Lessons learned from recent cardiovascular clinical trials: Part I.
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Endpoint Determination↗
Biomedical subjects
Robert M Califf
Publications and source records attributed to Robert M Califf.
An independently derived and validated predictive model for selecting patients with myocardial infarction who are likely to benefit from tissue plasminogen activator compared with streptokinase.
BACKGROUND: In the Global Utilization of Streptokinase and tPA for Occluded coronary arteries (GUSTO) trial, patients with myocardial infarction who were treated with tissue plasminogen activator (tPA) had a 6.3% 30-day mortality, compared with a mortality of 7.3% among those treated with streptokinase, despite a greater risk of intracranial hemorrhage with tPA. However, in part because of its higher cost, tPA has not been adopted universally. METHODS: Using an independently developed model, we predicted the benefits of tPA therapy in the 24,146 patients in the GUSTO trial and compared these predictions with the actual benefits of tPA, after classifying patients by their risks of mortality and intracranial hemorrhage. We also performed a "patient-specific" cost-effectiveness analysis among different strata of expected benefit of tPA. RESULTS: Our model predicted that among patients with myocardial infarction, 61% of the benefit of tPA use in reducing mortality accrued to only 25% of patients; treating half of patients could capture 85% of the benefit. Including the risk of intracranial hemorrhage, our model predicted that treating half the GUSTO patients with tPA and the others with streptokinase would yield similar outcomes as treating all patients with tPA, because the additional risk of intracranial hemorrhage exceeded the expected benefit in some patients. When patients were stratified into quartiles of risk, the observed outcomes in the GUSTO patients corresponded well with these predicted results. The estimated cost-effectiveness of tPA was sensitive to patient characteristics. CONCLUSION: For selected patients, use of tPA yields substantially better outcomes than streptokinase, and use of the less expensive agent is difficult to justify. For many patients, however, tPA is unlikely to provide any additional benefit and, in some patients, it may even cause net harm.
Adult↗
Sustained ventricular arrhythmias among patients with acute coronary syndromes with no ST-segment elevation: incidence, predictors, and outcomes.
BACKGROUND: The prognosis of ventricular arrhythmias among patients with non-ST-elevation acute coronary syndromes is unknown. We studied the incidence, predictors, and outcomes of sustained ventricular arrhythmias in 4 large randomized trials of such patients. METHODS AND RESULTS: We pooled the datasets of the Global Use of Streptokinase and tPA for Occluded Arteries (GUSTO)-IIb, Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON)-A, and PARAGON-B trials (n=26 416). We identified independent predictors of ventricular fibrillation (VF) and ventricular tachycardia (VT) and compared the 30-day and 6-month mortality rates of patients who did (n=552) and did not (n=25 864) develop these arrhythmias during the index hospitalization. Independent predictors of in-hospital VF included prior hypertension, chronic obstructive pulmonary disease, prior myocardial infarction, and ST-segment changes at presentation. Except for hypertension, these variables also independently predicted in-hospital VT. In Cox proportional-hazards modeling, in-hospital VF and VT were independently associated with 30-day mortality (hazard ratio [HR], 23.2 [95% CI, 18.1 to 29.8] for VF and HR, 7.6 [95% CI, 5.5 to 10.4] for VT) and 6-month mortality (HR, 14.8 [95% CI, 12.1 to 18.3] for VF and HR, 5.0 [95% CI, 3.8 to 6.5] for VT). These differences remained significant after excluding patients with heart failure or cardiogenic shock and those who died <24 hours after enrollment. CONCLUSIONS: Despite the use of effective therapies for non-ST-elevation acute coronary syndromes, ventricular arrhythmias in this setting are associated with increased 30-day and 6-month mortality. More effective therapies are needed to improve the survival of patients with these arrhythmias.
Acute Disease↗
Comparison of coronary artery bypass grafting versus medical therapy on long-term outcome in patients with ischemic cardiomyopathy (a 25-year experience from the Duke Cardiovascular Disease Databank).
In this observational treatment comparison in a single center over 25 years, we sought to assess long-term outcomes of coronary artery bypass surgery (CABG) or medical therapy in patients with heart failure, coronary artery disease, and left ventricular systolic dysfunction. The benefit of CABG compared with medical therapy alone in these patients is a source of continuing clinical debate. This analysis considered all patients with New York Heart Association class II or greater symptoms, 1 or more epicardial coronary vessels with a > or = 75% stenosis, and a left ventricular ejection fraction <40% who underwent an initial cardiac catheterization at Duke University Medical Center from 1969 to 1994. Patients were classified into the medical therapy group (n = 1,052) or CABG group (n = 339) depending on which therapy they received within 30 days of catheterization. Cardiovascular event and mortality follow-up commenced on the day of CABG, or at catheterization plus 8 days (the mean time to CABG) for the medical therapy arm. A Cox proportional-hazards model was employed to adjust for differences in baseline characteristics. In the first 30 days from baseline, there was an interaction between treatment strategy and number of diseased vessels. Unadjusted, event-free, and adjusted survival strongly favored CABG over medical therapy after 30 days to >10 years regardless of the extent of coronary disease (p <0.001). Thus, regardless of the severity of coronary disease, heart failure symptoms, or ventricular dysfunction, CABG provides extended event-free and survival advantage over medical therapy alone in patients with an ischemic cardiomyopathy.
Aged↗
Inhaled ethyl nitrite gas for persistent pulmonary hypertension of the newborn.
Inhaled nitric oxide is used to alleviate pulmonary hypertension and hypoxaemia, but generates toxic free radicals and oxides of nitrogen (NO(x)), which can cause rebound-hypoxia and additional pulmonary and other morbidity. To address these problems, we assessed the efficacy of inhaled O-nitrosoethanol gas (ENO) as a novel alternative means of providing nitric oxide bioactivity in the treatment of persistent pulmonary hypertension of newborns. We administered ENO over 4 h to seven neonates who required assisted ventilation, and who had an oxygenation index of 25 or more. ENO was then shut off for 15 min before start of treatment with inhaled nitric oxide. Our results show that ENO produced sustained improvements in postductal arterial oxygenation and systemic haemodynamics, which were maintained during the off-drug observation period. Increases in methaemoglobinaemia were modest and toxic NO(x) were not detected. Thus, ENO can improve oxygenation and systemic haemodynamics in neonates, and seems to reduce rebound hypoxaemia and production of toxic byproducts.
Administration, Inhalation↗
Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction.
BACKGROUND: Among patients with suspected acute coronary syndromes, cardiac troponin T levels have prognostic value. However, there is concern that renal dysfunction may impair the prognostic value, because cardiac troponin T may be cleared by the kidney. METHODS: We analyzed the outcomes in 7033 patients enrolled in the Global Use of Strategies to Open Occluded Coronary Arteries IV trial who had complete base-line data on troponin T levels and creatinine clearance rates. The troponin T level was considered abnormal if it was 0.1 ng per milliliter or higher, and creatinine clearance was assessed in quartiles. The primary end point was a composite of death or myocardial infarction within 30 days. RESULTS: Death or myocardial infarction occurred in 581 patients. Among patients with a creatinine clearance above the 25th percentile value of 58.4 ml per minute, an abnormally elevated troponin T level was predictive of an increased risk of myocardial infarction or death (7 percent vs. 5 percent; adjusted odds ratio, 1.7; 95 percent confidence interval, 1.3 to 2.2; P<0.001). Among patients with a creatinine clearance in the lowest quartile, an elevated troponin T level was similarly predictive of increased risk (20 percent vs. 9 percent; adjusted odds ratio, 2.5; 95 percent confidence interval, 1.8 to 3.3; P<0.001). When the creatinine clearance rate was considered as a continuous variable and age, sex, ST-segment depression, heart failure, previous revascularization, diabetes mellitus, and other confounders had been accounted for, elevation of the troponin T level was independently predictive of risk across the entire spectrum of renal function. CONCLUSIONS: Cardiac troponin T levels predict short-term prognosis in patients with acute coronary syndromes regardless of their level of creatinine clearance.
Abciximab↗
Early statin initiation and outcomes in patients with acute coronary syndromes.
CONTEXT: The secondary prevention benefit of therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has been clearly demonstrated; however, the role of early initiation of statins after acute coronary syndromes (ACSs) is unknown. OBJECTIVE: To evaluate the association of early statin initiation (< or = 7 days) after ACS with 90-day and 1-year outcomes. DESIGN: Observational cohort from databases of 2 randomized clinical trials, SYMPHONY and 2nd SYMPHONY. SETTING: Nine hundred thirty-one clinical centers in 37 countries. PATIENTS: A total of 12,365 ACS patients randomized from August 1997 to August 1999 who were not taking statins prior to the index ACS and who either started statin therapy early (median, 2.0 [interquartile range, 1.0-3.1] days after ACS; n = 3952) or survived more than 5 days after ACS and never received statin therapy (n = 8413). MAIN OUTCOME MEASURES: Ninety-day incidence of death; death or myocardial infarction (MI); and death, MI, or severe recurrent ischemia; as well as 1-year incidence of death. RESULTS: Ninety-day and 1-year unadjusted mortality comparison suggested early statin benefit (1.2% for early statins vs 2.1% for no statins; hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.42-0.81 for 90-day comparisons and 2.3% for early statins vs 4.4% for no statins; HR, 0.52; 95% CI, 0.40-0.68 for 1-year comparison). However, no benefit was evident for 90-day death or MI (6.5% vs 6.9%; HR, 0.95; 95% CI, 0.82-1.11) or death, MI, or severe recurrent ischemia (9.2% vs 8.9%; HR, 1.04; 95% CI, 0.92-1.18). After propensity and covariate adjustment, there were no 90-day or 1-year differences between the early-statin group and the no-statin group. The 90-day adjusted HR for death was 1.08 (95% CI, 0.75-1.56); for death or MI, 1.08 (95% CI, 0.91-1.29); and for death, MI, or severe recurrent ischemia, 1.15 (95% CI, 0.99-1.34). One-year mortality-adjusted HR was 0.99 (95% CI, 0.73-1.33). Among 2711 patients with core laboratory lipid analysis, early statin was associated with higher adjusted risk for death or death or MI at cholesterol levels below treatment guidelines but was more favorable at higher levels. CONCLUSIONS: In this study, there was no relationship between early initiation of statin therapy and improved outcomes although our subset analysis suggests that outcomes after early statin initiation may vary with cholesterol levels. Confirmation of early treatment effects of statins on outcomes awaits the results of adequately powered randomized clinical trials.
Acute Disease↗
Early angioplasty in acute coronary syndromes without persistent ST-segment elevation improves outcome but increases the need for six-month repeat revascularization: an analysis of the PURSUIT Trial. Platelet glycoprotein IIB/IIIA in Unstable angina: Receptor Suppression Using Integrilin Therapy.
OBJECTIVES: We explored the effect of timing of percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS) without persistent ST-segment elevation on the need for repeat revascularization, and we related this effect to other events. BACKGROUND: Percutaneous coronary intervention is widely used to treat ACS without persistent ST-segment elevation. Moreover, restenosis and subsequent revascularization after PCI are more frequent in ACS than in stable angina. The optimal timing of PCI in ACS without persistent ST-segment elevation is unknown. METHODS: In the Platelet glycoprotein IIB/IIIA in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) database, patients were stratified by the time of PCI. In the PURSUIT trial, 9,461 patients received a platelet glycoprotein IIb/IIIa inhibitor, eptifibatide or placebo for 72 h. The investigators decided on other treatments. RESULTS: A total of 2,430 patients underwent PCI within 30 days. Repeat revascularization (during 165 days) was notably higher for PCI within 24 h of enrollment (n = 620 [19%]) than for PCI at 24 to 72 h (n = 624 [16.7%]), 3 to 7 days (n = 614 [13.2%]), or 8 to 30 days (n = 561 [7.7%]; p < 0.001), regardless of eptifibatide use. This gradual reduction in the revascularization rate for later PCI was also observed after multivariate analysis correcting for baseline characteristics and with time as a continuous variable. CONCLUSIONS: Percutaneous coronary intervention within 24 is associated with improved outcome (other analysis) but more repeat revascularization. Prospective analyses are needed to test the hypothesis that rapid PCI in ACS with a platelet glycoprotein IIb/IIIa receptor antagonist reduces myocardial infarction (and possibly death) and is therefore most suited for patients at highest risk of infarction, despite a higher need for repeat revascularization.
Aged↗
Prognostic significance of elevated troponin I after percutaneous coronary intervention.
OBJECTIVES: We sought to assess the incidence and clinical significance of elevated cardiac troponin I (cTnI) after percutaneous coronary intervention (PCI). BACKGROUND: Elevated creatine kinase-MB (CK-MB) is prognostically important after PCI, but the prognostic significance of elevated cTnI after PCI is uncertain. METHODS: In a prospective substudy of the Sibrafiban Versus Aspirin to Yield Maximum Protection From Ischemic Heart Events Post-acute Coronary Syndromes (SYMPHONY) trials, which randomized patients with acute coronary syndromes (ACS) to receive aspirin or sibrafiban, we measured cTnI (positive, > or =1.5 ng/ml) and CK-MB (positive, > or =7 ng/ml) in 481 patients with PCI. Samples were collected immediately before and at 0, 8 and 16 h after PCI and analyzed by a core laboratory. The primary end point was the Kaplan-Meier estimate of death, myocardial infarction or severe, recurrent ischemia at 90 days. RESULTS: Overall, 230 patients (48%) had elevated cTnI after PCI. Such patients underwent PCI sooner and were more likely to have coronary stenting. Elevated cTnI was associated with nonsignificantly higher risks of the primary end point (11.5% vs. 8.7%; p = 0.15) and of death (1.8% vs. 0.4%; p = 0.4) and a significantly higher risk of death or infarction (10.6% vs. 4.2%; p = 0.005). This pattern was more pronounced for patients who became positive only after PCI: primary end point, 20.7% vs. 10.1% for patients who remained negative after PCI (p = 0.05); death, 5.2% vs. 0% (p = 0.02); death or infarction, 18.1% vs. 4.1% (p = 0.007). CONCLUSIONS: Elevated cTnI, often observed after PCI in patients with ACS, is associated with worse 90-day clinical outcomes. This marker, therefore, is a useful prognostic indicator in such patients.
Angina, Unstable↗
The failure of orally administered glycoprotein IIb/IIIa inhibitors to prevent recurrent cardiac events.
PURPOSE: Despite the success of intravenous glycoprotein IIb/IIIa antagonists, oral formulations have failed to show benefit and have been associated with increased mortality. To understand these findings, we performed a meta-analysis of results from four phase 3 trials. SUBJECTS AND METHODS: Trials were identified by MEDLINE search; review of abstracts from American College of Cardiology, European Society of Cardiology, and American Heart Association scientific sessions; or querying investigators in the field. Published, phase 3, randomized, placebo-controlled trials involving more than 1000 patients with coronary artery disease that compared an oral glycoprotein IIb/IIIa antagonist with or without background aspirin versus aspirin, and that had a planned follow-up of > or =30 days, were included. Four trials met these criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were generated from results, and combined using an empirical Bayes random-effects model. RESULTS: Among 33,326 patients, oral glycoprotein IIb/IIIa agents were associated with 31% increased mortality (OR = 1.31; 95% CI: 1.12 to 1.53; P= 0.0001). Results were similar whether the agent was added to (OR = 1.38; 95% CI: 1.15 to 1.67) or substituted for (OR = 1.37; 95% CI: 1.00 to 1.86) aspirin. Ischemic events or sudden death (OR = 1.22; 95% CI: 0.91 to 1.63) were also more common. Among patients with acute coronary syndromes, the incidence of myocardial infarction was increased (OR = 1.16; 95% CI: 1.03 to 1.29). CONCLUSION: Oral glycoprotein IIb/IIIa inhibitor therapy is associated with increased mortality and myocardial infarction. No single explanation for these findings is satisfactory; the problem is likely to be multifactorial.
Administration, Oral↗
Patient-reported frequency of taking aspirin in a population with coronary artery disease.
Despite the established benefits of antiplatelet agents in coronary artery disease (CAD), many appropriate patients are not receiving them. We investigated the prevalence of and factors associated with aspirin use and nonuse within a large referral population with CAD. The goal was to identify an approach to increase the use of antiplatelet agents by such patients. We surveyed a subset (n = 2,694) of a large CAD referral population (n = 16,174) to determine the use of aspirin and factors associated with its use or nonuse. The subset was made up of all of the CAD referral population who were considered nonusers of aspirin and a 5% sample of those considered aspirin users. We then extrapolated survey data to the overall population to estimate how many eligible patients were not taking antiplatelet agents. In all, 1,626 (63%) of the surviving patients responded to the survey. Of these, 948 (58%) reported taking aspirin, and 678 (42%) reported no aspirin use. The extrapolated rate of aspirin use in the overall population was 85%. Of 2,367 nonusers, 998 (42%, or 6% of the overall cohort) were eligible for antiplatelet agents but were not taking such therapy. Although the rate of aspirin use in this population was higher than previously reported, an estimated 6% of eligible patients were not receiving antiplatelet therapy.
Anti-Inflammatory Agents, Non-Steroidal↗
Differential influence of diabetes mellitus on increased jeopardized myocardium after initial angioplasty or bypass surgery: bypass angioplasty revascularization investigation.
BACKGROUND: Data are absent that compare midterm angiographic outcome between patients with and without diabetes after initial percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft surgery (CABG). Importantly, diabetes mellitus may differentially influence long-term survival after PTCA or CABG. METHODS AND RESULTS: Patients with multivessel coronary disease who were previously enrolled in the Bypass Angiopathy Revascularization Investigation to compare initial PTCA versus CABG (n=1829) and who had a reduction in jeopardized myocardium after initial revascularization and at least 1 angiogram during 5-year follow-up were analyzed (n=897). This included 369 CABG-treated patients (16% with diabetes) and 528 PTCA-treated patients (18% with diabetes). The influence of diabetes on angiographic increase in percentage of jeopardized myocardium after initial revascularization with either PTCA or CABG was investigated. Among PTCA patients, the mean percentage increase in total jeopardized myocardium was significantly greater in those with diabetes than in those without at 1-year protocol-directed angiography (42% versus 24%, P=0.05) and on the first clinically performed (unscheduled) angiogram within 30 months (63% versus 50%, P=0.01) but not at 5-year protocol-directed angiography (34% versus 26%, P=0.33). This excess midterm risk associated with diabetes persisted after statistical adjustment. In contrast, among CABG patients, diabetes was not associated with percentage increase in jeopardized myocardium at any angiographic follow-up interval. CONCLUSIONS: Presence of diabetes differentially influences worsening of jeopardized myocardium after initial PTCA compared with CABG. This differential effect occurs irrespective of whether follow-up angiography is undertaken for clinical or nonclinical purposes.
Aged↗
The coxib story: some lessons and more questions.
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Anti-Inflammatory Agents, Non-Steroidal↗
Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial.
CONTEXT: Extracts of Hypericum perforatum (St John's wort) are widely used for the treatment of depression of varying severity. Their efficacy in major depressive disorder, however, has not been conclusively demonstrated. OBJECTIVE: To test the efficacy and safety of a well-characterized H perforatum extract (LI-160) in major depressive disorder. DESIGN AND SETTING: Double-blind, randomized, placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States. PARTICIPANTS: Adult outpatients (n = 340) recruited between December 1998 and June 2000 with major depression and a baseline total score on the Hamilton Depression Scale (HAM-D) of at least 20. INTERVENTIONS: Patients were randomly assigned to receive H perforatum, placebo, or sertraline (as an active comparator) for 8 weeks. Based on clinical response, the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg. Responders at week 8 could continue blinded treatment for another 18 weeks. MAIN OUTCOME MEASURES: Change in the HAM-D total score from baseline to 8 weeks; rates of full response, determined by the HAM-D and Clinical Global Impressions (CGI) scores. RESULTS: On the 2 primary outcome measures, neither sertraline nor H perforatum was significantly different from placebo. The random regression parameter estimate for mean (SE) change in HAM-D total score from baseline to week 8 (with a greater decline indicating more improvement) was -9.20 (0.67) (95% confidence interval [CI], -10.51 to -7.89) for placebo vs -8.68 (0.68) (95% CI, -10.01 to -7.35) for H perforatum (P =.59) and -10.53 (0.72) (95% CI, -11.94 to -9.12) for sertraline (P =.18). Full response occurred in 31.9% of the placebo-treated patients vs 23.9% of the H perforatum-treated patients (P =.21) and 24.8% of sertraline-treated patients (P =.26). Sertraline was better than placebo on the CGI improvement scale (P =.02), which was a secondary measure in this study. Adverse-effect profiles for H perforatum and sertraline differed relative to placebo. CONCLUSION: This study fails to support the efficacy of H perforatum in moderately severe major depression. The result may be due to low assay sensitivity of the trial, but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy.
Adult↗
Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial.
CONTEXT: Little randomized evidence is available to guide the in-hospital management of patients with an acute exacerbation of chronic heart failure. Although intravenous inotropic therapy usually produces beneficial hemodynamic effects and is labeled for use in the care of such patients, the effect of such therapy on intermediate-term clinical outcomes is uncertain. OBJECTIVE: To prospectively test whether a strategy that includes short-term use of milrinone in addition to standard therapy can improve clinical outcomes of patients hospitalized with an exacerbation of chronic heart failure. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial conducted from July 1997 through November 1999. SETTING: Seventy-eight community and tertiary care hospitals in the United States. PARTICIPANTS: A total of 951 patients admitted with an exacerbation of systolic heart failure not requiring intravenous inotropic support (mean age, 65 years; 92% with baseline New York Heart Association class III or IV; mean left ventricular ejection fraction, 23%). INTERVENTION: Patients were randomly assigned to receive a 48-hour infusion of either milrinone, 0.5 microg/kg per minute initially (n = 477), or saline placebo (n = 472). MAIN OUTCOME MEASURE: Cumulative days of hospitalization for cardiovascular cause within 60 days following randomization. RESULTS: The median number of days hospitalized for cardiovascular causes within 60 days after randomization did not differ significantly between patients given milrinone (6 days) compared with placebo (7 days; P =.71). Sustained hypotension requiring intervention (10.7% vs 3.2%; P<.001) and new atrial arrhythmias (4.6% vs 1.5%; P =.004) occurred more frequently in patients who received milrinone. The milrinone and placebo groups did not differ significantly in in-hospital mortality (3.8% vs 2.3%; P =.19), 60-day mortality (10.3% vs 8.9%; P =.41), or the composite incidence of death or readmission (35.0% vs 35.3%; P =.92) CONCLUSION: These results do not support the routine use of intravenous milrinone as an adjunct to standard therapy in the treatment of patients hospitalized for an exacerbation of chronic heart failure.
Acute Disease↗
Underuse of aspirin in a referral population with documented coronary artery disease.
Despite substantial evidence that antiplatelet therapy saves lives and reduces adverse events in patients with coronary artery disease (CAD), use of the most widely available and lowest cost antiplatelet agent, aspirin, continues to be disappointingly low. In a large database of patients with known CAD, we (1) explored trends in the use of aspirin over time, (2) characterized patients most likely to take aspirin regularly, and (3) estimated the effectiveness of aspirin use by examining long-term outcomes. Using patients entered in the Duke Databank for Cardiovascular Diseases, we explored the use of aspirin from 1969 to 1999. More than 25,000 patients were sent a questionnaire that included several questions about medication use, including 1 question specifically about aspirin. Patients who failed to respond to the questionnaire received a follow-up telephone call. Aspirin use increased substantially over the most recent 4 years in the study, from 59% in 1995 to 81% in 1999. Predictors of aspirin use included younger age, male sex, being a nonsmoker, and having had a myocardial infarction or revascularization procedure. Patients who never took aspirin had a risk ratio for death of 1.85 compared with patients who regularly took aspirin. Despite the well-known beneficial effects of aspirin, too many patients without contraindications to aspirin fail to take it regularly. The health care system currently lacks effective methods to ensure that patients who have CAD have adequate follow-up concerning aspirin use.
Adult↗
Long-term efficacy of platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention.
CONTEXT: In the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial, treatment with eptifibatide, a platelet glycoprotein IIb/IIIa integrin blocker, was found to reduce the ischemic complications of nonurgent coronary stent implantation at 48 hours and 30 days. OBJECTIVE: To determine whether eptifibatide treatment continues to provide durable, long-term benefit after coronary stent intervention. DESIGN AND SETTING: The ESPRIT trial was a randomized, double-blind, placebo-controlled, parallel-group, crossover-permitted trial conducted from June 1999 through February 2000 at 92 tertiary care centers in the United States and Canada. PARTICIPANTS: A total of 2064 patients scheduled to undergo nonurgent percutaneous coronary intervention with stent implantation. INTERVENTION: Patients were randomly assigned to receive placebo (n = 1024) or eptifibatide (two 180-microg/kg boluses, 10 minutes apart, with a continuous infusion of 2.0 microg/kg per minute; n = 1040), started immediately before stent implantation and continued for 18 to 24 hours. Patients also received aspirin, heparin, and a thienopyridine. MAIN OUTCOME MEASURES: Composite rates of death or myocardial infarction (MI) and death, infarction, or target vessel revascularization during the 12 months after enrollment. RESULTS: Complete follow-up data were available for 988 patients given eptifibatide (95.0%) and 976 patients given placebo (95.3%). By 12 months, the composite of death or MI had occurred in 8.0% of eptifibatide-treated patients and in 12.4% of placebo-treated patients (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.48-0.83; P =.001). The composite rate of death, MI, or target vessel revascularization was 17.5% in eptifibatide-treated patients vs 22.1% in placebo-treated patients (HR, 0.76; 95% CI, 0.63-0.93; P =.007). CONCLUSIONS: Long-term outcomes of nonurgent coronary stent implantation appear to be improved through blockade of the platelet glycoprotein IIb/IIIa integrin with eptifibatide.
Aged↗
Outcomes of patients with acute coronary syndromes and prior coronary artery bypass grafting: results from the platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial.
BACKGROUND: Patients with prior CABG with a subsequent non-ST-segment elevation acute coronary syndrome (ACS) pose an increasingly important clinical problem. Although GP IIb/IIIa inhibitors have improved the outcome of patients with ACS, their efficacy in patients with prior CABG has not been previously evaluated. Methods and Results- We analyzed the 30- and 180-day outcomes of patients with prior CABG enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial. In this trial, which evaluated the efficacy of eptifibatide in patients with ACS, 1134 patients (12%) with prior CABG and 8321 without prior CABG were enrolled. After adjusting for differences in baseline characteristics and treatment, patients with prior CABG had a significantly higher mortality rates at 30 days (hazard ratio [HR], 1.45 [95% CI, 1.06 to 1.98]; P=0.019) and at 180 days (HR, 1.32 [95% CI, 1.04 to 1.67]; P=0.021). At 30 days, there was a similar effect on the primary end point of death or myocardial infarction in the eptifibatide group versus the placebo group in prior CABG patients (unadjusted HR, 0.90 [95% CI, 0.67 to 1.20]) and in patients without a history of CABG (unadjusted HR, 0.89 [95% CI, 0.80 to 0.99]). CONCLUSIONS: Patients with prior CABG with non-ST-segment elevation ACS have a significantly worse prognosis than do patients without a history of CABG. The treatment effect of eptifibatide in the prior CABG group was similar to the effect seen in patients without prior CABG.
Acute Disease↗