Conservative Strategy-Thrombolysis In Myocardial Infarction Research Articles

Predicting Likelihood for Coronary Artery Bypass Grafting After Non–ST-Elevation Myocardial Infarction: Finding the Best Prediction Model

Up to half of patients with non-ST-elevation myocardial infarction (NSTEMI) do not receive dual antiplatelet therapy before angiography "pretreatment" because of the risk of increased bleeding if coronary artery bypass grafting (CABG) operation is needed. Several models have been published that predict thelikelihood of CABG after NSTEMI, but they have notbeen independently validated. The purpose of this study was to validate these models and improve the best one. We studied patients with NSTEMI who were enrolled in the 24-center Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) registry between 2005 and 2008. Previous CABG prediction models were assessed using c-statistics and calibration assessments to determine the best model. Variables from TRIUMPH likely to be associated with CABG were tested to see whether they could improve the best model's performance. Among 2,473 patients with NSTEMI, 11.8% underwent in-hospital CABG. C-statistics for the Modified Thrombolysis in Myocardial Infarction, Treat Angina With Aggrastat and Determine the Cost of Therapy With an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction 18, Poppe, and Global Risk of Acute Coronary Events (GRACE) models were 0.54, 0.61, 0.61, and 0.62, respectively. The GRACE model showed the best discrimination and calibration. From the TRIUMPH registry, preselected variables were added to the GRACE model but did not significantly improve model discrimination. A GRACE model risk score of less than 9 had high sensitivity (96%), thus making it useful for predicting patients with NSTEMI who were at low risk for requiring CABG, which included approximately 21% of patients with NSTEMI. This study could not improve on the GRACE model, which had the best predictive value for identifying a need for CABG after NSTEMI with a broader range of predicted risk levels and high sensitivity, especially in patients with scores lower than 9.

Should We Manage Patients With Non-ST Segment Elevation Myocardial Infarction With Renal Failure With an Invasive Strategy?

Szummer and colleagues raise an important question: Should we manage patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) with an early invasive strategy?1 It makes good sense to do this. We know that patients with renal dysfunction are at high risk,2 and the American College of Cardiology/American Heart Association and European Society of Cardiology guidelines both recommend an early invasive strategy for patients with unstable angina/NSTEMI who are high risk.3,4 Neither guideline, however, specifically notes that renal dysfunction should be a specific indication for an invasive strategy. Article see p 851 The investigators analyzed 23262 consecutive NSTEMI patients who had been included in a nationwide coronary care unit registry between 2003 and 2006 called the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART).1 Patients were divided into medically or invasively treated if revascularized within 14 days of admission. They found that for patients with worse renal function, the rate of performing revascularization was lower. This “risk paradox” has been seen in other registries, in which higher-risk patients are actually managed less intensively.5 They also found that 1-year mortality was substantially higher for those on dialysis or having an estimated glomerular filtration rate (GFR) <15 mL/min (≈55%) versus ≈40% for those with estimated GFR 15 to 29 mL/min and <5% for those with normal renal function. Thus, estimated GFR is clearly an important risk marker. They went on to compare mortality between medically managed patients and those who had revascularization and found overall a difference in mortality, with 36% lower adjusted mortality among those who had revascularization. They then split out the group by baseline renal function and found a lower mortality for those who had been revascularized versus not in most groups but not …

Benchmarks for the Assessment of Novel Cardiovascular Biomarkers

The investigation of novel circulating serum and plasma biomarkers in patients with cardiovascular disease has been accelerating at a remarkable pace. For example, a Medline search that uses the terms “biomarkers” and “acute coronary syndromes” (ACS) reveals an approximate tripling in the number of published reports during the 2-year interval from 2003 to 2004 compared with the period from 2001 to 2002, and this number more than doubled from 2005 to 2006. Although this expanding body of research has established firm evidence for the value of biomarkers, such as for diagnosis and risk assessment among patients with suspected ACS,1 it has also deluged the clinical and research communities with candidate biomarkers, very few of which are likely to survive the test of time as useful clinical tools.2,3 It is thus increasingly important for researchers, manufacturers, regulators, and clinicians to critically appraise the value of new biomarkers as they emerge as candidates for further investigation and possible clinical application. The superb report by Wollert and colleagues4 in the present issue of Circulation on growth differentiation factor-15 (GDF-15) as a biomarker for prognostic assessment in ACS provides an opportunity to outline a basic set of benchmarks against which new markers can be evaluated. Article p 962 Assessment of the clinical potential of a novel biomarker5 may be structured around 3 fundamental questions (Figure): (1) Can the clinician measure it? (2) Does it add new information? (3) Does it help the clinician to manage patients? A, Criteria for assessment of novel cardiovascular biomarkers for clinical use. Statements in bold font are given the highest priority. B, Clinical applications of cardiovascular biomarkers. To be clinically useful, analytical methods must be available that allow reliable measurement, optimally with capability for high throughput tests, prompt turnaround time, and reasonable cost. Evaluation of …

Early Invasive Strategy Improves Outcomes in Patients With Acute Coronary Syndrome With Previous Coronary Artery Bypass Graft Surgery

Patients with previous coronary artery bypass graft surgery (CABG) have been classified as a high-risk subset of patients who experience non-ST elevation acute coronary syndrome (ACS). Recent studies suggest that an early invasive strategy is beneficial in moderate- and high-risk patients with non-ST elevation ACS. We hypothesized that an early invasive strategy is associated with improved outcomes in patients with non-ST elevation ACS with prior CABG. In the Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction 18 trial (TACTICS-TIMI 18), 2220 patients with non-ST segment elevation ACS were randomized to an early invasive or conservative (selectively invasive) strategy. All patients were treated with aspirin, heparin, and tirofiban. Four hundred eighty-four (22%) of these patients had undergone CABG before enrollment. We analyzed whether patients with previous CABG had different 6-month outcomes and whether an early invasive strategy was associated with an improvement in long-term outcomes. Prior CABG was associated with a higher risk of adverse outcomes by 6 months, including a higher rate of readmission for ACS (17.4% vs 11.0%, P < 0.001) and a higher incidence of the composite end point of death, myocardial infarction, or rehospitalization for ACS (22.3% vs 16.4%, P = 0.002). There was a trend toward a higher incidence of myocardial infarction (7.1% vs 5.3%, P = 0.051). An early invasive strategy was associated with a reduction in the composite of death or myocardial infarction (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.31-1.0; P = 0.089) and a significant reduction in the incidence of myocardial infarction at 6 months (OR, 0.44; 95% CI, 0.21-0.93; P=0.032). Patients with non-ST segment elevation ACS who have had previous CABG are a high-risk subset. An early invasive strategy reduces risk of myocardial infarction in this high-risk group.

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

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. Early invasive management would be well tolerated and effective among patients with NSTE ACS and PAD. 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. 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. 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.

Prognostic implications of elevated troponin in patients with suspected acute coronary syndrome but no critical epicardial coronary disease: A TACTICS-TIMI-18 substudy

The purpose of this study is to determine whether there is clinical significance to elevated troponin I in patients with suspected acute coronary syndromes (ACS) with non-critical angiographic coronary stenosis.Elevation of troponin in patients admitted with ACS symptoms with non-critical coronary artery disease (CAD) may result from coronary atherothrombosis not evident using standard angiography or from other ischemic and non-ischemic causes that may confer increased risk for future events.Patients with ACS enrolled in the Treat Angina With Aggrastat and Determine Cost of Therapy With Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction (TACTICS-TIMI)-18 were included. Of 2,220 patients enrolled in the trial, 895 were eligible. Patients were divided into four groups according to troponin status on admission and presence of significant angiographic stenosis. Baseline brain natriuretic peptide (BNP) and C-reactive protein (CRP) were obtained on all patients.The median troponin I levels were 0.71 ng/ml in patients with CAD compared with 0.02 ng/ml in patients without CAD (p <0.0001). Troponin-positive patients with or without angiographic CAD had higher CRP and BNP levels compared with troponin-negative patients (p <0.01 for both). The rates of death or reinfarction at six months were 0% in troponin-negative patients with no CAD, 3.1% in troponin-positive patients with no CAD, 5.8% in troponin-negative patients with CAD, and 8.6% in troponin-positive patients with CAD (p=0.012).Elevated troponin in ACS is associated with a higher risk for death or reinfarction, even among patients who do not have significant angiographic CAD. The mechanisms conferring this adverse prognosis merit further study.

The Effect of Routine, Early Invasive Management on Outcome for Elderly Patients with Non–ST-Segment Elevation Acute Coronary Syndromes

Although increasing age is an important risk factor for adverse outcome among patients with acute coronary syndromes, elderly patients are more often managed conservatively. To examine outcome according to age and management strategy for patients with unstable angina and non-ST-segment elevation myocardial infarction (MI). Randomized, controlled trial conducted from December 1997 to June 2000. 169 community and tertiary care hospitals in 9 countries. 2220 patients hospitalized with unstable angina and non-ST-segment elevation MI who were randomly assigned to an early invasive or conservative management strategy. Medical therapy and coronary angiography at 4 to 48 hours versus medical therapy and predischarge exercise testing. Rates of 30-day and 6-month mortality, nonfatal MI, rehospitalization, stroke, and hemorrhagic complications. Among patients 65 years of age and older, the early invasive strategy compared with the conservative strategy yielded an absolute reduction of 4.8 percentage points (8.8% vs. 13.6%; P = 0.018) and a relative reduction of 39% in death or MI at 6 months. Outcomes of the 2 strategies were similar, however, among patients younger than 65 years of age (6.1% vs. 6.5%; P > 0.2). Among patients older than 75 years of age, the early invasive strategy conferred an absolute reduction of 10.8 percentage points (10.8% vs. 21.6%; P = 0.016) and a relative reduction of 56% in death or MI at 6 months. The additional cost per death or MI prevented with the early invasive strategy was lower for elderly patients, but major bleeding rates were higher with this strategy in patients older than 75 years of age (16.6% vs. 6.5%; P = 0.009). Because this study involved patients in the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction (TACTICS-TIMI) 18 trial, its generalizability to elderly patients with excluded comorbid conditions is unknown. Despite an increased risk for major bleeding in patients older than 75 years of age, a routine early invasive strategy can significantly improve ischemic outcomes in elderly patients with unstable angina and non-ST-segment elevation MI.

Association between duration of tirofiban therapy before percutaneous intervention and tissue level perfusion (a TACTICS-TIMI 18 substudy)

In the setting of acute coronary syndromes, thrombotic embolization and activation of platelets with release of vasoconstrictors into the downstream microvasculature may occur before cardiac catheterization. In the Treat Angina with tirofiban and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction 18 (TACTICS-TIMI 18) trial angiographic substudy, a shorter duration of tirofiban infusion before percutaneous coronary intervention was associated with impaired myocardial perfusion before and after intervention.

Validated risk score predicts the development of congestive heart failure after presentation with unstable angina or non-ST–elevation myocardial infarction: results from OPUS-TIMI 16 and TACTICS-TIMI 18

Background Few data are available about development of congestive heart failure (CHF) in patients with unstable angina/non-ST–elevation myocardial infarction (UA/NSTEMI). We developed and validated a risk score to predict which patients will develop CHF. Methods A subset of 4681 patients from the Orbofiban in Patients With Unstable Coronary Syndromes-Thrombolysis in Myocardial Infarction (OPUS-TIMI 16) trial with UA/NSTEMI and without a history of CHF were included in this analysis and stratified according to the development of CHF at 10 months. A risk score was created from significant variables and validated in the Treat Angina With Aggrastat and Determine Cost of Therapy With an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction (TACTICS-TIMI 18) trial. B-type natriuretic peptide (BNP) was then added to the initial multivariate analysis and validated in the TACTICS-TIMI 18 trial. Results The incidence of CHF at 30 days was 4.9%, and at 10 months it was 5.6%. Significant variables on multivariate analysis included age >65 years, heart rate >100 beats/min, history of diabetes mellitus, lateral electrocardiographic changes, and history of angiographically confirmed coronary artery disease. The risk of CHF increased 10-fold across the number of risk factors ( P < .001). When validated in the TACTICS-TIMI 18 trial, the risk score was significantly associated with CHF at 6 months ( P = .01). The median BNP value doubled across the number of risk factors ( P <.001 for trend). The addition of BNP to the risk score improved its discriminatory capacity. Conclusions In patients with UA/NSTEMI, a simple clinical risk score can aid in assessing the risk of developing CHF. BNP adds to the predictive capacity of this risk score. This score may assist in identifying patients who warrant more careful monitoring and therapy for CHF prevention inhospital and during follow-up.

Relationship between baseline white blood cell count and degree of coronary artery disease and mortality in patients with acute coronary syndromes. A TACTICS-TIMI 18 substudy

Abstract Objectives This study was designed to determine the relationship between baseline white blood cell (WBC) count and angiographic and clinical outcomes in patients with unstable angina (UA)/non–ST-segment elevation myocardial infarction (NSTEMI) and to see if WBC count was a significant predictor of outcomes independent of other biomarkers. Background Inflammation has been shown to play a role in atherosclerosis and acute coronary syndromes. Methods We evaluated the relationship between baseline WBC count, other baseline variables and biomarkers, angiographic findings, and clinical outcomes in 2,208 patients in the Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction 18 (TACTICS-TIMI 18) trial. Results Higher baseline WBC counts were associated with lower Thrombolysis In Myocardial Infarction (TIMI) flow grades (p = 0.0045) and TIMI myocardial perfusion grades (p = 0.03) as well as a greater extent of coronary artery disease (CAD) (p Conclusions In patients with UA/NSTEMI, elevations in a simple, widely available blood test, the WBC count, were associated with impaired epicardial and myocardial perfusion, more extensive CAD, and higher six-month mortality. After adjustment for traditional risk factors and other biomarkers, assessment of two inflammatory markers, WBC count and CRP, can be used to stratify patients across an eightfold gradation of six-month mortality risk.

Relationship between baseline white blood cell count and degree of coronary artery disease and mortality in patients with acute coronary syndromes: A TACTICS-TIMI 18 substudy

ObjectivesThis study was designed to determine the relationship between baseline white blood cell (WBC) count and angiographic and clinical outcomes in patients with unstable angina (UA)/non–ST-segment elevation myocardial infarction (NSTEMI) and to see if WBC count was a significant predictor of outcomes independent of other biomarkers. BackgroundInflammation has been shown to play a role in atherosclerosis and acute coronary syndromes. MethodsWe evaluated the relationship between baseline WBC count, other baseline variables and biomarkers, angiographic findings, and clinical outcomes in 2,208 patients in the Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction 18 (TACTICS-TIMI 18) trial. ResultsHigher baseline WBC counts were associated with lower Thrombolysis In Myocardial Infarction (TIMI) flow grades (p = 0.0045) and TIMI myocardial perfusion grades (p = 0.03) as well as a greater extent of coronary artery disease (CAD) (p < 0.0001). A higher baseline WBC count was predictive of higher six-month mortality, ranging from 1.5% to 3.6% to 5.1% for patients with low, intermediate, and high WBC counts, respectively (p = 0.0017). In a multivariable proportional hazards model, patients with a low C-reactive protein (CRP) but an elevated WBC remained at significantly higher risk of death at six months (hazard ratio [HR] 4.3, p = 0.049), and patients with a high CRP were at even higher risk (HR 8.6, p = 0.004). ConclusionsIn patients with UA/NSTEMI, elevations in a simple, widely available blood test, the WBC count, were associated with impaired epicardial and myocardial perfusion, more extensive CAD, and higher six-month mortality. After adjustment for traditional risk factors and other biomarkers, assessment of two inflammatory markers, WBC count and CRP, can be used to stratify patients across an eightfold gradation of six-month mortality risk.

Efficacy and safety of multivessel percutaneous revascularization and tirofiban therapy in patients with acute coronary syndromes

For patients with acute coronary syndromes (ACS) without persistent ST-segment elevation, the strategy of early coronary angiography and appropriate revascularization has been demonstrated to be superior to conservative medical management with selective coronary angiography and revascularization. 1 FRagmin and Fast Revascularisation during InStability in Coronary artery disease InvestigatorsInvasive compared with non-invasive treatment in unstable coronary- artery disease FRISC II prospective randomised multicentre study. Lancet. 1999; 354: 708-715 Abstract Full Text Full Text PDF PubMed Scopus (1254) Google Scholar , 2 Cannon C.P. Weintraub W.S. Demopoulos L.A. Vicari R. Frey M.J. Lakkis N. Neumann F.J. Robertson D.H. DeLucca P.T. DiBattiste P.M. Gibson C.M. Braunwald E. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med. 2001; 344: 1879-1887 Crossref PubMed Scopus (1895) Google Scholar This benefit has been most evident in patients with high-risk characteristics. 2 Cannon C.P. Weintraub W.S. Demopoulos L.A. Vicari R. Frey M.J. Lakkis N. Neumann F.J. Robertson D.H. DeLucca P.T. DiBattiste P.M. Gibson C.M. Braunwald E. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med. 2001; 344: 1879-1887 Crossref PubMed Scopus (1895) Google Scholar Nevertheless, early percutaneous coronary intervention (PCI) has been historically associated with a higher rate of complications 3 Bourassa M.G. Yeh W. Holubkov R. Sopko G. Detre K.M. Long-term outcome of patients with incomplete vs complete revascularization after multivessel PTCA. A report from the NHLBI PTCA Registry. Eur Heart J. 1998; 19: 103-111 Crossref PubMed Scopus (74) Google Scholar that are probably related to platelet-mediated flow abnormalities, which are present even in the nonculprit vessel in patients with ACS. 4 Gibson C.M. Ryan K.A. Murphy S.A. Mesley R. Marble S.J. Giugliano R.P. Cannon C.P. Antman E.M. Braunwald E. Impaired coronary blood flow in nonculprit arteries in the setting of acute myocardial infarction. The TIMI Study Group. Thrombolysis In Myocardial Infarction. J Am Coll Cardiol. 1999; 34: 974-982 Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar It is not known whether systematic, upstream treatment with tirofiban can attenuate the excessive risk of PCI in the setting of ACS and permit safe multivessel revascularization. We compared the in-hospital and 6-month outcome of patients who underwent single-vessel (SV) or multivessel (MV) PCI in the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction 18 (TACTICS-TIMI 18) trial.