelet therapy (DAPT) with aspirin. At 360 days (after treatment start), 62.2% continued DAPT. Cumulative incidences of major adverse cardiovascular events and stent thrombosis were 1.6% and 0.2%, respectively. Cumulative incidences of Thrombolysis In Myocardial Infarction (TIMI) major bleeding and TIMI major or minor bleeding were 1.0% and 2.0%, respectively. Risk factors for TIMI major or minor bleeding in the first 30 days of treatment were age ≥80 years, anemia, female sex, and liver disease, and from day 31 to the end of month 12, hypertension and peptic ulcer. The 1-year follow-up results showed long-term effectiveness and safety of prasugrel at dosages approved in Japan for the treatment of IHD patients undergoing PCI.

Ticagrelor versus clopidogrel in acute myocardial infarction patients with multivessel disease; From Korea Acute Myocardial Infarction Registry-National Institute of Health

BackgroundThe clinical efficacy of ticagrelor is questionable in East Asian populations. Patients with acute myocardial infarction (AMI) with multivessel disease (MVD) are considered as high risk patients who might benefit from ticagrelor treatment. The purpose of this study is to compare the clinical effect of ticagrelor and clopidogrel in AMI patients with MVD in Korea. Methods and resultsA total of 2275 patients between November 2011 and June 2015, diagnosed with AMI with MVD after successful percutaneous coronary intervention who were registered in the Korea Acute Myocardial Infarction Registry – National Institute of Health (KAMIR-NIH) were enrolled. Patients were divided into ticagrelor (n = 837) and clopidogrel group (n = 1438). The primary endpoint was major adverse cardiac events (MACE) defined as cardiac death, non-fatal MI, target vessel revascularization, or ischemic stroke during 2 years of clinical follow-up. Secondary endpoints were thrombolysis in myocardial infarction (TIMI) major or minor bleeding, net clinical event composed of MACE and TIMI major bleeding, any repeated percutaneous coronary intervention, heart failure requiring re-hospitalization, and stent thrombosis. After propensity score matching analysis, the primary endpoint was lower in ticagrelor group compared to the clopidogrel group (8.6 % vs. 11.9 %; HR: 0.68; 95 % CI: 0.50-0.94; p = 0.018). The risk of TIMI major or minor bleeding was higher in the ticagrelor group (10.8 % vs. 4.8 %; HR: 2.51; 95 % CI: 1.68–3.76; p < 0.001). The net clinical event was similar between ticagrelor and clopidogrel group (11.3 % vs. 13.6 %; HR 0.82; 95 % CI: 0.60–1.11; p = 0.195). ConclusionTicagrelor significantly reduced the risk of MACE than clopidogrel for AMI patients with MVD in Korea. However, the risk of TIMI major or minor bleeding was higher and the net clinical benefit was similar. Further large-scale multi-center randomized clinical trials are needed to clarify the proper use dual antiplatelet therapy in East Asian populations.

DUAL ANTITHROMBOTIC THERAPY IS SAFE AND EFFECTIVE IN PATIENTS WITH ATRIAL FIBRILLATION UNDERGOING PCI: UPDATED SYSTEMATIC REVIEW AND META-ANALYSIS

Optimal antithrombotic therapy regimen in patients with atrial fibrillation (AF), presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention (PCI) is unclear. We performed a systematic review and meta-analysis to evaluate the safety and efficacy of dual versus triple antithrombotic therapy. MEDLINE, EMBASE, and Web of Science were systematically searched. All randomized trials of dual versus triple antithrombotic therapy were included. The primary safety and efficacy outcomes were Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding and myocardial infarction (MI), respectively. Secondary outcomes included stent thrombosis, stroke, trial-defined major adverse cardiac events (MACE) and cardiac death. Bayesian network meta-analyses and subgroup analyses were pre-specified. Hazard ratios (HR, 95%CI) were calculated using random-effects model. Five trials involving 9,961 patients were included (73% male; mean age 71 years). Compared to triple antithrombotic therapy (TAT), dual antithrombotic therapy (DAT) resulted in a 48% reduction in TIMI major or minor bleeding (4.0% vs. 7.7%, HR 0.52, 95%CI 0.42-0.65, I2= 22%, p < 0.001). There were no significant differences in ischemic outcomes of MI (3.4 % vs. 2.9%, HR 1.14, 0.90-1.45, I2= 0%, p=0.27), stent thrombosis (0.98% vs. 0.70%, HR 1.26, 0.69-2.29), stroke (1.1% vs. 1.1%, HR 0.93, 0.62-1.40), trial-defined MACE (9.1% vs. 8.2%, HR 0.94, 0.74-1.19), or cardiac death (2.6% vs. 2.4%, HR 1.00, 0.74-1.34). Network meta-analysis pairwise comparisons for TIMI major or minor bleeding showed significantly lower bleeding with DAT-NOAC compared to TAT-VKA (OR 0.43, 95% CrI 0.21-0.91). Subgroup analyses showed that trial-specified bleeding was significantly lower for dual antithrombotic therapy compared to triple antithrombotic therapy regardless of age (interaction p-value=0.21), sex (p=0.32), ACS or elective indication for PCI (p=0.75), and presence of diabetes (p=0.38). Compared to triple therapy, dual antithrombotic therapy resulted in reduced bleeding without a significant increase in ischemic events. Current evidence supports the use of dual antithrombotic therapy over triple therapy for patients with AF following PCI.

Safety and Efficacy of Antithrombotic Strategies in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

The antithrombotic treatment of patients with atrial fibrillation (AF) and coronary artery disease, in particular with acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), poses a significant treatment dilemma in clinical practice. To study the safety and efficacy of different antithrombotic regimens using a network meta-analysis of randomized controlled trials in this population. PubMed, EMBASE, EBSCO, and Cochrane databases were searched to identify randomized controlled trials comparing antithrombotic regimens. Four randomized studies were included (n = 10 026; WOEST, PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and network meta-analysis between 4 regimens using a Bayesian random-effects model. A pre hoc statistical analysis plan was written, and the review protocol was registered at PROSPERO. Data were analyzed between November 2018 and February 2019. The primary safety outcome was Thrombolysis in Myocardial Infarction (TIMI) major bleeding; secondary safety outcomes were combined TIMI major and minor bleeding, trial-defined primary bleeding events, intracranial hemorrhage, and hospitalization. The primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE); secondary efficacy outcomes were individual components of MACE. The overall prevalence of ACS varied from 28% to 61%. The mean age ranged from 70 to 72 years; 20% to 29% of the trial population were women; and most patients were at high risk for thromboembolic and bleeding events. Compared with a regimen of vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT; P2Y12 inhibitor plus aspirin), the odds ratios (ORs) for TIMI major bleeding were 0.58 (95% CI, 0.31-1.08) for VKA plus P2Y12 inhibitor, 0.49 (95% CI, 0.30-0.82) for non-VKA oral anticoagulant (NOAC) plus P2Y12 inhibitor, and 0.70 (95% CI, 0.38-1.23) for NOAC plus DAPT. Compared with VKA plus DAPT, the ORs for MACE were 0.96 (95% CI, 0.60-1.46) for VKA plus P2Y12 inhibitor, 1.02 (95% CI, 0.71-1.47) for NOAC plus P2Y12 inhibitor, and 0.94 (95% CI, 0.60-1.45) for NOAC plus DAPT. A regimen of NOACs plus P2Y12 inhibitor was associated with less bleeding compared with VKAs plus DAPT. Strategies omitting aspirin caused less bleeding, including intracranial bleeding, without significant difference in MACE, compared with strategies including aspirin. Our results support the use of NOAC plus P2Y12 inhibitor as the preferred regimen post-percutaneous coronary intervention for these high-risk patients with AF. A regimen of VKA plus DAPT should generally be avoided.

Association of potent P2Y12 blockers with ischemic and bleeding outcomes in non-ST-segment elevation myocardial infarction

BackgroundPotent P2Y12 blockers are preferred in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). However, the risk of bleeding remains a major concern. We assessed the association of potent P2Y12 blockers with ischemic and bleeding outcomes in patients with NSTEMI. MethodsFrom the Korea Acute Myocardial Infarction Registry-National Institute of Health database, 4927 patients with NSTEMI receiving drug-eluting stents (DES) were divided into potent P2Y12 blocker (ticagrelor or prasugrel, n=901) and clopidogrel (n=3180) groups. Propensity-matched 12-month ischemic and bleeding events were compared. Patients who received anticoagulants or who discontinued P2Y12 blockers or switched between potent P2Y12 blockers and clopidogrel were excluded. ResultsIn the overall population, patients at higher ischemic and bleeding risks more often received clopidogrel. After propensity matching (n=901 in each group), 12-month rates of major adverse cardiac and cerebrovascular events were lower (7.3% vs. 10.1%, p=0.038), but Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding rates were higher (5.9% vs. 2.2%, p<0.001) with potent P2Y12 blockers. Twelve-month rates of death from any cause, MI, stroke, or TIMI major bleeding were not different. On multivariate analysis, 12-month risk of TIMI major or minor bleeding was higher with B2 or C lesion, potent P2Y12 blocker use, body weight <60kg, and lower with time to PCI <12h and radial artery access. ConclusionsIn patients with NSTEMI receiving DES, potent P2Y12 blockers were associated with reduced ischemic but increased bleeding risk with similar net clinical benefits.

The Use of Aspirin to Reduce the Risk of Thrombotic Events in Patients With End-Stage Renal Disease: Protocol for a Randomized Controlled Trial.

BackgroundEnd-stage renal disease (ESRD) is the last stage of chronic kidney disease, mainly caused by type 2 diabetes mellitus and characterized by an increased mortality risk related to cardiovascular disease. Low-dose aspirin (acetylsalicylic acid or ASA) seems to effectively prevent cardiovascular events in patients with ESRD. However, the number of interventional studies in this population remains limited and the mechanisms of aspirin-related bleeding remain poorly understood. Aspirin’s efficacy and safety may be modified by the presence of type 2 diabetes mellitus or platelet hyperreactivity.ObjectiveThe overall objective of this protocol is to (1) evaluate aspirin’s safety and efficacy in reducing the risk of thrombotic events in patients with ESRD on hemodialysis and (2) examine whether aspirin’s efficacy is modified by the presence of type 2 diabetes mellitus or platelet hyperreactivity. Specifically, the primary objective is to compare the 12-month rate of any thrombotic event (cardiac death, nonfatal myocardial infarction, nonfatal stroke, arteriovenous fistula thrombosis) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding in patients treated with aspirin compared to those on placebo. Secondary objectives are to test for effect modification of treatment by the presence of type 2 diabetes mellitus or platelet hyperreactivity and compare the rate of TIMI minor bleeding between treatment groups.MethodsWe developed a protocol for a phase 2 randomized, single-center, placebo-controlled, triple-blind, superiority clinical trial to assess the prophylactic efficacy and safety of aspirin in patients with ESRD and on hemodialysis. It follows the ethical principles of the Declaration of Helsinki of the World Medical Association. A total of 342 participants would be enrolled over 12 months at a large dialysis center. Patients will be randomized in a 1:1 ratio and stratified by presence of type 2 diabetes mellitus and platelet hyperreactivity to receive either oral aspirin (100 mg/d) or placebo for a treatment period of 12 months. An intention-to-treat statistical analysis will be performed.ResultsThe randomized clinical trial will be performed after approval by the ethical committee of the participating center and registration at ClinicalTrials.gov.ConclusionsWe provide a protocol for a randomized controlled trial to evaluate the safety and efficacy of treatment with aspirin to reduce the risk of thrombotic events. In addition, such a study would further our understanding of the mechanism of aspirin-related bleeding and help identify subgroups of best-responders and patients with a higher risk of adverse events.Registered Report IdentifierRR1-10.2196/10516

Safety and efficacy of dual vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of randomized clinical trials.

AimsOf patients with atrial fibrillation (AF), approximately 10% undergo percutaneous coronary intervention (PCI). We studied the safety and efficacy of dual vs. triple antithrombotic therapy (DAT vs. TAT) in this population.Methods and resultsA systematic review and meta-analysis was conducted using PubMed, Embase, EBSCO, Cochrane database of systematic reviews, Web of Science, and relevant meeting abstracts for Phase 3, randomized trials that compared DAT vs. TAT in patients with AF following PCI. Four trials including 5317 patients were included, of whom 3039 (57%) received DAT. Compared with the TAT arm, Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding showed a reduction by 47% in the DAT arm [4.3% vs. 9.0%; hazard ratio (HR) 0.53, 95% credible interval (CrI) 0.36–0.85, I2 = 42.9%]. In addition, there was no difference in the trial-defined major adverse cardiac events (MACE) (10.4% vs. 10.0%, HR 0.85, 95% CrI 0.48–1.29, I2 = 58.4%), or in individual outcomes of all-cause mortality, cardiac death, myocardial infarction, stent thrombosis, or stroke between the two arms.ConclusionCompared with TAT, DAT shows a reduction in TIMI major or minor bleeding by 47% with comparable outcomes of MACE. Our findings support the concept that DAT may be a better option than TAT in many patients with AF following PCI.

Comparison of prasugrel versus clopidogrel in Korean patients with acute myocardial infarction undergoing successful revascularization

BackgroundAlthough there have been several reports that prasugrel can improve clinical outcomes, the efficacy and safety of prasugrel is unknown in Korean patients with acute myocardial infarction (AMI) undergoing successful revascularization. MethodsA total of 4421 patients [637 patients were prescribed prasugrel (60/10 or 5mg, loading/maintenance dose) and 3784 patients clopidogrel (600 or 300/75mg)] with AMI undergoing successful revascularization were enrolled from the core clinical cohort of Korea Acute Myocardial Infarction Registry-National Institute of Health. ResultsAfter propensity score matching (637 pairs), there were no significant differences in baseline clinical and procedural characteristics and in-hospital medications between the two groups. The primary efficacy endpoint, defined as the composite of cardiac death, MI, stroke, or target vessel revascularization at 6 months showed no significant difference between prasugrel and clopidogrel (2.4% vs. 2.9%, p=0.593). Also, no difference was observed in the composite of cardiac death, MI, or stroke during hospitalization between two groups (0.8% vs. 0.9%, p=0.762). However, the incidence of in-hospital Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding was significantly higher in prasugrel compared with clopidogrel (5.3% vs. 2.7%, p=0.015). In multivariate linear regression analysis, trans-femoral intervention, use of glycoprotein IIb/IIIa inhibitors, use of calcium channel blocker, and use of prasugrel were independent predictors of in-hospital TIMI major or minor bleeding [odds ratio (OR)=6.918; 95% confidence interval (CI)=2.453–19.510, OR=2.577; 95% CI=1.406–4.724, OR=4.016; 95% CI=1.382–11.668, OR=2.022; 95% CI=1.101–3.714]. ConclusionsOur study shows that the recommended dose of prasugrel had significantly higher in-hospital bleeding complications without reducing ischemic events compared with clopidogrel. However, further large-scale, long-term, randomized clinical trials are required to accurately assess the efficacy and safety of prasgurel and to find out the optimal dose for Korean AMI patients.

Predictors of bleeding in patients with acute coronary syndromes treated with prasugrel

BackgroundWhen considering antiplatelet therapy for acute coronary syndrome (ACS), it is essential to balance benefits (less thrombotic/ischaemic events) versus bleeding risks related to intense platelet inhibition via antagonism of P2Y12...

Evaluation of procedure-related bleeding risk in patients receiving bivalirudin during percutaneous coronary intervention.

Bivalirudin has historically been considered an attractive anticoagulant during percutaneous coronary intervention (PCI) because of reduced bleeding complications reported by early trials. Bivalirudin use during PCIs has been a subject of controversy because of conflicting data and recent findings. To evaluate the clinical characteristics of patients receiving bivalirudin to determine if an opportunity to improve use exists based on risk of procedure-related bleeding. This was a single-center, retrospective, observational study (n = 100) of all adult patients who received bivalirudin during cardiac catheterization at St John Hospital and Medical Center from June to August 2013. The risk of bleeding complications associated with PCI was estimated using a clinical risk algorithm developed from the National Cardiovascular Data Registry (NCDR). Treatment with bivalirudin was safe and effective. Of the 100 patients who received bivalirudin, only 34% were identified as having a high risk of procedure-related bleeding according to the NCDR clinical risk algorithm. There was no incidence of stent thrombosis noted and only 1 case of provisional glycoprotein IIb/IIIa inhibitor use. No episodes of Thrombolysis in Myocardial Infarction (TIMI) major bleeding were noted in the study population; however, 1 patient met TIMI minor bleeding criteria. Limitations of this study include small sample size and retrospective nature of the study. Opportunities to establish a more cost-effective use of bivalirudin may exist through implementation of protocols incorporating the NCDR risk assessment model.