Low molecular weight heparins and coronary artery disease

Coronary artery disease encompasses a wide spectrum of conditions including silent ischemia, exertional angina, unstable angina, and myocardial infarction. Acute coronary syndromes (unstable angina and myocardial infarction) are caused by the rupture of an atherosclerotic plaque, platelet activation, and fibrin deposition resulting in thrombosis. Aspirin and unfractionated heparin (UFH) have traditionally been the treatment of choice in patients with acute coronary syndromes; however, low molecular weight heparins (LMWHs) offer potential advantages over UFH. Available evidence indicates that LMWH is superior to UFH in reducing ischemic events or death in the acute phase of unstable angina or non-Q-wave myocardial infarction. Long-term therapy with lower doses of LMWH may not offer any advantage to aspirin in the prevention of coronary events or death. Major bleeding complications are similar for LMWH and UFH although minor bleeding complications are more common with LMWH, primarily due to injection-site hematomas. Finally, use of LMWH appears to be costeffective compared with UFH. The available evidence supports improved clinical outcomes, favorable safety profile, and cost savings associated with LMWH use in the management of unstable angina and non-Q-wave myocardial infarction and should be favored over UFH.     

Treatment of stable angina.

Severe atherosclerotic narrowing of one or more coronary arteries is responsible for myocardial ischemia and angina pectoris in most patients with stable angina pectoris. The coronary arteries of patients with stable angina also contain many nonobstructive plaques, which are prone to fissures or rupture resulting in presentation of acute coronary syndromes (unstable angina, myocardial infarction, sudden ischemic death). In addition to symptomatic relief of symptoms and an increase in angina-free walking time with antianginal drugs or revascularization procedures, the recent emphasis of treatment has been to reduce adverse clinical outcomes (coronary death and myocardial infarction). The role of smoking cessation, aspirin, treatment of elevated lipids, and treatment of high blood pressure in all patients and of beta-blockers and angiotensin-converting enzyme inhibitors in patients with diminished systolic left ventricular systolic function in reducing adverse outcomes has been well established. What is unknown, however, is whether any anti-anginal drugs (beta-blockers, long-acting nitrates, calcium channel blockers) effect adverse outcomes in patients with stable angina pectoris. Recent trials evaluated the usefulness of suppression of ambulatory ischemia in patients with stable angina pectoris, but it remains to be established whether suppression of ambulatory myocardial ischemia with antianginal agents or revascularization therapy is superior to pharmacologic therapy targeting symptom relief. Patients who have refractory angina despite optimal medical treatment and are not candidates for revascularization procedures may be candidates for newer techniques of transmyocardial revascularization, enhanced external counterpulsation, spinal cord stimulation, or sympathectomy. The usefulness of these techniques, however, needs to be confirmed in large randomized clinical trials.     

Prognostic value of pharmacological stress echocardiography in women with chest pain and unknown coronary artery disease

Objectives. In this study we sought to investigate the prognostic value of pharmacological stress echocardiography in women referred for chest pain, having unknown coronary artery disease.

Background. The noninvasive identification of a high-risk subgroup among women with chest pain and unknown coronary artery disease is an unresolved task to date.

Methods. A total of 456 women (mean [±SD] age 63 ± 10 years) underwent pharmacological stress echocardiography with either dipyridamole (n = 305) or dobutamine (n = 151) for evaluation of chest pain and were followed-up for 32 ± 19 months. None of them had a previous diagnosis of coronary artery disease.

Results. No major complication occurred during stress testing. Five tests (1.1%) were prematurely interrupted because of the appearance of side effects. Echocardiographic positivity was identified in 51 patients. During the follow-up, 23 cardiac events occurred: 3 deaths, 10 infarctions and 10 cases of unstable angina; an additional 21 patients underwent coronary revascularization. At Cox analysis, the echocardiographic evidence of ischemia was found as the only independent predictor of hard cardiac events (death, infarction) (odds ratio [OR] = 27.5; 95% confidence interval [CI] = (6.5 to 115.5; p = 0.0000). When spontaneous cardiac events (death, infarction and unstable angina) were considered as endpoints, the positive echocardiographic result (OR = 23.9; 95% CI = 8.6 to 66.8; p = 0.0000) and family history of coronary artery disease (OR = 3.7; 95% CI = 1.5 to 9.1; p = 0.0037) were independently correlated with prognosis. By using an interactive stepwise procedure, the prognostic value of stress echocardiography was found to be incremental to that provided by clinical variables, both considering hard and spontaneous cardiac events as endpoints. The 3-year survival rate for the negative and the positive population was respectively, 99.5% and 69.5% (p = 0.0000) considering hard cardiac events, 99.2% and 50.6% (p = 0.0000) considering spontaneous cardiac events.

Conclusions. Pharmacological stress echocardiography is safe, highly feasible and effective in risk stratification of women with chest pain and unknown coronary artery disease, also when hard endpoints are considered. Its use can have relevant implications in daily clinical practice for selection of patients needing further investigations.     

Attenuated severity of new acute ischemic events in patients with previous coronary heart disease receiving long-acting nitrates

BACKGROUND: Platelet aggregation and secondary vasoconstriction are key events in the genesis of acute coronary syndromes. HYPOTHESIS: Since nitrates have vasodilatory and antiaggregant effects, treatment with long-acting nitrates at the time of onset of acute coronary syndromes could be associated with attenuation of their severity. METHODS: A consecutive series of 533 patients with acute coronary syndrome and past history of coronary artery disease admitted to the Cardiology Service of a general hospital was studied. A specific questionnaire assessed the use of nitrates and other relevant drugs, as well as other clinical variables. The diagnosis of unstable angina or acute myocardial infarction (MI) was established according to clinical, electrocardiographic, and enzymatic criteria. RESULTS: In the whole cohort, 169 patients had MI and 364 had unstable angina. Previous use of long-acting nitrates was significantly more common in patients with unstable angina (56%) than in those with MI (37%) (p < 0.0001). Multivariate analysis identified being a nonsmoker [odds ratio: 95%, confidence limits (CL) 0.37, 0.23-0.59], previous unstable angina (CL 0.62, 0.41-0.92), use of aspirin (CL 0.58, 0.41-0.92), and use of long-acting nitrates (CL 0.61, 0.40-0.93) as the independent predictors of the development of unstable angina rather than MI; of these the combination of nitrates and aspirin was the strongest predictor. CONCLUSIONS: Long-acting nitrates as well as aspirin are suggested to have a protective or modifying effect on the development of acute coronary syndromes, favoring unstable angina rather than acute MI.     

Akute Koronarsyndrome – ein Update Teil I: Pathogenese und medikamentöse Therapie

BACKGROUND: Unstable angina accounts for more than one million hospital admissions annually. 6-8% of patients with this condition have non-fatal myocardial infarction or die within the first year after diagnosis. Recently, the term "acute coronary syndromes" has been used to describe the spectrum of conditions that includes unstable angina, non-Q-wave myocardial infarction (which generally presents without ST-segment elevation), and Q-wave myocardial infarction (which generally presents with ST-segment elevation). PATHOGENESIS: Disruption of a formed plaque is a complex pathologic process that is central to the initiation of the acute coronary syndromes. Local thrombosis occurring after plaque disruption results from complex interactions among the lipid core, smooth-muscle cells, macrophages, and collagen. TREATMENT: Multiple huge clinical trials confirmed that aspirin reduces the risk of death from cardiac causes and fatal and non-fatal myocardial infarction by about 50-70% in patients presenting with unstable angina. Ticlopidine may be substituted for aspirin in patients with hypersensitivity to aspirin or gastrointestinal intolerance. Clopidogrel acts similarly to ticlopidin but has fewer side effects than ticlopidine and has not been reported to cause neutropenia. High-risk patients with refractory unstable angina and elevated troponin levels may have substantial benefit of glycoptotein (GP) IIb/IIIa inhibition. Current practice guidelines support the use of the combination of unfractionated heparin and aspirin for the treatment of unstable angina. Clinical studies have demonstrated that the incidence of the composite end point of death, myocardial infarction, or recurrent angina was lower with enoxaparin than with unfractionated heparin. Beta-blockers, nitrates, and calcium-channel blockers are useful for antiischemic therapy in patients with acute coronary syndromes.     

Predictors of angina pectoris versus myocardial infarction from the Women's Health Initiative Observational Study

Although risk factors for acute coronary syndromes have been extensively studied, characteristics distinguishing women who will develop unstable angina rather than acute myocardial infarction (MI) are less well understood. This analysis evaluates baseline demographic, physical, and medical characteristics as predictors of angina versus MI in the Women's Health Initiative Observational Study. During a prospective 4.5-year follow-up of 92,152 postmenopausal women, 1,527 hospitalizations for angina and 797 for MI were confirmed by centrally trained physician adjudicators. In a multivariate analysis of women with incident angina or MI, high cholesterol (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.47 to 0.80; p = 0.0004) and prior coronary disease (OR 0.70, 95% CI 0.55 to 0.89; p = 0.004) independently predicted angina (referent), whereas current cigarette smoking (OR 1.60, 95% CI 1.13 to 2.26; p = 0.007) and diabetes mellitus (1.44, 95% CI 1.10 to 1.87; p = 0.007) predicted MI. Older age and hypertension were independently, but less strongly, predictive of MI. Aspirin or statin use, physical activity, body mass index, and educational levels were not independently associated with one or the other type of acute coronary syndrome. Thus, specific risk factors strongly and independently predicted whether women with an acute coronary syndrome would present with angina or with MI.     

Unstable Angina: Good Long-Term Outcome After a Complicated Early Course

Objectives. This study was performed to investigate the long-term outcome of patients with unstable angina within subgroups of the Braunwald classification.

Background. Long-term follow-up studies of patients with unstable angina are rare and date from more than two decades ago. This study was performed to establish the prognosis of different subgroups of patients with unstable angina (Braunwald criteria) during a 7-year follow-up period.

Methods. We registered a well defined group of 417 consecutive patients, admitted to the hospital for suspected unstable angina. The definite diagnosis was unstable angina in 282 patients (68%) and evolving myocardial infarction in 26; in 109 patients (26%), the symptoms were attributed to other or nonspecific causes. Patients with definite unstable angina were subclassified according to the Braunwald classification. Survival, survival without infarction and survival without infarction or intervention were determined for each class.

Results. After a median follow-up period of 94 months, the mortality rate in the first year was 6% and 2% to 3% in the following years. The frequency of revascularization was 47% in the first year, and that for myocardial infarction was 11% in the first year and 1% to 3% thereafter. The Braunwald classification appeared to be appropriate for risk stratification in the first year. However, at 7 years the event rates in all classes were similar. In particular, the Braunwald classification had no long-term impact on mortality or infarction rates. However, patients with acute angina at rest or postinfarction angina and patients with extensive anginal treatment had high intervention rates.

Conclusions. To our knowledge, this study is the first to demonstrate that despite a complicated course during the first year, current management results in good long-term outcome in patients with unstable angina.     

One-year outcome of patients after acute coronary syndromes (from the Canadian Acute Coronary Syndromes Registry)

The objective of this study was to determine the management and outcome of fewer selected patients with an acute coronary syndrome during hospitalization and up to 1 year after discharge. The Canadian Acute Coronary Syndromes Registry was a prospective observational study of patients admitted with suspected acute coronary syndromes. Data on demographic and clinical characteristics, in-hospital treatment, and outcomes were recorded. At 1 year, vital status, medication use, recurrent cardiac events, and procedures were determined by telephone contact. Of the 5,312 patients enrolled, 4,627 had a final diagnosis of acute coronary syndrome, with Q-wave myocardial infarction in 27.7%, non-Q-wave myocardial infarction in 33.2%, and unstable angina pectoris in 39.1%. During hospitalization, coronary angiography and revascularization were performed in 39.6% and 20.3% of patients, respectively. The in-hospital mortality rate was 2.4% overall. At discharge, 87.8%, 76.4%, 56.0%, and 54.8% of patients were prescribed aspirin, β blockers, angiotensin-converting enzyme inhibitors, and lipid-lowering agents, respectively. Unadjusted 1-year mortality rates for hospital survivors were 6.5%, 10%, and 5.4% for those with Q-wave myocardial infarction, non-Q-wave myocardial infarction, and unstable angina pectoris groups, respectively (p <0.0001). This difference in mortality rate remained significant after adjusting for other prognosticators, whereas the use of coronary angiography and revascularization after discharge was similar across patients. At 1 year, fewer patients were maintained on aspirin and β blockers, whereas the use of lipid-lowering therapy increased (all p <0.0001). Despite similar rates of coronary angiography and revascularization after discharge, patients with non-Q-wave myocardial infarction had worse outcomes at 1 year. Moreover, there was a significant opportunity to enhance the discharge and long-term use of evidence-based secondary prevention therapies.     

Unstable angina: Relationship of clinical presentation,coronary artery pathology,and clinical outcome

Patients with unstable angina are heterogeneous with respect to presentation, coronary artery morphology, and clinical outcome. Subclassification of these patients based on clinical history has been proposed as a means of identifying individuals at increased cardiac risk. We applied such a classification system to 129 patients discharged from a coronary care unit with a diagnosis of acute myocardial ischemia. Patients were then assessed for cardiac events (recurrent angina requiring revascularization, myocardial infarction, death) 12 months following hospital discharge. Patients were classified as recent onset unstable angina preinfarction (n = 42), crescendo unstable angina preinfarction (n = 48), and unstable angina postinfarction (n = 39). Within each of these groups, the patients were further subclassified based on the occurrence of angina on effort, at rest, or both. No attempt was made to subset patients taking antiischemic drugs at the time of clinical presentation to the physician. Coronary angiographic pathology (morphology and number of vessels involved) was similar in the subgroups, but coronary artery thrombus was statistically more likely to be found in patients with crescendo rest angina preinfarction or with frequent anginal episodes at rest postinfarction. Mortality was significantly higher for patients with unstable angina postinfarction (7.7%) than preinfarction (1.1%). No statistical differences were noted between the subgroups with respect to the occurrence of myocardial infarction or recurrent unstable angina requiring revascularization. These data suggest that subclassification of unstable angina patients based on clinical characteristics at presentation is not useful to predict subsequent myocardial infarction or recurrent angina requiring revascularization. However, as one might expect, patients with recurrent angina postinfarction have a higher mortality rate than patients with unstable angina preinfarction, and patients with recurrent rest angina, either pre- or postinfarction, are more likely to have intracoronary thrombus than patients with new onset angina or crescendo effort angina; however, the presence of thrombus did not predict a poor clinical outcome.     

Cigarette smoking and acute coronary syndromes: a multinational observational study

PURPOSE: To determine the impact of cigarette smoking on the presentation, treatment, and in-hospital outcomes of patients admitted with the full spectrum of acute coronary syndromes. METHODS: GRACE is a multinational observational registry involving 94 hospitals in 14 countries. This analysis is based on 19,325 patients aged at least 18 years admitted for acute coronary syndromes as a presumptive diagnosis with at least one of the following: electrocardiographic changes consistent with acute coronary syndromes, serial increases in serum biochemical markers of cardiac necrosis, and/or documentation of coronary artery disease. The main outcomes measured were mode of presentation, treatment and in-hospital death in the ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina groups to assess the impact of smoking status. RESULTS: Smokers were more frequently diagnosed with ST-segment elevation myocardial infarction (46.0%) than former smokers (27.4%) and non-smokers (30.2%) (P<0.001). Smokers were mostly men, were younger and more aggressively treated than former smokers and non-smokers across the three acute coronary syndrome groups. Unadjusted in-hospital mortality rates were lower in smokers compared with former smokers and non-smokers in the study population (3.3%, 4.5%, and 6.9%, respectively, P<0.001), and in the ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction groups. However, by multivariate logistic analysis, the adjusted in-hospital mortality rate was similar regardless of smoking status. CONCLUSIONS: There is no survival advantage related to current or prior cigarette smoking in patients admitted with acute coronary syndromes, regardless of presentation. In this large multinational registry, the smokers' paradox does not exist.     

Comparison of one-year outcomes of percutaneous coronary intervention versus coronary artery bypass grafting in patients with unprotected left main coronary artery disease and acute coronary syndromes (from the CUSTOMIZE Registry)

Uncertainty surrounds the optimal revascularization strategy for patients with left main coronary artery disease presenting with acute coronary syndromes (ACSs), and adequately sized specific comparisons of percutaneous and surgical revascularization in this scenario are lacking. The aim of this study was to evaluate the incidence of 1-year major adverse cardiac events (MACEs) in patients with left main coronary artery disease and ACS treated with percutaneous coronary intervention (PCI) and drug-eluting stent implantation or coronary artery bypass grafting (CABG). A total of 583 patients were included. At 1 year, MACEs were significantly higher in patients treated with PCI (n = 222) compared to those treated with CABG (n = 361, 14.4% vs 5.3%, p <0.001), driven by a higher rate of target lesion revascularization (8.1% vs 1.7%, p = 0.001). This finding was consistent after statistical adjustment for MACEs (adjusted hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.2 to 5.9, p = 0.01) and target lesion revascularization (adjusted HR 8.0, 95% CI 2.2 to 28.7, p = 0.001). No statistically significant differences between PCI and CABG were noted for death (adjusted HR 1.1, 95% CI 0.4 to 3.0, p = 0.81) and myocardial infarction (adjusted HR 4.8, 95% CI 0.3 to 68.6, p = 0.25). No interaction between clinical presentation (ST-segment elevation myocardial infarction or unstable angina/non-ST-segment elevation myocardial infarction) and treatment (PCI or CABG) was observed (p for interaction = 0.68). In conclusion, in patients with left main coronary artery disease and ACS, PCI is associated with similar safety compared to CABG but higher risk of MACEs driven by increased risk of repeat revascularization.     

Stable ischemic heart disease in the older adults

Ischemic heart disease (IHD) is caused by atherosclerotic and/or thrombotic obstruction of coronary arteries. Clinical spectrum of IHD expands from asymptomatic atherosclerosis of coronary arteries to acute coronary syndromes (ACS) including unstable angina, acute myocardial infarction (non-ST elevation myocardial infarction and ST elevation myocardial infarction). Stable IHD (SIHD) refers to patients with known or suspected IHD who have no recent or acute changes in their symptomatic status, suggesting no active thrombotic process is underway. These patients include those with i) recent-onset or stable angina or ischemic equivalent symptoms, such as dyspnea or arm pain with exertion; ii) post-ACS stabilized after revascularization or medical therapy; and iii) asymptomatic IHD diagnosed by abnormal stress tests or imaging studies. This review summarizes clinical features and management of SIHD in the older adult. ACS in older adults is not considered in this review.     

Comparison of risk factors in acute myocardial infarction and unstable angina pectoris in patients < or =66 versus >66 years of age

A prospective study was conducted of the differences in clinical characteristics between patients with acute myocardial infarction and those with unstable angina pectoris admitted to hospitals in the South-Osaka district of Japan. Gender and smoking were identified as discriminant risk factors for the incidence of acute myocardial infarction in patients < or =66 years with acute coronary syndromes; however, age alone affected the mode of presentation in older patients.     

Detection of aspirin resistance by PFA-100: prevalence and aspirin compliance in patients with chronic stable angina

Most acute coronary syndromes result from a platelet-rich occlusion of the coronary arteries. Antiplatelet drugs are of proven efficacy in preventing myocardial infarction, unstable angina, and stroke. However, not all patients on aspirin (ASA) benefit. We studied the phenomenon of aspirin resistance with a simple and reliable platelet function analyzer--the PFA-100. Studying 31 patients with unstable angina and 105 controls, we found aspirin resistance in 42% of patients, most of whom were shown to be compliant utilizing concomitant salicylate levels.     

急性冠状动脉综合征中C反应蛋白的临床意义及阿司匹林的作用

为探讨Ｃ反应蛋白与急性冠状动脉综合征的关系及阿司匹林对其的影响,观察４６例急性心肌梗死患者、４０例不稳定性心绞痛虱及４２例稳定性心绞痛患者的Ｃ反应蛋白浓度以及不同剂量的阿司匹林对心肌梗死患者Ｃ反应蛋白浓度的影响。结果发现心肌梗死及不稳定性心绞痛患者的Ｃ反应蛋白浓度较稳定性心绞痛患者显著增高（Ｐ〈０．００１）。小剂量（每天３００ｍｇ）阿司匹林可降低心肌梗死患者的Ｃ反应蛋白浓度（Ｐ〈０．０５）。提示Ｃ反应蛋白浓度可作为评价急性冠状动脉综合征患者预后的一个参考指标。     

Prognostic value of fibrinogen in patients admitted with suspected unstable angina and non-q-wave myocardial infarction

INTRODUCTION AND OBJECTIVE: In recent years, the relation between biological markers of inflammation and prognosis in patients suffering from acute coronary syndromes has been investigated. The aim of this study was to evaluate the association between baseline fibrinogen concentrations and the development of clinical events in patients admitted with suspicion of unstable angina and non-Q-wave myocardial infarction. MATERIAL AND METHOD: Levels of fibrinogen at enrollment were analyzed in 325 consecutive patients with acute coronary syndromes. Fibrinogen values were divided into tertiles and the incidence of clinical events was evaluated at each level. The combination of death and/or myocardial infarction was the main endpoint. RESULTS: Fibrinogen levels were significantly higher in patients who subsequently had myocardial infarction, cardiac death, or both during follow up. The probabilities of death and/or myocardial infarction were 6%, 13%, and 29% (p < 0.0001), respectively, in patients grouped by fibrinogen tertiles (304, 305-374 and 375 mg/dl). Multivariate predictors of combined events were age, previous angina, ST-segment depression in the admission ECG, and fibrinogen into tertiles. The adjusted hazard ratio (95% CI) for patients in the upper tertile was 4.8 (1.6-14; p = 0.004). CONCLUSIONS: High fibrinogen levels were related to a less favorable long-term or short-term outcome in patients admitted for suspicion of unstable angina and non-Q-wave myocardial infarction. This association persists after adjustment for other classical risk factors such as age, prior angina, and ST-segment depression in the ECG.     

Clinical risk stratification correlates with the angiographic extent of coronary artery disease in unstable angina

OBJECTIVES

We sought to determine whether clinical risk stratification correlates with the angiographic extent of coronary artery disease (CAD) in patient with unstable angina.

BACKGROUND

The Agency for Health Care Policy and Research (AHCPR) guidelines stratify patients with unstable angina according to short-term risk of myocardial infarction or death. Whether these guidelines are useful in predicting the extent of CAD is unknown.

METHODS

All residents of Olmsted County, Minnesota, undergoing emergency department evaluation from January 1, 1985 through December 31, 1992 for unstable angina without a history of prior coronary artery bypass grafting, and who underwent early angiography (within seven days of presentation) were classified into low, intermediate and high risk subgroups based on AHCPR criteria.

RESULTS

Seven hundred ninety-five patients underwent early angiography: 159 high risk, 572 intermediate risk and 64 low risk patients. Logistic regression analysis demonstrated that low risk patients had a greater likelihood of normal or mild CAD relative to intermediate risk (odds ratio [OR], 4.67; 95% confidence interval [CI], 2.70–8.06; p < 0.001) and high risk (OR, 11.1; 95% CI, 5.71–22.2; p < 0.001). Significant 1-, 2-, 3-vessel coronary disease or left main coronary disease was more likely in high relative to low risk (OR, 8.09; 95% CI, 4.22–15.5; p < 0.001), intermediate relative to low risk (OR, 4.11; 95% CI, 2.34–7.22; p < 0.001), and high relative to intermediate risk (OR, 1.97; 95% CI, 1.31–2.96; P = 0.0012).

CONCLUSIONS

Among patients with unstable angina undergoing early coronary angiography, risk stratification according to the AHCPR guidelines correlates with the angiographic extent of CAD.     

Antithrombotic therapy in patients with acute coronary syndromes

The potential armamentarium of agents used in the treatment of acute coronary syndromes continues to expand, including such well-tested agents as aspirin, unfractionated heparin, and earlier-generation fibrinolytic agents, and newer agents such as low-molecular-weight heparins, direct thrombin inhibitors, thienopyridines, platelet glycoprotein IIb/IIIa receptor inhibitors, and bolus-administration fibrinolytic agents. Older and newer antithrombotic agents have undergone and continue to undergo intensive clinical investigation in patients with the clinical spectrum of acute coronary syndromes, which includes unstable angina, non-Q-wave (non-ST-segment elevation) myocardial infarction, and ST-segment elevation myocardial infarction. These studies, often conducted on an international scope and involving thousands of patients, provide data allowing practitioners to optimize the care of patients with acute coronary syndromes. In this article, studies of these established and newer agents in the treatment of patients with acute coronary syndromes are reviewed critically and summarized. Recommendations regarding use of antithrombotic agents in patients with acute coronary syndromes are then given.     

Echocardiographic determination of left atrial function and its application for assessment of mitral flow velocity pattern

Forty-three patients presenting with unstable angina or myocardial infarction were randomised double blind to warfarin [target international normalised ratio (INR), 2.0 to 2.5] and aspirin (150 mg) daily or placebo plus aspirin (150 mg) daily. Coronary flow was assessed with the thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC). Coronary artery flow was reduced (higher CTFC) at baseline in culprit arteries (mean +/-SD, 37.1+/-15.4 frames) compared to nonculprit arteries (22.5+/-6.7 frames, P<0.0001). In patients with a patent artery at follow-up, coronary flow was unchanged after ten weeks of warfarin and aspirin (-2.0+/-19.9 frames) or aspirin alone (3.8+/-10.4 frames, P = 0.20). Patients randomised to aspirin alone were more likely to progress to total occlusion [aspirin, 7 of 19 (37%) vs. warfarin and aspirin, 1 of 24 (4%); P = 0.01). Higher baseline culprit artery CTFC was also associated with an increased risk of late occlusion [+10 frames; odds ratio (OR), 1.65; 95% CI, 1.01 to 2.33]. Coronary flow remained impaired ten weeks after presentation with myocardial infarction or unstable angina. Combination warfarin and aspirin therapy did not improve flow in vessels that remained patent but did reduce the risk of progression to occlusion.     

Emerging antithrombotic treatments for acute coronary syndromes

In the last few years the hypothesis of coronary thrombosis, frequently triggered by plaque ulceration or fissuration, has gained wide acceptance as one of the key events in the pathophysiology of acute coronary syndromes. Plaque ulceration may activate both platelets and the coagulation cascade via exposure of a variety of substances, such as von Willebrand factor and tissue factor. It has been demonstrated that aspirin reduces mortality and improves the prognosis of patients with such syndromes. More recently, newer drugs have been identified for the treatment of acute coronary syndromes; in particular, platelet glycoprotein IIb/IIIa inhibitors have been found to be more effective than aspirin in a variety of clinical conditions, such as unstable angina, acute myocardial infarction, and coronary angioplasty. Other drugs with different mechanisms of action will be soon available for large scale clinical trials.