Ninety-minute exclusion of acute myocardial infarction by use of quantitative point-of-care testing of myoglobin and troponin I.

BACKGROUND: Diagnostic strategies with ECG and serum cardiac markers have been used to rule out acute myocardial infarction in 6 to 12 hours. The present study evaluated whether a multimarker strategy that used point-of-care measurement of myoglobin, creatine kinase (CK)-MB, and troponin I could exclude acute myocardial infarction in

Double-blind, randomized trial of an anti-CD18 antibody in conjunction with recombinant tissue plasminogen activator for acute myocardial infarction: limitation of myocardial infarction following thrombolysis in acute myocardial infarction (LIMIT AMI) study.

BACKGROUND: Inhibition of leukocyte adhesion can reduce myocardial infarct size in animals. This study was designed to define the safety and efficacy of a recombinant, humanized, monoclonal antibody to the CD18 subunit of the beta2 integrin adhesion receptors (rhuMAb CD18), in reducing infarct size in patients treated with a thrombolytic agent. METHODS AND RESULTS: The Limitation of Myocardial Infarction following Thrombolysis in Acute Myocardial Infarction Study (LIMIT AMI) was a randomized, double-blind, placebo-controlled, multicenter study conducted in 60 centers in the United States and Canada. A total of 394 subjects who presented within 12 hours of symptom onset with ECG findings (ST-segment elevation) consistent with AMI were treated with recombinant tissue plasminogen activator and were also given an intravenous bolus of 0.5 or 2.0 mg/kg rhuMAb CD18 or placebo. Coronary angiography was performed at 90 minutes, 12-lead ECGs were obtained at baseline, 90, and 180 minutes, and resting sestamibi scans were performed at >/=120 hours. Adjunctive angioplasty and use of glycoprotein IIb/IIIa antiplatelet agents at the time of angiography were discretionary. There were no treatment effects on coronary blood flow, infarct size, or the rate of ECG ST-segment elevation resolution, despite the expected induction of peripheral leukocytosis. A slight trend toward an increase in bacterial infections was observed with rhuMAb CD18 (P=0.33). CONCLUSIONS: RhuMAb CD18 was well tolerated but not effective in modifying cardiac end points.

Risks associated with renal dysfunction in patients in the coronary care unit.

OBJECTIVES: The purpose of this study was to quantify the impact of baseline renal dysfunction on morbidity and mortality in patients in the coronary care unit (CCU). BACKGROUND: The presence of renal dysfunction is an established independent predictor of survival after acute myocardial infarction and revascularization procedures. METHODS: We analyzed a prospective CCU registry of 12,648 admissions by 9,557 patients over eight years at a single, tertiary center. Admission serum creatinine was available in 9,544 patients. Those not on long-term dialysis were classified into quartiles of corrected creatinine clearance, with cut-points of 46.2, 63.1 and 81.5 ml/min per 72 kg. Dialysis patients (n = 527) were considered as a fifth comparison group. RESULTS: Baseline characteristics, including older age, African-American race, diabetes, hypertension, previous coronary disease and heart failure, were incrementally more common across increasing renal dysfunction strata. There were graded increases in the relative risk for atrial and ventricular arrhythmias, heart block, asystole, development of pulmonary congestion, acute mitral regurgitation and cardiogenic shock across the risk strata. Survival analysis demonstrated an early mortality hazard for those with renal dysfunction, but not on dialysis, for the first 60 months, followed by graded decrements in survival across increasing renal dysfunction strata. CONCLUSIONS: Baseline renal function is a powerful predictor of short- and long-term events in the CCU population. There is an early hazard for in-hospital and postdischarge mortality for those with a corrected creatinine clearance <46.2 ml/min per kg, but not on dialysis.

Discordance between effects of anti-ischemic therapy on ambulatory ischemia, exercise performance and anginal symptoms in patients with stable angina pectoris. The Angina and Silent Ischemia Study Group (ASIS).

OBJECTIVES: We sought to define the extent to which the therapeutic efficacy of three single-drug regimens on ambulatory ischemia paralleled efficacy on other clinical manifestations of ischemia, specifically exercise test performance and anginal symptoms. BACKGROUND: Some studies have shown that the presence and severity of ambulatory ischemia are predictive of anginal symptoms and exercise test performance, whereas other studies have not. Less is known about effects of antianginal treatment and whether response to therapy for one clinical manifestation reflects therapeutic responses for other clinical manifestations. METHODS: We studied 50 patients in the Angina and Silent Ischemia Study who had documented coronary disease, an exercise test positive for ischemia, the presence of ambulatory and asymptomatic ischemia on ambulatory electrocardiographic (ECG) Holter monitoring and stable anginal symptoms. Patients received maximally tolerated doses of sustained release propranolol (mean 293 mg/day), sustained release diltiazem (mean 350 mg/day), nifedipine (mean 79 mg/day) and placebo, each for 2-week periods in a double-blind, crossover fashion. Patients' responses to treatment were assessed by 48-h ambulatory ECG monitoring, exercise test (standard Bruce protocol) and diaries of angina. Levels of efficacy for each agent and for each clinical measure were compared using Spearman correlation analysis. RESULTS: With placebo there was no correlation among the frequency of ischemic episodes by ambulatory ECG monitoring, exercise time to 1.0-mm ST segment depression or frequency of anginal episodes. Furthermore, for a given patient the efficacy of each active medication in reducing ambulatory ischemia was not correlated with response in anginal symptoms or exercise test performance (r = -0.21 to 0.24, p = NS). Within each of these clinical measures, efficacy of one drug was more strongly correlated with efficacy of another drug (r = 0.64 to 0.81 for ambulatory ischemia, 0.48 to 0.56 for exercise test performance and 0.16 to 0.54 for anginal symptoms). CONCLUSIONS: Different measures of ischemia, specifically ambulatory ischemia assessed by ambulatory ECG monitoring, exercise performance on exercise test and anginal symptoms, are independent. Efficacy for each clinical end point must be assessed separately when considering response to drug treatment.

Low-molecular-weight heparins in the management of acute coronary syndromes.

Acute coronary syndromes (unstable angina and non-Q-wave myocardial infarction) are caused by the rupture of an atherosclerotic plaque, platelet activation, and fibrin deposition resulting in thrombosis. Aspirin and unfractionated heparin have traditionally been the treatments of choice for patients with acute coronary syndromes. Low-molecular-weight heparins offer potential advantages over unfractionated heparin, having proven equally effective for the treatment and prevention of many thromboembolic processes. Recently, a number of randomized controlled trials have been conducted to evaluate the role of low-molecular-weight heparins in the management of patients with unstable angina or non-Q-wave myocardial infarction. The purpose of this article is to review and evaluate the available literature on the use of low-molecular-weight heparins in the management of acute coronary syndromes to establish their role in therapy.

Prevention of peripheral venous catheter complications with an intravenous therapy team: a randomized controlled trial.

BACKGROUND: More than 25 million patients have peripheral intravenous (IV) catheters placed each year in US hospitals. Infusion therapy is believed to account for one third of all nosocomial bacteremias. METHODS: We performed a randomized, prospective, controlled study in a university-affiliated hospital to determine whether the use of an IV therapy team decreases peripheral venous catheter-related complications in adult medical patients. Patients were randomized to undergo peripheral catheter insertion and/or maintenance either by the IV team or by medical house staff. A dedicated observer reviewed catheter sites daily; findings were applied to a scoring system to define the severity of complications. Bacteremic complications were reviewed by a physician. RESULTS: Patients with catheters started by the house staff and maintained by ward nursing staff more often had signs or symptoms of inflammation (21.7%) than did patients with catheters maintained by the IV team (7.9%) (P<.001). Patients monitored by the IV team had a greater mean number of catheters placed per patient than did patients monitored by house staff (2.1 and 1.6, respectively) (P<.01). Three episodes of catheter-related sepsis occurred in house staff patients and none in IV team patients (P=.004). CONCLUSIONS: An IV therapy team significantly reduced both local and bacteremic complications of peripheral IV catheters. Timely replacement of the catheter appeared to be the most important factor in reducing the occurrence of complications.

Effect of delay on racial differences in thrombolysis for acute myocardial infarction.

OBJECTIVE: To analyze the effect of delay times on racial differences in thrombolysis for acute myocardial infarction. BACKGROUND: Lower rates of thrombolytic therapy in blacks with acute myocardial infarction have recently been reported, but the reasons for this disparity are unknown. We hypothesized that lower rates of thrombolysis are caused by delay in presentation after symptom onset. METHODS: From November 1992 through November 1996, consecutive patients with a first acute myocardial infarction presenting to a large, urban teaching hospital were prospectively enrolled. Delay times were determined retrospectively from review of medical records. Patients were prospectively followed up for in-hospital cardiac events and death. A multivariable regression model was built to relate presentation times and other variables to thrombolysis administration. RESULTS: A total of 395 patients were included in the study, of which 33% were black. Symptom onset to emergency department presentation and door-to-needle times were significantly longer in blacks. Thrombolysis was administered significantly less often in blacks compared with whites (47% vs 68%, P =.001). Black race and age above 60 years were independently associated with delayed presentation and prolonged door-to-needle times. Black race, time to presentation, and non-Q-wave myocardial infarction were independently associated with not receiving thrombolysis. In-hospital mortality rates were similar in both groups. CONCLUSIONS: Blacks presented later than whites for first acute myocardial infarction. Late arrival strongly influenced the rate of thrombolysis administration. Lower rates of thrombolysis and prolonged door-to-needle times were apparent in blacks after adjustment for delay times and other clinical factors, a finding that merits further investigation.

Underutilization of reperfusion therapy in eligible African Americans with acute myocardial infarction: Role of presentation and evaluation characteristics.

BACKGROUND: Immediate reperfusion therapy to restore coronary blood flow is recommended for all eligible patients with acute myocardial infarction. However, reperfusion therapy is reportedly underutilized among African Americans, even when they are eligible. Reasons for the lack of use have not been fully explored. METHODS: We examined the demographic, clinical, and treatment data of 10,469 African Americans with acute myocardial infarction who were eligible for reperfusion therapy, enrolled in the National Registry of Myocardial Infarction-2 from June 1994 through March 1998. RESULTS: The mean age was 62.58 (+/-14.4) years, and 44.7% were female. Although eligible, 47% of the African Americans in this study did not receive reperfusion therapy. In a multivariate analysis, the absence of chest pain at presentation (odds ratio [OR] 0.31, 95% CI 0.26-0.37) and initial admission diagnoses other than definite myocardial infarction (OR for receipt of reperfusion <0.12) were the strongest predictors of lack of early reperfusion therapy. Progressive delays in hospital arrival and hospital evaluation predicted a lower likelihood of early reperfusion. Prior stroke (OR 0.63, 95% CI 0.50-0.78), myocardial infarction (OR 0.75, 95% CI 0.65-0.86), and congestive heart failure (OR 0.49, 95% CI 0.40-0.60) were all associated with lack of reperfusion therapy. CONCLUSION: Almost half of eligible African American patients with myocardial infarction did not receive reperfusion therapy. Potential reasons may include atypical presentation, patient and institutional delay, and underappreciation of myocardial infarction by care providers. Strategies to address these factors may improve the rate of use of reperfusion therapy.

Usefulness of intravenous magnesium for multifocal atrial tachycardia in patients with chronic obstructive pulmonary disease.

Intravenous magnesium is an effective drug for rate control in multifocal atrial tachycardia. In addition, magnesium may be helpful in restoring sinus rhythm.

Intravenous clofilium for conversion of atrial fibrillation.

Clofilium was administered to 14 patients with mainly chronic atrial fibrillation in a pilot study. QTc prolongation was observed, and 2 patients had conversion to sinus rhythm after drug infusion.

Psychosocial factors related to unrecognized acute myocardial infarction.

Acute myocardial infarction (AMI) often is unrecognized (i.e., a patient fails to notice or report the event to the physician, or the physician fails to diagnose it). Psychosocial differences between patients with recognized and unrecognized AMI have not been examined. We compared 40 patients who sought treatment for a documented AMI with 30 patients who were found on routine electrocardiogram to have had an AMI for which they did not seek medical care. Patients with unrecognized AMI showed greater "alexithymia," or deficient psychologic awareness (p = 0.04; Alexithymia Provoked Response Interview), and a greater belief that chance factors determine their health (p = 0.004; Multidimensional Health Locus of Control Scale). Patients with unrecognized AMI were less likely to have angina, yet did not differ from those with recognized AMI with regard to demographics, smoking, systemic hypertension, diabetes mellitus, AMI location, depression, or hypochondriasis. We hypothesize that deficient psychologic awareness may impede AMI symptom perception or recognition, and that the belief in chance or fate as determining health may inhibit treatment-seeking.

Effects of prior aspirin and anti-ischemic therapy on outcome of patients with unstable angina. TIMI 7 Investigators. Thrombin Inhibition in Myocardial Ischemia.

Both aspirin and beta-adrenergic blocking drugs have been shown to reduce the risk of death or acute myocardial infarction (AMI) in patients with unstable angina, but their effect during chronic use on the presentation of acute coronary syndromes is less well defined. Calcium antagonists and oral nitrates are also widely prescribed for patients with coronary disease, but their effect on presentation of acute myocardial ischemia is unknown. We retrospectively examined the effects of prior aspirin and anti-ischemic medical therapy on clinical events in 410 patients hospitalized for unstable angina. Ischemic pain occurred at rest for a duration of 5 to 60 minutes. During hospitalization, 97% of patients received aspirin and all received the direct thrombin inhibitor bivalirudin for at least 72 hours. Despite being older and more likely to have risk factors for coronary disease and poor outcome, patients receiving aspirin before admission were less likely to present with non-Q-wave AMI (5% vs 14% in patients not on aspirin, p = 0.004). Prior beta blocker, calcium antagonist, or nitrate administration did not appear to modify presentation as unstable angina or non-Q-wave AMI. In a multivariate model, the combined incidence of death, AMI not present at enrollment, or recurrent angina was best predicted by age (adjusted odds ratio [95% confidence interval] 2.38 [1.14 to 3.98]) and presence of electrocardiographic changes with pain on presentation (adjusted odds ratio 2.83 [1.50 to 5.35]) but was not related to prior or in-hospital medical therapy. Thus, aspirin but not anti-ischemic therapy before hospitalization of patients with unstable angina was associated with a decreased incidence of non-Q-wave AMI on admission.

Determinants of mortality after myocardial infarction in patients with advanced renal dysfunction.

Previous studies using administrative data have shown high mortality in patients with renal failure requiring dialysis after acute myocardial infarction (AMI). There has been little investigation into the mortality after AMI in those with advanced renal disease who are not on dialysis therapy. We analyzed a prospective coronary care unit registry of 1,724 patients with ST segment elevation myocardial infarction admitted over an 8-year period at a single tertiary-care center. Those not on chronic dialysis therapy were stratified into groups based on corrected creatinine clearance, with cutoff values of 46.2, 63.1, and 81.5 mL/min/72 kg. Dialysis patients (n = 47) were considered as a fifth comparison group. Older age, black race, diabetes, hypertension, previous coronary disease, and heart failure were incrementally more common across increasing renal dysfunction strata. There were also graded increases in the relative risk for atrial and ventricular arrhythmias, heart block, asystole, development of pulmonary congestion, acute mitral regurgitation, and cardiogenic shock. Primary angioplasty, thrombolysis, and beta-blockers were used less often across the risk strata (P < 0.0001 for all trends). There was an early mortality hazard (age-adjusted relative risk, 8.76; P < 0.0001) for those with renal dysfunction but not on dialysis therapy for the first 60 months, followed by graded decrements in survival across increasing renal dysfunction strata. The excess mortality in this population appears to be mediated through arrhythmias, adverse hemodynamic events, and the lower use of mortality-reducing therapy.

Multifocal atrial tachycardia.

Multifocal atrial tachycardia is typically seen in elderly patients with severe illnesses, most commonly COPD. The mechanism of the arrhythmia may be delayed afterdepolarizations leading to triggered activity, but this has not been firmly established. The initial treatment of multifocal atrial tachycardia should include supportive measures and aggressive reversal of precipitating causes. Since multifocal atrial tachycardia is commonly a secondary phenomenon, the role for antiarrhythmic therapy is unclear. Metoprolol, magnesium, and verapamil have been evaluated in a few treatment studies, and may have a role in the treatment of multifocal atrial tachycardia.

Quality of history taking in patients with aortic dissection.

STUDY OBJECTIVES: Aortic dissection generally is an acute catastrophe. Rapid diagnosis is critical. We hypothesized that the quality of history taking contributes to the accuracy of diagnosis in patients with dissection. DESIGN: Retrospective chart review of 83 patients, whose diagnosis of aortic dissection was confirmed by autopsy, surgery, CT scan, echocardiogram, or angiogram. The quality of the initial history was reviewed using predetermined criteria. The physicians' initial clinical impressions were recorded. RESULTS: The examining physician correctly suspected aortic dissection after the initial clinical evaluation in 54 of 83 patients (65%). Only 33 of 78 patients with symptoms (42%) were asked about the quality, location, and onset of their pain, the three descriptors identified a priori as important. In 19 patients (24%), only zero or one descriptor was recorded. When all three questions were asked, dissection was suspected in 30 of 33 patients (91%); when zero, one, or two questions were asked, dissection was suspected in 22 of 45 patients (49%). CONCLUSION: Despite important advances in diagnostic imaging, accurate diagnosis of aortic dissection requires an accurate history. In our series, the quality of initial history was associated with the accuracy of the initial clinical impression in patients with aortic dissection.

How safely and for how long can warfarin therapy be withheld in prosthetic heart valve patients hospitalized with a major hemorrhage?

STUDY OBJECTIVES: To identify the risk of thromboembolism after withholding or reversing the effect of warfarin therapy following a major hemorrhage. DESIGN: Retrospective medical record review. SETTING: Tertiary-care hospital. PATIENTS: Twenty-eight patients with prosthetic heart valves receiving warfarin were hospitalized for major hemorrhage from 1990 to 1997. The mean +/- SD age was 61 +/- 11 years (15 men and 13 women). Twenty patients had St. Jude valves, 4 patients had Carpentier-Edwards bioprosthetic valves, 2 patients had Starr Edwards valves, and 2 patients had Bjork-Shiley valves. Valves were in the mitral position in 12 patients, the aortic position in 12 patients, and both mitral and aortic positions in 4 patients. The average interval from valve surgery to index bleeding was 7 years. Twenty-five patients had GI or retroperitoneal hemorrhage, 2 patients had an intracranial hemorrhage, and 1 patient had a subdural hematoma. INTERVENTIONS: Vitamin K was administered to five patients and fresh frozen plasma was given to seven patients to reverse anticoagulation. The mean duration of anticoagulation withholding was 15 +/- 4 days. MEASUREMENTS AND RESULTS: None of the patients had thromboembolic complications. There were four in-hospital deaths. Twenty-two of the 24 hospital survivors resumed warfarin therapy at hospital discharge. At 6-month follow-up, 10 of 19 patients remaining on warfarin therapy had recurrent GI bleeding. CONCLUSIONS: Thromboembolic risk is low in prosthetic heart valve patients hospitalized with major hemorrhage when their warfarin therapy is reversed or withheld. Recurrent bleeding within 6 months of the resumption of anticoagulation is common, and aggressive treatment of the bleeding source and the risk-benefit ratio of continued anticoagulation need to be considered.

Atrial fibrillation after bypass surgery: does the arrhythmia or the characteristics of the patients prolong hospital stay?

STUDY OBJECTIVES: The goal of this study was to determine whether prolonged hospital stay associated with atrial fibrillation or flutter (AF) after coronary artery bypass graft (CABG) surgery is attributable to the characteristics of patients who develop this arrhythmia or to the rhythm disturbance itself. DESIGN: An investigation was conducted through a prospective case series. SETTING: Patients were from a single urban teaching hospital. PARTICIPANTS: Consecutive patients undergoing isolated CABG surgery between December 1994 and May 1996 were included in the study. INTERVENTIONS: No interventions were involved. RESULTS: Of 436 patients undergoing isolated CABG surgery, 101 (23%) developed AF. AF patients were older and more likely to have obstructive lung disease than patients without AF, but both patients with and without AF had similar left ventricular function and extent of coronary disease. ICU and hospital stays were longer in patients with AF. Multivariate analysis, adjusted for age, gender, and race, demonstrated that postoperative hospital stay was 9.2+/-5.3 days in patients with AF and 6.4+/-5.3 days in patients without AF (p<0.001). CONCLUSIONS: Although AF is strongly associated with advanced age, most of the prolonged hospital stay appears to be attributable to the rhythm itself and not to patient characteristics.

Inhibition of N-acetylation of procainamide and renal clearance of N-acetylprocainamide by para-aminobenzoic acid in humans.

Procainamide administration often results in excessively high serum N-acetylprocainamide (NAPA) concentrations and subtherapeutic serum procainamide concentrations. Inhibition of N-acetylation of procainamide may prevent accumulation of excessive NAPA while maintaining therapeutic serum procainamide concentrations. The purpose of this randomized, two-way crossover study was to determine if para-aminobenzoic acid (PABA) inhibits N-acetylation of procainamide in healthy volunteers. Eleven (7 female, 4 male) fast acetylators of caffeine received, in random order, PABA 1.5 g orally every 6 hours for 5 days, with a single intravenous dose of procainamide 750 mg administered over 30 minutes on the third day, or intravenous procainamide alone. Blood samples were collected during a 48-hour period after initiation of the infusion. Urine was collected over a 72-hour period. Serum procainamide and NAPA concentrations were analyzed using fluorescence polarization immunoassay. Urine procainamide and NAPA concentrations were measured with high performance liquid chromatography. PABA did not significantly influence total or renal procainamide clearance, elimination rate constant, AUC0-00, amount of procainamide excreted unchanged in the urine, or volume of distribution. However, concomitant PABA administration with procainamide resulted in increases in NAPA AUC0-00 and t1/2 and reductions in NAPA Ke, procainamide acetylation (NAPA formation) clearance, and NAPA renal clearance. Although PABA inhibits metabolic conversion of procainamide to NAPA, it also impairs the renal clearance of NAPA (but not procainamide) in healthy subjects. Therefore, PABA may not be useful for optimizing the safety of efficacy of procainamide in patients.

Disposition of procainamide in patients with chronic congestive heart failure receiving medical therapy.

Dosage reduction of procainamide has been recommended in patients with congestive heart failure (CHF). However, these recommendations are based primarily on studies with unmatched control groups, suboptimal blood sampling, and in patients not receiving angiotensin-converting enzyme (ACE) inhibitors. These agents increase renal blood flow, which theoretically may offset alterations in drug disposition in patients with CHF. The pharmacokinetics of procainamide in patients with chronic CHF and in matched controls were compared. A single intravenous dose of 750 mg of procainamide was administered to 9 patients with chronic New York Heart Association (NYHA) class II or III CHF (mean +/- SD left ventricular ejection fraction 22 +/- 9%) receiving medical therapy and 7 control subjects matched for age and gender. Blood and urine samples were collected at intervals over a period of 48 and 72 hours, respectively. Patients with CHF and control subjects were demographically similar, with the exception of concomitant medications, including ACE inhibitors (8/9 versus 1/7, respectively). There were no significant differences between patients with CHF and control subjects in mean +/- SD peak serum concentrations (Cmax), area under the serum concentration-time curve (AUC0-infinity), total clearance, renal clearance, half-life (t1/2), or volume of distribution (Vd) of procainamide. Similarly, there were no significant differences between patients with CHF and control subjects in the mean +/- SD Cmax, AUC0-infinity, renal clearance, or t1/2 of N-acetylprocainamide (NAPA). Procainamide dosage reduction may not be necessary in patients with chronic stable CHF who are receiving medical therapy.

Combination therapy with tirofiban and enoxaparin in acute coronary syndromes.

BACKGROUND: Tirofiban, an intravenous glycoprotein IIb/IIIa antagonist, and enoxaparin, a low molecular weight heparin, have each been shown to be effective at reducing cardiac ischemic events compared to unfractionated heparin alone in separate trials of patients with unstable angina and non-Q-wave myocardial infarction. The combination of these agents may offer further therapeutic benefit. MATERIALS AND METHODS: Fifty-five patients with non-Q-wave myocardial infarction were randomized to receive double-blind treatment with tirofiban (0.1 microgram/kg/min i.v.) for 48-108 h coadministered with either enoxaparin (1 mg/kg sc q 12 h) (n=26) or unfractionated heparin (i.v. adjusted to activated partial-thromboplastin time) (n=27) to evaluate pharmacokinetics, pharmacodynamics, and safety. The primary objective of the study was to investigate the effect of unfractionated heparin versus enoxaparin on the plasma clearance of tirofiban. RESULTS: Coadministration of tirofiban and enoxaparin was generally well tolerated. Plasma clearance of tirofiban was 176.7+/-59.8 and 187.5+/-81.8 ml/min, respectively, for enoxaparin and unfractionated heparin-treated patients (P=NS). The mean difference was well within the prespecified criterion for comparability. Administration of tirofiban with enoxaparin vs. unfractionated heparin resulted in lesser variability and a trend towards greater inhibition of platelet aggregation using 5 microM adenosine phosphate agonist. More patients achieved target inhibition of platelet aggregation >70% in the tirofiban and enoxaparin group (84% vs. 65%, P=0.19). Median bleeding time was 21 min for tirofiban and enoxaparin vs. > or =30 min for tirofiban and unfractionated heparin (P=NS). For a given level of inhibition of platelet aggregation, bleeding time was less prolonged with tirofiban and enoxaparin than tirofiban and unfractionated heparin (adjusted mean bleeding time 19.6 vs. 24.9 min, P=0.02). Tirofiban plasma concentration and clearance were comparable whether coadministered with enoxaparin or unfractionated heparin. There were no major or minor bleeding events in either group by the TIMI criteria. INTERPRETATION: The more consistent inhibition of platelet aggregation and lower adjusted bleeding time of tirofiban and enoxaparin vs. tirofiban and unfractionated heparin support the therapeutic potential of combining these two agents. These data from the first clinical report of coadministration of a glycoprotein IIb/IIIa receptor antagonist and a low molecular weight heparin are consistent with prior data which show differential pharmacodynamic effects of enoxaparin and unfractionated heparin on platelet aggregation.