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R M Califf

Publications and source records attributed to R M Califf.

At least 361 records · Page 20Linked to original sources
PubMed1995

An overview of the results of the EPIC trial.

The Evaluation of 7E3 for the Prevention of Ischaemic Complications (EPIC) trial assessed the use of abciximab in the treatment of patients at high risk undergoing percutaneous revascularization procedures. Abciximab (c7E3) is a chimeric monoclonal antibody targeted to block the glycoprotein IIb/IIIa receptor on the surface of the platelet; this receptor is believed to be the final common pathway of platelet aggregation. Administered at the time of angioplasty or directional coronary atherectomy, abciximab had a beneficial effect in the population studied, which included patients considered to be at high risk from complications of the procedure, based on the presence of acute or recent myocardial infarction, severe unstable angina or adverse coronary morphological characteristics. Abciximab reduced the risk of the primary endpoint at 30 days (death, myocardial infarction, repeat angioplasty or bypass surgery for recurrent ischaemia, balloon pump or stent insertion for ischaemia) by 35%: from 12.8% in the placebo group to 8.3% in patients treated with abciximab bolus and infusion. This trend was observed as a whole and in each component of the primary endpoint. At 6 months follow-up, the effect of the treatment was modestly enhanced beyond 30 days. A variety of substudies have documented substantial evidence of treatment benefit in patients with acute myocardial infarction and unstable angina. Non-fatal infarction, observed as beyond that normally expected in other studies with directional coronary atherectomy, was not above normal in patients treated with abciximab, and there was evidence of a treatment benefit in the elderly, although more information would be helpful in patients over the age of 70. The substantial site-to-site variability indicates that standardization of percutaneous revascularization could enhance the benefit of abciximab, while reducing bleeding complications.

Abciximab↗
PubMed1995

How should clinicians interpret clinical trials?

Given the rapid evolution of cardiovascular medicine, clinicians must sift through an enormous array of information about new therapies in order to determine how best to treat patients with ischemic heart disease. They should first consider the evidence from randomized clinical trials, because these trials eliminate bias and permit broad statistical analyses. If randomized clinical trial data are not available, next in order of the strength of their evidence are observational studies, historically controlled studies, case series, and case reports. Clinicians must additionally ascertain that an investigation has the elements of good design, including a clear question, adequate sample size, appropriate inclusion and exclusion criteria, evidence that the right amount of data was collected carefully, and allowances in the analyses for patients taking multiple therapies and randomized into several clinical trials.

Case-Control Studies↗
PubMed1994

A pooled analysis of coronary arterial patency and left ventricular function after intravenous thrombolysis for acute myocardial infarction.

Individual studies of patency rates and left ventricular (LV) function after thrombolysis have generally been limited by small numbers of observations, wide confidence intervals, and limited numbers of time points. To obtain a more reliable estimate of patterns of patency and LV ejection fraction, a systemic overview of angiographic studies was performed after intravenous thrombolytic therapy. A total of 14,124 angiographic observations from 58 studies evaluating patency after no thrombolytic agent, streptokinase, standard dose tissue-type plasminogen activator (t-PA), accelerated dose t-PA, or anistreplase (anisoylated plasminogen streptokinase activator complex [APSAC]) were included. At 60 and 90 minutes, streptokinase had the lowest patency rates of 48% and 51%, respectively, standard dose t-PA and APSAC had similar intermediate rates of approximately 60% and 70%, and accelerated t-PA had the highest patency rates of 74% and 84%. By 2 to 3 hours and longer, the patency rates were similar for the various regimens. Reocclusion rates in studies including 1,172 patients randomized to t-PA versus a nonfibrin-specific agent were higher after t-PA (13.4% vs 8.0%, p = 0.002). Ten studies enrolling 4,088 patients treated with thrombolytic therapy versus control demonstrated a modest improvement in mean LV ejection fraction in the thrombolytic group at each of the times after thrombolytic therapy: hour 4, day 1, day 4, day 7 to 10, and day 10 to 28 after thrombolysis. By 4 days, mean ejection fraction was 53% versus 47% (thrombolytic vs control therapy, p < 0.01); by 10 to 28 days it was 54.1% and 51.5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1994

Use of medical resources and quality of life after acute myocardial infarction in Canada and the United States.

BACKGROUND: Much attention has been directed to the use of medical resources and to patients' outcomes in Canada as compared with the United States. We compared U.S. and Canadian patients with respect to their use of medical resources and their quality of life during the year after acute myocardial infarction. METHODS: A total of 2600 U.S. and 400 Canadian patients were randomly selected from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial. Base-line data from their initial hospitalizations were analyzed, and the patients were then interviewed by telephone 30 days, 6 months, and 1 year after myocardial infarction to determine their use of medical care and quality of life. RESULTS: The Canadian patients typically stayed in the hospital one day longer (P = 0.009) than the U.S. patients but had a much lower rate of cardiac catheterization (25 percent vs. 72 percent, P < 0.001), coronary angioplasty (11 percent vs. 29 percent, P < 0.001), and coronary bypass surgery (3 percent vs. 14 percent, P < 0.001). At one year 24 percent of the Canadian and 53 percent of the U.S. patients had undergone angioplasty or bypass surgery at least once (P < 0.001). The Canadian had more visits to physicians during the follow-up year (P < 0.001), but fewer visits to specialists (P < 0.001). At 30 days, functional status was equivalent in the patients from the two countries. However, after one year the U.S. patients had substantially more improvement than the Canadian patients (P < 0.001). The prevalence of chest pain and dyspnea at one year was higher among the Canadian patients (34 percent vs. 21 percent and 45 percent vs. 29 percent, respectively; P < 0.001). CONCLUSIONS: The Canadian patients had more cardiac symptoms and worse functional status one year after acute myocardial infarction than the U.S. patients. The Canadian patients also underwent fewer invasive cardiac procedures and had fewer visits to specialist physicians. These results suggest, but do not prove, that the more aggressive pattern of care in the United States may have been responsible for the better quality of life.

Aged↗
PubMed1994

Comparison of continuous ST-segment recovery analysis with methods using static electrocardiograms for noninvasive patency assessment during acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 7 Study Group.

Continuous ST-segment recovery analysis and 5 static methods using ST-segment comparison between a pre- and post-treatment electrocardiogram were compared for their ability to predict infarct-related artery patency in 82 patients with acute myocardial infarction who underwent angiography a median of 124 minutes after onset of thrombolytic treatment. Accuracy at the moment of angiography was 85% (95% confidence interval [CI] 77% to 93%) for the continuous method, and 68% (CI 57% to 78%), 78% (CI 69% to 87%), 83% (CI 74% to 91%), 82% (CI 73% to 90%), and 80% (CI 71% to 89%) for the static methods. At the moment of angiography the most accurate static method and the continuous method agreed in patency assessment in 90% of the patients (CI 84% to 97%). Agreement was reduced to 83% (CI 75% to 91%) of patients when a patency assessment was performed earlier at 90 minutes after treatment onset, and was only 77% (CI 68% to 86%), at 60 minutes. Early disagreement was mainly seen when the continuous ST recording showed ST recovery from a delayed peak ST elevation after the pretreatment static electrocardiogram or when dynamic ST changes suggesting cyclic reperfusion occurred. Continuous ST-segment recovery analysis appears to be as accurate as the most accurate static methods. Continuously updated reference points appear to give important additional information when ST recovery follows a delayed peak ST elevation or when re-elevation occurs, suggesting cyclic flow changes. Such findings appear to affect about half of patients with acute myocardial infarction treated with intravenous thrombolysis, particularly early after administration of therapy.

Aged↗
PubMed1994

Holding GUSTO up to the light. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial, a recent randomized "megatrial" of thrombolytic therapies in acute myocardial infarction, showed a statistically significant decrease of 30-day mortality in patients treated with accelerated-dose tissue plasminogen activator (tPA) compared with streptokinase. The therapeutic and cost implications of the results have been intensely scrutinized, and several commentaries have been written on the interpretation of the study. Questions have been raised about the treatment benefit in certain subgroups, the validity of the results because of the open-label design, the relevance of a 1% absolute benefit in mortality rates, the cost-effectiveness of the drug, and the generalizability of the results. These issues are all important considerations for translating the results of this study into clinical practice worldwide. This article sheds additional light on the interpretation of GUSTO, clarifies misconceptions that may have clouded understanding of the trial results, and discusses the contributions of this trial in advancing our understanding of modern myocardial reperfusion therapy.

Cost-Benefit Analysis↗
PubMed1994

A meta-analysis of randomized trials of calcium antagonists to reduce restenosis after coronary angioplasty.

The usefulness of calcium antagonists to reduce restenosis after coronary angioplasty remains uncertain despite 5 randomized trials involving 919 patients. Review and meta-analysis of these trials are performed to provide insight into whether calcium antagonists reduce angiographic restenosis. In aggregate, these trials suggest that patients treated with calcium antagonists had approximately a 30% reduction in the odds of angiographic restenosis (odds ratio = 0.68; 95% confidence interval of 0.49 to 0.94, p = 0.03) compared with control patients. Given the relatively low toxicity and cost of these agents, this reduction in angiographic restenosis may translate into a meaningful clinical benefit. A large, randomized clinical trial should be performed to confirm these findings before widespread adoption of this treatment strategy.

Adult↗
PubMed1994

Absence of sex bias in the referral of patients for cardiac catheterization.

BACKGROUND: It has been suggested that women with clinical evidence of coronary artery disease are less often referred for cardiac catheterization than are men. To determine whether there is sex-related bias in referral for cardiac catheterization, we prospectively studied a cohort of 410 symptomatic outpatients (280 men and 130 women) who were being evaluated with exercise testing for possible-coronary artery disease. METHODS: Before the patients underwent exercise testing, 15 cardiologists from an academic medical center were asked to predict the probability that the patients they saw in the cardiology clinic would have angiographic evidence of any obstructive coronary disease (stenosis of 75 percent or more); the probability of severe coronary disease (three-vessel or left main coronary artery disease); the probability of left main coronary artery disease; and the probability of survival one, three, and five years after the evaluation. Similar predictions were generated by previously validated statistical models with use of data collected before exercise testing from the history, physical examination, and 12-lead electrocardiography with the patient at rest. RESULTS: Overall, women were referred for cardiac catheterization significantly less often than men (18 percent vs. 27 percent, P = 0.03). As compared with men, women had a significantly lower pretest probability of coronary disease (as estimated by their physicians) and a lower rate of positive exercise-test results. After accounting for differences in these two factors, sex was not an independent predictor of referral for catheterization. Comparing physicians' estimates of outcome with those generated by the statistical models revealed no evidence that the physicians were underestimating the risk of coronary disease in women. Furthermore, physicians' predictions did not underestimate the probability of any obstructive coronary disease in men and women who subsequently underwent catheterization. CONCLUSIONS: Academic cardiologists made appropriately lower pretest predictions of categories of disease in women with possible coronary artery disease than in men, and these assessments, along with women's lower rate of positive exercise tests, rather than bias based on sex, accounted for the lower rate of catheterization among women.

Aged↗
PubMed1994

Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months. The EPIC Investigators.

Restenosis after coronary angioplasty occurs in at least 30% of patients in the first six months and, as yet, there is no known treatment to decrease this event. We tested a monoclonal antibody Fab fragment (c7E3) directed against the platelet glycoprotein IIb/IIIa integrin, the receptor mediating the final common pathway of platelet aggregation, to see whether it reduced the frequency of clinical restenosis. Patients who had unstable angina, recent or evolving myocardial infarction, or high-risk angiographic morphology, were randomised to receive c7E3 bolus and a 12 hour infusion of c7E3 (708 patients), c7E3 bolus and placebo infusion (695 patients), or placebo bolus and placebo infusion (696 patients). With maintenance of the double-blind state, patients were followed-up for at least 6 months to determine the need for repeat angioplasty or surgical coronary revascularisation and the occurrence of ischaemic events. By 30 days, 12.8% of placebo bolus/placebo infusion patients had had a major ischaemic event (death, myocardial infarction, urgent revascularisation), compared with 8.3% of c7E3 bolus/c7E3 infusion patients, yielding a 4.5% difference (35% reduction, p = 0.008). At 6 months, the absolute difference in patients with major ischaemic event or elective revascularisation was 8.1% between placebo bolus/placebo infusion and c7E3 bolus/c7E3 infusion patients (35.1% vs 27.0%; 23% reduction p = 0.001). The favourable long-term effect was mainly due to less need for bypass surgery or repeat angioplasty in patients with an initial successful procedure, since need for repeat target vessel revascularisation was 26% less for c7E3 bolus/c7E3 infusion than for placebo treatment (16.5% vs 22.3%; p = 0.007). The c7E3 bolus/placebo infusion group had an intermediate outcome which was not significantly better than that of the placebo bolus/placebo infusion group. These results extend the benefit of c7E3 bolus/c7E3 infusion from reducing abrupt closure and acute-phase adverse outcomes to a diminished need for subsequent coronary revascularisation procedures. Because this therapy carries a risk of bleeding complications and has been studied only in high-risk angioplasty patients, further evaluation is needed before it can be applied to other patient groups.

Angioplasty, Balloon, Coronary↗
PubMed1994

Clinical importance of thrombocytopenia occurring in the hospital phase after administration of thrombolytic therapy for acute myocardial infarction. The Thrombolysis and Angioplasty in Myocardial Infarction Study Group.

OBJECTIVES: The purpose of this study was to examine the incidence and clinical implications of thrombocytopenia that occurs in hospital after administration of thrombolytic therapy for acute myocardial infarction. BACKGROUND: The use of thrombolytic therapy in patients with acute myocardial infarction has improved mortaltiy rates, but hemorrhage remains a major complication. Because thrombocytopenia may be associated with hemorrhage after thrombolytic therapy, we examined the incidence and clinical implications of thrombocytopenia after administration of thrombolytic therapy for acute myocardial infarction. METHODS: The patient population comprised 1,001 patients enrolled in Phases 2, 3 and 5 of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trial and the urokinase trial. Patients received recombinant tissue-type plasminogen activator, urokinase or combination therapy in various dosing schemes. All patients received heparin, aspirin and a calcium-channel blocking agent. Thrombocytopenia occurring anytime after thrombolytic therapy was defined as a nadir platelet count either < 100,000/microliters or < 1/2 baseline. Blood loss was quantified by a bleeding index. Multiple logistic regression was used to evaluate the independent contribution of thrombocytopenia in a model predicting in-hospital mortality. RESULTS: Thrombocytopenia occurred in 16.4% of patients, with no difference among the thrombolytic regimens. Patients with thrombocytopenia had a lower median acute ejection fraction and a higher likelihood of three-vessel coronary artery disease than patients without thrombocytopenia. Patients with thrombocytopenia had more hemorrhage, a higher in-hospital mortality rate and a more complicated hospital course than patients without thrombocytopenia, even after consideration of other important variables, including age, acute ejection fraction, number of diseased vessels, bypass surgery and use of intraaortic balloon counterpulsation. CONCLUSIONS: Thrombocytopenia after thrombolytic therapy is a common event and is associated with excess hemorrhage and mortality. Platelet counts should be monitored daily after administration of thrombolytic therapy because the appearance of thrombocytopenia identifies a subset of patients at increased risk for hemorrhage and death.

Aged↗