Novel anti-platelet agents in acute coronary syndrome: mechanisms of action and opportunities to tailor therapy.

Dual anti-platelet therapy, most commonly aspirin and clopidogrel, has been the standard of care for over a decade in patients who have experienced acute coronary syndrome, particularly when treated with coronary stenting. However, residual risk in patients receiving dual anti-platelet therapy post-acute coronary syndrome raises an unmet need for alternative therapy to clopidogrel. Consequently, novel anti-platelets agents including the P2Y12 receptor antagonists, such as prasugrel and ticagrelor, have emerged. Furthermore, using new methods to assess genetic polymorphisms and functional phenotypic assessments of platelet reactivity may become important in the development of personalized medicine and in developing tailored approaches to individual treatment. While robust large-scale evidence for genotypic- and phenotypic-guided therapy in improving outcomes is currently lacking, tremendous interest from various stakeholders including researchers, funding agencies, and industry continues to spur research endeavors in this arena. Further investigation is required in this emerging field to potentially offer improved platelet inhibition that may optimize cardioprotection and minimize bleeding risk in patients with acute coronary syndrome.

Cost-Comparison of Mechanical Thrombectomy and Catheter-Directed Thrombolysis in Intermediate-Risk Pulmonary Embolism.

Background: Catheter-directed thrombolysis (CDT) and large-bore mechanical thrombectomy (MT) are the leading percutaneous-based therapies for the management of intermediate-risk pulmonary embolism (PE). While previous studies have demonstrated their procedural safety and efficacy, the cost implications of these interventions remain unclear. This study aims to conduct a cost-benefit analysis to evaluate the economic advantages associated with CDT and MT from the perspective of the treating hospital. Methods: A total of 372 consecutive patients with intermediate-risk acute PE who underwent either MT or CDT at 3 academic centers between 2013 and 2021 were included in this analysis. The costs of care incurred during the index hospitalization for the 2 treatment groups were collected and compared using an adjusted cost model. Results: This study compared the hospital costs of 226 patients who underwent CDT and 146 patients who underwent MT. In the unadjusted overall cohort, the use of CDT was associated with a numerical but nonsignificant increase in costs amounting to $5120 relative to MT (P = .062). This cost difference was primarily driven by the longer length of stay in the intensive care unit and hospital for CDT patients, particularly earlier in the studied timeframe. However, when accounting for confounders including variations between the treating institutions and the timing of treatment during the study period, the adjusted cost differential between CDT and MT narrowed to $1351 (P = .71). Conclusions: This multicenter cost analysis does not reveal a clear cost advantage of 1 treatment over the other for intermediate-risk PE. The observed cost differences were influenced by variations in practice patterns across the study period and among the 3 participating institutions. Future efforts should also focus on strategies to reduce the length of stay, improve efficiency, and minimize the overall cost of care for intermediate-risk PE patients.

A Safety and Feasibility Single-Arm Study of a Novel Catheter Thrombectomy Device for the Treatment of Pulmonary Embolism (ENGULF).

Background: Despite advances in therapy options, pulmonary embolism (PE) continues to carry a high risk of mortality and morbidity. Currently, therapeutic options are limited with only 2 US Food and Drug Administration-cleared catheter-based embolectomy devices approved for the treatment of intermediate-risk PE. The novel Helo PE thrombectomy catheter (Endovascular Engineering, Inc) has a flexible and collapsible funnel with an internal agitator for a dual mechanism of treatment for acute PE. We sought to investigate the safety and feasibility of the novel Helo PE thrombectomy catheter in intermediate-risk PE. Methods: A prospective, single-arm feasibility study evaluating the Helo PE catheter was performed in patients presenting with intermediate-risk PE. Patients underwent preprocedural and postprocedural computed tomography angiography. Primary efficacy was the difference in preprocedural to postprocedural right ventricle/left ventricle (RV/LV) ratio. Primary and secondary safety outcomes were all-cause mortality, major life-threatening bleeding, device-related serious adverse events, pulmonary or cardiac injury, and clinical decompensation at 48 hours postprocedure and at 30 days. Results: A total of 25 patients from 8 centers were consented and included in the analysis. Preprocedural computed tomography angiography revealed an RV/LV ratio of 1.53 ± 0.27. All patients underwent a successful thrombectomy procedure. Postprocedure, the RV/LV ratio was reduced to 1.15 ± 0.18, translating into a 23.2 ± 12.81% decrease from baseline. No patients underwent adjunctive thrombolysis. Two patients had adjunctive catheter-directed embolectomy with an alternative device. Two patients had postprocedural anemia requiring transfusion but did not meet criteria for major life-threatening bleeding by VARC-2 criteria. There were no major adverse events including no deaths, major bleeding, pulmonary injury, or vascular complications at 48 hours or 30 days post procedure. Conclusions: In this multicenter first-in-human study, use of the Helo PE thrombectomy catheter was feasible and safe for the treatment of acute PE.

Effective management of acute coronary thrombosis in a young woman with lupus using aggressive medical therapy.

Systemic lupus erythematosus is a chronic inflammatory disorder that predisposes to acute coronary thrombosis. To demonstrate how the pathophysiology of lupus-mediated coronary events may be unique, we offer the case and management of a young woman with lupus who presented with acute myocardial infarction. She was initially managed with medical therapy including the standard regimen of aspirin, heparin, and clopidogrel. Despite a Thrombolysis in Myocardial Infarction risk score of only 2, she was also given eptifibatide infusion because of clinical concerns. Repeated cardiac catheterization showed marked regression of the thrombus, and coronary fractional flow reserve calculation demonstrated full recovery of coronary vasculature with this therapy. This case demonstrates effective management of life-threatening coronary thrombosis with medical therapy only in a young woman with lupus. We briefly review the pathophysiology of acute coronary thrombosis in lupus patients and distinguish this from the more common process of age-related atherosclerosis. Given the lack of evidence in this specific population, we discuss a pathophysiology-based clinical decision-making tool. Assessing clinical risk factors and using technologies such as intravascular ultrasound can help make the correct treatment decision.

Evaluation of thrombocytopenia in the acute coronary syndrome.

PURPOSE OF REVIEW: Thrombocytopenia is relatively common in patients with acute coronary syndromes and is associated with an increased risk of adverse outcomes, regardless of the etiology of the low platelet count. Treatment strategies, both medical and mechanical, may cause thrombocytopenia. This review will introduce a differential diagnosis, diagnostic strategies, and treatment options for patients with an acute coronary syndrome. RECENT FINDINGS: Recent data has strengthened the relationship between thrombocytopenia and adverse outcomes, particularly death and bleeding, in this population of cardiac patients. In addition, bleeding is recognized as a strong independent predictor of an adverse event. Thrombocytopenia may be a marker for acuity of illness and often may be only an association between a low platelet count and therapeutic interventions in this population. Nevertheless, thrombocytopenia due to glycoprotein 2b3a receptor inhibitors, heparins, thienopyridines, and intra-aortic balloon pumps must be recognized and managed appropriately. SUMMARY: Surveillance for and early recognition of thrombocytopenia, an appropriate differential diagnosis, and early institution of treatment are critically important in the management of patients with acute coronary syndromes.

One-Year Outcomes of Percutaneous Coronary Intervention in Patients with End-Stage Liver Disease.

BACKGROUND: Patients with cirrhosis and coronary artery disease (CAD) are at high risk for morbidity during surgical revascularization so they are often referred for complex percutaneous coronary intervention (PCI). Percutaneous coronary intervention in the cirrhotic population also has inherent risks; however, quantifiable data on long-term outcomes are lacking. METHODS: Patients with angiographically significant CAD and cirrhosis were identified from the catheterization lab databases of the University of Pennsylvania Health System between 2007 and 2015. Outcomes were obtained from the medical record and telephonic contact with patients/families. RESULTS: Percutaneous coronary intervention was successfully performed in 42 patients (51 PCIs). Twenty-nine patients with significant CAD were managed medically (36 angiograms). The primary outcome (a composite of mortality, subsequent revascularization, and myocardial infarction) was not significantly different between the 2 groups during a follow-up period at 1 year (PCI: 50%, Control: 40%, P = .383). In the PCI group, a composite adverse outcome rate that included acute kidney injury (AKI), severe bleed, and peri-procedural stroke was elevated (40%), with severe bleeding occurring after 23% of PCI events and post-procedural AKI occurring after 26% of events. The medical management group had significantly fewer total matched adverse outcomes (17% vs 40% in the PCI group, P = .03), with severe bleeding occurring after 11% of events and AKI occurring after 6% of events. Increased risk of adverse events following PCI was associated with severity of liver disease by Child-Pugh class. CONCLUSIONS: Percutaneous coronary intervention in patients with cirrhosis is associated with an elevated risk of adverse events, including severe bleeding and AKI.

Revascularization strategies and in-hospital management in acute coronary syndromes complicated by hemophilia A or hemophilia B.

: Among adult patients with hemophilia A and hemophilia B the emergent management of acute coronary syndromes (ACSs) is challenging, and exposure to antithrombotic agents and/or revascularization procedures may confer an enhanced risk of bleeding. We sought to identify clinical characteristics and in-hospital outcomes among ACS patients with hemophilia A/hemophilia B, compared with matched noncoagulopathic ACS controls. Case discharges from the Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality (1998-2011) had International Classification of Diseases, 9th Revision codes for hemophilia A/hemophilia B and ACS. Control discharges were matched to cases by year of discharge and hospital. Discharges in both groups were assessed for cardiovascular risk factors, type of ACS, use of coronary artery bypass grafting, percutaneous coronary intervention (PCI), bare-metal stent and/or drug-eluting stent, bleeding, and death. In total, 237 cases and 148 848 matched controls were identified. Among cases, HIV/Hepatitis C positivity was more common and obesity/hyperlipidemia less common. ST-elevation myocardial infarction (STEMI) occurred less frequently among hemophilia A cases than controls. hemophilia A and hemophilia B cases were more likely to be managed medically. Cases treated with coronary stent placement were more likely to receive a bare-metal stent than controls. Among PCI, bleeding was more common among hemophilia A cases. The death rates were comparable between groups. ACS-hemophilia A/hemophilia B cases were more often treated noninvasively compared with controls, suggesting an avoidance of PCI/coronary artery bypass grafting in this population, and bleeding (among hemophilia A) was more common. These findings support further study of the management of ACS and in-hospital outcomes among individuals with hemophilia.

Safety and efficacy of argatroban in patients with heparin-induced thrombocytopenia.

Argatroban is a synthetic direct thrombin inhibitor. It is indicated for use in patients with heparin-induced thrombocytopenia (HIT). The greatest experience is in prevention and treatment of the disorder, but argatroban is also indicated for percutaneous coronary interventions in patients with HIT. There is somewhat limited experience with its use in a number of other clinical scenarios in these patients. The current data on the use of argatroban in patients with HIT are reviewed.

Thrombocytopenia in cardiovascular patients: diagnosis and management.

Thrombocytopenia is a common problem in cardiovascular patients, but the etiology and management of this condition may be different than those in other populations. Around the time that percutaneous coronary interventions are performed, the drugs most commonly associated with thrombocytopenia are the glycoprotein (GP) IIb/IIIa receptor inhibitors and heparin. Thienopyridines only rarely cause thrombocytopenia. Patients with non-ST-elevation acute coronary syndromes may be exposed to prolonged heparin infusions, GPIIb/IIIa inhibitors, and thienopyridines. After open-heart surgery, as opposed to other surgical procedures, the platelet count falls, primarily due to platelet damage and destruction in the bypass circuit and hemodilution. Heparin is the most common drug to be implicated in thrombocytopenia in ICU patients. Determining the etiology for the low platelet count is important for the implementation of appropriate management. The use of a direct thrombin inhibitor in treatment should be considered early if a diagnosis of heparin-induced thrombocytopenia is possible.

Argatroban anticoagulation in patients with a history of heparin-induced thrombocytopenia.

INTRODUCTION: Heparin therapy is not recommended for patients with a history of heparin-induced thrombocytopenia (HIT), except in specialized situations, because this treatment can lead to severe reactions including thrombocytopenia and thrombosis. However, the optimal management of patients with a history of HIT requiring acute anticoagulation has not yet been clarified because of the lack of prospective studies. We evaluated the safety and efficacy of argatroban, a direct thrombin inhibitor, as an anticoagulant in patients with a history of HIT needing acute anticoagulation. METHODS: Thirty-six patients with a history of serologically confirmed HIT were treated prospectively with argatroban [median (5th-95th percentile) dose of 2.0 (1.0-4.3) microg/kg/min for 4.0 (0.7-8.4) days]. Prospectively defined endpoints included successful anticoagulation (therapeutic activated partial thromboplastin time), and bleeding, new thromboembolic events, or other adverse effects during therapy or within 30 days following its cessation. RESULTS: All patients required acute anticoagulation with the most common admission diagnoses being deep venous thrombosis or pulmonary embolism (n=13) and chest pain or acute coronary syndrome (n=12). Eleven patients had previously received argatroban therapy for HIT; one patient underwent two treatment courses of argatroban for a history of HIT. The median (5th-95th percentile) time between the past diagnosis of HIT and initiation of argatroban was 7.5 (0.4-114.6) months. All evaluable patients were successfully anticoagulated. No patient had major bleeding, new thromboembolic events, or other adverse effects. There were no adverse events related to reexposure. CONCLUSIONS: Argatroban can provide safe and effective anticoagulation, on initial or repeat exposure, in patients with a history of HIT.

Patient satisfaction is comparable to early discharge versus overnight observation after elective percutaneous coronary intervention.

BACKGROUND: Previous investigation has suggested that early discharge after percutaneous coronary intervention (PCI) is feasible and safe, but these studies have utilized largely radial approaches or been conducted in non-U.S. cohorts. We sought to assess patient satisfaction, safety and cost of a strategy of selective early discharge in U.S. patients undergoing PCI via a femoral approach with contemporary adjunctive pharmacologic and hemostasis agents. METHODS AND RESULTS: Patients with stable coronary artery disease undergoing elective PCI were prospectively recruited and randomized to either routine care, with an overnight hospital stay, versus early discharge 2 hours following successful PCI with adjunctive bivalirudin therapy and a femoral arterial closure device at the end of the procedure. The primary endpoints were safety and patient satisfaction as measured by a validated patient satisfaction survey during the index hospital stay and at 30 days. A total of 39 patients were randomized, with 20 to routine care and 19 to early discharge. There was no difference in major safety endpoints including death, non-fatal MI, urgent target lesion revascularization and thrombolysis in myocardial infarction (TIMI) major bleeding, with none in either group. Mean patient satisfaction scores were similar and high in both groups (89.6 for early discharge patients and 90.7 for routine care patients, p = 0.68). There was lower cost in the early discharge group, with a mean cost of 8,604 USD versus 10,565 USD in the routine care group (mean difference 1,961 USD, 95% confidence interval, -96 USD to 4,017 USD). CONCLUSION: Patients undergoing elective PCI for stable coronary artery disease may have similar safety and satisfaction with early discharge when using a careful strategy that incorporates optimal stent and hemostasis results and contemporary adjunctive anticoagulation therapy, with lower cost. This strategy may serve as a basis for a larger-scale randomized trial.

Treatment of heparin-induced thrombocytopenia in cardiovascular patients.

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated syndrome associated with heparin exposure, a falling platelet count and a high risk of thrombosis. Cardiovascular patients are at increased risk of HIT due to wide use of heparin in this population. Should HIT be suspected, heparin must be avoided in most situations, and anticoagulation with an alternative anticoagulant should be instituted. Preferred agents include the direct thrombin inhibitors argatroban and lepirudin, whilst bivalirudin or desirudin (other direct thrombin inhibitors) can be used in some situations. The indirect thrombin inhibitors, danaparoid and fondaparinux, can also be considered at times. These agents and their use in cardiac patients, including patients with acute coronary syndrome, percutaneous coronary interventions, acute ST elevation myocardial infarction or cardiac surgery, will be reviewed.

Evaluating the etiology of mechanical valve obstruction: use of clinical parameters, fluoroscopy, and echocardiography.

Prosthetic valve obstruction is a life-threatening complication most commonly caused by thrombus, pannus, or both. We report a St. Jude tricuspid valve obstruction, initially treated with thrombolytic therapy, found to be caused by pannus on pathologic examination. Clinical evaluation and diagnostic evaluation with fluoroscopy and echocardiography in distinguishing pannus from thrombus are reviewed.

Argatroban anticoagulation in conjunction with glycoprotein IIb/IIIa inhibition in patients undergoing percutaneous coronary intervention: an open-label, nonrandomized pilot study.

BACKGROUND: Argatroban, a direct thrombin inhibitor, blocks clot-bound thrombin more effectively than does heparin. This multicenter, prospective pilot study evaluated the efficacy and safety of argatroban in combination with glycoprotein IIb/IIIa inhibition in patients undergoing percutaneous coronary intervention. METHODS: Patients (N = 152) received argatroban as a 250- or 300-mug/kg bolus, followed by a 15-mug/kg/min infusion during percutaneous coronary intervention. An additional 150-mug/kg bolus was administered if activated clotting times 5-15 min after initiating argatroban were <275 s. Abciximab (N = 150) or double-bolus eptifibatide (N = 2) was administered simultaneously. RESULTS: Median activated clotting times at the beginning and end of the procedure were approximately 300 s. The primary efficacy endpoint-a composite of death, myocardial infarction, or urgent revascularization at 30 days-occurred in 4 (2.6%) patients (no death, 4 myocardial infarctions, and 2 revascularizations). Two (1.3%) patients had major bleeding by the Thrombolysis in Myocardial Infarction criteria (1 retroperitoneal, 1 groin hematoma). CONCLUSIONS: Argatroban in combination with glycoprotein IIb/IIIa inhibition appears to provide adequate anticoagulation and be well tolerated with an acceptable bleeding risk for patients undergoing percutaneous coronary intervention. Additional studies are warranted.

Argatroban anticoagulation during percutaneous coronary intervention in patients with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated syndrome associated with thrombosis. Alternative anticoagulation to heparin is needed for HIT patients during percutaneous coronary intervention (PCI). We evaluated argatroban, a direct thrombin inhibitor, for anticoagulation in this setting. Ninety-one HIT patients underwent 112 PCIs while on intravenous argatroban (25 microg/kg/min [350 microg/kg initial bolus], adjusted to achieve an activated clotting time of 300-450 sec). Primary efficacy endpoints were subjective assessments of the satisfactory outcome of the procedure and adequate anticoagulation during PCI. Among patients undergoing initial PCIs with argatroban (n = 91), 94.5% had a satisfactory outcome of the procedure and 97.8% achieved adequate anticoagulation. Death (zero patients), myocardial infarction (four patients), or revascularization (four patients) at 24 hr after PCI occurred in seven (7.7%) patients overall. One patient (1.1%) experienced periprocedural major bleeding. For patients who had subsequent hospitalizations (mean separation of 150 days) for repeat PCI using argatroban anticoagulation (n = 21), there were no unsatisfactory outcomes. Overall, outcomes were comparable with those historically reported for heparin. Argatroban therefore is a reasonable anticoagulant option in this setting, where current options are limited.

Role of cardiac troponin T in the long-term risk stratification of patients undergoing percutaneous coronary intervention.

AIMS: To investigate the long-term prognostic significance of pre- and post-procedure troponin T (TnT) elevations in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: TnT and CK-MB were measured pre- and post-procedure in 212 patients undergoing PCI. Major adverse events (composite of death, myocardial infarction and revascularization) were ascertained 6 years later. Pre-procedural TnT was a significant independent predictor of time to major events (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.16-2.64) and death or myocardial infarction. Post-procedural TnT elevation above normal was the only independent predictor of the primary end-point at 1 year (HR 2.39, 95% CI 1.09-5.26) but was not significantly related to event-free survival throughout follow-up. Post-PCI elevation of TnT 5x above normal, however, did significantly predict time to events during the entirety of follow-up. By contrast, CK-MB was not an independent predictor in any of the analyses. CONCLUSIONS: Our study confirms the long-term prognostic value of pre-procedural TnT elevation in patients undergoing PCI, and demonstrates the superior predictive ability of a post-procedural increase in TnT 5x normal for long-term adverse events. Whether the prognostic significance of smaller post-procedural TnT elevations extends beyond the intermediate-term awaits further investigation.

One-year clinical outcomes of protected and unprotected left main coronary artery stenting.

AIMS: To evaluate outcomes for left main coronary artery (LMCA) stenting and compare results between protected (left coronary grafted) and unprotected LMCA stenting in the current bare-metal stent era. METHODS: We reviewed outcomes among 142 consecutive patients who underwent protected or unprotected LMCA stenting since 1997. All-cause mortality, myocardial infarction (MI), target-lesion revascularization (TLR), and the combined major adverse clinical event (MACE) rates at one year were computed. RESULTS: Ninety-nine patients (70%) underwent protected and 43 patients (30%) underwent unprotected LMCA stenting. In the unprotected group, 86% were considered poor surgical candidates. Survival at one year was 88% for all patients, TLR 20%, and MACE 32%. At one year, survival was reduced in the unprotected group (72% vs. 95%, P<0.001) and MACE was increased in the unprotected patients (49% vs. 25%, P=0.005). CONCLUSIONS: In the current era, stenting for both protected and unprotected LMCA disease is still associated with high long-term mortality and MACE rates. Stenting for unprotected LMCA disease in a high-risk population should only be considered in the absence of other revascularization options. Further studies are needed to evaluate the role of stenting for unprotected LMCA disease.