Heparin In Acute Coronary Syndromes Research Articles

Post-PCI anticoagulation with unfractionated heparin in acute coronary syndrome: insight from the STOPDAPT-3 trial

Abstract Background The guidelines recommend the post-procedural anticoagulation should be discontinued after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) except for the specific indications.(1) However, these guideline recommendations were not well supported by data, and therefore, post-PCI parental anticoagulation has been commonly implemented in patients with ACS in the previous studies.(2-5) Purpose To clarify the preference and clinical situations of post-PCI unfractionated heparin (UFH) in ACS patients and to explore the influence of post-PCI UFH on cardiovascular and bleeding outcomes. Methods STOPDAPT-3 trial is a randomized controlled trial to demonstrate the efficacy and safety of the aspirin-free prasugrel monotherapy strategy compared to the conventional dual antiplatelet therapy after PCI in patients with high-bleeding risk or ACS.(6) Data on periprocedural heparin use and its doses were vigorously collected. The current study population was the ACS patients enrolled in the STOPDAPT-3 without use of mechanical circulatory support devices. The two co-primary endpoints were the bleeding outcome defined as the BARC 3 or 5 criteria and the cardiovascular outcome defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Outcomes were assessed at 30 days from index PCI. Results Among 4088 ACS study patients, 2339 (57.2%) patients received post-PCI UFH. Median dose of UFH was 7.1 (IQR 6.0-8.8) units/kg/hour and the median duration was 25 (IQR 24-48) hours. As many as 57.7% of patients received 10000 units/day of heparin after PCI irrespective of body weight. STEMI patients more frequently received post-PCI UFH compared to NSTE-ACS (72.3% and 38.8%, P<0.001) and the patients with intraprocedural adverse angiographic findings such as thrombus, slow-flow, no-reflow, or final TIMI flow <=2 also more frequently received post-PCI UFH than those without (67.6% and 47.5%, P<0.001). Post-PCI UFH was associated with a significantly increased risk of bleeding endpoint (4.75% and 2.52%, adjusted HR 1.69 [95%CI 1.15-2.46], P=0.007) and a numerically increased risk of cardiovascular endpoint (3.16% and 1.72%, adjusted HR 1.56 [95%CI 0.98-2.46], P=0.06). Even in the patients with intraprocedural adverse angiographic findings, post-PCI UFH did not show a clear benefit for cardiovascular endpoint (3.15% and 1.72%, adjusted HR 1.73 [95%CI 0.88-3.41]. P=0.11). Conclusion(s) Post-PCI anticoagulation with UFH was frequently implemented in ACS patients enrolled in the latest large Japanese clinical trial. Post-PCI UFH use was associated with harm in terms of bleeding without a benefit in reducing cardiovascular events.

Post-procedural Anticoagulation With Unfractionated Heparin in Acute Coronary Syndrome: Insight from the STOPDAPT-3 Trial

The current guidelines for acute coronary syndrome (ACS) discourage the use of anticoagulation after percutaneous coronary intervention (PCI) without specific indications, although the recommendation is not well supported by evidence. In this post hoc analysis of the ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-3 (STOPDAPT-3) trial, 30-day outcomes were compared between the 2 groups with and without post-PCI heparin administration among patients with ACS who did not receive mechanical support devices. The co-primary end points were the bleeding end point, defined as the Bleeding Academic Research Consortium type 3 or 5 bleeding, and the cardiovascular end point, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Among 4,088 patients with ACS, 2,339 patients (57.2%) received post-PCI heparin. The proportion of patients receiving post-PCI heparin was higher among those with ST-elevation myocardial infarction compared with others (72.3% and 38.8%, p <0.001), and among patients with intraprocedural adverse angiographic findings compared with those without (67.6% and 47.5%, p <0.001). Post-PCI heparin compared with no post-PCI heparin was associated with a significantly increased risk of the bleeding end point (4.75% and 2.52%, adjusted hazard ratio 1.69, 95% confidence interval 1.15 to 2.46, p = 0.007) and a numerically increased risk of the cardiovascular end point (3.16% and 1.72%, adjusted hazard ratio 1.56, 95% confidence interval 0.98 to 2.46, p = 0.06). Higher hourly dose or total doses of heparin were also associated with higher incidence of both bleeding and cardiovascular events within 30 days. In conclusion, post-PCI anticoagulation with unfractionated heparin was frequently implemented in patients with ACS. Post-PCI heparin use was associated with harm in terms of increased bleeding without the benefit of reducing cardiovascular events. Trial identifier: STOPDAPT-3 ClinicalTrials.gov number, NCT04609111.

61-Year-Old Man With Nausea and Vomiting

61-Year-Old Man With Nausea and Vomiting

Prediction of risk of major bleeding with using CRUSADE bleeding score in Acute coronary syndrome patients: A case series

Use of intravenous heparin in Acute coronary syndrome possess a major risk of bleeding to patients. However, the estimation of risk using bleeding scores in Indian settings is yet to be established. These case series assess the risk of major bleeding associated with the use of Antithrombotic agents in patients with acute coronary syndrome using CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) bleeding score. Relevant patient data was collected from hospital records and patients were followed up till discharge. All the four cases reported showed the risk of in-hospital bleeding with anti-thrombotic agents evident as two cases of hematuria, one case of gum bleeding and one case of hemorrhagic stools. All the patient presented with chest pain to the hospital; following a diagnosis of the acute coronary syndrome, they were prescribed with antiplatelets and anticoagulants. This accompanied a bleeding event which was categorized using CRUSADE bleeding risk score. In-hospital major bleeding imposes a burden on the patient's quality of life. Use of CRUSADE bleeding score helps to predict the severity of risk in a less expensive, non-invasive manner. Further, large scale studies will pave the way for using CRUSADE as an efficient bleeding predictor score.

Bivalirudin Versus Unfractionated Heparin for Acute Coronary Syndromes: Do We Have a Winner?

Bivalirudin Versus Unfractionated Heparin for Acute Coronary Syndromes: Do We Have a Winner?

Bivalirudin Versus Unfractionated Heparin in Acute Coronary Syndromes: An Updated Meta-analysis of Randomized Trials

Introduction and objectivesContrasting data have been reported on bivalirudin as an anticoagulation strategy during percutaneous coronary interventions, offering theoretical benefits on bleeding complications but raising concerns on a potential increase in the risk of stent thrombosis. We performed an updated meta-analysis to evaluate the efficacy and safety of bivalirudin compared with unfractionated heparin in patients undergoing percutaneous interventions for acute coronary syndromes. MethodsLiterature archives and main scientific sessions were scanned. The primary efficacy endpoint was 30-day overall mortality. Secondary endpoints were stent thrombosis and major bleeding. A prespecified analysis was conducted according to clinical presentation. ResultsTwelve randomized trials were included, involving 32 746 patients (52.5% randomized to bivalirudin). Death occurred in 1.8% of the patients, with no differences between bivalirudin and heparin (odds ratio = 0.91; 95% confidence interval, 0.77-1.08; P = .28; P for heterogeneity = .41). Similar results were obtained for patients with non—ST-segment elevation and in ST-segment elevation myocardial infarction. A significantly higher rate of stent thrombosis was observed with bivalirudin (odds ratio = 1.42; 95% confidence interval, 1.09-1.83; P = .008; P for heterogeneity = .09). Bivalirudin was associated with a significant reduction in the rate of major bleeding (odds ratio = 0.60; 95% confidence interval, 0.54-0.75; P < .00001; P for heterogeneity < .0001), which, however, was related to the differential use of glycoprotein IIb/IIIa inhibitors (r = −0.02 [−0.033 to –0.0032]; P = .02) and did not translate into survival benefits. ConclusionsIn patients undergoing percutaneous coronary interventions, bivalirudin is not associated with a reduction in mortality compared with heparin but does increase stent thrombosis. The reduction in bleeding complications observed with bivalirudin does not translate into survival benefits but is rather influenced by a differential use of glycoprotein IIb/IIIa inhibitors.

Ischemic Outcomes After Coronary Intervention of Calcified Vessels in Acute Coronary Syndromes: Pooled Analysis From the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) Trials

This study sought to determine the frequency and impact of coronary calcification among patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS).Small studies in patients with stable coronary artery disease have suggested a worse prognosis after PCI of calcified compared with noncalcified lesions. Little is known about the impact of coronary calcification on outcomes after PCI for patients presenting with non-ST-segment elevation and ST-segment elevation ACS.Data from 6,855 patients presenting with ACS in whom PCI was performed were pooled from 2 large-scale randomized, controlled trials, ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction). One-year outcomes were analyzed according to the severity of PCI target lesion calcification (none/mild, moderate, or severe) as assessed by an independent angiographic core laboratory.Target lesion calcification was severe in 402 patients (5.9%), moderate in 1,788 (26.1%), and none/mild in 4,665 (68.1%). Moderate/severe target lesion calcification was more frequent in older patients, men, hypertensive patients, and those presenting with ST-segment elevation myocardial infarction (STEMI). The unadjusted 1-year rates of death, cardiac death, definite stent thrombosis, and ischemic target lesion revascularization (TLR) and target vessel revascularization were significantly increased in patients with moderate/severe target lesion calcification. By multivariable analysis, the presence of moderate/severe target lesion calcification was an independent predictor of 1-year definite stent thrombosis (hazard ratio [HR]: 1.62; 95% confidence interval [CI]: 1.14 to 2.30; p = 0.007) and ischemic TLR (HR: 1.44; 95% CI: 1.17 to 1.78; p = 0.0007).Moderate/severe lesion calcification was relatively frequent in patients with non-ST-segment elevation ACS and STEMI and was strongly predictive of stent thrombosis and ischemic TLR at 1 year. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158; Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966).

Development and Validation of a Stent Thrombosis Risk Score in Patients With Acute Coronary Syndromes

This study sought to develop a practical risk score to predict the risk of stent thrombosis (ST) after percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS). ST is a rare, yet feared complication after PCI with stent implantation. A risk score for ST after PCI in ACS can be a helpful tool to personalize risk assessment. This study represents a patient-level pooled analysis of 6,139 patients undergoing PCI with stent implantation for ACS in the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trials who were randomized to treatment with bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor. The cohort was randomly divided into a risk score development cohort (n = 4,093) and a validation cohort (n = 2,046). Cox regression methods were used to identify clinical, angiographic, and procedural characteristics associated with Academic Research Consortium-defined definite/probable ST at 1 year. Each covariate in this model was assigned an integer score based on the regression coefficients. Variables included in the risk score were type of ACS (ST-segment elevation myocardial infarction, non-ST-segment elevation ACS with ST deviation, or non-ST-segment elevation ACS without ST changes), current smoking, insulin-dependent diabetes mellitus, prior PCI, baseline platelet count, absence of early (pre-PCI) anticoagulant therapy, aneurysmal/ulcerated lesion, baseline TIMI (Thrombolysis In Myocardial Infarction) flow grade 0/1, final TIMI flow grade <3, and number of treated vessels. Risk scores 1 to 6 were considered low risk, 7 to 9 intermediate risk, and 10 or greater high risk for ST. Rates of ST at 1 year in low-, intermediate-, and high-risk categories were 1.36%, 3.06%, and 9.18%, respectively, in the development cohort (p for trend <0.001), and 1.65%, 2.77%, and 6.45% in the validation cohort (p for trend = 0.006). The C-statistic for this risk score was over 0.65 in both cohorts. The individual risk of ST can be predicted using a simple risk score based on clinical, angiographic, and procedural variables. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966) (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACUITY]; NCT00093158).

A New Score for Risk Stratification of Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: The ACUITY-PCI (Acute Catheterization and Urgent Intervention Triage Strategy–Percutaneous Coronary Intervention) Risk Score

This study sought to develop a new score specific for patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) undergoing percutaneous coronary intervention (PCI) (the ACUITY-PCI [Acute Catheterization and Urgent Intervention Triage Strategy-Percutaneous Coronary Intervention] risk score). The TIMI (Thrombolysis In Myocardial Infarction) and GRACE (Global Registry for Acute Coronary Events) risk scores are recommended for risk stratification of patients with NSTEACS. However, these scores were not optimized for patients undergoing an early invasive strategy with PCI. The ACUITY-PCI risk score was created from data for 1,692 patients enrolled in the formal angiographic substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial by integrating clinical, angiographic, laboratory, and electrocardiographic variables selected by multivariable analysis. The score was subsequently validated in a different population of 846 patients and compared with the GRACE and TIMI risk scores, and the SYNTAX (Synergy Between PCI with Taxus and Cardiac Surgery) and Clinical SYNTAX scores. Six variables (2 clinical, 1 laboratory/electrocardiographic, and 3 angiographic) were included in the ACUITY-PCI score: insulin-treated diabetes; renal insufficiency; baseline cardiac biomarker elevation or ST-segment deviation; bifurcation lesion; small vessel/diffuse coronary artery disease; and the extent of coronary artery disease. Event rates increased significantly across tertiles of ACUITY-PCI score. Compared with the other scores, the ACUITY-PCI score had the best discrimination (C-statistic), calibration (Hosmer-Lemeshow statistic), and index of separation. Moreover, the net reclassification improvement varied from 9% to 38% and the integrated discrimination index from 1.9% to 2.7%. The ACUITY-PCI risk score is a new tool integrating clinical, angiographic, and laboratory/electrocardiographic variables specifically developed for patients with NSTEACS undergoing PCI. This score displayed better prognostic accuracy in terms of discrimination and calibration than other currently available scores for risk stratification of patients with NSTEACS. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158).

Quantification and Impact of Untreated Coronary Artery Disease After Percutaneous Coronary Intervention: The Residual SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) Score

The purpose of this study was to quantify the extent and complexity of residual coronary stenoses following percutaneous coronary intervention (PCI) and to evaluate its impact on adverse ischemic outcomes. Incomplete revascularization (IR) after PCI is common, and most studies have suggested that IR is associated with a worse prognosis compared with complete revascularization (CR). However, formal quantification of the extent and complexity of residual atherosclerosis after PCI has not been performed. The baseline Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score (bSS) from 2,686 angiograms from patients with moderate- and high-risk acute coronary syndrome (ACS) undergoing PCI enrolled in the prospective ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial was determined. The SS after PCI was also assessed, generating the “residual” SS (rSS). Patients with rSS >0 were defined as having IR and were stratified by rSS tertiles, and their outcomes were compared to the CR group. The bSS was 12.8 ± 6.7, and after PCI the rSS was 5.6 ± 2.2. Following PCI, 1,084 patients (40.4%) had rSS = 0 (CR), 523 (19.5%) had rSS >0 but ≤2, 578 (21.5%) had rSS >2 but ≤8, and 501 patients (18.7%) had rSS >8. Age, insulin-treated diabetes, hypertension, smoking, elevated biomarkers or ST-segment deviation, and lower ejection fraction were more frequent in patients with IR compared with CR. The 30-day and 1-year rates of ischemic events were significantly higher in the IR group compared with the CR group, especially those with high rSS. By multivariable analysis, rSS was a strong independent predictor of all ischemic outcomes at 1 year, including all-cause mortality (hazard ratio: 1.05, 95% confidence interval: 1.02 to 1.09, p = 0.006). The rSS is useful to quantify and risk-stratify the degree and complexity of residual stenosis after PCI. Specifically, rSS >8.0 after PCI in patients with moderate- and high-risk ACS is associated with a poor 30-day and 1-year prognosis. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes; NCT00093158)

Prognostic Value of the SYNTAX Score in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Analysis From the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) Trial

We sought to investigate the predictive value of the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score (SS) for risk assessment of 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention (PCI). In the SYNTAX trial, the SS was effective in risk-stratifying patients with left main and triple-vessel coronary disease, the majority of whom had stable ischemic heart disease. The SS was determined in 2,627 patients with non-ST-segment elevation acute coronary syndromes undergoing PCI in the angiographic substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) trial. Patients were stratified according to tertiles of the SS: <7 (n = 854), ≥ 7 and <13 (n = 825), and ≥ 13 (n = 948). Among patients in the first, second, and third SS tertiles, the 1-year rates of mortality were 1.5%, 1.6%, and 4.0%, respectively (p = 0.0005); the cardiac mortality rates were 0.2%, 0.9%, and 2.7%, respectively (p < 0.0001); the myocardial infarction (MI) rates were 6.3%, 8.3%, and 12.9%, respectively (p < 0.0001); and the target vessel revascularization (TVR) rates were 7.4%, 7.0%, and 9.8%, respectively (p = 0.02). By multivariable analysis, the SS was an independent predictor of 1-year death (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 1.01 to 1.07; p = 0.005), cardiac death (HR: 1.06, 95% CI: 1.03 to 1.09; p = 0.0002), MI (HR: 1.03, 95% CI: 1.02 to 1.05; p < 0.0001), and TVR (HR: 1.03, 95% CI: 1.02 to 1.05; p < 0.0001). The SS affected death, cardiac death, and MI both within the first 30 days after PCI and between 30 days and 1 year, whereas it affected TVR primarily within the first 30 days. The predictive value of an increased SS was consistent among multiple pre-specified subgroups. In patients with non-ST-segment elevation acute coronary syndromes undergoing PCI, the SS is an independent predictor of the 1-year rates of death, cardiac death, MI, and TVR. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158).

The Use of Low-Molecular Weight Heparins in Acute Coronary Syndromes

Acute coronary syndrome (ACS) comprises of unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI). ACS is the consequence of a sudden rupture of the coronary artery plaque and the immediate formation of thrombosis around the plaque. The presence of coronary occlusion and thrombus might result in cardiac muscle damage and loss of effective cardiac output, leading to cardiac failure. Anticoagulants, therefore, play an important role in medical management for ACS. This article assesses the role of low molecular weight heparin (LMWH) in ACS based on current available data in clinical trials and clinical practice guidelines from the American College of Cardiology (ACC)/the American Heart Association (AHA) and the American College of Chest Physicians (ACCP) antithrombotic and thrombolytic therapy consensus guidelines. Overall, the use of enoxaparin is generally preferred over other LMWHs when LMWH is indicated, and there is strong support for its role across the continuum of treatment for ACS patients.

Surgical Versus Percutaneous Revascularization for Multivessel Disease in Patients With Acute Coronary Syndromes: Analysis From the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) Trial

The aim of this study was to evaluate outcomes of patients with moderate- and high-risk acute coronary syndromes (ACS) and multivessel coronary artery disease managed with percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). There is uncertainty about the preferred revascularization strategy for high-risk patients with multivessel disease. Among 13,819 moderate- and high-risk ACS patients enrolled in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, 5,627 had multivessel disease (including left anterior descending artery involvement) and were managed by PCI (n = 4,412) or CABG (n = 1,215). Propensity score matching was applied to adjust for differences in baseline clinical and angiographic characteristics, yielding a total of 1,056 patients (528 managed by PCI, and 528 managed by CABG). Propensity-matched patients undergoing CABG had higher 1-month rates of stroke (1.1% vs. 0.0%, p = 0.03) and myocardial infarction (13.3% vs. 8.8%, p = 0.03), received more blood transfusions (40.3% vs. 6.3%, p < 0.0001) and more frequently developed acute renal injury (31.7% vs. 14.2%, p < 0.0001), whereas PCI was associated with higher rates of unplanned revascularization at both 1 month and at 1 year (0.8% vs. 5.2%, p < 0.0001; and 3.8% vs. 16.5%, p < 0.0001, respectively). There were no significant differences between the CABG and PCI groups in 1-month or 1-year mortality (2.5% vs. 2.1%, p = 0.69; and 4.4% vs. 5.7%, p = 0.58, respectively). In this propensity-matched comparison from the ACUITY trial, moderate- and high-risk patients with ACS and multivessel disease treated with PCI rather than CABG had lower rates of peri-procedural stroke, myocardial infarction, major bleeding, and renal injury, with comparable 1-month and 1-year rates of mortality, but more frequently developed recurrent ischemia requiring repeat revascularization procedures during follow-up. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158).

Prognostic Significance of Periprocedural Versus Spontaneously Occurring Myocardial Infarction After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndromes: An Analysis From the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) Trial

The aim of this study was to evaluate the relative impact of spontaneously occurring and periprocedural myocardial infarction (MI) on survival after percutaneous coronary intervention (PCI). The clinical significance of periprocedural MI after PCI remains uncertain. Outcomes during a 1-year follow-up were evaluated among 7,773 patients enrolled in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial with a non-ST-segment elevation acute coronary syndrome in whom PCI was performed. Periprocedural MI developed in 466 patients (6.0%), and spontaneous MI unrelated to PCI subsequently developed in 200 patients (2.6%). Patients developing spontaneous and periprocedural MI compared with those patients without MI had significantly greater unadjusted rates of mortality at 30 days (5.0% vs. 3.2% vs. 0.8%, respectively, p < 0.0001) and at 1 year (16.0% vs. 6.0% vs. 2.6%, respectively, p < 0.0001). In a time-updated multivariable analysis, after adjusting for differences in baseline and procedural characteristics between the groups, we found that spontaneous MI was a powerful independent predictor of subsequent mortality (hazard ratio: 7.49, 95% confidence interval: 4.95 to 11.33, p < 0.0001), whereas periprocedural MI was not a significant predictor of mortality (hazard ratio: 1.30, 95% confidence interval: 0.85 to 1.98, p = 0.22). Among patients with acute coronary syndrome undergoing PCI, the spontaneous development of an MI unrelated to PCI is a powerful predictor of subsequent mortality. In contrast, periprocedural MI is a marker of baseline risk, atherosclerosis burden, and procedural complexity but in most cases does not have independent prognostic significance. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158).

Outcomes Following Pre-Operative Clopidogrel Administration in Patients With Acute Coronary Syndromes Undergoing Coronary Artery Bypass Surgery: The ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) Trial

This study sought to evaluate the impact of upstream clopidogrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) requiring coronary artery bypass grafting (CABG) from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial. Despite benefits of clopidogrel in patients with NSTE-ACS undergoing percutaneous coronary intervention, this agent is often not administered upstream (before angiography) as recommended by the American College of Cardiology/American Heart Association guidelines because of potential bleeding in the minority of patients who require CABG. The ACUITY trial enrolled 13,819 patients with NSTE-ACS undergoing early invasive management. The timing of clopidogrel initiation was per investigator discretion. A 5-day washout period before CABG was recommended for patients having received clopidogrel. Of 13,819 patients enrolled, 1,539 (11.1%) underwent CABG before discharge. Clopidogrel-exposed patients had a longer median duration of hospitalization (12.0 days vs. 8.9 days, p < 0.0001), but fewer adverse composite ischemic events (death, myocardial infarction, or unplanned revascularization) at 30 days; 12.7% vs. 17.3%, p = 0.01), with nonsignificantly different rates of non-CABG-related major bleeding (3.4% vs. 3.2%, p = 0.87) and post-CABG major bleeding (50.3% vs. 50.9%, p = 0.83) compared with those patients not administered clopidogrel. By multivariable analysis, clopidogrel use before CABG was an independent predictor of reduced 30-day composite ischemia (odds ratio: 0.67, 95% confidence interval: 0.48 to 0.92, p = 0.001) but not of increased post-CABG major bleeding (odds ratio: 0.98, 95% confidence interval: 0.80 to 1.19, p = 0.80). Clopidogrel administration before catheterization in patients with NSTE-ACS requiring CABG is associated with significantly fewer 30-day adverse ischemic events without significantly increasing major bleeding, compared to withholding clopidogrel until after angiography. These findings support the American College of Cardiology/American Heart Association guidelines for upstream clopidogrel administration in all NSTE-ACS patients, including those who subsequently undergo CABG. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158).

Influence of Timing of Clopidogrel Treatment on the Efficacy and Safety of Bivalirudin in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: An Analysis of the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) Trial

This study sought to determine if the efficacy of bivalirudin alone versus heparin plus a glycoprotein (GP) IIb/IIIa inhibitor is dependent upon the duration of clopidogrel pre-treatment in patients undergoing percutaneous coronary intervention (PCI) in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial. The administration of a clopidogrel loading dose several hours before PCI reduces the risk of periprocedural thrombotic events. Patients with an acute coronary syndrome were randomized to heparin plus a GP IIb/IIIa inhibitor (control), bivalirudin plus a GP IIb/IIIa inhibitor, or bivalirudin alone. Dose and timing of clopidogrel were left to the investigator's discretion. Of 13,819 patients randomized, 7,789 underwent PCI. When clopidogrel was initiated at any time before angiography or within 30 min after PCI, randomization to bivalirudin alone (n = 2,284) or control (n = 2,189) was associated with similar ischemic outcomes (8.2% vs. 8.3%, risk ratio: 0.98, 95% confidence interval: 0.81 to 1.20). Those patients who received clopidogrel >30 min after PCI or not at all experienced an increase in ischemic events when randomized to bivalirudin alone (n = 290) versus control (n = 317) (14.1% vs. 8.5%, risk ratio: 1.66, 95% confidence interval: 1.05 to 2.63). Major bleeding was significantly less frequent in patients treated with bivalirudin alone. This post-hoc analysis suggests that in acute coronary syndrome patients, as long as clopidogrel is administered before or within 30 min of PCI treatment with bivalirudin alone is similarly effective to heparin plus a GP IIb/IIIa inhibitor in suppressing 30-day ischemic events with significantly less bleeding. If it is anticipated that clopidogrel will be given late or not at all after PCI, bivalirudin alone may be associated with worse ischemic outcomes. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes; NCT00093158).

Economic Evaluation of Bivalirudin With or Without Glycoprotein IIb/IIIa Inhibition Versus Heparin With Routine Glycoprotein IIb/IIIa Inhibition for Early Invasive Management of Acute Coronary Syndromes

The aim of this study was to determine the economic impact of several anticoagulation strategies for moderate- and high-risk non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients managed invasively. The ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial demonstrated that bivalirudin monotherapy yields similar rates of ischemic complications and less bleeding than regimens incorporating glycoprotein IIb/IIIa receptor inhibitors (GPI) for moderate- and high-risk NSTE-ACS. In ACUITY, 7,851 U.S. patients were randomized to: 1) heparin (unfractionated or enoxaparin) + GPI; 2) bivalirudin + GPI; or 3) bivalirudin monotherapy. Patients assigned to GPI were also randomized to upstream GPI before catheterization or selective GPI only with percutaneous coronary intervention. Resource use data were collected prospectively through 30-day follow-up. Costs were estimated with standard methods including resource-based accounting, hospital billing data, and the Medicare fee schedule. At 30 days, ischemic events were similar for all groups. Major bleeding was reduced with bivalirudin monotherapy compared with heparin + GPI or bivalirudin + GPI (p < 0.001). Length of stay was lowest with bivalirudin monotherapy or bivalirudin + catheterization laboratory GPI (p = 0.02). Despite higher drug costs, aggregate hospital stay costs were lowest with bivalirudin monotherapy (mean difference range: $184 to $1,081, p < 0.001 for overall comparison) and at 30 days (mean difference range: $123 to $938, p = 0.005). Regression modeling demonstrated that hospital savings were primarily due to less major and minor bleeding with bivalirudin ($8,658/event and $2,282/event, respectively). Among U.S. patients in the ACUITY trial, bivalirudin monotherapy compared with heparin + GPI resulted in similar protection from ischemic events, reduced bleeding, and shorter length of stay. Despite higher drug costs, aggregate hospital and 30-day costs were lowest with bivalirudin monotherapy. Thus bivalirudin monotherapy seems to be an economically attractive alternative to heparin + GPI for patients with moderate- and high-risk NSTE-ACS. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158).

Superior efficacy of low-molecular-weight heparin vs unfractionated heparin in acute coronary syndrome without ST elevation

To evaluate the 5-year efficacy of a foldable, hydrophobic, angle-supported phakic intraocular lens (pIOL) when used to correct moderate to high myopia.Prospective, nonrandomized, multicenter, open-label cohort study conducted in the United States, the European Union, and Canada (3 separate protocols).This was a pooled analysis of 515 eyes from 360 patients 18 to 49 years of age with moderate to high myopia (preoperative corrected distance visual acuity [CDVA] ≤0.34 logarithm of the minimum angle of resolution [logMAR]) and with variance in the manifest refraction spherical equivalent within ±0.5 diopter (D) for a minimum of 12 months.Implantation of the AcrySof Cachet angle-supported anterior chamber pIOL (Alcon Laboratories, Inc., Fort Worth, TX).Uncorrected distance visual acuity (UDVA), CDVA, predictability and stability of manifest refraction spherical equivalent (MRSE), serious adverse events, endothelial cell density, and patient satisfaction.Of 360 patients who received implantation in at least 1 eye (515 eyes), 326 (90.6%) completed the study (5-year best-corrected visual acuity data available for 415 eyes). At 5 years, a decrease in CDVA of 2 lines or more was observed in 0.5% of eyes (n = 2/415) compared with preoperative baseline. At 5 years, all 415 eyes achieved a CDVA of 0.34 logMAR or less; 91.3% (n = 379/415) had a CDVA of 0.04 logMAR or less. Mean UDVA ± standard deviation (SD) was 0.01±0.18 logMAR; 94.7% (n = 393/415) and 66.3% (n = 275/415) of eyes had a UDVA of 0.34 logMAR or less or 0.04 logMAR or less, respectively, at 5 years. Mean MRSE ± SD was −0.34±0.57 D (range,−2.50 to 1.63 D). Most eyes (89.8%; n = 371/413) had an MRSE within ±1.00 D of their target refractive error at 5 years and 67.3% (n = 278/413) were within ±0.50 D. Mean annualized central endothelial cell loss was 1.46% (90% confidence interval [CI], −1.6% to −1.3%) from 6 months to 5 years. The most common pIOL-related serious adverse event was adhesion between the cornea and the iris (synechia; n = 24). Most patients (98.1%) indicated that they would have the same pIOL implanted again.In patients with moderate to high myopia, the AcrySof Cachet angle-supported pIOL provided excellent refractive correction for up to 5 years after implantation, with a low rate of mean central endothelial cell loss. Careful patient selection is necessary to achieve optimal postsurgical outcomes.

Low-Molecular-Weight Heparin vs Unfractionated Heparin in Acute Coronary Syndromes—Reply

Low-Molecular-Weight Heparin vs Unfractionated Heparin in Acute Coronary Syndromes—Reply

Low-Molecular-Weight Heparin vs Unfractionated Heparin in Acute Coronary Syndromes

Low-Molecular-Weight Heparin vs Unfractionated Heparin in Acute Coronary Syndromes