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E M Ohman

Publications and source records attributed to E M Ohman.

At least 37 records · Page 2Linked to original sources
PubMed2001

Determination of the falloff constant (k(f)) from modeling biochemical marker release: a new variable for discriminating therapies.

A new variable termed the falloff constant (k(f)) was derived from the curve fitting of serial CK-MB measurements. k(f) represents the rate constant of maximal decline in serum CK-MB and is determined from the slope of the lognormal curve at the inflection point. Physiologically, kf's magnitude reflects the balance between CK-MB's rate of release from tissue and the rate of elimination. We examined k(f) in two myocardial infarction (MI) patient sets. The first set was homogeneous and taken from the TAMI 7 study (n = 147) and included 111 patients having TIMI 2-3 flow after thrombolytic therapy and 36 patients who initially had TIMI 0-1 flow. The TIMI 0-1 patients were opened to TIMI 3 by angioplasty within 3 h. The second set consisted of 196 patients enrolled in the IMPACT-AMI study that demonstrated the efficacy of the glycoprotein (GP) IIb/IIIa antagonist eptifibatide. This second set consisted of 93 patients in the GP IIb/IIIa treatment group and 103 in the placebo group. Log-normal curve-fitting parameters including peak maximum and curve area were also compared to k(f) in the GP IIb/IIIa versus placebo set. The Wilcoxon test showed no difference between the two groups of TAMI 7 patients (p = 0.22). However, there was a highly significant difference in kf between the GP IIb/IIIa treatment group versus the placebo group (p = 0.0014). Both k(f) and peak maximum from curve fitting showed significant differences between the GP IIb/IIIa treatment group and the placebo group; however, k(f) showed a substantially lower p-value (p = 0.0014 and p = 0.023, respectively). As expected, k(f) showed no difference between the TAMI 7 groups because this was a homogeneous patient set in that they all had TIMI 3 patency status within 3 h of treatment. However, in the patient set having very different treatments, GP IIb/IIIa versus placebo, there was a highly significant difference in the kf variable. These data suggest that differences in reperfusion are reflected by kf and that this variable may represent a valuable new nonmortality end point derived from curve fitting analysis.

Algorithms↗
PubMed2000

Facilitation of early percutaneous coronary intervention after reteplase with or without abciximab in acute myocardial infarction: results from the SPEED (GUSTO-4 Pilot) Trial.

OBJECTIVES: We examined the utility of early percutaneous coronary intervention (PCI) in a trial that encouraged its use after thrombolysis and glycoprotein IIb/IIIa inhibition for acute myocardial infarction (MI). BACKGROUND: Early PCI has shown no benefit when performed early after thrombolysis alone. METHODS: We studied 323 patients (61%) who underwent PCI with planned initial angiography, at a median 63 min after reperfusion therapy began. A blinded core laboratory reviewed cineangiograms. Ischemic events, bleeding, angiographic results, and clinical outcomes were compared between early PCI and no-PCI patients (n = 162), between patients with Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 or 1 before PCI versus flow grade 2 or 3, and among three treatment regimens. RESULTS: Early PCI patients showed a procedural success (<50% residual stenosis and TIMI flow grade 3) rate of 88% and a 30-day composite incidence of death, reinfarction, or urgent revascularization of 5.6%. These patients had fewer ischemic events and bleeding complications (15%) than did patients not undergoing early PCI (30%, p = 0.001). Early PCI was used more often in patients with initial TIMI flow grade 0 or 1 versus flow grade 2 or 3 (83% vs. 60%, p < 0.0001). Patients receiving abciximab with reduced-dose reteplase (5 U double bolus) showed an 86% incidence of TIMI grade 3 flow at approximately 90 min and a trend toward improved outcomes. CONCLUSIONS: In this analysis, early PCI facilitated by a combination of abciximab and reduced-dose reteplase was safe and effective. This approach has several advantages for acute MI patients, which should be confirmed in a dedicated, randomized trial.

Abciximab↗
PubMed2000

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.

Acute Disease↗
PubMed2000

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.

Acute Disease↗
PubMed2000

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 </=50%), and 6% had no CAD (no stenosis identified). The frequency of death or nonfatal myocardial infarction at 30 days was reduced with eptifibatide treatment in patients with significant CAD (18.3% versus 15.6% for placebo, P=0.006) but not in those with mild CAD (6.6% versus 5.4%, P=0.62) and with no CAD (3.0% versus 1. 2%, P=0.28). We identified independent baseline predictors of insignificant CAD (mild or no CAD) and used them to develop a simple predictive nomogram of the probability of insignificant CAD for use at hospital presentation. This nomogram was validated in a separate population of patients with non-ST-segment elevation ACS. CONCLUSIONS: Patients with suspected ACS found to have insignificant CAD have a low risk of adverse outcomes, do not appear to benefit from treatment with eptifibatide, and can be predicted with a simple nomogram drawn from baseline characteristics. Because patients with significant CAD appear to have an enhanced benefit from eptifibatide treatment, the predictive nomogram developed can be used to determine indications for glycoprotein IIb/IIIa blockade.

Acute Disease↗
PubMed2000

Use of resources, quality of life, and clinical outcomes in patients with and without new Q waves after thrombolytic therapy for acute myocardial infarction (from the GUSTO-I trial).

Previous reports indicate that patients who do not develop Q waves after thrombolytic therapy are a different population with a better long-term survival than those who do develop Q waves. However, the use of resources, quality of life, and health status of this population have not been fully evaluated. Using data from the Economics and Quality of Life subset of the Global Utilization of Streptokinase and tPA for Occluded Arteries study, we examined 30-day and 1-year mortality, use of resources, and quality-of-life measures among 1,830 of 3,000 patients with acute myocardial infarction and ST-segment elevation treated with thrombolytic therapy. At hospital discharge, 555 patients (30.2%) had not developed Q waves. These patients had lower mortality than patients with Q waves at 30 days (1.6% vs 4.5%, p <0.01) and at 1 year (4.7% vs 6.8%, p <0.04). Recurrent chest pain and dyspnea were similar at 30 days and 1 year. Patients without Q waves had significantly more angiography and trends toward higher readmission, revascularization, and use of calcium antagonists at 30 days. Angiography, revascularization, readmission, and quality of life were equivalent from 30 days to 1 year, with no sign of late instability. Logistic regression analysis showed an association between in-hospital revascularization and better survival and quality of life at 1 year. Conversely, there was no association between in-hospital use of calcium antagonists and outcome to explain the lower mortality in non-Q-wave patients. The absence of Q waves after thrombolytic therapy is a marker of success, implying better prognosis and equivalent quality of life, use of resources, and health status than for patients with Q-wave acute myocardial infarction and no sign of long-term unstable clinical course.

Aged↗
PubMed2000

The use of glycoprotein IIb/IIIa inhibitor therapy in acute ST-segment elevation myocardial infarction: current practice and future trends.

The goal of therapy in acute myocardial infarction is complete and timely restoration of coronary blood flow. Current strategies for reperfusion fail to achieve ideal results and resolution of ischemia in all patients. The platelet plays a pivotal role in the pathophysiology of an acute myocardial infarction, and antiplatelet therapy has been shown to improve clinical outcomes. The final common pathway for platelet activation and aggregation in acute myocardial infarction is the activation of the glycoprotein (GP) IIb/IIIa receptor. Newer reperfusion strategies target the GP IIb/IIIa receptor, thereby preventing the prothrombotic effects of platelets in an acute myocardial infarction. In the past decade, several strategies targeting the use of GP IIb/IIIa inhibitors have been evaluated. GP IIb/IIIa inhibitors have been shown to improve angiographic Thrombolysis in Myocardial Infarction (TIMI) 3 flow rates when used as reperfusion therapy given with heparin and aspirin as compared with heparin and aspirin alone. When GP IIb/IIIa inhibitors are used with full-dose fibrinolytics, early studies have suggested a trend toward more rapid and more complete reperfusion in an acute myocardial infarction. Later trials have examined the use of GP IIb/IIIa inhibitors in conjunction with reduced-dose fibrinolytics. Results from TIMI 14 and Global Use of Strategies to Open occluded arteries-IV pilot trials support the use of combination therapy with reduced- dose fibrinolytics and the GP IIb/IIIa inhibitor abciximab. Given the promising role of GP IIb/IIIa inhibitor therapy in acute myocardial infarction, investigators questioned the need for concomitant antithrombin therapy. However, data from several investigations suggest that antithrombin therapy is required when GP IIb/IIIa inhibitors are used with fibrinolytics, although it appears that the dose of heparin may be reduced. Finally, recent investigations have addressed the safety and efficacy of facilitated early percutaneous intervention. In this strategy, patients presenting with an acute myocardial infarction are treated with reduced-dose fibrinolytics and GP IIb/IIIa inhibitors and are taken to the interventional cardiac catheterization laboratory within the first 60 minutes of therapy.

Animals↗
PubMed2000

Comparison of cardiac troponin T versus creatine kinase-MB for risk stratification in a chest pain evaluation unit.

We evaluated cardiac troponin T (cTnT) and creatine kinase-MB (CK-MB) for risk stratification of chest pain unit (CPU) patients. We studied 383 consecutive patients with chest pain assigned to our CPU by emergency department physicians. At baseline all had normal or nondiagnostic electrocardiograms, no high-risk clinical features, and negative CK/CK-MB. CK-MB and electrocardiograms were taken at 0, 4, 8, and 12 hours and cTnT at 0, 4, and 8 hours. Eight patients (2.1%) were CK-MB positive and 39 (10.2%) were cTnT positive, including all but 1 CK-MB-positive patient. All marker-positive patients were detected by 8 hours. Seven cTnT-positive patients and 1 cTnT-negative patient had myocardial infarction (p <0.0001). cTnT-positive patients were older, less likely to be women or smokers, and more often had diabetes mellitus or known coronary disease (CAD). Seventy-one percent of patients underwent diagnostic testing. cTnT-positive patients more often underwent angiography (46% vs 20%) and underwent stress testing less often (28% vs 57%) than cTnT-negative patients. When performed, their stress tests were more often positive (46% vs 14%) and they more often had angiographically significant lesions (89% vs 49%) and multivessel disease (67% vs 29%). There were no short-term deaths. Long-term mortality was higher in cTnT-positive patients (27% vs 7%, p <0.0001). Thus, cTnT identified more CPU patients with myocardial necrosis and multivessel CAD than CK-MB and a population with high long-term mortality risk. Routine use of cTnT in CPUs could facilitate risk stratification and management.

Aged↗
PubMed2000

Relation of temporal creatine kinase-MB release and outcome after thrombolytic therapy for acute myocardial infarction. TAMI Study Group.

Measuring biochemical marker release after acute myocardial infarction helps in estimating infarct size and prognosis. We sought to relate in-hospital outcomes and curve-fitted creatine kinase (CK)-MB variables after thrombolysis. We measured CK-MB mass initially and at 30 and 90 minutes, and at 3, 8, and 20 hours after thrombolysis in 130 patients also undergoing cardiac catheterization at 90 minutes and at 5 to 7 days. Data were fitted, and maximums and curve areas calculated. CK-MB maximums related to infarct location (p = 0.014) and time to therapy (p = 0.002); curve area did not. Neither maximums nor curve area related to Thrombolysis in Myocardial Infarction trial flow grade at 90 minutes. Maximums related to ejection fraction at 90 minutes (p = 0.0004) and at 5 to 7 days (p = 0.0014), as did curve area (p = 0.0076 and 0.030, respectively). Maximums related to infarct zone function at 90 minutes (p = 0.024) and at 5 to 7 days (p = 0.042); curve area related only at 90 minutes (p = 0.027). Both maximums and curve area predicted congestive heart failure (p = 0.008 and p = 0.042, respectively) and a composite of congestive heart failure or death (p = 0.004 and p = 0.047, respectively); however, after adjusting for maximums, curve area no longer predicted congestive heart failure (p = 0.92). Maximums predicted the composite outcome after adjustment for curve area, and showed a trend toward predicting congestive heart failure (p = 0.089). We conclude that CK-MB maximums relate to infarct zone function, left ventricular function, and in-hospital outcomes after thrombolysis for acute myocardial infarction.

Biomarkers↗
PubMed2000

Association between minor elevations of creatine kinase-MB level and mortality in patients with acute coronary syndromes without ST-segment elevation. PURSUIT Steering Committee. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy.

CONTEXT: Controversy surrounds the diagnostic and prognostic importance of slightly elevated cardiac markers in patients with acute coronary syndromes without ST-segment elevation. OBJECTIVES: To investigate the relationship between peak creatine kinase (CK)-MB level and outcome and to determine whether a threshold CK-MB level exists below which risk is not increased. DESIGN AND SETTING: Retrospective observational analysis of data from the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, conducted from November 1995 to January 1997. PATIENTS: A total of 8250 patients with acute coronary syndromes without ST-segment elevation who had at least 1 CK-MB sample collected during their index hospitalization. MAIN OUTCOME MEASURE: Mortality at 30 days and 6 months, was assessed by category of index-hospitalization peak CK-MB level (0-1, >1-2, >2-3, >3-5, >5-10, or >10 times the upper limit of normal). Multivariable logistic regression was used to determine the independent prognostic significance of peak CK-MB level after adjustment for baseline predictors of 30-day and 6-month mortality. RESULTS: Mortality at 30 days and 6 months increased from 1.8% and 4.0%, respectively, in patients with normal peak CK-MB levels, to 3.3% and 6.2 % at peak CK-MB levels 1 to 2 times normal, to 5.1% and 7.5% at peak CK-MB levels 3 to 5 times normal, and to 8.3% and 11.0% at peak CK-MB levels greater than 10 times normal. Log-transformed peak CK-MB levels were predictive of adjusted 30-day and 6-month mortality (P<.001 for both). CONCLUSIONS: Our data show that elevation of CK-MB level is strongly related to mortality in patients with acute coronary syndromes without ST-segment elevation, and that the increased risk begins with CK-MB levels just above normal. In the appropriate clinical context, even minor CK-MB elevations should be considered indicative of myocardial infarction.

Acute Disease↗
PubMed2000

Local delivery of heparin post-PTCA: a multicenter randomized pilot study.

Bailout stenting for major dissection and threatened closure has high rates of ischemic complications. We performed a randomized trial of local heparin delivery using the infusion sleeve before bailout stenting for suboptimal angioplasty results. In phase I, 20 patients were randomized to local delivery with either 40- or 100-psi infusion pressure. In phase II, 37 patients were randomized to local delivery at 100 psi or standard therapy. Local delivery succeeded in all but one patient; overall there was no significant worsening of intimal dissection. One patient treated with 100-psi drug infusion suffered a perforation after stent placement. There were no significant differences in the composite endpoint of death, MI, CABG, urgent repeat angioplasty, and stent thrombosis at 30 days (21% vs. 0%; P = 0.18). At 6 months, the rates of myocardial infarction in phase II were 27% with local delivery vs. 10% with standard treatment (P = 0.4). Local heparin delivery in dissected vessels may be associated with increased complications and should be approached with caution.

Aged↗
PubMed2000

Reduced thrombus burden with abciximab delivered locally before percutaneous intervention in saphenous vein grafts.

BACKGROUND: Existing thrombus can complicate percutaneous saphenous vein graft (SVG) intervention. Local delivery of thrombolytics has been used to reduce the thrombus burden often associated with these interventions. We sought to determine whether local delivery of a platelet glycoprotein IIb/IIIa inhibitor is feasible and can reduce thrombus burden before percutaneous SVG intervention. METHODS: We performed a multicenter pilot study of abciximab (0.25 mg/kg) given by local delivery catheter before percutaneous intervention for de novo SVG stenoses followed by intravenous infusion. All patients (n = 58) had >/=60% stenosis and Thrombolysis In Myocardial Infarction (TIMI) grade >0 flow in an SVG of 3 to 4 mm in diameter. Percent diameter stenosis, TIMI thrombus grade, and TIMI flow grade were measured before and after delivery of abciximab and after intervention. RESULTS: Median percent diameter stenosis improved from 69% to 45% (P =.0001) after local delivery, and TIMI thrombus grade >/=1 incidence reduced from 68% to 34% (P =.0001). TIMI flow grade was not significantly affected (P =.12). All patients had a successful intervention (</=50% residual stenosis). CONCLUSIONS: Local abciximab delivery before percutaneous SVG intervention is associated with significantly reduced thrombus burden, significantly improved percent diameter stenosis, and excellent acute procedural results. Further studies of this approach are warranted to define its clinical utility.

Abciximab↗
PubMed2000

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.

Blood Vessel Prosthesis Implantation↗