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R M Califf

Publications and source records attributed to R M Califf.

At least 127 records · Page 7Linked to original sources
PubMed2000

Lack of progress in cardiogenic shock: lessons from the GUSTO trials.

AIMS: We used the GUSTO-I and GUSTO-III databases to evaluate our performance in treating cardiogenic shock patients over much of the 1990s. METHODS AND RESULTS: GUSTO-I (1990-1993) and GUSTO-III (1995-1997) prospectively identified all patients with cardiogenic shock complicating acute myocardial infarction. Demographics, clinical presentation and outcomes for cardiogenic shock patients in the two trials were compared. Only patients enrolled with cardiogenic shock in countries common to both trials were included in these analysis. The 695 patients with cardiogenic shock in GUSTO-III were compared with the 2814 patients with cardiogenic shock in GUSTO-I. GUSTO-III patients were older (P=0.0001) and more likely to be diabetic (P=0.009) and hypertensive (P=0.025). They had a higher Killip class (P=0.002) and significantly greater index anterior infarction than cardiogenic shock patients enrolled in GUSTO-I. Time to treatment, presentation heart rate, and diastolic blood pressure were similar; however, systolic blood pressure at presentation was higher among GUSTO-III patients (P=0.002). Rates of coronary angiography, pulmonary artery catheterization, and mechanical ventilation declined in GUSTO-III compared with GUSTO-I (P=0.001); rates of angioplasty and bypass surgery were similar. Cardiogenic shock mortality in GUSTO-III was significantly higher than in GUSTO-I (62 vs 54%, P=0.001), as were rates of reinfarction (14 vs 11%, P=0.013) and recurrent ischaemia (35 vs 27%, P=0.00001). Mortality at non-U.S. sites (68 and 64%) was higher than at U.S. sites (53 and 50%) in both GUSTO-I and GUSTO-III studies, respectively. Angioplasty, bypass surgery, and balloon pump rates were lower for non-U.S. patients. CONCLUSIONS: Cardiogenic shock continues to be associated with high mortality in thrombolytic-treated patients. Lower mortality observed in the U.S.A. supports consideration for percutaneous and surgical revascularization.

Aged↗
PubMed2000

Influence of diabetes mellitus on clinical outcomes across the spectrum of acute coronary syndromes. Findings from the GUSTO-IIb study. GUSTO IIb Investigators.

AIMS: We examined the characteristics, outcomes, and effects of hirudin vs heparin treatment of diabetic patients across the spectrum of acute coronary syndromes. METHODS AND RESULTS: We studied the 12,142 patients enrolled in the randomized GUSTO-IIb study. Diabetic patients (n=2175) were older, more often female, more often had prior cardiovascular disease, hypertension, and hyperlipidaemia, and less often were current smokers. Diabetic patients had a higher overall incidence of death or (re)infarction at 30 days (13.1% vs 8.5%, P=0.0001), whether they presented with ST-segment elevation (13.9% vs 9.9%, P=0.0017) or not (12.8% vs 7.8%, P=0.0001), and at 6 months (18.8% vs 11.4%, P=0.0001). Among diabetic patients, hirudin was associated with a tendency toward a lower risk of death or (re)infarction at 30 days (12.2% vs 13.9% with heparin) and 6 months (17.8% vs 20.2%). Diabetic patients had more major bleeding, stroke, heart failure, shock, atrioventricular block, and atrial arrhythmias, but no increased risk for ocular bleeding. CONCLUSIONS: Diabetic patients with acute coronary syndromes had worse 30-day and 6-month outcomes, particularly those without ST-segment elevation. The statistically non-significant trend toward improved outcomes with hirudin was similar among patients with and without diabetes, with a greater point estimate for the absolute difference in patients with diabetes.

Aged↗
PubMed2000

Cardiac protection: evolving role of angiotensin receptor blockers.

Congestive heart failure (HF) is a common and serious public health problem affecting approximately 5 million Americans. Recent treatment strategies have focused on attenuating the effects of angiotensin (Ang) II, which include vasoconstriction, sodium retention, sympathetic activation, and cell growth. Angiotensin-converting enzyme (ACE) inhibitors, which primarily block the systemic formation of Ang II, reduce HF-related morbidity and mortality rates. However, ACE inhibitors may not suppress Ang II activity over their entire dosing interval and, with long-term therapy, Ang II levels tend to return to normal. It is now known that Ang II can be formed independent of ACE by the action of enzymes such as chymase in local tissues, including the heart. Despite the established benefits of ACE inhibitor treatment, HF-related morbidity and mortality rates continue to increase because the aging of the population is placing more patients at risk of HF. By acting at the receptor level, Ang II receptor blockers (ARBs) should, at least theoretically, provide more "complete" Ang II blockade. Early evidence suggests that ARBs induce hemodynamic improvement in patients with HF and may reduce mortality rates. Because ACE inhibitors and ARBs block Ang II through fundamentally different mechanisms, the combination may provide additive therapeutic effects in patients with HF. Results from a pilot study suggest that the combination of an ACE inhibitor and valsartan results in a more thorough inhibition of Ang II and an additive improvement in cardiac hemodynamics. Clinical trials now in progress will elucidate the effects of combined ACE inhibitor and ARB therapy on HF-related morbidity and mortality rates.

Aged↗
PubMed2000

Combination therapy for acute myocardial infarction: fibrinolytic therapy and glycoprotein IIb/IIIa inhibition.

Reperfusion with a regimen of fibrinolytic therapy, aspirin, and unfractionated heparin is limited by a less than desirable reperfusion rate, an excessive reocclusion rate, a dose-limiting intracranial hemorrhage rate, and a competitive posture relative to direct coronary angioplasty. Only 50% to 60% of patients achieve early Thrombolysis in Myocardial Infarction grade 3 flow within 90 minutes with the most effective thrombolytic regimens. Even after initial reperfusion is achieved, transient and permanent reocclusion occurs too often and is associated with a high mortality rate. As more older patients are being treated, intracranial hemorrhage is becoming more common. Finally, the risk of bleeding and procedural failure has been high in patients who received an acute percutaneous interventional procedure shortly after treatment with fibrinolytic therapy. Early studies combining full-dose fibrinolytic treatment and glycoprotein IIb/IIIa inhibitors have been promising with regard to overcoming these limitations, but concern about bleeding has hindered this strategy. Several recent trials have evaluated full-dose abciximab with reduced-dose fibrinolytic therapy and have yielded promising results. The complementary nature of the results from different trials is striking, with substantial evidence that approximately half the conventional dose of fibrinolytic therapy combined with full-dose glycoprotein IIb/IIIa inhibition with abciximab achieves high rates of grade 3 flow and excellent clinical outcomes. This approach will now be tested in a large-scale mortality trial.

Abciximab↗
PubMed2000

Hierarchy of risk based on history and location of prior myocardial infarction in the thrombolytic era. GUSTO-I Investigators.

BACKGROUND: Among patients receiving thrombolytic therapy for myocardial infarction, the outcome for those with a history of infarction is dramatically worse than for those with their first event. Methods And Results We performed a post hoc analysis of patients with a history of myocardial infarction enrolled in the Global Utilization of Streptokinase and TPA for Occluded arteries (GUSTO)-I trial, focusing on the impact of the location of their current and prior events on mortality rates. Within the first 24 hours, mortality rate was greatest among patients with a current infarction in a territory remote from their previous event. By 48 hours after examination, mortality rates among patients with a second anterior infarct had overtaken that among patients with a current inferior/prior anterior infarct. This hierarchy of risk persisted at both 30 days and 1 year (mortality rate at 1 year: current anterior/prior inferior 23.2% +/- 1.4%, current anterior/prior anterior 20% +/- 1.5%, current inferior/prior anterior 17% +/- 1.2%, current inferior/prior inferior 10.8% +/- 0. 9%). CONCLUSIONS: In patients with ST-elevation myocardial infarction on a background of prior infarction, the location of current and prior events predicts a hierarchy of short- and long-term risk of death.

Aged↗
PubMed2000

Clinical correlates and course of thrombocytopenia during percutaneous coronary intervention in the era of abciximab platelet glycoprotein IIb/IIIa blockade.

BACKGROUND: Thrombocytopenia is infrequently associated with abciximab therapy but may contribute to hemorrhagic risk. Factors associated with development of thrombocytopenia, the role of weight-adjustment in concomitant heparin administration, and clinical outcomes in patients with thrombocytopenia are not well defined. METHODS AND RESULTS: Pooled data from 3 placebo-controlled, randomized trials (EPIC, EPILOG, and EPISTENT) of abciximab therapy during percutaneous coronary intervention identified 178 patients (2. 4% of 7290 patients) in whom thrombocytopenia (platelet count <100 x 10(9)/L) developed after enrollment. Multivariate regression analysis identified age (>65 years; P <.001), weight (<90 kg; P =. 023), baseline platelet count (<200 x 10(9)/L; P <.001), abciximab therapy (P =.002), and enrollment into the EPIC trial (P <.001) to be associated with development of thrombocytopenia. Major and minor nonsurgical hemorrhage and transfusion were more frequent (all P <. 001) in thrombocytopenic patients. Although the primary composite clinical end point of these trials (death, myocardial infarction, or urgent revascularization to 30 days) was observed with similar frequency in patients with (11.2%) and those without (7.9%; P =.114) thrombocytopenia, 30-day mortality rate was higher in thrombocytopenic patients (8.4% vs 0.6%, respectively; P <.001). This excess mortality rate persisted after excluding patients in whom thrombocytopenia was first noted after the performance of coronary bypass surgery (4.8% vs 0.6%; P <.001). Among patients in whom thrombocytopenia developed during these trials, those who received prophylactic abciximab had fewer primary end point events (7.1% vs 23.1%; P =.056) and had a lower 30-day mortality rate (3.5% vs 15.4%; P =.048) than patients with thrombocytopenia who had received prophylactic placebo. CONCLUSIONS: Thrombocytopenia associated with abciximab therapy for percutaneous coronary intervention was more frequent in older, lighter-weight patients, those with lower baseline platelet counts, and in those patients who were enrolled into the EPIC trial. Both bleeding and transfusion events occur more frequently in patients with thrombocytopenia. Patients in whom thrombocytopenia developed during these trials had increased mortality rates to 30 days not attributable to the performance of coronary bypass surgery. Among patients with thrombocytopenia, those who received prophylactic abciximab had better clinical outcomes including survival than those who did not.

Abciximab↗
PubMed2000

Predictors of recurrent ischemic events and death in unstable coronary artery disease after treatment with combination antithrombotic therapy.

BACKGROUND: Patients with non-Q-wave acute coronary syndromes (ACS) have substantial rates of recurrent ischemic events, but prognostic studies have been small or preceded the routine use of aggressive combination antithrombotic therapy. We sought to identify predictors of these events after antithrombotic treatment of non-Q-wave ACS. METHODS: We assessed 30-day rates of a composite triple end point (death, infarction, or refractory angina) and double end point (death or infarction) among 3171 patients with non-ST-segment elevation ACS randomly assigned to enoxaparin or heparin, plus aspirin, for 2 to 8 days. We created multivariable regression models to predict these end points from baseline factors. RESULTS: Overall, 682 patients (21%) reached the triple end point and 220 (6.8%) reached the double end point. Independent predictors of the triple end point were admission with myocardial necrosis, ST-segment depression, prior angina severity, symptom duration, and allocation to enoxaparin treatment in patients with ST-segment depression (significant interaction). Independent predictors of the double end point were admission with myocardial necrosis, ST-segment depression, enrollment region, age >75 years, prior angina severity, and rales. By deciles, the average predicted risk for the double end point ranged from 2% to 20%: a patient aged <75 years with no risk factors had a 3.5% risk, whereas a patient aged >75 years with 2 additional high-risk features (myonecrosis and ST depression) had a risk of death or reinfarction of 26%. CONCLUSIONS: Patients with non-ST-segment elevation ACS exhibit a broad range of risk of adverse recurrent ischemic events. The predictive power of the model for the triple end point, using baseline variables, was modest. However, a subgroup at very low risk of the double end point (average 2%) can be identified with baseline variables.

Aged↗
PubMed2000

Negative T waves shortly after ST-elevation acute myocardial infarction are a powerful marker for improved survival rate.

BACKGROUND: Recent studies have reported that negative T waves in the setting of acute coronary events are associated with Thrombolysis In Myocardial Infarction flow grade 3 in the infarct-related artery and with improved parameters of ventricular function rather than with ischemia. METHODS: Patients enrolled in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) angiographic substudy (ie, patients with acute infarction randomly assigned to one of 4 thrombolytic regimens who then underwent coronary angiography) were included in this study if they survived at least 24 hours and had no confounding electrocardiographic factors (n = 1505). RESULTS: More patients had negative T waves develop (NT group, n = 938 [62%]) than not (PT group, n = 567 [38%]). Peak creatine kinase MB, time to thrombolysis, and randomization to accelerated alteplase were no different between the groups. Thirty days after admission, 12 patients in the NT group had died versus 25 patients in the PT group (1.3% vs. 4.4%; P <.001; odds ratio for negative T waves 0.28; 95% confidence interval 0.14-0.56). The difference persisted when only patients who survived at least 3 days were analyzed. After adjusting for relevant covariates (including presence of new Q waves in the follow-up electrocardiogram), negative T waves were an independent predictor for survival (P =. 007; odds ratio for negative T waves 0.38; 95% confidence interval 0. 18-0.78). Patients in the NT group were 35% more likely to have achieved patency of the infarct-related artery, although this difference was not statistically significant. CONCLUSIONS: Negative T waves shortly after acute myocardial infarction treated with thrombolysis were markers for improved 30-day survival rate. This finding merits prospective testing.

Adult↗
PubMed2000

New atrial fibrillation after acute myocardial infarction independently predicts death: the GUSTO-III experience.

BACKGROUND: Atrial fibrillation (AF) or flutter occurring after myocardial infarction may occur alone or in association with other complications. Whether the arrhythmia portends a poor prognosis independent of other complications with contemporary therapy is unknown. METHODS AND RESULTS: As part of the Global Use of Strategies To Open occluded coronary arteries (GUSTO-III) trial, we evaluated whether postinfarction complications were associated with the subsequent development of AF and whether AF independently predicted death over periods of 30 days and 1 year. Information including exact timing was collected on deaths and major in-hospital postinfarction complications up to 30 days. Of the 13,858 patients with sinus rhythm at enrollment, 906 later had AF or flutter and 12, 952 did not. We compared outcomes between these 2 groups, adjusting for differences in baseline characteristics and prefibrillation complications. Worsening heart failure, hypotension, third-degree heart block, and ventricular fibrillation were independent predictors of new-onset AF. The unadjusted odds ratio (OR) for death among patients with versus those without AF was 2.74 (95% confidence interval [95% CI], 2.56-3.34). After adjusting for baseline differences, the OR was reduced to 1.63 (95% CI, 1.31-2.02). Adjustment for other in-hospital complications before the onset of AF further reduced the OR to 1.49 (95% CI, 1.17-1.89). CONCLUSIONS: Atrial fibrillation or flutter occurs secondary to other postinfarction complications but independently portends a worse prognosis. Prevention and management may improve outcome.

Aged↗
PubMed2000

Evaluating the potential 'economic attractiveness' of new therapies in patients with non-ST elevation acute coronary syndrome.

OBJECTIVE: To evaluate the relationship between how much a new cardiovascular therapy improves clinical outcomes over current therapies and how much more it can cost while still remaining 'economically attractive'. DESIGN: We developed a decision model to predict the 6-month cumulative cost savings and increased life expectancy that could be associated with new therapies for patients with non-ST elevation acute coronary syndrome. SETTING: This modelling study used outcome and cost data from US sources. METHODS: Event probabilities at 30 days and 6 months were estimated from US patients with non-ST elevation in the Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO) IIb trial; cost estimates were derived from patients enrolled in the Economics and Quality of Life substudy of this trial. Patient life expectancy estimates were calculated using survival estimates for similar patients treated at Duke University Medical Center. RESULTS: We found that new therapies costing up to $US2000 per episode that reduce 6-month mortality by 0.5%, death and nonfatal myocardial infarction (MI) by 1%, or death, nonfatal MI and revascularisation by 3%, may be cost effective by current standards. When new therapies costing up to $US1000 per episode reduce the absolute rate of death, nonfatal MI and revascularisation at 6 months by 6.5% or more, they may be cost saving. CONCLUSION: Our analysis suggests that economic constraints should not inhibit the development of effective new therapies.

Acute Disease↗
PubMed2000

Temporal evolution in the management of acute ST elevation myocardial infarction: the seven-year GUSTO experience from canada and the united states. The North American GUSTO-I and GUSTO-III investigators.

BACKGROUND: Temporal changes in baseline characteristics, treatment and clinical outcomes of patients presenting with acute ST elevation myocardial infarction in Canada and the United States have not been examined comprehensively over time. OBJECTIVES: To evaluate baseline characteristics, process of care and clinical outcomes. Also, to explore whether earlier process-of-care differences between Canada and the United States had changed and, if so, whether they influenced clinical outcomes. PATIENTS AND METHODS: A total of 13, 888 American and 3011 Canadian patients enrolled in 184 American and 38 Canadian hospitals that participated in both the Global Utilization of Streptokinase and Tissue Plasminogen Activator (alteplase) for Occluded Coronary Arteries (GUSTO-I) trial (1990 to 1993) and the Global Utilization of Strategies to Open Occluded Coronary Arteries (GUSTO-III) trial (1995 to 1997) were studied. Logistic regression was used to identify significant prognostic factors, to assess illness severity at hospital presentation and to classify trends between Canada and the United States. RESULTS: In both countries, illness severity on admission increased, door-to-needle time for thrombolysis was reduced, intensive care unit stay was shortened and hospital stay decreased from GUSTO-I to GUSTO-III. Whereas the administration of oral nitrates, calcium blockers and beta-blockers at discharge converged over time between countries, the disparity in the use of angiography and revascularization widened; the rise in American revascularization rate was most evident in patients without in-hospital ischemia. The 30-day and one-year mortality rates were comparable and declined nonsignificantly in both countries. CONCLUSIONS: Despite increased illness severity and varying medication and procedure rates, there was no increase over time in 30-day or one-year mortality; this remained comparable between countries throughout the seven-year observation period.

Aged↗
PubMed1999

Outcomes at 1 year and economic implications of platelet glycoprotein IIb/IIIa blockade in patients undergoing coronary stenting: results from a multicentre randomised trial. EPISTENT Investigators. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting.

BACKGROUND: We assessed in a randomised trial the long-term outcomes for potent adjunctive antiplatelet therapy given at the time of coronary stenting. METHODS: In 63 hospitals in the USA and Canada, 2399 patients were randomly assigned stenting with abciximab, stenting with placebo, or balloon angioplasty with abciximab. Standard adjunctive therapy with aspirin, ticlopidine, and heparin was used. The major outcomes of death and myocardial infarction were assessed at 1-year follow-up by intention to treat. We also investigated the 1-year cost-effectiveness of combined stenting and abciximab therapy. FINDINGS: At 1-year follow-up, eight (1.0%) of 794 patients in the stent plus abciximab group had died, compared with 19 (2.4%) of 809 in the stent plus placebo group (hazard ratio 0.43 [95% CI 0.19-0.97], p=0.037). The combined endpoint of death or large myocardial infarction occurred in 42 (5.3%) and 89 (11.0%), respectively (0.46 [0.32-0.67], p<0.001). By multivariate modelling, the factors independently associated with improved survival were assignment to stenting with abciximab (p=0.027) and greater preprocedural stenosis (p=0.002); those associated with worse survival were age greater than 70 years (p<0.001), previous heart failure (p=0.001), diabetes treated with insulin (p=0.02), and postprocedural occlusion (p<0.001). Relative to stenting plus placebo and balloon angioplasty plus abciximab, the incremental 1-year costs of stenting plus abciximab were US$581 and $932. The corresponding cost-effectiveness ratios were US$5291 and $6213 per added life-year. INTERPRETATION: Coronary stenting with abciximab, compared with stenting alone or balloon angioplasty with abciximab, is associated with improved survival and is an economically attractive therapy by conventional standards.

Abciximab↗
PubMed1999

Risk stratification with a point-of-care cardiac troponin T test in acute myocardial infarction. GUSTOIII Investigators. Global Use of Strategies To Open Occluded Coronary Arteries.

Troponin T has been used successfully to risk stratify patients with acute coronary syndromes, but the utility of this approach using a rapid bedside assay in patients undergoing thrombolysis for ST-segment elevation acute myocardial infarction has not been assessed in a large population. We assessed whether a point-of-care, qualitative troponin T test at enrollment could independently risk-stratify patients randomized to receive alteplase or reteplase in the GUSTO-III trial. Complete troponin T data were available for 12,666 patients (84%) enrolled at 550 hospitals. The primary end point was mortality at 30 days, and the predictive ability of an elevated baseline troponin T level was analyzed (after adjustment for baseline characteristics) with multiple logistic regression. Patients with an elevated troponin T result at enrollment (8.9%) had significantly higher mortality at 30 days (unadjusted 15.7% vs 6.2% for negative patients; p = 0.001), which persisted even after adjustment for age, heart rate, location of infarction, Killip class, and systolic blood pressure. In a multivariable regression model, a positive troponin T result added independently to the prediction of 30-day mortality (chi-square 46, p = 0.001). A positive result with qualitative troponin T testing on admission is an independent marker of higher 30-day mortality. Troponin T testing could be a valuable addition to the evaluation strategy for patients with acute myocardial infarction.

Aged↗
PubMed1999

Platelet glycoprotein IIb/IIIa receptor inhibition in non-ST-elevation acute coronary syndromes: early benefit during medical treatment only, with additional protection during percutaneous coronary intervention.

BACKGROUND: Glycoprotein (GP) IIb/IIIa receptor blockers prevent life-threatening cardiac complications in patients with acute coronary syndromes without ST-segment elevation and protect against thrombotic complications associated with percutaneous coronary interventions (PCIs). The question arises as to whether these 2 beneficial effects are independent and additive. METHODS AND RESULTS: We analyzed data from the CAPTURE, PURSUIT, and PRISM-PLUS randomized trials, which studied the effects of the GP IIb/IIIa inhibitors abciximab, eptifibatide, and tirofiban, respectively, in acute coronary syndrome patients without persistent ST-segment elevation, with a period of study drug infusion before a possible PCI. During the period of pharmacological treatment, each trial demonstrated a significant reduction in the rate of death or nonfatal myocardial infarction in patients randomized to the GP IIb/IIIa inhibitor compared with placebo. The 3 trials combined showed a 2.5% event rate in this period in the GP IIb/IIIa inhibitor group (N=6125) versus 3.8% in placebo (N=6171), which implies a 34% relative reduction (P<0.001). During study medication, a PCI was performed in 1358 patients assigned GP IIb/IIIa inhibition and 1396 placebo patients. The event rate during the first 48 hours after PCI was also significantly lower in the GP IIb/IIIa inhibitor group (4. 9% versus 8.0%; 41% reduction; P<0.001). No further benefit or rebound effect was observed beyond 48 hours after the PCI. CONCLUSIONS: There is conclusive evidence of an early benefit of GP IIb/IIIa inhibitors during medical treatment in patients with acute coronary syndromes without persistent ST-segment elevation. In addition, in patients subsequently undergoing PCI, GP IIb/IIIa inhibition protects against myocardial damage associated with the intervention.

Abciximab↗