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Biomedical subjects

R M Califf

Publications and source records attributed to R M Califf.

At least 55 records · Page 3Linked to original sources
PubMed2001

Initiation of hormone replacement therapy after acute myocardial infarction is associated with more cardiac events during follow-up.

OBJECTIVES: This study explored the association between the initiation of hormone replacement therapy (HRT) and early cardiac events (<1 year) in women with a recent myocardial infarction (MI). BACKGROUND: Observational studies have linked postmenopausal hormone use with a reduced risk of death from heart disease. However, a recent randomized trial of HRT found no long-term benefit, primarily due to an increase in cardiac events in the first year. METHODS: The Coumadin Aspirin Reinfarction Study (CARS) database contains information on HRT use and menopausal status for women with a recent MI. We classified the 1,857 postmenopausal women in CARS as prior/current HRT users if they took HRT before enrollment, new users if they began HRT during the study period or never users. We assessed the incidence of cardiac events (death, MI, unstable angina [UA]) during follow-up. RESULTS: In our cohort, 28% (n = 524) used HRT at some point. Of these, 21% (n = 111) began HRT after their MI. New users had a higher incidence of death/MI/UA (41% vs. 28%, p = 0.001) during follow-up than never users, largely due to a higher incidence of UA (39% vs. 20%, p = 0.001). After adjustment, new users still had a significantly higher risk of death/MI/UA than never users during follow-up (relative risk [RR] = 1.44 [1.05-1.99]). Prior/current users had no excess risk of the composite end point after adjustment. Users of estrogen/progestin had a lower incidence of death/MI/UA during follow-up than users of estrogen only (RR = 0.56 [0.37-0.85]). CONCLUSIONS: Postmenopausal women who initiated HRT after a recent MI had an increased risk of cardiac events largely due to excess UA during follow-up.

Aged↗
PubMed2001

Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents: a comparison of TNK-tPA and rt-PA.

BACKGROUND: Fibrinolytic therapy increases the risk of bleeding events. TNK-tPA (tenecteplase) is a variant of rt-PA with greater fibrin specificity and reduced plasma clearance that can be given as a single bolus. We compared the incidence and predictors of bleeding events after treatment with TNK-tPA and rt-PA. METHODS AND RESULTS: In the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-2 trial, 16 949 patients with acute myocardial infarction were randomly assigned a single weight-adjusted bolus of TNK-tPA or a 90-min infusion of rt-PA. A total of 4.66% of patients in the TNK-tPA group experienced major non-cerebral bleeding, in comparison with 5.94% in the rt-PA group (P=0.0002). This lower rate was associated with a significant reduction in the need for blood transfusion (4.25% vs 5.49%, P=0.0003) and was consistent across subgroups. Independent risk factors for major bleeding were older age, female gender, lower body weight, enrolment in the U.S.A. and a diastolic blood pressure <70 mmHg. Females at high risk (age >75 years and body weight <67 kg) were less likely to have major bleeding when treated with TNK-tPA even after other risk factors were taken into account. A total of 0.93% of patients in the TNK-tPA and 0.94% of patients in the rt-PA group experienced an intracranial haemorrhage. Female patients >75 years of age who weighed <67 kg tended to have lower rates of intracranial haemorrhage when treated with TNK-tPA (3/264, 1.14% vs 8/265, 3.02%). CONCLUSIONS: The increased fibrin specificity and single bolus administration of TNK-tPA do not increase the risk of intracranial haemorrhage but are associated with less non-cerebral bleeding, especially amongst high-risk patients.

Adult↗
PubMed2001

Hemodynamic profiles of advanced heart failure: association with clinical characteristics and long-term outcomes.

BACKGROUND: Classifying patients with advanced congestive heart failure (CHF) by baseline measures of congestion and perfusion has been used to estimate hemodynamic status and to select and titrate therapy. We describe clinical characteristics of 4 hemodynamic profiles-wet/cold, wet/warm, dry/cold, and dry/warm-in patients with advanced CHF and assess relations between symptoms, physical signs, and outcomes with each profile. METHODS AND RESULTS: We retrospectively assessed baseline symptoms, physical-examination variables, and 1-year outcomes of 440 patients in a randomized trial. With univariable and multivariable logistic regression, we examined relations of physical-examination variables to hemodynamic profiles. We also assessed the rates of death and death or readmission by profile. Severity of CHF symptoms did not predict the wet-versus-dry profile or cold-versus-warm status, despite significant differences in hemodynamics among groups. Of the physical-examination variables, only a lower proportional pulse pressure was a significant multivariable predictor of the wet category. Among wet patients (n = 348), this same variable was the only significant multivariable predictor of the cold category. For dry patients (n = 92), the cold category was predicted in multivariable analysis by supine heart rate and hepatomegaly. Survival was similar among profiles: wet/cold, 54.2% (n = 91); wet/warm, 58.3% (n = 105); dry/cold, 78.9% (n = 15); and dry/warm, 67.1%, P =.13 (n = 49). Event-free survival also was similar among profiles: wet/cold, 22.0% (n = 37); wet/warm, 29.4% (n = 53); dry/cold, 42.1% (n = 8); and dry/warm, 31.5%, P =.44 (n = 23). CONCLUSIONS: The patient's history and physical examination alone may lead to inaccurate estimation of hemodynamic status and thus suboptimal management for patients with advanced CHF.

Aged↗
PubMed2001

Outcome of acute ST-segment elevation myocardial infarction in patients with prior coronary artery bypass surgery receiving thrombolytic therapy.

BACKGROUND: Patients with prior coronary bypass surgery with acute ST-segment elevation myocardial infarction (MI) pose an increasingly common clinical problem. We assessed the characteristics and outcomes of such patients undergoing thrombolysis for acute MI. METHODS AND RESULTS: We compared the characteristics and outcomes of patients in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries trial (GUSTO-I) who had had prior bypass (n = 1784, 4% of the population) with those without prior coronary artery bypass grafting (CABG), all of whom were randomized to receive one of four thrombolytic strategies. Patients with prior bypass were older with significantly more prior MI and angina. Overall, 30-day mortality was significantly higher in patients with prior bypass (10.7% vs 6.7% for no prior bypass, P <.001); these patients also had significantly more pulmonary edema, sustained hypotension, or cardiogenic shock. Patients with prior bypass showed a 12.5% relative reduction (95% confidence interval, 0% to 41.9%) in 30-day mortality with accelerated alteplase over the streptokinase monotherapies. In the 62% of patients with prior CABG who underwent coronary angiography, the infarct-related vessel was a native coronary artery in 61.9% and a bypass graft in 38.1% of cases. The Thrombolysis in Myocardial Infarction (TIMI) 3 flow rate was 30.5% for culprit native coronary arteries and 31.7% for culprit bypass grafts. Patients with prior bypass had more severe infarct-vessel stenoses (99% [90%, 100%] vs 90% [80%, 99%], P <.001). CONCLUSIONS: The 30-day mortality in patients with prior CABG was significantly higher than that for patients without prior CABG. As in the overall trial, these patients derived an incremental survival benefit from treatment with accelerated alteplase, but mortality remained high (16.7%) at 1 year. These results are at least partially explained by the higher baseline risk of these patients and by the lower rate of patency of the infarct-related artery.

Coronary Angiography↗
PubMed2001

Variation in patient management and outcomes for acute coronary syndromes in Latin America and North America: results from the Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial.

BACKGROUND: Although more than 9500 patients have been enrolled in major clinical trials in Latin America, practice patterns in this region have rarely been examined. We sought to compare characteristics, resource utilization, and outcomes of patients treated for acute coronary syndromes in Latin America with those in North America. METHODS: The Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Theraphy Trial (PURSUIT) enrolled 10,948 patients with non-ST-segment elevation acute coronary syndromes, including 585 in Latin America and 4358 in North America. We analyzed regional differences in patient groups, treatment patterns, and outcomes and used logistic regression analysis to identify association of enrollment region and survival. RESULTS: For patients in Latin America, the length of hospital stay was significantly longer (10 [7, 15] days vs 6 [4, 9], P <.001). Angiograms, angioplasty, and bypass surgery were significantly less common in Latin America (46.2%, 17.6%, and 11.3% vs 79.4%, 33.6%, and 19.4%, P <.001). Thirty-day death/myocardial infarction was not significantly higher, although mortality alone was significantly higher (6.8% vs 3.1%, P <.001). After adjustment for baseline characteristics, enrollment in Latin America remained an independent predictor for death at 30 days (odds ratio [OR] [95% confidence interval (CI)] 2.42 [1.60-3.67]) and persisted at 6 months (OR [95% CI] 2.5 [1.8-3.4]). CONCLUSIONS: Latin American patients treated for acute coronary syndromes were managed less invasively and were twice as likely as their North American counterparts to die within 6 months. This mortality difference was not explained by imbalances in baseline risk.

Angina, Unstable↗
PubMed2001

Recurrent ischemia after thrombolysis for acute myocardial infarction.

BACKGROUND: Reliable predictors have yet to be found for recurrent ischemia after thrombolysis for acute myocardial infarction (AMI), nor do we know whether early angiography can herald recurrent ischemia. This study sought to investigate the relationship between recurrent ischemia and cardiac procedures after thrombolysis for AMI. METHODS: The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial prospectively studied recurrent ischemia, which was defined as the presence of angina and changes in hemodynamics or the electrocardiogram. Cox regression analysis was used to identify predictors of recurrent ischemia. Other variables examined included time to coronary angiography and revascularization. RESULTS: Of 21,772 US GUSTO-I patients, 6313 (29%) had recurrent ischemia before discharge. Women (hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.17-1.33) and patients with hypercholesterolemia (HR 1.14, 95% CI 1.07-1.22) or prior angina (HR 1.40, 95% CI 1.32-1.49) had a higher likelihood of recurrent ischemia. Current smoking and hours to thrombolysis were inversely related to recurrent ischemia (HR 0.86, 95% CI 0.81-0.92, HR 0.97, 95% CI 0.95- 0.99, respectively). Patients who underwent angiography before recurrent ischemia had a marginally increased risk of ischemia within 12 hours after angiography (HR 1.2, 95% CI 1.1-1.4); ultimately, they had a considerably lower risk 1 week after angiography than did patients without angiography (HR 0.57, 95% CI 0.45-0.72). CONCLUSIONS: Female sex, hypercholesterolemia, prior angina, and nonsmoking status weakly predict recurrent ischemia. Early coronary angiography reduces recurrent ischemia, probably because high-risk patients are identified and revascularized.

Cardiac Catheterization↗
PubMed2001

Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE): design and rationale.

BACKGROUND: There is little information about how to adjust pharmacologic agents in the treatment of patients with advanced congestive heart failure (CHF). Some studies have suggested that use of pulmonary artery catheterization to guide reductions in filling pressures may improve outcomes for patients with heart failure who are hospitalized with evidence of elevated filling pressures. However, there is no consensus regarding the true utility of this strategy. A randomized clinical trial is needed to test the safety, efficacy, and treatment benefit of pulmonary artery catheterization in patients with advanced CHF. STUDY DESIGN: The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial is a multicenter, randomized trial designed to test the long-term safety and efficacy of treatment guided by hemodynamic monitoring and clinical assessment versus that guided by clinical assessment alone in patients hospitalized with New York Heart Association class IV CHF. Five hundred patients will be randomly assigned to receive either medical therapy guided by a combination of clinical assessment and hemodynamic monitoring (PAC arm) or medical therapy guided by clinical assessment alone (CLIN arm). The primary end point of ESCAPE will be the number of days that patients are hospitalized or die during the 6-month period after randomization. Secondary end points will include changes in mitral regurgitation, peak oxygen consumption, and natriuretic peptide levels. Other secondary end points will be pulmonary artery catheter-associated complications, resource utilization, quality of life measures, and patient preferences regarding survival. IMPLICATIONS: The primary goal of ESCAPE will be to provide information about the utility of the pulmonary artery catheter in patients with advanced heart failure, independent of various treatment approaches used by individual physicians. In addition, this study will define current outcomes for this severely compromised population.

Catheterization, Swan-Ganz↗
PubMed2001

Hemodynamics as surrogate end points for survival in advanced heart failure: an analysis from FIRST.

BACKGROUND: Hemodynamics often are used as surrogate end points in phase II trials of acute heart failure (HF). We reviewed the Flolan International Randomized Survival Trial (FIRST) database to identify the hemodynamic variables that best predict survival in patients with advanced HF receiving epoprostenol therapy and to determine whether hemodynamics could predict the overall effect of a drug. METHODS: The trial enrolled 471 patients with class IIIb/IV HF and ejection fraction or=3 months, all of whom underwent screening pulmonary artery catheter insertion. Patients were randomly assigned to receive either epoprostenol (n = 201) or placebo (n = 235); epoprostenol therapy was guided by pulmonary artery catheter measures, and standard treatment was guided by clinical findings. Multivariable modeling was used to identify and quantify the demographic, clinical, and hemodynamic variables most associated with 1-year survival. RESULTS: In multivariable modeling, HF class, decreased pulmonary capillary wedge pressure (PCWP), and age best predicted 1-year survival. After adjustment for age and HF class, decreased PCWP still significantly predicted survival (hazard ratio, 0.96 for every 1-mm Hg decrease; 95% confidence interval, 0.94 to 0.99; P = .003). Survival was significantly higher with decreases in PCWP >or=9 versus <9 mm Hg, even after adjustment for age and HF class. Survival of patients in the PCWP >or=9 group was comparable with, and that of the PCWP <9 group was significantly higher than, survival of patients in the control group (hazard ratio, 1.44; 95% confidence interval, 1.05 to 1.99; P = .024). CONCLUSIONS: The reduction in PCWP was the hemodynamic measure most predictive of survival in patients with advanced HF. However, patients with a >or=9-mm Hg decrease had no better survival than patients in the control group, who had limited changes in hemodynamics. Thus, improvement in hemodynamics may not predict the overall effect of a drug.

Aged↗
PubMed2001

Cardiac rehabilitation and survival in patients with left ventricular systolic dysfunction.

BACKGROUND: Exercise training, the major component of cardiac rehabilitation (CR), has been shown in previous trials to improve many pathophysiologic changes found in patients with left ventricular systolic dysfunction. It remains unproven whether exercise training improves survival. METHODS: By using the Duke Databank for Cardiovascular Disease, we identified patients with an ejection fraction < or = 40% and no recent myocardial infarction, congenital heart disease, or primary valvular disease who survived > or = 30 days after a cardiac catheterization (n = 1902). Participation in CR (n = 70) was identified through computer billing records. We developed a multivariable Cox proportional hazards regression model to estimate survival by using variables known to be independent predictors of survival in patients with systolic dysfunction. RESULTS: Patients participating in CR were less likely to be female or black and more likely to have a history consistent with ischemic cardiomyopathy. Participation in CR was associated with significantly improved survival after adjustment for baseline characteristics (hazard ratio, 0.39; 95% confidence interval, 0.15 to 0.62, P < .0001). Survival increased when patients participated in > 6 CR sessions (hazard ratio, 0.10; 95% confidence interval, 0.03 to 0.39; P < .0001). CONCLUSIONS: Participation in CR was associated with improved survival for patients with cardiomyopathy. There appears to be a dose response with improved survival benefit for patients with left ventricular systolic dysfunction participating in cardiac rehabilitation.

Aged↗
PubMed2001

Predictors of left ventricular function after acute myocardial infarction: effects of time to treatment, patency, and body mass index: the GUSTO-I angiographic experience.

BACKGROUND: Despite the significant survival benefit associated with successful reperfusion therapy for acute myocardial infarction, global indices of outcome left ventricular function, such as ejection fraction, have often demonstrated little or no improvement. Although these measurements are confounded by numerous clinical, physiologic, and angiographic variables, no comprehensive analysis of this issue in a large series of patients is available. We used the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) database to better understand this phenomenon by determining independent predictors of left ventricular function and their interplay with regard to outcome ventricular function and improvement in function during the initial postinfarction week. METHODS: Ninety-minute and 5- to 7-day posttreatment global and regional indices derived from left ventriculograms were analyzed from a population of 676 patients. These observations were combined with clinical data to describe independent determinants of ventricular function outcome. RESULTS: Clinical factors predictive of global and regional ventricular function as well as improvement in function between 90 minutes and 5 to 7 days included time to treatment, early infarct-related artery flow grade, and body mass index. These same factors contribute significantly to compensatory hyperkinesis of the noninfarct zone, which is critical to maintenance of global ventricular function during this time period. CONCLUSIONS: The ventricular function benefits of early complete reperfusion after myocardial infarction are readily demonstrable after adjustment for multiple covariables and include (1) maintenance of global ventricular function and (2) prevention or delay in ventricular dilatation.

Aged↗
PubMed2001

The A-to-Z Trial: Methods and rationale for a single trial investigating combined use of low-molecular-weight heparin with the glycoprotein IIb/IIIa inhibitor tirofiban and defining the efficacy of early aggressive simvastatin therapy.

BACKGROUND: The A-to-Z Trial is an ongoing international, multicenter, randomized study designed to investigate 2 issues concerning contemporary care of patients with acute coronary syndromes (ACS). The first issue is whether the use of low-molecular-weight heparin versus unfractionated heparin affects outcomes and safety when used as a therapy adjunctive to baseline treatment with tirofiban and aspirin in patients with non-ST-elevation (nSTE) ACS. The second issue is whether early use of an aggressively dosed statin is superior to a current trial-based "accepted care" regimen of a lower-dose statin started 3 to 6 months after an acute event. METHODS: The study is conceptually and functionally divided into 2 sequential parts-the "A" Aggrastat and "Z" Zocar phases. The primary A-phase end point is a composite of all-cause mortality, myocardial infarction (MI), and documented refractory ischemia at 7 days. Both nSTE-ACS patients from the A phase and patients with ST-elevation ACS who meet specific risk criteria are eligible to enter the subsequent "Z" (Zocor) chronic phase (Z phase). The primary end point of the Z phase is a composite of cardiovascular death, MI, readmission for ACS, and stroke. The trial will continue until 970 primary events have occurred in the Z-phase population. CONCLUSION: This trial is evaluating 2 temporally connected sequences of phamacotherapy for ACS. At completion, trial results will provide definitive evidence regarding efficacy and safety of early, intensive statin therapy and better define the role of low-molecular-weight heparin in patients with nSTE ACS.

Anticoagulants↗
PubMed2001

Advanced coronary artery disease: Appropriate end points for trials of novel therapies.

BACKGROUND: The segment of patients with advanced coronary artery disease, or disease that is not amenable to conventional revascularization therapies, continues to grow. Because the natural history of these patients is less defined, the appropriate end points for trials of novel revascularization therapies involving patients with advanced coronary artery disease are not certain. METHODS AND RESULTS: The Mediators of Social Support Study (MOSS) prospectively followed up outcomes of long-term survival, quality of life, resource use, and costs for 1189 patients and compared outcomes of patients with advanced coronary artery disease with those of a reference group who underwent bypass surgery or angioplasty. CONCLUSIONS: Despite greater disease burden, cost, and mortality for patients with advanced coronary artery disease, a number of self-reported measures of general health status improved in a similar fashion to that of patients eligible for angioplasty or bypass surgery. These findings should inform the design of trials involving novel therapies, suggesting that angina status and mortality be included as primary end points in the consideration of efficacy. This work also suggests that additional studies of novel therapies involving larger sample sizes may be required to confidently characterize efficacy.

Cardiac Catheterization↗