Non-Q-wave myocardial infarction following thrombolytic therapy: a comparison of outcomes in patients randomized to invasive or conservative post-infarct assessment strategies in the Veterans Affairs non-Q-wave Infarction Strategies In-Hospital (VANQWISH) Trial

OBJECTIVES: We wished to determine the effect of post-infarct management strategy on event rates (death or recurrent nonfatal myocardial infarction [MI]) in patients who evolved non-Q-wave MI (NQMI) following thrombolytic therapy. BACKGROUND: Patients who evolve NQMI following thrombolytic therapy are often considered to be at high risk and are frequently managed with routine early invasive testing despite a lack of data supporting improved outcome. METHODS: The Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) study included 115 patients who evolved NQMI following thrombolytic therapy. We compared the event rates in patients randomized to routine early coronary angiography with those in patients randomized to a conservative strategy of noninvasive functional assessment, with angiography reserved for patients with spontaneous or induced ischemia. RESULTS: During an average follow-up of 23 months, 19 of 58 patients (33%) randomized to the invasive management strategy died or suffered recurrent nonfatal MI, compared with 11 of 57 patients (19%) randomized to the conservative strategy (p = 0.152). Equivalent numbers of patients were subjected to revascularization (percutaneous transluminal coronary angioplasty or coronary artery bypass graft). There were more deaths in the invasive management group than in the conservative management group (11 vs. 2). Excess deaths could not be attributed to periprocedural mortality. CONCLUSIONS: Overall event rates (death or recurrent nonfatal MI) are comparable with conservative and invasive strategies in patients who evolve NQMI following thrombolytic therapy. Mortality rate in patients managed conservatively is low (3.5%), and routine invasive management may be associated with an increased risk of death.     

How should patients with unstable angina and non-ST-segment elevation myocardial infarction be managed? A meta-analysis of randomized trials

PURPOSE: Patients with unstable angina or non-ST-segment elevation myocardial infarction (MI) may be managed with either an "invasive" or "conservative" strategy. It is unclear which of these strategies is superior. METHODS: We identified studies with MEDLINE and EMBASE searches (1966-September 2003) and by reviewing reference lists. Studies were included if they were randomized controlled trials comparing management strategies for patients in the early post-unstable angina/non-ST-segment elevation MI period and had follow-up data for at least 3 months. RESULTS: Seven trials that randomized a total of 9212 patients were included. The pooled odds ratio (OR) for all-cause mortality was 0.96 (95% confidence interval [CI]: 0.72 to 1.27). The occurrence of fatal or nonfatal re-infarction was reduced with an invasive strategy (OR 0.73; 95% CI: 0.61 to 0.88) as was readmission to hospital (OR 0.67; 95% CI: 0.48 to 0.94). The endpoints of nonfatal MI and the composite of death or nonfatal MI showed nonsignificant trends favoring an invasive strategy. Trials that included a higher proportion of patients with ST-segment depression on admission and trials in which a larger proportion of patients underwent revascularization showed a greater magnitude of benefit for an invasive strategy. CONCLUSION: For patients with unstable angina/non-ST-segment elevation MI, an invasive strategy reduces rates of fatal or nonfatal re-infarction and hospital readmission, but not all-cause mortality, when compared with a noninvasive strategy. These results suggest that an invasive management strategy should be considered for all patients with unstable angina/non-ST-segment elevation MI and perhaps in particular those with ST-segment depression.     

Independent prognostic value of C-reactive protein and troponin I in patients with unstable angina or non-Q-wave myocardial infarction.

OBJECTIVES: Elevated concentrations of C-reactive protein (CRP), a non-specific acute phase reactant, and troponin I (TnI), a cardiac-specific marker of myocardial damage, have been found to be associated with a higher risk for cardiac events in patients with an acute coronary syndrome. We evaluated CRP alone and in combination with TnI for predicting the incidence of major cardiac complications within 6 months in patients with unstable angina or non-Q-wave infarction (NQMI). METHODS: CRP and TnI was measured on admission in patients with unstable angina or NQMI, but results were kept blinded. Patients were treated according to a conservative management strategy, and the incidence of major cardiac events within 6 months was assessed. RESULTS: An abnormal CRP (> 5 mg/l) and an abnormal TnI (> 0.4 microgram/l) were more frequent in patients that suffered a major cardiac event (CRP: 93 vs. 35%, P < 0.0001; TnI: 73 vs. 26%, P < 0.001). The incidence of major cardiac events was higher in patients with an abnormal CRP than in patients with a normal CRP, both when TnI was abnormal (42 vs. 4.5%, P = 0.003) and when TnI was normal (11 vs. 0%, P = 0.014). Mean event-free survival was excellent in patients with both a normal CRP and TnI, whereas survival was poorest in patients with both an abnormal CRP and TnI (121 +/- 16 vs. 180 days, P < 0.0001). CONCLUSIONS: An abnormal CRP on admission in patients with unstable angina or NQMI is associated with increased incidence of major cardiac events within 6 months, both in patients with normal and abnormal TnI. CRP and TnI have independent and additive prognostic value in this patient group, and the combination may be useful for early risk stratification.     

Economic consequences of routine coronary angiography in low- and intermediate-risk patients with unstable angina pectoris

In low- and intermediate-risk patients with unstable angina pectoris (UAP) and non-ST-elevation acute myocardial infarction (NSTEAMI), routine early invasive management with coronary angiography does not decrease the risk of death or AMI. The economic consequences of this strategy in low- and intermediate-risk patients are unknown. We applied a risk prediction rule to a multihospital practice database and to the population of the Thrombolysis In Myocardial Ischemia trial, phase IIIB (TIMI 3B), which compared early invasive with conservative therapy for UAP and NSTEAMI. We then analyzed the effect of an early invasive strategy with regard to the composite end point of death, AMI, or rehospitalization for ischemia at rest. A logistic regression model was used to compare outcomes in patients with high versus low or intermediate risk scores. The costs and benefits of early invasive management in low- or intermediate-risk patients were assessed. In the practice database, 56% of patients with UAP and NSTEAMI who had low or intermediate risk scores underwent early cardiac catheterization, although early invasive management of these lower risk patients has not been associated with a reduction in the rate of death or MI. In TIMI 3B, when rehospitalization for ischemia at rest was added to the composite end point, invasive management was superior to conservative management at 42 days (p = 0.005) and at 1 year (p = 0.03). If all low- or intermediate-risk patients randomized to conservative therapy in that trial had been treated instead with an early invasive strategy, an estimated 5.4% of rehospitalizations would have been avoided. Within TIMI 3B, such a routine invasive strategy would have resulted in an additional cost of 2,695,700 US dollars with no effect on death or AMI, but it would have led to 34 fewer rehospitalizations. This expenditure of 79,285 US dollars per hospitalization prevented far exceeds the monetary cost of rehospitalization (14,000 US dollars). Although common in clinical practice, routine early invasive management of low- or intermediate-risk patients with UAP generates substantial health-care costs without a mortality benefit or decrease in the risk of AMI. Unless the incremental benefit in quality of life from prevented rehospitalizations for UAP is judged to be worth the large incremental cost (79,285 US dollars per hospitalization prevented), such a strategy is unlikely to be cost effective.     

Risk stratification in patients with unstable angina and non-ST-elevation myocardial infarction

Opinion statement Risk stratification in acute coronary syndromes is important both for prognosis and for treatment. Consistently, using any of a variety of clinical predictors of risk, patients at highest risk for poor outcomes derive the greatest benefit from aggressive therapy with early coronary angiography, glycoprotein IIb/IIIa antagonists, or low molecular weight heparins. By contrast, patients at low risk may be managed conservatively without long-term impact on their risk of death or myocardial infarction. Several clinical and laboratory parameters have been identified as independent, powerful predictors of poor outcome, helping to distinguish high-risk from low-risk patients. Although not a substitute for astute clinical judgment, risk prediction scores may help clinicians to synthesize the relevant clinical data at presentation into an overall assessment of risk, allowing for cost-effective utilization of therapies that add significant expense and morbidity. With the ever-expanding range of pharmacologic and interventional therapies that impact the treatment of patients with unstable angina and non-ST-elevation myocardial infarction (NSTEMI), risk stratification will become increasingly important in targeting therapies to those who are likely to achieve the most benefit. In this review, we first consider the identifiable components of risk in patients presenting with unstable angina or NSTEMI and then evaluate the emerging information regarding differential response to treatment based on the presence of these risk factors.     

Design and Baseline Characteristics of the Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) Trial

Objectives. The Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) trial was designed to compare outcomes of patients with a non–Q wave myocardial infarction (NQMI) who were randomized prospectively to an early “invasive” strategy versus an early “conservative” strategy. The primary objective was to compare early and late outcomes between the two strategies using a combined trial end point (all-cause mortality or nonfatal infarction) during at least 1 year of follow-up.Background. Because of the widely held view that survivors of NQMI are at high risk for subsequent cardiac events, management of these patients has become more aggressive during the last decade. There is a paucity of data from controlled trials to support such an approach, however.Methods. Appropriate patients with a new NQMI were randomized to an early “invasive” strategy (routine coronary angiography followed by myocardial revascularization, if feasible) versus an early “conservative” strategy (noninvasive, predischarge stress testing with planar thallium scintigraphy and radionuclide ventriculography), where the use of coronary angiography and myocardial revascularization was guided by the development of ischemia (clinical course or results of noninvasive tests, or both).Results. A total of 920 patients were randomized (mean follow-up 23 months, range 12 to 44). The mean patient age was 61 ± 10 years; 97% were male; 38% had ST segment depression at study entry; 30% had an anterior NQMI; 54% were hypertensive; 26% had diabetes requiring insulin; 43% were current smokers; 43% had a previous acute myocardial infarction; and 45% had antecedent angina within 3 weeks of the index NQMI.Conclusions. Baseline characteristics were compatible with a moderate to high risk group of patients with an NQMI.     

Quantitative analysis of the admission electrocardiogram identifies patients with unstable coronary artery disease who benefit the most from early invasive treatment

OBJECTIVES: The aim of the present study was to evaluate whether the effect of an early invasive treatment strategy differed between patients sub-grouped according to their severity of myocardial ischemia, as evaluated by quantitative electrocardiographic (ECG) analysis at the time of presentation. The present study is a sub-study of the previously published Fast Revascularization during InStability in Coronary artery disease trial (FRISC-II). BACKGROUND: An early invasive treatment strategy has been shown to be the preferable treatment for non-ST-segment elevation acute coronary syndromes (ACS). The population of patients with unstable coronary artery disease is heterogeneous regarding both the underlying pathology and prognosis. Early risk stratification is important to select patient subgroups that will benefit the most from a given treatment. METHODS: In 2,201 patients with non-ST-segment elevation ACS, the ischemic burden at hospital admission was determined by quantitative measurements of ST-T-segment deviations on the ECG. The patients were subsequently sub-grouped in tertiles based on the amount of ST-segment deviation. The primary end point for this analysis was death or myocardial infarction (MI) within one year after study inclusion. RESULTS: The invasive treatment strategy produced a reduction of approximately 50% in death or MI among the patients with intermediate or major ST-segment deviation. The findings were independent of age, gender, or troponin T status. The patients with confounding factors precluding ST analysis had a poor outcome regardless of the treatment strategy. CONCLUSIONS: Ischemic burden on the admission ECG identifies patients with ACS who benefit the most from an invasive treatment strategy. When the standard ECG is scrutinized with complete quantitative measurements, it provides independent information on prognosis and benefit of treatment.     

Head-to-head comparison of two different low-molecular-weight heparins in acute coronary syndrome: a single center experience

Low-molecular-weight heparins (LMWH) of different types have yielded different results when used in the setting of unstable angina (UA) or non Q-wave myocardial infarction (NQMI). We compared the safety and therapeutic efficacy of two different LMWHs, namely dalteparin (Dalt.) and enoxaparin (Enox.), in the acute phase (first 5 days) of UA or NQMI. One hundred and forty-two patients with UA/NQMI were randomly assigned to treatment with either Dalt. [120 IU/kg twice daily by subcutaneous (SC) injection] or Enox. [1 mg/kg twice daily by SC injection]. The occurrence of any one of death, myocardial infarction, or angina recurrence within 5 days of the first LMWH injection was the endpoint of the study. There were 69 patients in the Enox. group (53 males, 16 females, mean age: 60.3+/-11.9) and 73 patients in the Dalt. group (54 males, 19 females, mean age: 59.6 +/-10.3). The baseline characteristics of the patients in the two groups were similar. There were no deaths in either group. Myocardial infarction occurred in two patients in the Dalt. group (4%). Angina recurrence was seen in 11 patients in the Enox. group (16%) and in 11 patients in the Dalt. group (15%). Overall, any of the events that made up the endpoint occurred in 11 (16%) and 14 (19%) patients in the Enox. and Dalt. groups, respectively (P>0.05). The time to occurrence of the first event, however, was significantly longer in the Enox. group (82.3+/-33.2 versus 37.6+/-23.4 hours, P=0.007). Thrombocytopenia and allergic reactions were not detected in any patient. Major bleeding was seen in I patient in the Enox. group. Minor bleeding occurred in 17 (25%) and 21 (29%) patients in the Enox. and Dalt. groups, respectively (P>0.05). Enoxaparin and dalteparin were found to be equally safe and effective for the early management of UA/NQMI, but enoxaparin appeared to delay the occurrence of MI or angina recurrence as compared to dalteparin in this setting.     

Acute Coronary Syndromes

Acute coronary syndromes represent a broad spectrum of ischemic myocardial events including unstable angina, non-ST elevation myocardial infarction and acute ST elevation myocardial infarction, which are associated with high morbidity and mortality. They constitute the most frequent cause of hospital admission related to cardiac disease. Early diagnosis and risk stratification are essential for initiation of optimal medical and invasive management. Therapeutic measures comprise aggressive antiplatelet, antithrombotic, and anti-ischemic agents. In addition, patients with high-risk features, notably positive troponin, ST segment changes and diabetes, benefit from an early invasive as compared to a conservative strategy. Importantly, lifestyle interventions, modification of the risk factor profile, and long-term medical treatment are of pivotal importance in reducing the long-term risk of recurrence.     

Stratification scores for risk in the context of acute coronary syndromes

The patients presenting acute coronary syndrome with or without ST segment elevation form a heterogeneous population and thus the short and long-term risk of death or recurrent ischemic events can vary considerably. During ACS without ST elevation (unstable angina and non-ST elevation MI), the evaluation of risk is an essential step in the management of such patients, because it determines ulterior strategy. This evaluation is simple and reliable, and is principally based on three scores: the TIMI, the GRACE Score or the PURSUIT. Thanks to this stratification, high and medium-risk patients are able to benefit from early invasive management (stents and anti-GPIIb/IIIa) as recent studies have clearly shown. Even if immediate management of patients with non-ST elevation ACS does not take account of risk stratification, using such information in the medium and long-term does help determine the prognosis. Finally, the risk profile score, whatever the score used is today an essential tool, which helps qualify and especially compare patients included in international clinical studies.     

High-risk Acute Coronary Syndrome Patients with Non-ST-Elevation Myocardial Infarction: Definition and Treatment

Introduction  Early risk stratification of patients with acute coronary syndromes (ACS), unstable angina, or non-ST-elevation myocardial infarction ensures patients receive appropriate care. Materials and methods  Many risk-stratification models have been developed to identify high-risk ACS patients who would benefit most from an early invasive strategy and to determine patients at greater risk for bleeding complications. Although high-risk patients seem to benefit most from a combination of aggressive antithrombotic and early invasive therapies, stratification for risk of bleeding also helps in the choice and dosing of appropriate medical therapy. Results  The effective use of glycoprotein IIb/IIIa inhibitors, in particular, is dependent on accurate risk assessment, whereas the risk-to-benefit ratio of direct thrombin inhibitors in high-risk versus low-risk patients as part of an initial therapy plan requires clarification. Nevertheless, use of the same anticoagulant throughout the care pathway may reduce the rates of death or recurrent myocardial infarction, and bleeding complications.     

Validated risk stratification model accurately predicts low risk in patients with unstable angina

BACKGROUND: In the mid 1990s, two unstable angina risk prediction models were proposed but neither has been validated on separate population or compared. OBJECTIVES: The purpose of this study was to compare patient outcome among high, medium and low risk unstable angina patients defined by the Agency for Health Care Policy and Research (AHCPR) guideline to similar risk groups defined by a validated model from our institution (RUSH). METHODS: Four hundred sixteen patients consecutively admitted to the hospital with unstable angina between January 1, 1995, and December 31, 1997, were prospectively evaluated for risk factors. The presence of major adverse events such as myocardial infarction (MI), death and heart failure was assessed for each patient by chart review. RESULTS: The composite end point of heart failure, MI or death occurred in 3% and 5% of the RUSH and AHCPR low risk categories, respectively, and in 8% and 10% of AHCPR and RUSH high risk categories, respectively. Recurrent ischemic events were best predicted by the RUSH model (high: 24% vs. medium: 12% and low: 10%, p = 0.029), but not by the AHCPR model (high: 14% vs. medium: 13% and low: 9%, p = 0.876). The RUSH model identified five times more low risk patients than the AHCPR model. CONCLUSIONS: Both models identify patients with low and high event rates of MI, death or heart failure. However, the RUSH model allowed for five times more patients to be candidates for outpatient evaluation (low risk) with a similar observed event rate to the AHCPR model; also, the RUSH model more successfully predicted ischemic complications. We conclude that the RUSH model can be used clinically to identify patients for early noninvasive evaluation, thereby improving cost effectiveness of care.     

Peripheral arterial disease, acute coronary syndromes, and early invasive management: the TACTICS TIMI 18 trial

BACKGROUND: Patients with peripheral arterial disease (PAD) represent a high-risk patient subset in the setting of non-ST-segment elevation acute coronary syndromes (NSTE ACS). The efficacy and safety of early invasive management for such patients remains unclear. Hypothesis: Early invasive management would be well tolerated and effective among patients with NSTE ACS and PAD. METHODS: Patients from the Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction (TACTICS-TIMI) 18 trial were stratified by the presence or absence of PAD and assessed with respect to baseline clinical factors. The outcomes of patients with PAD and NSTE ACS were examined with respect to treatment assignment to either early invasive therapy or conservative treatment of NSTE ACS. Finally, the bleeding and stroke rates of patients with PAD managed invasively were compared with patients with PAD managed conservatively. RESULTS: Of 2219 patients with NSTE ACS overall, 166 (7.5%) had concomitant PAD. Compared with those patients without PAD, those with PAD were older (75 vs. 62 years, p < 0.001) and were more likely to have high-risk clinical features, including prior histories of bypass surgery (39 vs. 20%, p < 0.001) or diabetes mellitus (38 vs. 27%, p = 0.002), and more ST-segment depression on their 12-lead electrocardiogram (43 vs. 29%, p < 0.001). Among such patients, early invasive management was associated with significant reductions in the risk of myocardial infarction (MI) at 30 days (11.4 vs. 2.3%, p = 0.03). At 180 days, compared with early conservative management, early invasive treatment for patients with PAD and NSTE ACS was associated with similar reductions in MI (12.7 vs. 3.5%, p = 0.04), and was also accompanied by significant reductions in risk of death (10.1 vs. 2.3%, p = 0.05). No excess in bleeding or stroke rates was noted among patients with PAD managed invasively. CONCLUSIONS: Among patients with NSTE ACS and a history of PAD, early invasive management is well tolerated and accompanied by significant reductions in morbidity and mortality when compared with a more conservative, ischemia-driven approach.     

TIMI risk score underestimates prognosis in unstable angina/non-ST segment elevation myocardial infarction

OBJECTIVES: To determine the value of the TIMI risk score in the individual risk stratification of patients with unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI). BACKGROUND: TIMI risk score is a validated tool to identify groups of patients at high risk for major cardiac events. Its prognostic value in individual patients with current diagnostic tools and therapy is unknown. METHODS: TIMI risk score was assessed in patients with UA/NSTEMI admitted to six Belgian hospitals and related to clinical outcome at 30 days. RESULTS: Of the 500 patients enrolled, 49.4% were placed in the low TIMI risk group (score = 0-3) and 50.6% in the high-risk group (score = 4-7). Multivariate analysis identified raised cardiac markers and invasive strategy, but not high TIMI risk score as independent predictors of death and new myocardial infarction (MI). Moreover, the incidence of death and MI in the low TIMI risk group with positive cardiac markers was not lower than in the high TIMI risk group with positive markers: 15.1% versus 17.8% (P = 0.7). CONCLUSIONS: TIMI risk score is of limited value for individual risk stratification. The presence of positive cardiac markers (troponin) appears to be a more powerful prognostic marker.     

N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease

OBJECTIVES: We sought to examine whether measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP), in addition to cardiac troponin T (cTnT) and interleukin-6 (IL-6), improve the ability to identify high-risk patients who benefit from an early invasive strategy. BACKGROUND: Biochemical indicators of cardiac performance (e.g., NT-proBNP), inflammation (e.g., IL-6), and myocardial damage (e.g., cTnT) predict mortality in unstable coronary artery disease (UCAD) (i.e., unstable angina or non-ST-segment elevation myocardial infarction [MI]). In these patients, an early invasive treatment strategy improves the outcome. METHODS: Levels of NT-proBNP, cTnT, and IL-6 were measured in 2,019 patients with UCAD randomized to an invasive or non-invasive strategy in the FRagmin and fast revascularization during InStability in Coronary artery disease (FRISC-II) trial. Patients were followed up for two years to determine death and MI. RESULTS: Patients in the third NT-proBNP tertile had a 4.1-fold (95% confidence interval [CI] 2.4 to 7.2) and 3.5-fold (95% CI 1.8 to 6.8) increased mortality in the non-invasive and invasive groups, respectively. An increased NT-proBNP level was independently associated with mortality. In patients with increased levels of both NT-proBNP and IL-6, an early invasive strategy reduced mortality by 7.3% (risk ratio 0.46, 95% CI 0.21 to 1.00). In patients with lower NT-proBNP or IL-6 levels, the mortality was not reduced. Only elevated cTnT was independently associated with future MI and a reduction of MI by means of an invasive strategy. CONCLUSIONS: N-terminal proBNP is independently associated with mortality. The combination of NT-proBNP and IL-6 seems to be a useful tool in the identification of patients with a definite survival benefit from an early invasive strategy. Only cTnT is independently associated with future MI and a reduction of MI by an invasive strategy.     

Clinical significance of early percutaneous coronary intervention in patients with Braunwald III-B type unstable angina pectoris

OBJECTIVES: To assess the efficacy of early invasive strategy for the treatment of Braunwald III-B type unstable angina pectoris. METHODS: This study included 573 consecutive patients of whom 267 underwent percutaneous coronary intervention (PCI) (312 lesions). The patients were divided into two groups, 95 treated with the early invasive strategy of coronary angiography within 24 hr of admission (Group PCI-I) and the remaining 172 treated with the early conservative strategy of coronary angiography 24 hr after admission (Group PCI-C). RESULTS: No significant differences were noted in the baseline characteristics of the two groups except for ST segment elevation on electrocardiography at presentation, which occurred significantly less frequently in Group PCI-C (36.8% vs 8.1%, p < 0.0001). The initial success rate of percutaneous coronary intervention was sufficiently high in both groups (Group PCI-I: 96.9% vs Group PCI-C: 97.7%, NS). Acute myocardial infarction occurred in six patients of Group PCI-C (3.5%) because of the side branch occlusion. There was no in-hospital death or emergent coronary artery bypass grafting. During the 6-month follow-up, there were no significant differences in the death rates (2.1% vs 1.7%), the death or myocardial infarction rates (5.3% vs 5.8%) and the target lesion revascularization ratio (26.0% vs 25.7%) between Group PCI-I and Group PCI-C. CONCLUSIONS: The clinical outcomes of the early invasive strategy for unstable angina pectoris were almost equivalent to those of the early conservative strategy, despite more frequent ST segmental elevation at admission in Group PCI-I. These findings suggest that the early invasive strategy for unstable angina pectoris may be acceptable even in the current Japanese clinical setting without the use of GP IIb/IIIa receptor antagonist, low molecular weight heparin or clopidogrel.     

Update on the management of acute coronary syndromes

At present there is debate as to whether an invasive or a conservative strategy should form the basis of an optimal management strategy for unstable angina/non-Q wave myocardial infarction (UA/NQMI). However, these approaches are complementary, not necessarily mutually exclusive. On the basis of current evidence, all patients should receive optimized medical therapy, with surgical interventions targeted at high-risk patients, to improve both clinical outcomes and cost effectiveness. While standard antithrombotic combinations have improved short-term outcomes, they do not fully eliminate the risk of recurrent ischemic episodes. The recent introduction of direct thrombin inhibitors, platelet fibrinogen receptor antagonists and low-molecular-weight heparins (LMWHs) has offered an opportunity to develop more aggressive antithrombotic regimens. Enoxaparin, an LMWH, has demonstrated improved efficacy compared with standard heparin in both the acute and chronic phases of UA/NQMI, without an increase in major complications caused by bleeding. Further studies are justified to investigate the potential of combined antithrombotic regimens containing enoxaparin as an alternative to heparin in conservative strategies and as adjuncts to interventional procedures. Recommendations for the management of UA/NQMI should be continually reviewed in response to the impact of novel treatment modalities.     

Benefit of early invasive therapy in acute coronary syndromes: a meta-analysis of contemporary randomized clinical trials.

OBJECTIVES: This study sought to systematically determine whether early invasive therapy improves survival and reduces adverse cardiovascular events in the management of non-ST-segment elevation acute coronary syndromes. BACKGROUND: Although early invasive therapy reduces recurrent unstable angina, the magnitude of benefit on other important adverse outcomes is unknown. METHODS: Clinical trials that randomized non-ST-segment elevation acute coronary syndrome patients to early invasive therapy versus a more conservative approach were included for analysis. RESULTS: In all there were 7 trials with 8,375 patients available for analysis. At a mean follow-up of 2 years, the incidence of all-cause mortality was 4.9% in the early invasive group, compared with 6.5% in the conservative group (risk ratio [RR] = 0.75, 95% confidence interval [CI] 0.63 to 0.90, p = 0.001), and at 1 month (RR = 0.82, 95% CI 0.50 to 1.34, p = 0.43). At 2 years of follow-up, the incidence of nonfatal myocardial infarction was 7.6% in the invasive group, versus 9.1% in the conservative group (RR = 0.83, 95% CI 0.72 to 0.96, p = 0.012), and at 1 month (RR = 0.93, 95% CI 0.73 to 1.19, p = 0.57). At a mean of 13 months of follow-up, there was a reduction in rehospitalization for unstable angina (RR = 0.69, 95% CI 0.65 to 0.74, p < 0.0001). CONCLUSIONS: Managing non-ST-segment elevation acute coronary syndromes by early invasive therapy improves long-term survival and reduces late myocardial infarction and rehospitalization for unstable angina.     

Routine Invasive Versus Conservative Management Strategies in Acute Coronary Syndrome: Time for a “Hybrid” Approach

The acute coronary syndrome is most often caused by plaque rupture and can result in a variety of clinical conditions. There are two general strategies (early invasive versus conservative) currently employed in the treatment of unstable angina or non-ST elevation myocardial infarction. Pooled data from recent clinical trials have demonstrated that high-risk patients benefit from a routine or early invasive approach while certain low-risk subgroups have similar outcomes with a conservative approach. Most patients in the USA are treated aggressively given advances in technology and the relative ease of interventional therapy. The routine invasive approach, however, remains controversial and has important limitations that are not well identified in trials. Furthermore, data from trials are difficult to interpret given their relevance to contemporary practice in today’s cost conscious, health care environment. The decision to pursue an invasive or conservative approach should be based upon an individual patient’s risk profile, and the level of medical therapy should be based on the underlying pathophysiology. The best strategy incorporates aggressive anti-atherosclerotic therapy with early risk stratification and invasive therapy when appropriate—the so-called hybrid approach. Identifying plaque rupture helps identify patients that would benefit from potent antiplatelet, antithrombotic, and anti-inflammatory therapies, and further insight into the natural history of coronary artery disease coupled with continued advances in diagnostic and interventional approaches will hopefully help guide long-term primary and secondary management.     

Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes

Antagonists of the platelet fibrinogen receptor glycoprotein IIb/IIIa are potent inhibitors of platelet function and provide marked protection from ischemic events in patients undergoing PCI. These agents are also of benefit in patients with unstable angina or non-ST segment elevation myocardial infarction (MI) and provide a 9% reduction in the combined endpoint of 30-day death or MI. This benefit is most marked in patients undergoing early PCI or those at increased risk due to history of diabetes or elevation of the cardiac marker troponin. Based on these findings, the combined American Heart Association and American College of Cardiology guidelines on the management of unstable angina and non-ST segment elevation MI recommend intravenous GPIIb/IIIa in patients in whom PCI is planned particularly those with elevated troponin or diabetes. The use of these agents is associated with a slight increase in major bleeding and in rare instances thrombocytopenia that usually resolves quickly after therapy is discontinued.