Clinical Outcomes In Acute Coronary Syndromes Research Articles

Stress hyperglycemia ratio and long-term clinical outcome in patients with acute coronary syndrome

Abstract Background Stress hyperglycemia is strongly associated with adverse prognosis in patients with acute coronary syndrome (ACS). Recently, the stress hyperglycemia ratio (SHR- relationship between acute/chronic glycemic values) has been proposed as a better measurement of stress hyperglycemia. Studies on SHR and long-term clinical outcome in ACS are limited. This study aimed to clarify the association between SHR and 3-year adverse clinical events in patients with ACS. Methods We analyzed data of 795 patients admitted to our center for ACS who were enrolled in the PRATO-ACS Registry (ClinicalTrials.gov ID: NCT04087200) and underwent laboratory analyses 1 month after the index event. All patients had undergone early invasive strategy and received high intensity statins during hospitalization and at discharge. Patients were stratified in baseline SHR tertiles: < 0.95, ≥ 0.95 to < 1.17 and ≥ 1.17. The primary end point was 3-year all cause death; secondary end points were major adverse clinical events (MACE) including all-cause death, myocardial infarction or congestive heart failure. The association between SHR and outcome measures was evaluated with Cox proportional analysis expressed by hazard ratio (HR) and 95% confidence intervals (CI). Results With increasing SHR, there was a significant progressive increase in mortality (4.2, 8.3, and 11.7% in the 1st, 2nd, and 3rd tertile, respectively, p= 0.006) and MACE (10.6, 14, and 20.8% in the 1st, 2nd, and 3rd tertile, respectively, p=0.004). Multivariable analysis shows that SHR was an independent predictor of 3-year all-cause death (HR 1.65, 95% CI 1.12-2.4; p= 0.012). Subgroup analysis evidenced that the relationship between SHR and mortality was statistically significant only for patients with poor glycemic control at 1 month follow up (HR 3.4, 95% CI 1.14-10.9, p= 0.02 in the 2nd tertile and HR 3.9, 95% CI 1.3-11.8, p= 0.015 in the 3rd tertile). Conclusion Baseline SHR is significantly associated with 3-year all-cause death and MACE in patients with ACS. However, its prognostic impact is much stronger in patients who do not achieve desired glycemic targets at 1 month after the index event. Therefore, insistent attention to glycemic values is mandatory in ACS patients even after discharge.

The impact of circulating IGF-1 and IGFBP-2 on cardiovascular prognosis in patients with acute coronary syndrome.

While insulin-like growth factor 1 (IGF-1) exerts a cardioprotective effect in the setting of atherosclerosis, insulin-like growth factor binding protein 2 (IGFBP-2) is involved in metabolic syndrome. Although IGF-1 and IGFBP-2 are known to be predictors for mortality in patients with heart failure, their use in clinic as prognostic biomarkers for acute coronary syndrome (ACS) requires investigation. We evaluated the relationship between IGF-1 and IGFBP-2 levels at admission and the risk of major adverse cardiovascular events (MACEs) in patients with ACS. A total of 277 ACS patients and 42 healthy controls were included in this prospective cohort study. Plasma samples were obtained and analyzed at admission. Patients were followed for MACEs after hospitalization. Among patients who suffered acute myocardial infarction, plasma levels of IGF-1 and IGFBP-2 were lower and higher, respectively, as compared to healthy controls (both p < 0.05). The mean follow-up period was 5.22 (1.0-6.0) months and MACEs incidence was 22.4% (62 of 277 patients). Kaplan-Meier survival analysis revealed that patients with low IGFBP-2 levels had a greater event-free survival rate than patients with high IGFBP-2 levels (p < 0.001). Multivariate Cox proportional hazards analysis revealed IGFBP-2, but not IGF-1, to be a positive predictor of MACEs (hazard ratio 2.412, 95% CI 1.360-4.277; p = 0.003). Our findings suggest that high IGFBP-2 levels are associated with the development of MACEs following ACS. Moreover, IGFBP-2 is likely an independent predictive marker of clinical outcomes in ACS.

Age prediction from coronary angiography using a deep neural network: Age as a potential label to extract prognosis-related imaging features.

Coronary angiography (CAG) is still considered the reference standard for coronary artery assessment, especially in the treatment of acute coronary syndrome (ACS). Although aging causes changes in coronary arteries, the age-related imaging features on CAG and their prognostic relevance have not been fully characterized. We hypothesized that a deep neural network (DNN) model could be trained to estimate vascular age only using CAG and that this age prediction from CAG could show significant associations with clinical outcomes of ACS. A DNN was trained to estimate vascular age using ten separate frames from each of 5,923 CAG videos from 572 patients. It was then tested on 1,437 CAG videos from 144 patients. Subsequently, 298 ACS patients who underwent percutaneous coronary intervention (PCI) were analysed to assess whether predicted age by DNN was associated with clinical outcomes. Age predicted as a continuous variable showed mean absolute error of 4 years with R squared of 0.72 (r = 0.856). Among the ACS patients stratified by predicted age from CAG images before PCI, major adverse cardiovascular events (MACE) were more frequently observed in the older vascular age group than in the younger vascular age group (p = 0.017). Furthermore, after controlling for actual age, gender, peak creatine kinase, and history of heart failure, the older vascular age group independently suffered from more MACE (hazard ratio 2.14, 95% CI 1.07 to 4.29, p = 0.032). The vascular age estimated based on CAG imaging by DNN showed high predictive value. The age predicted from CAG images by DNN could have significant associations with clinical outcomes in patients with ACS.

Hyperacute postprocedural high platelet reactivity: a novel predictor for in-hospital adverse events in acute coronary syndrome with prasugrel loading

Abstract Introduction Postprocedural High platelet reactivity (HPR) seems to associate long term adverse cardiovascular events, mainly intrastent thrombosis. However, the relationship between hyper-acute postprocedural HPR with prasugrel loading and clinical outcomes in acute coronary syndrome (ACS) is still unclear. Moreover, factors contributing HPR in ACS with prasugrel loading are also unknown. Purpose This study aimed to assess the impact of hyper-acute postprocedural HPR with prasugrel loading on clinical outcomes in ACS during hospitalization, as well as to define appropriate cut-off values and identify contributing factors of HPR. Methods We performed a single-centre, retrospective observational study that enrolled 207 patients who underwent emergent PCI for ACS with prasugrel loading. The P2Y12reaction unit (PRU) value was measured immediately after PCI with the VerifyNow System. The primary endpoint was major adverse cardiac events (MACE, defined as the composite of death, myocardial infarction, stroke, heart failure, ventricular arrhythmia needing defibrillation). Results Mean patient age (standard deviation) was 70.5 (±13.0) years, 78.7% were male, and average time from prasugrel intake to PRU calculation was 98.3 (±49.1) min. During a mean hospital stay of 15.9 (±9.3) days, there were 34 in-hospital MACE (16.4%) and 10 deaths (4.8%). Thrombosis events, didn't stand out and mechanical complications, such as cardiac rupture and cardiac tamponade occupies most of cardiovascular death which occurred before 10 days on admission. PRU was significantly higher in MACE group than Non-MACE group (279±65 vs 227±72, p&amp;lt;0.001 respectively). The ROC curve analysis of PRU for discriminating significant in-hospital MACE showed the cut off value of 293 (sensitivity:52.9%, specificity:83.2% [AUC=0.709, p&amp;lt;0.0001]). 47patients (29.4%) were thus categorized as HPR (PRU&amp;gt;293) immediately after emergent PCI. Kaplan-Meyer curve showed MACE events occurred in HPR group than non-HPR group (38.2% vs 10.0%, p&amp;lt;0.001). Multiple cox analysis demonstrated that HPR was independent predictors of MACE in patients with ACS underwent PCI (OR 5.416, 95% CI 2.157–13.598, p&amp;lt;0.0001). Multiple logistic regression model showed female sex, low haemoglobin value, and large mean platelet volume were independent predictors of HPR. Conclusion PRU was significantly higher in MACE group, and appropriate cut-off value of HPR in this study was 293. HPR was independent predictor of MACE during hospitalization, however thrombosis event was not significant. Evidence of clinical impact with postprocedural HPR within 120 minutes after prasugrel loading is scarce. This study shows post-procedural HPR, even without sufficient time after prasugrel intake, can be a useful predictive marker of adverse events during hospitalization. Funding Acknowledgement Type of funding sources: None. PRU between Non-MACE and MACE groupKaplan-Meyer curve

Post-procedural high platelet reactivity with prasugrel loading predicts in-hospital adverse events in ACS patients

Abstract Background/Introduction High platelet reactivity (HPR) is associated with adverse cardiovascular events, primarily intrastent thrombosis, after a percutaneous coronary intervention (PCI). However, the relationship between hyperacute postprocedural HPR with prasugrel loading and clinical outcomes in acute coronary syndrome (ACS) remains unclear. Moreover, factors contributing to HPR in ACS with prasugrel loading are also unknown. Purpose To assess the effects of post-procedural HPR with prasugrel loading on clinical outcomes in ACS during hospitalization, and to define the appropriate cut-off values and identify factors contributing to HPR. Methods A single-center, retrospective observational study that enrolled 154 patients who underwent emergent PCI for ACS with prasugrel loading was performed. The P2Y12 reaction unit (PRU) value was measured immediately after PCI using the VerifyNowR system. The primary end-point was major adverse cardiac events (MACE, defined as the composite of death, myocardial infarction, stroke, heart failure, ventricular arrhythmia needing defibrillation). Results The mean patient age (standard deviation) was 70.7 (±12.5) years, 76.6% were men, and the average time from the prasugrel intake to PRU calculation was 103.2 (±48.5) min. During the mean hospital stay of 15.6 (±8.5) days, 24 in-hospital MACE (15.5%) and 8 deaths (5.2%) occurred. Thrombosis events, including myocardial infarction recurrence, did not occur (only one case of spontaneous coronary artery dissection was considered as myocardial infarction recurrence). PRU was significantly higher in the MACE group than that in Non-MACE group (287±55 and 232±64, respectively, p&amp;lt;0.001). The ROC curve analysis of PRU for discriminating the significant in-hospital MACE showed the cut-off value of 293 (sensitivity: 62.5%, specificity: 83.1% [AUC=0.756, p&amp;lt;0.0001]). A total of 37 patients (24%) were thus categorized as HPR (PRU&amp;gt;293) immediately after the emergent PCI. Kaplan-Meier curve showing MACE events occurred in the HPR group than that in the non-HPR group (40.5% vs 7.6%, p&amp;lt;0.001). Multiple cox analysis demonstrated that HPR was independent predictors of MACE in patients with ACS who underwent PCI (OR 11.01, 95% CI 2.39–20.2, p&amp;lt;0.0001). Multiple logistic regression model showed old age, female sex, low systolic blood pressure, short prasugrel intake to measure time, and large acute gain were independent predictors of HPR. Conclusion PRU was significantly higher in the MACE group, with an appropriate cut-off value of HPR of 293 in this study. HPR was an independent predictor of MACE during hospitalization; however, thrombosis events were not significant. HPR predictors were old age, female sex, low systolic blood pressure, short prasugrel intake to measure time, and large acute gain. This study shows the post-procedural HPR with prasugrel loading in patients with ACS can be a useful predictive marker of adverse events during hospitalization. Funding Acknowledgement Type of funding source: None

Impact of Platelet Volume on the Clinical Outcomes of Patients with Acute Coronary Syndrome.

Platelets with high hemostatic activity play an important role in the pathophysiology of acute coronary syndrome (ACS), and mean platelet volume (MPV) has been proposed to be an indicator of platelet reactivity. We evaluated the predictive value of MPV and the responsive value of MPV with different antiplatelet agents in association with the clinical outcomes of ACS patients. A total of 1094 patients with ACS and 472 patients without ACS were included. Blood samples were taken at hospital admission, at routine follow-up within one year, and beyond one year. The patients were divided into a "high MPV group" (> 9.0 fl, n = 305), "medium MPV group" (7.9-9.0 fl, n = 517), and "low MPV group" (< 7.9 fl, n = 272). The average follow-up time was 2.4 years, and the endpoints were major adverse cardiovascular events (MACEs) including all-cause mortality, time to recurrent ACS, target vessel re-intervention and stroke. MPV was significantly higher in the patients with ACS than in those without ACS (8.6 ± 1.1 vs. 8.4 ± 1.0 fl, p = 0.007). MPV decreased in the following year (8.38 ± 1.02 fl, p < 0.001) and also beyond one year (8.38 ± 0.94 fl, p < 0.001) after ACS events. The changes in MPV were not significantly different between the patients receiving either clopidogrel or ticagrelor. The high MPV group had more cardiovascular risk factors and more MACEs than the low MPV group (p = 0.017). A higher MPV in patients with ACS was associated with more cardiovascular risk factors and more cardiovascular events during clinical follow-up.

P4634Acute-phase high platelet reactivity with prasugrel loading is correlated with clinical outcomes during hospitalization in acute coronary syndrome

Abstract Background/Introduction Although high platelet reactivity (HPR) seems to be associated with adverse cardiovascular events after percutaneous coronary intervention (PCI), the relationship between post-procedure HPR with prasugrel loading and clinical outcomes in acute coronary syndrome (ACS) is still unclear. Moreover, factors contributing to HPR in ACS with prasugrel loading are also unknown. Purpose This study aimed to assess the impact of post-procedure HPR with prasugrel loading on clinical outcomes in ACS during hospitalization, as well as to define appropriate cut-off values and identify factors contributing to HPR. Methods We performed a single-centre, retrospective observational study that enrolled 132 patients who underwent emergent PCI for ACS with prasugrel loading. The P2Y12 reaction unit (PRU) value was measured immediately after PCI with the VerifyNowR System. The primary endpoint was major adverse cardiac events (MACE, defined as the composite of death, myocardial infarction, stroke, heart failure, ventricular arrhythmia needing defibrillation). Results Mean patient age (standard deviation) was 70.7 (±12.5) years, 76% were male, and average time from prasugrel intake to PRU calculation was 101 (±48.8) min. During a mean hospital stay of 15.4 (±8.0) days, there were 22 (16%) MACE events and 6 (4%) deaths. The post-procedure PRU value was 241±66. HPR was significantly higher in MACE group than non-MACE group [287 (±55) vs 232 (±64), p&lt;0.001]. The ROC curve analysis of PRU for discriminating significant in-hospital MACE showed a cut off value of 293 (sensitivity: 64%, specificity: 84% [AUC=0.764, p&lt;0.0001]). Thus, 33 patients (25%) were found to have HPR (PRU&gt;293) immediately after emergent PCI. Kaplan-Meier curve analysis showed MACE events occurred more frequently in the HPR group than in the non-HPR group (42% vs 8%, log rank p&lt;0.001). Multiple Cox regression analysis showed that peak creatine phosphokinase &gt;3,000 U/L and HPR were independent predictors of MACE in patients with ACS who underwent PCI (OR 4.96, 95% CI 1.86–13.26, p=0.001, and OR 7.52, 95% CI 2.73–20.7, p&lt;0.0001, respectively). HPR was significantly correlated with age, female sex, and reference lumen short diameter (pre-dilation) used in PCI. Conclusion HPR was significantly associated with adverse event during hospitalization in ACS patients. Female patients with large culprit lesion diameter were more likely to have HPR. Appropriate cut-off value of HPR in this study was 293. HPR in early-phase of ACS with prasugrel loading is a useful predictor of adverse events during hospitalization.

Endothelial Cells Strengthening: Improving Functions in Management of Acute Coronary Syndrome (A Double Blind Randomized Interventional Control Trial)

Objective: Endothelial dysfunction/injury is the main reason for Acute Coronary Syndrome (ACS). Current therapy includes antiplatelet, lipid lowering and thrombus removal by drugs/ intervention. Endothelial strengthening in management of ACS is less narrated in literature. This study describes endothelial strengthening and clinical outcome in ACS with Triphala powder, a mixture of Amla (Phyllanthus emblica), Harad (Terminalia chebula), and Behda (Terminalia bellirica). Methods: This is a double blind randomized interventional control trial. 80 cases coming to the emergency department were selected for study, divided into two groups. Group 1 (n=40, control), group 2 (n=40, study). Further subdivided into subgroup 1A and 2A ST-Elevation Myocardial Infarction (STEMI) and subgroup 1B and 2B Unstable Angina (UA). All subgroups were given clopidogrel, aspirin and atorvastatin and subjected to thrombolysis or Coronary Angiography (CAG) according to requirement. In addition study group was given Triphala powder 10 grams in a cup of water. Outcome was observed for relief in chest pain, ECG, Echocardiography changes at 50 minutes; (SSR) Sympathetic Skin Response was done initially. Statistical analysis was done by SPSS 20 software. Results: In intervention subgroups 2A and 2B there was significant relief in chest pain, settling down of ECG changes, and improvement in regional wall motion in echocardiography (p&lt;0.001). There was increased sympathetic activity in all subgroups (spike response in SSR). Conclusion: Sudden mismatch in ATP (Adenosine Triphosphate) supply results in endothelial dysfunction. It occurs primarily due to increase in sympathetic discharge. Endothelial dysfunction results in UA/STEMI. Triphala increases ATP synthesis by increasing mitochondrial capacity to maximum; strengthens endothelium which behaves like normal endothelium and resolves symptoms and signs of ACS.

Effect of age on cardiac output after coronary angioplasty in patients of acute myocardial infarction

Background: Although most of the acute coronary syndrome (ACS) patients are elderly, less data available on the effect of age on outcome after percutaneous coronary interventions (PCI) and major adverse cardiovascular events. In this study, we evaluated the effect of age on clinical outcomes in patients with ACS undergoing PCI because it is a well-known fact that the ages of patients influence clinical outcomes in ACS. Aims and Objectives: The aim of the study was to find out the effect of age on outcome of angioplasty in acute myocardial infarction (AMI) patients. Materials and Methods: It is a cross-sectional, self-control, interventional study. In this study, cardiac output (CO) of 52 patients of AMI was measured by echocardiography before and after angioplasty. CO is calculated with the help of end diastolic volume, end systolic volume, and left ventricular outflow tract diameter. Statistical software IBM SPSS version 16 was used for analysis of data. Results: A negative and statistically significant coefficient of correlation (r = −0.384 and P = 0.005) was found between age of patients and the value of CO after coronary angioplasty. Linear regression analysis was also done taking CO after coronary angioplasty as dependent variable and age of the patient as the independent variable. It can be hypothesized that as the age advances, CO after angioplasty deteriorates. Conclusion: Advancing age is associated with deterioration in outcome after coronary angioplasty in AMI patients.

PROGNOSTIC BLOCK-SCHEME OF CLINICAL OUTCOME OF ACUTE CORONARY SYNDROME INTO Q-MYOCARDIAL INFARCTION. PART I

Aim. T o develop a block-scheme for short-term personified prognosis of clinical outcome of acute coronary syndrome (ACS) into Q-myocardial infarction at prehospital stage. Material and methods. Totally 68 patients included with the diagnosis of ACS. As prognostic factors we used the most informative intervals of concentrations of the markers for subclinical nonspecific inflammation, endothelial dysfunction, cardiospecific changes in the immune system and serum cardiomarkers. For testing of those mentioned we used the hard-phased immunoenzyme assay. The relative risk (RR) with confidence intervals (CI) were calculated, as the absolute risk (AR), diagnostic efficacy (DE) of the methods used related to clinical outcomes of ACS into Q0MI related to the risk factor studied (intervals of markers concentrations). Statistic processing was done with software Statistica 6.0 and Biostat 4.03. Results. Depending on the complex analysis of the results we formulated a blockscheme of short-term personified prognosis of clinical outcome of ACS into Q-MI. The scheme included the most informative intervals of concentrations. Personified shortterm prognosis of clinical outcome of ACS into Q-MI and prehospital stage was related to the concentrations of cardiomarkers: TP-I from 2,2 до 2,7 ng/ml, BNP-32 from 1079 to1270 pg/ml; inflammtion markers : CRP from 20 to 25 mg/L, IL-1β from 0,54 to 1,54 pg/ml and TNF-α from 1,1 to 1,6 pg/ml; endothelial dysfunction markers: NO from 7 to 11 mcM/L, ET from 5 to 6 fM/ml, ММР-9 from 270 to 370 ng/ml and TIMP-1 from 140 to 150 ng/ml; immunomarkers: N P from 20 to 28 nM/ml, AB to KL from 15 to 20 U/ml and in 75% cases there are AB to cardiomyocytes. Patients having these parameters at their admission are in the higher risk group of clinical outcome ACS into Q-MI. Conclusion. In the cases when at admission the parameters of inflammation, endothelial dysfunction, serum cardiomarkers and immunomakrers match with the intervals of concentrations mentioned in the block-scheme, these patients are in the group of higher risk of outcome ACS into Q-MI. This lets even at earlier stage of hospitalization to perform the treatment procedures in accordance with the standards of treatment of the patients with occlusing lesions of coronary arteries, that lead to a large focus of MI.

Thrombocytopenia in Acute Coronary Syndromes: Etiologies and Proposed Management

Thrombocytopenia in acute coronary syndromes (ACS) can arise from a variety of etiologies. Glycoprotein IIb/IIIa receptor antagonists have improved clinical outcomes in ACS, however, profound thrombocytopenia can occur with use of these agents. We present a case of profound thrombocytopenia due to administration of a glycoprotein IIb/IIIa receptor antagonist, eptifibatide, after percutaneous coronary intervention for an inferior ST-elevation myocardial infarction. We review the major causes and suggest an approach for diagnosis and management of thrombocytopenia in ACS.

Association of Hemoglobin Levels With Clinical Outcomes in Acute Coronary Syndromes

In the setting of an acute coronary syndrome (ACS), anemia has the potential to worsen myocardial ischemia; however, data relating anemia to clinical outcomes in ACS remain limited. We examined the association between baseline hemoglobin values and major adverse cardiovascular events through 30 days in 39,922 patients enrolled in clinical trials of ACS. After adjustment for differences in baseline characteristics and index hospitalization treatments, a reverse J-shaped relationship between baseline hemoglobin values and major adverse cardiovascular events was observed. In patients with ST-elevation myocardial infarction, when those with hemoglobin values between 14 and 15 g/dL were used as the reference, cardiovascular mortality increased as hemoglobin levels fell below 14 g/dL, with an adjusted OR of 1.21 (95% CI 1.12 to 1.30, P<0.001) for each 1-g/dL decrement in hemoglobin. At the other end of the range of hemoglobin, patients with hemoglobin values >17 g/dL also had excess mortality (OR 1.79, 95% CI 1.18 to 2.71, P=0.007). In patients with non-ST-elevation ACS, with those with hemoglobin 15 to 16 g/dL used as the reference, the likelihood of cardiovascular death, myocardial infarction, or recurrent ischemia increased as the hemoglobin fell below 11 g/dL, with an adjusted OR of 1.45 (95% CI 1.33 to 1.58, P<0.001) for each 1 g/dL decrement in hemoglobin. Patients with hemoglobin values >16 g/dL also had an increased rate of death or ischemic events (OR 1.31, 95% CI 1.03 to 1.66, P=0.027). Anemia is a powerful and independent predictor of major adverse cardiovascular events in patients across the spectrum of ACS.

Supplement on acute coronary syndromes: introduction.

As a student of therapeutics for acute coronary syndromes (ACS) for more than 20 years, I have been gratified to see the remarkable changes that have benefited patients with these syndromes, which represent the leading cause of death and disability in technologically developed countries. In the course of my career, mortality rates among reperfusion-eligible patients with ST-elevation myocardial infarction (STEMI) have plummeted, and the outcomes of patients with non-ST-elevation (NSTE) myocardial infarction or unstable angina (collectively, NSTE ACS) have improved at an accelerated pace. To a large extent, the visible improvements in patient outcomes reflect the work of the authors of this supplement and the tremendous teamwork of similarly energetic investigators and clinicians around the globe, who take scientific discoveries and translate them into therapies backed by definitive and compelling outcome data, dictating widespread use. The timing of this supplement falls at a fascinating point in the history of therapeutics. Just as we are consolidating dramatic gains in clinical outcomes in ACS, we have an onslaught of new technologies that threaten to outstrip anything we have done before: cell-replacement therapy, mechanical heart replacements, and therapy tailored to the genes and proteins of individual patients. At the same time, we have major societal reminders that the quality of health care delivery can be measured and systematically improved, and early measures show that our pragmatic delivery falls far behind our technological capability. This gap is threatened even further by the crisis over payment for increasingly expensive and effective health care. All of the proposed approaches to therapeutics must be judged by the 6 attributes of quality defined by the Institute of Medicine: effectiveness, safety, timeliness, patient-centricity, efficiency, and equity.1 For patients with STEMI, Topol2 points out that percutaneous coronary intervention (PCI) has triumphed over fibrinolytic therapy, provided that the procedure …

The biology of thrombin in acute coronary syndromes.

Thrombin, a serine protease, is the keystone of the twin processes of hemostasis and thrombosis. Through procoagulant, anticoagulant, and antifibrinolytic mechanisms, thrombin helps maintain vascular integrity in the face of hemorrhage. These same mechanisms, however, allow for the pathologic formation of thrombi in response to endothelial damage, which accompanies the erosion or rupture of atherosclerotic plaques. Alone or incorporated into plaques, thrombi can cause vessel occlusion resulting in acute coronary syndromes (ACS). Inhibiting thrombin can improve clinical outcomes in ACS, as well as in procedures such as percutaneous coronary interventions, which are designed to open the occluded vessels that cause ACS. Such improvements in outcomes with thrombin inhibition reflect the central and multivariate role of thrombin in thrombus formation.

Recent advances in anticoagulant therapy for acute coronary syndromes

Despite major advances in the treatment of acute coronary syndromes (ACS), ischemic heart disease is still the leading cause of death in the industrialized world. Although unfractionated heparin (UFH) has been the anticoagulant of choice in ACS treatments, both low-molecular-weight heparins and direct thrombin inhibitors are at least as effective as UFH in comparative clinical trials. UFH has been linked to a discontinuation rebound in thrombin generation, which is associated with greater ischemic end points than those with the direct thrombin inhibitor hirudin. Furthermore, UFH can increase platelet activation in ACS. This review summarizes the investigation of new molecular approaches to further improve clinical outcomes in ACS. The more recently developed synthetic pentasaccharide Org31540/SR90107A provides potent antithrombotic activity through selective inhibition of Factor Xa by high-affinity binding to antithrombin III. Unlike UFH, the pentasaccharide does not bind platelet factor 4 and is not associated with platelet activation. New approaches to coronary thrombosis prevention/treatment that involve inhibition higher up the extrinsic coagulation pathway have been suggested. In view of its undesirable features, UFH may become obsolete with the advent of newer antithrombotic agents. Applications for the pentasaccharide and other new anticoagulants await results from definitive, large-scale trials.