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Biomedical subjects

R M Califf

Publications and source records attributed to R M Califf.

At least 271 records · Page 15Linked to original sources
PubMed1997

TIMI grade 3 flow and reocclusion after intravenous thrombolytic therapy: a pooled analysis.

Early and sustained flow of grade 3 according to Thrombolysis in Myocardial infarction (TIMI) criteria and reocclusion rates are the key measures that define the physiologic efficacy of thrombolytic agents in the treatment of acute myocardial infarction. We performed a systematic overview of angiographic studies after intravenous thrombolysis with accelerated and standard-dose tissue-plasminogen activator (TPA), anisoylated plasminogen streptokinase activator complex (APSAC), and streptokinase. There were 5475 angiographic observations from 15 studies for TIMI flow analysis and 3147 angiographic observations from 27 studies for reocclusion. At 60 and 90 minutes, the rates of TIMI grade 3 flow were 57.1% and 63.2%, respectively, with accelerated TPA, 39.5% and 50.2% with standard-dose TPA, 40.2% and 50.1% with APSAC, and 31.5% at 90 minutes with streptokinase. Overall reocclusion with standard-dose TPA was 11.8% versus 6.0% for accelerated TPA, 4.2% for streptokinase, and 3.0% for APSAC. Although the incidence of TIMI grade 3 flow increased over time with all thrombolytic regimens, decreased patency was observed at 180 minutes with accelerated TPA. Still, accelerated TPA is the most effective agent to establish early (90-minute) TIMI grade 3 flow.

Anistreplase↗
PubMed1997

Developing systems for cost-effective auditing of clinical trials.

Auditing a clinical trial is a complex process designed to ensure that the trial will provide a reliable answer to the question being posed. Traditional auditing methods are expensive, and escalate the cost of clinical trials. This paper describes approaches to cost-effective monitoring of clinical trials, such as integrating them with clinical practice and focusing the data being collected. Sampling methods for source documentation can be used to eliminate costs incurred by reviewing every record. These measures, coupled with prospective clinical judgment about areas of concern in the conduct of trials, can reduce complications and costs without sacrificing quality.

Clinical Trials as Topic↗
PubMed1997

Gender and acute myocardial infarction: is there a different response to thrombolysis?

OBJECTIVES: This study sought to 1) determine the effect of gender on early and late infarct-related artery patency and reocclusion after thrombolytic therapy for acute myocardial infarction; 2) examine the effect of gender on left ventricular function in response to injury/reperfusion; and 3) assess the independent contribution of gender to early (30-day) mortality after acute myocardial infarction. BACKGROUND: Women have a higher mortality rate than men after myocardial infarction. However, the effect of gender on infarct-related coronary artery patency and left ventricular response to injury/reperfusion have not been fully defined in the thrombolytic era. METHODS: Patency rates and global and regional left ventricular function were determined in patients at 90 min and 5 to 7 days after thrombolytic therapy for acute myocardial infarction. The effect of gender on infarct-related artery patency and left ventricular function was determined. Thirty-day mortality differences between women and men were compared. RESULTS: Women were significantly older and had more hypertension, diabetes, hypercholesterolemia, heart failure and shock. They were less likely to have had a previous myocardial infarction, history of smoking or previous bypass surgery. Ninety-minute patency rates (Thrombolysis in Myocardial Infarction [TIMI] flow grade 3) in women and men were 39% and 38%, respectively (p = 0.5). Reocclusion rates were 8.7% in women versus 5.1% in men (p = 0.14). Women had more recurrent ischemia than men (21.4% vs. 17.0%, respectively, p = 0.01). Ninety-minute ejection fraction and regional ventricular function were clinically similar in women and men with TIMI 2 or 3 flow (ejection fraction [mean +/- SD]: 63.4 +/- 6% vs. 59.4 +/- 0.7%, p = 0.02; number of chords: 21.4 +/- 0.9 vs. 21.0 +/- 1.9, p = 0.7; SD/chord: -2.4 +/- 08 vs. -2.4 +/- 0.2, p = 0.9, respectively). No clinically significant differences in left ventricular function were noted at 5- to 7-day follow-up. Women had a greater hyperkinetic response than men in the noninfarct zone (SD/chord: 2.4 +/- 0.2 vs. 1.7 +/- 0.1, p = 0.005). The 30-day mortality rate was 13.1% in women versus 4.8% in men (p < or = 0.0001). After adjustment for other clinical and angiographic variables, gender remained an independent determinant of 30-day mortality. CONCLUSIONS: Women do not differ significantly from men with regard to either early infarct-related artery patency rates or reocclusion after thrombolytic therapy or ventricular functional response to injury/reperfusion. Gender was an independent determinant of 30-day mortality after acute myocardial infarction.

Aged↗
PubMed1997

Coronary revascularization surgery after myocardial infarction: impact of bypass surgery on survival after thrombolysis. GUSTO Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

OBJECTIVES: This study sought to investigate the impact of surgical revascularization on outcome after myocardial infarction. BACKGROUND: Small variations in rates of coronary artery bypass graft surgery (CABG) were noted among thrombolytic regimens in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial, prompting the question of whether survival differences were partly related to differences in CABG rates. METHODS: Patients in the GUSTO trial were randomized to one of four thrombolytic strategies. Of 40,861 patients with complete data, 3,526 underwent surgical revascularization during their initial hospital admission. Thirty-day and 1-year mortality rates were estimated using Kaplan-Meier techniques, and the impact of CABG as a time-dependent covariate on death was evaluated using a Cox survival model, adjusting for baseline prognostic factors. RESULTS: The median time from study enrollment to CABG was 7 days across treatment groups. A 15% reduction in mortality for the tissue-type plasminogen activator (t-PA)-treated group was evident by the seventh day. Bypass surgery was a significant independent predictor of 30-day mortality (risk ratio 1.87) and a weaker predictor of 1-year mortality (risk ratio 1.21). Operative mortality was highest in patients with acute mitral regurgitation, ventricular septal defect or poor left ventricular function and in those undergoing CABG within the first 4 days of randomization. CONCLUSIONS: The survival benefit of accelerated t-PA was not related to surgical revascularization. Bypass surgery was associated with excess mortality in the first year, but the added short-term mortality associated with CABG may be balanced by anticipated long-term benefit in specific groups of patients.

Aged↗
PubMed1997

Evidence for prevention of death and myocardial infarction with platelet membrane glycoprotein IIb/IIIa receptor blockade by abciximab (c7E3 Fab) among patients with unstable angina undergoing percutaneous coronary revascularization. EPIC Investigators. Evaluation of 7E3 in Preventing Ischemic Complications.

OBJECTIVES: We sought to evaluate whether patients with unstable angina undergoing coronary intervention derive particular clinical benefit from potent platelet inhibition. BACKGROUND: Plaque rupture and platelet aggregation are pathogenetic processes common to unstable angina and ischemic complications of percutaneous coronary intervention. METHODS: Of the 2,099 patients undergoing a coronary intervention in the Evaluation of 7E3 in Preventing Ischemic Complications (EPIC) trial, 489 were enrolled with the diagnosis of unstable angina and randomized to receive placebo, an abciximab (c7E3) bolus immediately before the intervention or an abciximab bolus followed by a 12-h infusion. The primary end point was a composite of death, myocardial infarction (MI) or urgent repeat revascularization within 30 days of randomization. The occurrence of death, MI or any revascularization within 6 months was also assessed. RESULTS: Compared with placebo, the bolus and infusion of abciximab resulted in a 62% reduction in the rate of the primary end point (12.8% vs. 4.8%, p = 0.012) among patients with unstable angina, due primarily to a reduction in the incidences of death (3.2% vs. 1.2%, p = 0.164) and MI (9% vs. 1.8%, p = 0.004). By 6 months, cumulative death and MI were further reduced by abciximab (6.6% vs. 1.8%, p = 0.018 and 11.1% vs. 2.4%, p = 0.002, respectively). The magnitude of the risk reduction with abciximab was greater among the patients with unstable angina than among other patients in the EPIC trial without unstable angina for the end points of death (interaction: p = 0.008 at 30 days, p = 0.002 at 6 months) and MI (interaction: p = 0.004 at 30 days, p = 0.003 at 6 months). CONCLUSIONS: The syndrome of unstable angina identifies patients who will experience particularly marked reductions in the risk of death and MI with abciximab during coronary intervention.

Abciximab↗
PubMed1997

Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. GUSTO-I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

OBJECTIVES: This study was undertaken to define and better understand the characteristics and outcomes of patients with diabetes treated for acute myocardial infarction with contemporary thrombolysis. BACKGROUND: Although thrombolysis has substantially improved survival of patients with myocardial infarction, diabetes mellitus remains an independent predictor for a poor prognosis. METHODS: We characterized the contemporary relation between diabetes and outcome after myocardial infarction treated with thrombolytic agents from a large international cohort. Of 41,021 patients randomized to receive accelerated tissue-type plasminogen activator (t-PA), streptokinase or a combination of both agents in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries study, there were 5,944 patients with diabetes and 34,888 patients without diabetes. RESULTS: Patients with diabetes were older and more likely to be female, to present with anterior wall infarction, to receive thrombolysis later and to have triple-vessel coronary artery disease. Mortality at 30 days was highest among diabetic patients treated with insulin (12.5%) compared with non-insulin-treated diabetic (9.7%) and nondiabetic (6.2%) patients (p < 0.001). Mortality was lowest among those with diabetes receiving accelerated t-PA, which is consistent with the results of the overall patient cohort. Although stroke occurred more frequently among diabetic (1.9%) than nondiabetic patients (1.4%, p < 0.001), there was no significant difference in the rates of intracranial hemorrhage. Cardiac failure, shock, atrioventricular block and atrial flutter/ fibrillation were more common among diabetic patients. The proportion of patients undergoing revascularization was similar between patients with and without diabetes, although diabetic patients were more likely to undergo coronary artery bypass graft surgery (10.4% vs. 8.3%). Diabetes remained an independent predictor for mortality at 1-year follow-up (14.5% vs. 8.9%, p < 0.001). CONCLUSIONS: Diabetes, alone and in association with its comorbidities, portends a substantially worse 30-day and 1-year prognosis for patients with myocardial infarction.

Aged↗
PubMed1997

Atrial fibrillation in the setting of acute myocardial infarction: the GUSTO-I experience. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.

OBJECTIVES: We examined the clinical predictors and angiographic and clinical outcomes associated with atrial fibrillation in the setting of acute myocardial infarction (MI). BACKGROUND: This condition has been studied primarily in prethrombolytic era small trials. METHODS: We compared baseline clinical characteristics, short-term clinical and angiographic outcomes and 1-year mortality of patients enrolled in the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial with atrial fibrillation on admission electrocardiography (n = 1,026 [2.5%]) or after enrollment (n = 3,254 [7.9%]) and those without atrial fibrillation (n = 36,611 [89.6%]). Univariable and multivariable analyses were used to assess relations between baseline factors and the development of atrial fibrillation. RESULTS: Patients with any atrial fibrillation more often had three-vessel coronary artery disease and initial Thrombolysis in Myocardial Infarction (TIMI) grade < 3 flow than those without the arrhythmia. In-hospital stroke was increased in patients with atrial fibrillation (3.1% vs. 1.3%, p = 0.0001), mainly ischemic stroke (1.8% vs. 0.5%, p = 0.0001). Significant multivariable predictors of later atrial fibrillation included advanced age, higher peak creatine kinase levels, worse Killip class and increased heart rate. The unadjusted mortality rate was significantly higher at 30 days (14.3% vs. 6.2%, p = 0.0001) and at 1 year (21.5% vs. 8.6%, p < 0.0001) in patients with atrial fibrillation. The adjusted 30-day mortality rate remained significantly higher with any (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.2 to 1.4) or later (OR 1.4, 95% CI 1.3 to 1.5) atrial fibrillation but not with baseline atrial fibrillation (OR 1.1, 95% CI 0.88 to 1.3). CONCLUSIONS: Atrial fibrillation in the setting of acute MI independently predicts stroke and 30-day mortality. More aggressive treatment strategies in this subgroup may be warranted and deserve further study.

Atrial Fibrillation↗
PubMed1997

Use of intraaortic balloon counterpulsation in patients presenting with cardiogenic shock: observations from the GUSTO-I Study. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.

OBJECTIVES: We sought to examine the use, complications and outcomes with early intraaortic balloon counterpulsation (IABP) in patients presenting with cardiogenic shock complicating acute myocardial infarction and treated with thrombolytic therapy. BACKGROUND: The use of IABP in patients with cardiogenic shock is widely accepted; however, there is a paucity of information on the use of this technique in patients with cardiogenic shock who are treated with thrombolytic therapy. METHODS: Patients who presented within 6 h of chest pain onset were randomized to one of four thrombolytic regimens. Cardiogenic shock was not an exclusion criterion, and data for these patients were prospectively collected. Patients presenting with shock were classified into early IABP (insertion within one calendar day of enrollment) or no IABP (insertion on or after day 2 or never). RESULTS: There were 68 (22%) IABP placements in 310 patients presenting with shock. Early IABP use occurred in 62 patients (20%) and none in 248 (80%). Most IABP use occurred in the United States (59 of 68 IABP placements) involving 32% of U.S. patients presenting with shock. Despite more adverse events in the early IABP group and more episodes of moderate bleeding, this cohort showed a trend toward lower 30-day and 1-year mortality rates. CONCLUSIONS: IABP appears to be underutilized in patients presenting with cardiogenic shock, both within and outside the United States. Early IABP institution is associated with an increased risk of bleeding and adverse events but a trend toward lower 30-day and 1-year all-cause mortality.

Aged↗
PubMed1997

Clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy.

OBJECTIVES: We sought to characterize the clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy. BACKGROUND: Patients with ischemic cardiomyopathy may have a worse prognosis than patients with nonischemic cardiomyopathy. Few studies have assessed the effect of ischemic versus nonischemic etiology on outcomes. METHODS: We analyzed prospectively collected data on 3,787 patients with a left ventricular ejection fraction < or = 40% who underwent coronary angiography. Patients were considered to have ischemic cardiomyopathy (n = 3,112) if they had a history of myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery or at least one major epicardial coronary artery with > or = 75% stenosis; all others were considered to have nonischemic cardiomyopathy (n = 675). RESULTS: The median age, ejection fraction and proportion of patients with New York Heart Association functional class III or IV symptoms for the nonischemic and ischemic groups were 55 years versus 63 years, 27% versus 32% and 57% versus 25%, respectively. After adjustment for baseline clinical risk factors and presenting characteristics, ischemic etiology remained an important independent predictor of 5-year mortality (p < 0.0001). The extent of coronary artery disease was a better predictor of survival than ischemic or nonischemic etiology (log likelihood chi-square 700 vs. 675, respectively). CONCLUSIONS: Ischemic etiology is a significant independent predictor of mortality in patients with cardiomyopathy. However, the extent of coronary artery disease contributes more prognostic information than the clinical diagnosis of ischemic or nonischemic cardiomyopathy. Further research is needed to refine the clinical definition of ischemic cardiomyopathy so that physicians can appropriately prescribe treatment and accurately predict outcome.

Adult↗
PubMed1997

Diabetic retinopathy should not be a contraindication to thrombolytic therapy for acute myocardial infarction: review of ocular hemorrhage incidence and location in the GUSTO-I trial. Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries.

OBJECTIVES: This study sought to evaluate the incidence of ocular hemorrhage in patients with and without diabetes after thrombolytic therapy for acute myocardial infarction. BACKGROUND: Ocular hemorrhage after thrombolysis has been reported rarely. However, there is concern that the risk is increased in patients with diabetes. In fact, diabetic hemorrhagic retinopathy has been identified as a contraindication to thrombolytic therapy without clear evidence that these patients have an increased risk for ocular hemorrhage. METHODS: We identified all suspected ocular hemorrhages from bleeding complications reported in patients enrolled in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-I trial. Additional information was collected on a one-page data form. We compared the incidence and location of ocular hemorrhages in patients with and without diabetes. RESULTS: There were 40,899 patients (99.7%) with information about diabetic history and ocular bleeding. Twelve patients (0.03%) had an ocular hemorrhage. Intraocular hemorrhage was confirmed in only one patient. There were 6,011 patients (15%) with diabetes, of whom only 1 had an ocular hemorrhage (eyelid hematoma after a documented fall). The upper 95% confidence intervals for the incidence of intraocular hemorrhage in patients with and without diabetes were 0.05% and 0.006%, respectively. CONCLUSIONS: Ocular hemorrhage and, more important, intraocular hemorrhage after thrombolytic therapy for acute myocardial infarction is extremely uncommon. The calculated upper 95% confidence interval for the incidence of intraocular hemorrhage in patients with diabetes was only 0.05%. We conclude that diabetic retinopathy should not be considered a contraindication to thrombolysis in patients with an acute myocardial infarction.

Aged↗
PubMed1997

Long-term follow-up of gender-specific outcomes after thrombolytic therapy for acute myocardial infarction from the GUSTO-I trial. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

Our objective was to assess gender differences in mortality 1 year after acute myocardial infarction (MI). The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial database of 41,021 patients with suspected acute MI was used to generate 1-year Kaplan-Meier survival plots. Risk quartiles and mortality of women and men were compared. The unadjusted 1-year mortality rate for the initial GUSTO-I population and 30-day survivors demonstrates a large gender gap [odds ratio for all patients = 2.2, 95% confidence interval (CI), 2.0-2.3, p < 0.001]. For the initial population, when adjusted for age, the gender gap is still apparent (odds ratio = 1.4, 95%, CI = 1.3-1.5, p < 0.001) although no longer significant when adjusted using the 30-day survival model (odds ratio = 1.06, 95% CI = 0.97-1.15, p < 0.001). For the 30-day survivors, adjustment based on age alone explained the 1-year mortality difference (risk ratio = 0.96, 95% CI 0.85-1.07, p = 0.441). When the population was divided into expected risk quartiles, women were more likely to fall into the higher expected risk quartiles, even after adjusting for age. A gender gap after acute MI is apparent, nearly all of which occurs within the first 30 days. A substantial portion of the gender gap is explained by the increased age of women, and the rest of the gap may be attributed to differences in variables predictive of 30-day mortality. During 1-year follow-up, the late mortality of women is no greater than that of age-matched men.

Female↗
PubMed1997

The GUSTO trial and the open artery theory.

The GUSTO trials have provided continuing insight into the complexities of a simple fundamental relationship: early and sustained coronary perfusion in patients with acute myocardial infarction leads to lower mortality and morbidity. To a large extent, the GUSTO trials have attempted to develop approaches to therapy that will ensure the highest early rate of reperfusion with the least risk. A table provides a summary of the completed trials and those that are planned in attempts to provide further knowledge in the continuing quest to improve the plight of patients with acute myocardial infarction.

Coronary Angiography↗
PubMed1997

Predictors of outcome of reperfusion therapy.

The physician wishing to estimate the risk of death for a patient experiencing acute myocardial infarction can rapidly use parameters available on first seeing the patient to estimate the expected mortality and can update this risk during the early phase of the event. From the initial evaluation, factors that exclude patients from reperfusion therapy constitute a substantially elevated risk. Older age, haemodynamic distress, and markers of ongoing ischaemia provide a large amount of prognostic information from the initial exam. Careful surveillance for additional complications allows continuous risk assessment during the early course.

Aged↗
PubMed1997

Assessing the value of newer pharmacologic agents in non-ST elevation patients: a decision support system application.

Newer pharmacologic agents have demonstrated significant clinical and economic benefit in high-risk percutaneous transluminal coronary angioplasty (PTCA) patients. However, the higher costs of these agents may prohibit their use in lower-risk coronary artery disease (CAD) populations. We developed a decision support system (DSS) to determine the level of clinical effectiveness these newer agents must exhibit to be either cost-neutral or cost-effective in non-ST elevation patients. Our DSS evaluated six month cumulative costs, increased years of life saved (YOLS), and lifetime cost-effectiveness. We found that these therapies can cost as much as $1500 and be cost-neutral at six months if they reduce the composite endpoint of death, myocardial infarction (MI), or revascularization by 15%, and they may cost as much as $3000 and be cost-effective if they reduce this endpoint by 10%.

Abciximab↗