Worse blood pressure control in patients with cerebrovascular or peripheral arterial disease compared with coronary artery disease.

OBJECTIVES: Poor blood pressure (BP) control is common amongst patients with symptomatic atherothrombotic disease. It is unclear whether BP control and management differ across atherothrombotic disease subtypes. METHODS: We analysed the baseline data of 44,984 patients with documented coronary artery disease (CAD) only (n = 30,414), cerebrovascular disease (CVD) only (n = 11,359) and peripheral arterial disease (PAD) only (n = 3211) from the international REduction of Atherothrombosis for Continued Health Registry and investigated the impact of atherothrombotic disease subtype on BP control and use of antihypertensive drugs. RESULTS: The proportion of patients with BP controlled (<140/90 mmHg) was higher in CAD (58.1%) than in CVD (44.8%) or PAD (38.9%) patients (P < 0.001). Amongst patients with treated hypertension, CAD patients were more likely to have BP controlled than were CVD patients [odds ratio (OR) = 1.67; 95% confidence interval (CI) = 1.59-1.75] or PAD (OR = 2.30; 95% CI = 2.10-2.52). These differences were smaller in women than in men and decreased with age. Amongst treated patients, CAD patients were more likely to receive > or =3-drug combination therapies than were CVD (OR = 1.73; 95% CI = 1.64-1.83) or PAD (OR = 1.64; 95% CI = 1.49-1.80) patients. Adjustment for age, gender, waist obesity, diabetes, education level and world region did not alter the results. CONCLUSIONS: Coronary artery disease patients are more likely than CVD or PAD patients to have BP controlled and to receive antihypertensive drugs, particularly combination therapies. Promotion of more effective BP control through combination antihypertensive therapies could improve secondary prevention and therefore prevent complications in CVD and PAD patients.

Long-term results after the glycoprotein IIb/IIIa inhibitor abciximab in unstable angina: one-year survival in the GUSTO IV-ACS (Global Use of Strategies To Open Occluded Coronary Arteries IV--Acute Coronary Syndrome) Trial.

BACKGROUND: This study was designed to investigate long-term effects of the glycoprotein IIb/IIIa inhibitor abciximab in patients with acute coronary syndrome without ST elevation who were not scheduled for coronary intervention. METHODS AND RESULTS: A total of 7800 patients were included with an acute coronary syndrome without ST elevation, documented by either elevated cardiac troponin or transient or persistent ST-segment depression. They were randomized to abciximab bolus and 24-hour infusion, abciximab bolus and 48-hour infusion, or matching placebo. The overall 1-year mortality rate was 8.3% (649 patients). One-year mortality was 7.8% in the placebo group and 8.2% in the 24-hour and 9.0% in the 48-hour abciximab infusion group. Compared with placebo, the hazard ratio for the 24-hour infusion of abciximab was 1.1 (95% CI 0.86 to 1.29), and for the 48-hour infusion, it was 1.2 (95% CI 0.95 to 1.41). The lack of benefit of abciximab was observed in every subgroup studied. Patients with negative troponin or elevated C-reactive protein had a higher mortality rate after treatment with abciximab for 48 hours than with placebo: 8.5% versus 5.8% in those with negative troponin (P=0.02), 16.3% versus 12.1% in those with elevated C-reactive protein (P=0.04). CONCLUSIONS: Compared with placebo, abciximab did not provide any survival benefit at 1 year in patients admitted with an acute coronary syndrome with ST depression and/or elevated troponin who were not scheduled to undergo early coronary revascularization. In subgroups of patients, in particular those with low cardiac troponin or elevated C-reactive protein, abciximab was associated with excess mortality.

Bedside multimarker testing for risk stratification in chest pain units: The chest pain evaluation by creatine kinase-MB, myoglobin, and troponin I (CHECKMATE) study.

BACKGROUND: Earlier, rapid evaluation in chest pain units may make patient care more efficient. A multimarker strategy (MMS) testing for several markers of myocardial necrosis with different time-to-positivity profiles also may offer clinical advantages. METHODS AND RESULTS: We prospectively compared bedside quantitative multimarker testing versus local laboratory results (LL) in 1005 patients in 6 chest pain units. Myoglobin, creatine kinase-MB, and troponin I were measured at 0, 3, 6, 9 to 12, and 16 to 24 hours after admission. Two MMS were defined: MMS-1 (all 3 markers) and MMS-2 (creatine kinase-MB and troponin I only). The primary assessment was to relate marker status with 30-day death or infarction. More patients were positive by 24 hours with MMS than with LL (MMS-1, 23.9%; MMS-2, 18.8%; LL, 8.8%; P=0.001, all comparisons), and they became positive sooner with MMS-1 (2.5 hours, P=0.023 versus LL) versus MMS-2 (2.8 hours, P=0.026 versus LL) or LL (3.4 hours). The relation between baseline MMS status and 30-day death or infarction was stronger (MMS-1: positive, 18.8% event rate versus negative, 3.0%, P=0.001; MMS-2: 21.9% versus 3.2%, P=0.001) than that for LL (13.6% versus 5.5%, P=0.038). MMS-1 discriminated 30-day death better (positive, 2.0% versus negative, 0.0%, P=0.007) than MMS-2 (positive, 1.8% versus negative, 0.2%; P=0.055) or LL (positive, 0.0% versus negative, 0.5%; P=1.000). CONCLUSIONS: Rapid multimarker analysis identifies positive patients earlier and provides better risk stratification for mortality than a local laboratory-based, single-marker approach.

Early reinfarction after fibrinolysis: experience from the global utilization of streptokinase and tissue plasminogen activator (alteplase) for occluded coronary arteries (GUSTO I) and global use of strategies to open occluded coronary arteries (GUSTO III) trials.

BACKGROUND: Trials report a 2% to 6% incidence of reinfarction after fibrinolysis for acute myocardial infarction (MI). We combined the Global Utilization of Streptokinase and Tissue plasminogen activator (alteplase) for Occluded coronary arteries (GUSTO I) and Global Use of Strategies To Open occluded coronary arteries (GUSTO III) populations to better define frequency, timing, and clinical predictors of in-hospital reinfarction. METHODS AND RESULTS: In 55 911 patients with ST-segment elevation myocardial infarction (MI) who were receiving fibrinolysis, we compared baseline characteristics and mortality rate by reinfarction incidence and developed multivariable logistic regression models to predict in-hospital reinfarction and composite of death or reinfarction. Reinfarction occurred in 2258 patients (4.3%) a median of 3.8 days after fibrinolysis; rates did not differ between GUSTO I (4.0%) and GUSTO III (4.2%) or by fibrinolytic assignment (streptokinase, 4.1%; alteplase, 4.3%; reteplase, 4.5%; combined streptokinase and alteplase, 4.4%; P=0.55). Advanced age, shorter time to fibrinolysis, non-US enrollment, nonsmoking status, prior MI or angina, female sex, anterior MI, and lower systolic blood pressure were associated significantly with reinfarction. Patients with reinfarction had higher mortality at 30 days (11.3% versus 3.5% without reinfarction; odds ratio, 3.5; P<0.001) and from 30 days to 1 year (4.7% versus 3.2%; hazard ratio, 1.5; P<0.001). Significant multivariate predictors of in-hospital death or reinfarction included age, Killip class, systolic and diastolic blood pressures, heart rate, anterior MI, smoking status, prior MI, sex, and country of enrollment (all P<0.001). CONCLUSIONS: Reinfarction occurs infrequently after fibrinolysis but confers increased risk of 30-day and 1-year mortality. Some predictors of reinfarction differ from known predictors of death after MI. Improved treatment and prevention strategies for reinfarction deserve study.

Benefit of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes and troponin t-positive status: the paragon-B troponin T substudy.

BACKGROUND: Troponin T (TnT) is valuable for short- and long-term risk stratification of patients with acute coronary syndromes (ACS). It also may predict which ACS patients will benefit from glycoprotein (GP) IIb/IIIa blockade. METHODS AND RESULTS: We prospectively studied 1160 patients with non-ST-segment elevation ACS randomized in PARAGON-B to receive lamifiban, an intravenous GP IIb/IIIa antagonist, or placebo. TnT levels were obtained before study treatment began and 24 to 72 hours later; assays were performed by a blinded core laboratory. At baseline, 40.2% of patients were TnT-positive (>/=0.1 ng/mL); these patients were older and more often male or smokers. Patients positive at baseline had a significantly higher rate of the primary end point (composite of death, myocardial [re]infarction, or severe recurrent ischemia at 30 days; odds ratio, 1.5; 95% CI, 1.1 to 2.1) than those who were TnT-negative. Lamifiban was associated with significant reduction in the primary end point (from 19.4% to 11.0%, P=0.01) among TnT-positive patients but not among TnT-negative patients (11.2% for placebo versus 10.8% for lamifiban, P=0.86; P=0.08 for test of interaction between TnT status and treatment assignment). This pattern held for the end points of death alone and death or myocardial (re)infarction at 30 days. Peak TnT level at 48 hours did not differ with lamifiban treatment. CONCLUSIONS: TnT predicts poor short-term outcomes in non-ST-segment elevation ACS. Treatment benefit with lamifiban is limited almost exclusively to TnT-positive patients, reducing 30-day adverse outcomes to a rate nearly identical to that of negative patients.

Management of patients with acute coronary syndromes in the United States by platelet glycoprotein IIb/IIIa inhibition. Insights from the platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial.

BACKGROUND: A multinational, randomized, placebo-controlled trial (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy, PURSUIT) demonstrated that the platelet glycoprotein IIb/IIIa receptor antagonist eptifibatide reduced the incidence of death or myocardial infarction among patients with acute ischemic syndromes without ST-segment elevation. Because of expected differences in practice patterns, a prospectively planned analysis of outcomes as a function of regions of the world was performed. The current study provides a detailed assessment of eptifibatide among the subgroup of patients enrolled within the United States. METHODS AND RESULTS: Patients presenting with chest pain within the previous 24 hours and ischemic ECG changes or creatine kinase-MB elevation were eligible for enrollment. Of the 10 948 patients randomized worldwide, 4035 were enrolled within the United States. Patients were allocated to placebo or eptifibatide infusion for up to 72 to 96 hours. Other medical therapies and revascularization strategies were at the discretion of the treating physician. Eptifibatide reduced the rate of the primary end point of death or myocardial infarction by 30 days from 15.4% to 11.9% (P=0.003) among patients in the United States. The treatment effect was achieved early and maintained over a period of 6 months (18.9% versus 15.2%; P=0.004). Bleeding events were more common in patients receiving eptifibatide but were predominantly associated with invasive procedures. The magnitude of clinical benefit from eptifibatide was greater among patients in the United States than elsewhere in the world. CONCLUSIONS: Platelet glycoprotein IIb/IIIa receptor blockade with eptifibatide reduces the incidence of death or myocardial infarction among patients treated for acute ischemic syndromes without ST-segment elevation within the United States.

Clinical and therapeutic profile of patients presenting with acute coronary syndromes who do not have significant coronary artery disease.The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial Investigators.

BACKGROUND: A proportion of patients who present with suspected acute coronary syndrome (ACS) are found to have insignificant coronary artery disease (CAD) during coronary angiography, but these patients have not been well characterized. METHODS AND RESULTS: Of the 5767 patients with non-ST-segment elevation ACS who were enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial and who underwent in-hospital angiography, 88% had significant CAD (any stenosis >50%), 6% had mild CAD (any stenosis >0% to

Survival outcomes 1 year after reperfusion therapy with either alteplase or reteplase for acute myocardial infarction: results from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) III Trial.

BACKGROUND: New recombinant plasminogen activators have been developed to simulate the fibrinolytic action of the physiological serine protease tissue plasminogen activator (alteplase, t-PA), and have prolonged half-life features permitting bolus administration. One such activator, reteplase (r-PA), was compared with t-PA in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-III Trial. METHODS AND RESULTS: At 1-year follow-up, survival status was ascertained in 97.4% of the 15 059 patients enrolled in the GUSTO-III trial. At 1 year, the mortality rate for the t-PA-assigned group was 11.06%, and for r-PA it was 11.20% (P:=0. 77). The absolute mortality difference of 0.14% has 95% CIs of -1. 21% to 0.93%. There were no significant differences in outcome by intention-to-treat for the 2 different plasminogen activators in the prespecified groups (age, infarct location, time-to-treatment). The absolute difference in mortality rates between t-PA and r-PA progressively narrowed over the predetermined observation times after random assignment; it was 0.31% at 24 hours, 0.26% at 7 days, 0.23% at 30 days, and 0.14% at 1 year. Of note, mortality rate in the trial between 30 days and 1 year in 13 883 patients was 4.02% and did not differ between the treatment groups. However, this mortality rate was substantially greater than in GUSTO-I, in which mortality rate for t-PA versus streptokinase between 30 days and 1-year was 2.97% (heart rate 1.36, 95% CI 1.23, 1.50, P:<0.001). CONCLUSIONS: The r-PA and t-PA strategies yielded similar survival outcomes after 30 days in this trial. The increase in mortality rate during extended follow-up compared with previous trials may reflect higher-risk patients and highlights the need for improved secondary prevention strategies.

Thrombolysis plus aortic counterpulsation: improved survival in patients who present to community hospitals with cardiogenic shock.

OBJECTIVES: We sought to explore the potential benefit of combining intraaortic balloon counterpulsation (IABP) with thrombolysis for acute myocardial infarction (MI) complicated by cardiogenic shock. BACKGROUND: In community hospitals, this condition is usually managed with thrombolysis alone. METHODS: We reviewed the charts of 335 patients from two community hospitals who presented with acute MI and had cardiogenic shock between 1985 and 1995. RESULTS: Of 46 patients who underwent thrombolysis within 12 h of acute infarction with confirmed cardiogenic shock, 27 underwent IABP and 19 did not. Age, systolic blood pressure with shock, pulmonary artery catheter use, pulmonary capillary wedge pressure and the incidence of diabetes mellitus and anterior MI did not differ between groups. Patients treated with IABP were somewhat more likely to have prior MI and had a significantly greater cardiac index (2.0 vs. 1.5 liters/min per m2, p = 0.04). Although no deaths occurred within 2 h of presentation, patients not treated with IABP tended to die earlier (6.8 +/- 5 vs. 23.8 +/- 19 h, p = 0.13). Patients treated with IABP had a significantly higher rate of community hospital survival (93% vs. 37%, p = 0.0002), and more of them were transferred for revascularization (85% vs. 37%). Of 30 patients transferred for revascularization, 27 underwent angioplasty or bypass surgery; hospital survival was 74%. Patients treated with IABP also had a significantly higher overall hospital and 1-year survival rate (67% vs. 32%, p = 0.019). CONCLUSIONS: Survival may be enhanced and transfer for revascularization facilitated when community hospitals use both thrombolysis and IABP to treat patients with acute MI complicated by cardiogenic shock.

Profound inhibition of platelet aggregation with monoclonal antibody 7E3 Fab after thrombolytic therapy. Results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 8 Pilot Study.

OBJECTIVES: This study was undertaken to establish evidence for physiologic activity and to study the safety of murine-derived monoclonal antibody 7E3 Fab (m7E3 Fab) in patients receiving recombinant tissue-type plasminogen activator (rt-PA). BACKGROUND: Platelet aggregation is believed to be a significant factor in the failure of pharmacologic reperfusion. By binding to the glycoprotein IIb/IIIa receptor, m7E3 Fab inhibits platelet aggregation and has been shown experimentally to decrease the time required for lysis and to prevent reocclusion. However, the safety of profound platelet inhibition after thrombolysis for acute myocardial infarction has not been tested in humans. METHODS: Sixty patients receiving rt-PA, aspirin and heparin for acute myocardial infarction received m7E3 Fab bolus injections in ascending doses at 3, 6 and 15 h after initiation of the thrombolytic infusion. Ten patients treated with rt-PA but not m7E3 Fab were studied as control subjects. RESULTS: Receptor site blockade and inhibition of platelet aggregation to 20 mumol/liter adenosine diphosphate were maximal at a dose of 0.25 mg/kg body weight of m7E3 Fab. Fifteen (25%) m7E3 Fab-treated patients and five (50%) control patients had major bleeding; eight of these events in seven m7E3 Fab-treated patients and one in a control patient occurred at the time of aortocoronary bypass surgery. Recurrent ischemia occurred in eight (13%) m7E3 Fab-treated patients and two (20%) control subjects. Coronary angiography was performed in 43 patients; the infarct-related coronary artery was patent in 5 of 9 (56%) control patients and 34 (92%) of 37 patients receiving m7E3 Fab. CONCLUSIONS: Profound inhibition of platelet aggregation after thrombolysis was associated with bleeding rates comparable to those in control patients and a low rate of recurrent ischemia. The combination of m7E3 Fab and rt-PA, heparin and aspirin appears to be a promising and safe combination that should be evaluated in further studies of patients with acute myocardial infarction.

Provisional stenting strategies: systematic overview and implications for clinical decision-making.

Coronary stents reduce the rates of abrupt closure, emergency coronary artery bypass graft surgery and restenosis, but do not prevent myocardial infarction or death at six months. The financial burden of increased stent use and the difficulty in managing in-stent restenosis have provided the impetus to develop provisional stenting strategies. Patients at low risk for restenosis after balloon angioplasty may not derive additional benefit from stent implantation and may be successfully managed with percutaneous transluminal coronary angioplasty (PTCA) alone. Numerous patient, lesion and procedural predictors of restenosis have been identified. Postprocedural assessment using quantitative coronary angiography, intravascular ultrasound (IVUS), coronary flow velocity reserve (CVR) or fractional flow reserve (FFR) may further enhance the ability to predict adverse outcomes after PTCA. Several studies have been performed to investigate the feasibility of provisional stenting strategies using various modalities to identify low risk patients who could be managed with PTCA alone. An optimal or "stent-like" angiographic result after PTCA is associated with favorable clinical outcomes. Preliminary results of studies using IVUS or CVR to guide provisional stenting appear promising. Angiography alone may be inadequate to identify truly low risk patients and may need to be combined with clinical factors, assessment of recoil, IVUS or physiologic indexes. Strategies that avoid unnecessary stenting in even a small proportion of patients may have large impacts on health care costs. Provisional stenting may potentially reduce costs and rates of in-stent restenosis without compromising the quality of health care delivery.

Prognostic value of congestive heart failure history in patients undergoing percutaneous coronary interventions.

OBJECTIVES: We sought to determine the prognostic significance of a history of congestive heart failure above that provided by baseline ejection fraction in patients undergoing percutaneous coronary interventions. BACKGROUND: Left ventricular function is a known predictor of survival in patients with coronary artery disease, as is a history of congestive heart failure. The contribution of heart failure history independent of left ventricular function is unknown. METHODS: Data were pooled from four interventional trials and the Duke University database. The combined dataset included 5,260 patients undergoing percutaneous interventions, 334 with and 4,926 without a history of heart failure. Patients were defined by the treating physician as having a clinical history of heart failure at the time of enrollment. RESULTS: The 30-day and 6-month mortality were higher in patients with a clinical history of congestive heart failure than in those without such a history (2% vs. <1%, p=0.002 at 30 days, 5% vs. 1%, p=0.001 at 6 months). Heart failure history did not influence the incidence of myocardial infarction, use of angioplasty or the use of bypass surgery during follow-up. Multivariable analysis revealed that heart failure history added significantly to ejection fraction in predicting intermediate-term (6-month) mortality (p=0.01). Stepwise logistic regression also revealed heart failure history to be an independent predictor of 6-month mortality (odds risk 1.9, 95% confidence interval 1.1 to 3.5). CONCLUSIONS: A clinical history of congestive heart failure is associated with increased early and intermediate-term mortality in patients undergoing percutaneous revascularization. Congestive heart failure history appears to provide prognostic information independent of that available from a patient's left ventricular function. These findings suggest that patients with a clinical history of congestive heart failure who undergo a percutaneous intervention should be closely monitored, especially those with the lowest ejection fractions.

Restenosis, reocclusion and adverse cardiovascular events after successful balloon angioplasty of occluded versus nonoccluded coronary arteries. Results from the Multicenter American Research Trial With Cilazapril After Angioplasty to Prevent Transluminal Coronary Obstruction and Restenosis (MARCATOR).

OBJECTIVES: This study sought to compare the frequency of restenosis, reocclusion and adverse cardiovascular events after angioplasty of occluded versus nonoccluded coronary arteries. BACKGROUND: Angioplasty of chronically occluded coronary arteries is believed to be associated with a higher frequency of restenosis and reocclusion than angioplasty of subtotal stenoses. Whether this leads to adverse cardiovascular events is unknown. METHODS: The Multicenter American Research Trial With Cilazapril After Angioplasty to Prevent Restenosis (MARCATOR) was a placebo-controlled trial with angiographic follow-up to determine the effect of the angiotensin-converting enzyme inhibitor cilazapril on the frequency of restenosis. In this trial, restenosis was defined as 1) angiographic reduction of minimal lumen diameter > or = 0.72 mm between angioplasty and the follow-up visit; and 2) > 50% diameter stenosis on the follow-up angiogram. We identified 139 patients with successful angioplasty of a coronary occlusion (Group 1) and compared the frequency of restenosis, reocclusion and adverse cardiovascular events with that in 1,295 patients with successful angioplasty of a subtotal stenosis (Group 2). RESULTS: Restenosis occurred in 36 patients with occluded arteries (29%) versus 264 with nonoccluded arteries (23%, p = 0.177) by definition 1 and in 62 patients with occluded arteries (49%) versus 478 with nonoccluded arteries (42%, p = 0.119) by definition 2. Occlusion was present in 24 Group 1 patients (19%) compared with 74 Group 2 patients (7%) (p < 0.001). During the 6 month follow-up period, two Group 1 patients (1.4%) and six Group 2 patients (0.5%) died; no Group 1 patients and 10 Group 2 patients (0.8%) developed severe congestive heart failure; nonfatal myocardial infarction occurred in 4 Group 1 patients (2.9%) and 31 Group 2 patients (2.4%); repeat coronary angioplasty or bypass surgery was performed in 29 Group 1 patients (21%) and 232 Group 2 patients (18%); and angina was present in 18 Group 1 and 163 Group 2 patients (13% for both). Eighty-six Group 1 patients (62%) and 853 Group 2 patients (66%) remained free of these adverse events during the 6-month follow-up period (p = 0.513). CONCLUSIONS: The frequency of restenosis was slightly but not significantly greater after successful angioplasty of an occluded artery than after angioplasty of a subtotal stenosis. Although reocclusion was more frequent, occurring in 19% of patients, the net clinical benefit of angioplasty in such patients was similar to that in patients with subtotal stenoses over the 6-month follow-up period.

Effects of reteplase and alteplase on platelet aggregation and major receptor expression during the first 24 hours of acute myocardial infarction treatment. GUSTO-III Investigators. Global Use of Strategies to Open Occluded Coronary Arteries.

OBJECTIVES: We sought to compare platelet characteristics after reteplase and alteplase therapy in the setting of the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO)-III trial. BACKGROUND: Platelet function may be impaired during thrombolysis in patients with an acute myocardial infarction. The effects of reteplase and alteplase on platelet aggregation and major surface antigen expression during the first 24 h of infarction therapy are unknown. METHODS: Platelet aggregation and receptor expression by flow cytometry were determined in 23 patients before thrombolysis and thereafter at 3, 6, 12 and 24 h. RESULTS: Aggregation was higher after reteplase at 24 h when induced by 5 micromol/liter adenosine diphosphate (ADP) (p = 0.007), 10 micromol/liter ADP (p = 0.02), collagen (p = 0.003) and thrombin (p = 0.009) than after alteplase. Reteplase therapy exhibited greater glycoprotein (GP) IIb/IIIa (p = 0.04), very late antigen-2 (p = 0.04) and platelet/endothelial cell adhesion molecule-I (p = 0.002) expression at 24 h. Trends toward decreased receptor expression early (3 to 6 h), followed by a progressive increase at 12 h and especially at 24 h occurred after both agents. CONCLUSIONS: In this prospective clinical ex vivo platelet study, similar patterns of platelet aggregation and surface receptor expression occurred during the first 24 h of coronary thrombolysis with reteplase and alteplase. However, after reteplase, indicators of platelet activity were higher at 24 h after thrombolysis than after alteplase. These data suggest that GP IIb/IIIa inhibitors or other antiplatelet strategies may be particularly advantageous when used 12 to 24 h after thrombolysis, especially after reteplase therapy. It is at this time point during the first day of coronary thrombolysis that GP IIb/IIIa is markedly expressed and platelets are most active.

Shifting the open-artery hypothesis downstream: the quest for optimal reperfusion.

Successful reperfusion after acute myocardial infarction (MI) has traditionally been considered to be restoration of epicardial patency, but increasing evidence suggests that disordered microvascular function and inadequate myocardial tissue perfusion are often present despite infarct vessel patency. Thus, optimal reperfusion is being redefined to include intact microvascular flow and restored myocardial perfusion, as well as sustained epicardial patency. Coronary angiography has been used as the gold standard to define failed reperfusion, according to the Thrombolysis In Myocardial Infarction (TIMI) flow grades. However, new angiographic techniques, including the corrected TIMI frame count and myocardial blush grade, have been used to show that epicardial TIMI flow grade 3 may be an incomplete measure of reperfusion success. Furthermore, evolving noninvasive diagnostic techniques, including measurement of infarct size with cardiac marker release patterns or technetium-99m-sestamibi single-photon emission computed tomographic imaging and analysis of ST segment resolution appear to be useful complements to angiography for the assessment of myocardial tissue reperfusion. Promising adjunctive therapies that target microvascular dysfunction, including platelet glycoprotein IIb/IIIa inhibitors, and agents designed to improve tissue perfusion and attenuate reperfusion injury are being evaluated to further improve clinical outcomes after acute MI. To accelerate development of these new reperfusion regimens, an integrated approach to phase II clinical trials that incorporates multiple efficacy variables, including angiography and noninvasive biomarkers of microvascular dysfunction, should be considered. Thus, as the reperfusion era moves into the next millennium, the open-artery hypothesis is expected to shift downstream and guide efforts to further improve myocardial salvage and clinical outcomes after acute MI.

Does the presence of thrombus seen on a coronary angiogram affect the outcome after percutaneous coronary angioplasty? An Angiographic Trials Pool data experience.

OBJECTIVES: This study aimed to determine whether pre-existing angiographic thrombus was associated with adverse in-hospital and six-month outcomes after percutaneous coronary interventions. BACKGROUND: There are conflicting data about whether pre-existing thrombus is an independent predictor of adverse in-hospital and short-term outcome after coronary interventions. METHODS: The Angiographic Trials Pool, a data set derived from eight prospective randomized trials, was analyzed. The study population consisted of 7,917 patients who underwent coronary interventions between 1986 and 1995. Two trials were excluded because they did not collect information regarding thrombus. Patients from the other six trials were divided on the basis of the presence or absence of thrombus. RESULTS: In patients with (n = 2,752) and without (5,165) thrombus, in-hospital mortality following angioplasty was low (0.8 vs. 0.6%, p = 0.207). Several adverse outcomes were higher in patients with thrombus: death/myocardial infarction (8.4 vs. 5.5%, p < or = 0.001), in-hospital abrupt closure (5.9 vs. 3.9%, p < or = 0.001) and an in-hospital composite of death, myocardial infarction and/or repeat revascularization (15.4 vs. 11.2%, p < or = 0.001). Six-month mortality was low and comparable between the two groups (2.1 vs. 1.8%, p = 0.34), but the incidence of six-month death/myocardial infarction was higher in patients with thrombus (11.7 vs. 8.7%, p < or = 0.0001). CONCLUSIONS: Percutaneous coronary angioplasty can be performed with low mortality in patients with pre-existing thrombus, although these patients are at higher risk of in-hospital and six-month death/myocardial infarction. Continued efforts are required to optimize the outcome in these high risk patients.

The current practice of intra-aortic balloon counterpulsation: results from the Benchmark Registry.

OBJECTIVES: This study presents clinical data from the first large registry of aortic counterpulsation, a computerized database that incorporates prospectively gathered data on indications for intra-aortic balloon counterpulsation (IABP) use, patient demographics, concomitant medication and in-hospital outcomes and complications. BACKGROUND: The intra-aortic balloon pump (IABP) is widely used to provide circulatory support for patients experiencing hemodynamic instability due to myocardial infarction, cardiogenic shock, or in very high risk patients undergoing angioplasty or coronary artery bypass grafting. METHODS: Between June 1996 and August 2000, 203 hospitals worldwide (90% U.S., 10% non-U.S.) collected 16,909 patient case records (68.8% men, 31.2% women; mean age 65.9 +/- 11.7 years). RESULTS: The most frequent indications for use of IABP were as follows: to provide hemodynamic support during or after cardiac catheterization (20.6%), cardiogenic shock (18.8%), weaning from cardiopulmonary bypass (16.1%), preoperative use in high risk patients (13.0%) and refractory unstable angina (12.3%). Major IABP complications (major limb ischemia, severe bleeding, balloon leak, death directly due to IABP insertion or failure) occurred in 2.6% of cases; in-hospital mortality was 21.2% (11.6% with the balloon in place). Female gender, high age and peripheral vascular disease were independent predictors of a serious complication. CONCLUSIONS: This registry provides a useful tool for monitoring the evolving practice of IABP. In the modern-day practice of IABP, complication rates are generally low, although in-hospital mortality remains high. There is an increased risk of major complications in women, older patients and patients with peripheral vascular disease.

Achieving optimal results with standard balloon angioplasty: can baseline and angiographic variables predict stent-like outcomes?

OBJECTIVES: To predict which patients might not require stent implantation, we identified clinical and angiographic characteristics associated with repeat revascularization after standard balloon angioplasty. BACKGROUND: Stents reduce the risk of repeat revascularization but are costly and may lead to in-stent restenosis, which remains difficult to treat. Identification of patients at low risk for repeat revascularization may allow clinicians to reserve stents for patients most likely to benefit. METHODS: Data from five interventional trials (5,146 patients) were pooled for analysis. We identified patients with optimal angiographic results (final diameter stenosis < or =30% and no dissection) after balloon angioplasty and determined the multivariable predictors of repeat revascularization. RESULTS: Optimal angiographic results were achieved in 18% of patients after angioplasty. The repeat revascularization rate at six months was lower for patients with optimal results (20% vs. 26%, p < 0.001) but still higher than observed in stent trials. Independent predictors of repeat revascularization were female gender (odds ratio [OR] 1.67, p = 0.01), lesion length > or =10 mm (OR 1.62, p = 0.03) and proximal left anterior descending coronary artery lesions (OR 1.62, p = 0.03). For the 8% of patients with optimal angiographic results and none of these risk factors, the repeat revascularization and target vessel revascularization rates were 14% and 8% respectively, similar to rates after stent implantation. Cost analysis estimated that $78 million per year might be saved in the U.S. with a provisional stenting strategy using these criteria compared with elective stenting. CONCLUSIONS: A combination of baseline characteristics and angiographic results can be used to identify a small group of patients at very low risk for repeat revascularization after balloon angioplasty. Provisional stenting for these low risk patients could substantially reduce costs without compromising clinical outcomes.

Characteristics and consequences of myocardial infarction after percutaneous coronary intervention: insights from the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT).

OBJECTIVES: We examined the results of the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT) to determine the characteristics and consequences of creatine kinase (CK) and creatine kinase, MB myocardial isoenzyme fraction (CK-MB) elevations after percutaneous coronary intervention. BACKGROUND: Enzyme elevations after interventional procedures have usually been thought to be without long-term clinical consequences. However, recent preliminary reports have suggested that there are important long-term clinical sequelae in patients with even mild enzyme elevations after coronary procedures. METHODS: Patients with new native lesions undergoing coronary intervention at 35 clinical sites were randomized to undergo percutaneous coronary angioplasty (n = 500) or directional coronary atherectomy (n = 512). Cardiac enzyme levels were measured 12 and 24 h after the interventional procedure and when clinically indicated for recurrent myocardial ischemia. Enzyme profiles were analyzed using a ratio that compared the peak enzyme level and the local laboratory upper limit of normal. Standard 12-lead electrocardiograms (ECGs) recorded before and after the procedure were interpreted by two independent readers who had no knowledge of the randomization data. Postprocedural myocardial infarction was defined as the appearance of new Q waves on the ECG, CK-MB levels three or more times the upper limit of normal or a total CK concentration two or more times the upper limit of normal when CK-MB levels were unavailable. Regression models were used to evaluate the predictive significance of a postintervention myocardial infarction with respect to clinical outcomes at 30 days and 1 year. RESULTS: There were 78 myocardial infarctions in the atherectomy group and 34 in the angioplasty group (15.2% vs. 6.8%, p = 0.001). Patients with a myocardial infarction more often had a repeat intervention or emergency coronary artery bypass surgery. Hospital length of stay was increased among patients with an infarction, as were mean hospital costs ($17,340.65 vs. $11,308.47, p = 0.0003). Postprocedural myocardial infarction was highly predictive of mortality, bypass surgery or repeat intervention within 30 days (p < 0.0001). CONCLUSIONS: Myocardial infarction occurred commonly after coronary intervention in CAVEAT and was associated with a worse clinical outcome. Although the incidence of myocardial infarction was higher with atherectomy than with angioplasty, the baseline characteristics and consequences of the infarctions were similar between the treatments with regard to 30-day outcome. Myocardial enzyme elevations after an otherwise successful interventional procedure may identify a population at risk for a future cardiac event.

Restenosis after coronary angioplasty: an overview.

Despite substantial basic and clinical efforts to address the problem of restenosis after percutaneous coronary intervention, effective preventive therapies have not yet been developed. Nevertheless, the accumulated information has provided much insight into the process of restenosis in addition to allowing standards to be developed for adequate clinical trials. The pathophysiology of restenosis increasingly appears to be distinct from that of primary atherosclerosis. Restenosis involves elastic recoil, incorporation of thrombus into the lesion and fibrocellular proliferation in varying degrees in different patients. Lack of an animal model that satisfactorily mimics restenosis is a major impediment to further understanding of the process. Clinical studies are hampered by difficulties in finding a single unifying definition of restenosis and by variable methods of reporting follow-up. Reporting of clinical outcomes of all patients in angiographic substudies would allow a more satisfactory interpretation of the results of clinical trials. Current noninvasive test results are not accurate enough to substitute for angiographic and clinical outcome data in intervention trials. In the majority of observational studies, only diabetes and unstable angina have emerged as consistently associated with restenosis; whereas most of the standard risk factors for atherosclerosis have a less consistent relation. Disappointingly, the new atherectomy and laser technologies have not affected restenosis rates. The one possible exception is coronary stenting, as a result of the larger luminal diameter achieved by the placement of the stent. In conclusion, although substantial continued effort is necessary to explore the basic aspects of cellular proliferation and mechanical alteration of atherosclerotic vessels, attention to the principles of clinical trials and observation are required to detect the impact of risk factors and interventions on the multifactorial problem of restenosis. Adequate sample sizes, collection of clinical and angiographic outcomes and factorial study designs hold promise for unraveling this important limitation of percutaneous intervention.