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Biomedical subjects

R M Califf

Publications and source records attributed to R M Califf.

At least 289 records · Page 16Linked to original sources
PubMed1996

How much do we gain by reducing time to reperfusion therapy?

Emphasis continues to be placed on the need to minimize the time elapsed between the onset of symptoms of myocardial infarction and the initiation of thrombolytic therapy. Numerous large-scale trials have revealed an inverse relation between time-to-treatment and the degree of reduction in the risk of adverse clinical outcomes. Still to be resolved is the question of whether additional benefit can be gained by treating within the first hour. Many factors that influence delays to presentation are also associated with a higher risk of mortality, and these factors vary with patient characteristics. These same factors are also associated with longer treatment delay and greater mortality risk. Although the greatest opportunity for reducing time-to-treatment lies in reducing presentation time, public education efforts have been largely unsuccessful. Despite the fact that treatment delay generally accounts for a smaller proportion of total delay time than does presentation delay, it may be more amenable to shortening through measures such as transmission of electrocardiograms from the field; emergency department protocols for the rapid triage, assessment, and treatment of patients with chest pain; training emergency department physicians to administer thrombolytic therapy without a cardiology consult; and storing thrombolytic agents in the emergency department.

Cardiology↗
PubMed1996

Outcome of acute myocardial infarction according to the specialty of the admitting physician.

BACKGROUND: In order to limit costs, health care organizations in the United States are shifting medical care from specialists to primary care physicians. Although primary care physicians provide less resource-intensive care, there is little information concerning the effects of this strategy on outcomes. METHODS: We examined mortality according to the specialty of the admitting physician among 8241 Medicare patients who were hospitalized for acute myocardial infarction in four states during a seven-month period in 1992. Proportional-hazards regression models were used to examine survival up to one year after the myocardial infarction. To determine the generalizability of our findings, we also examined insurance claims and survival data for all 220,535 patients for whom there were Medicare claims for hospital care for acute myocardial infarction in 1992. RESULTS: After adjustment for characteristics of the patients and hospitals, patients who were admitted to the hospital by a cardiologist were 12 percent less likely to die within one year than those admitted by a primary care physician (P<0.001). Cardiologists also had the highest rate of use of cardiac procedures and medications, including medications (such as thrombolytic agents and beta-blockers) that are associated with improved survival. CONCLUSIONS: Health care strategies that shift the care of elderly patients with myocardial infarction from cardiologists to primary care physicians lower rates of use of resources (and potentially lower costs), but they may also cause decreased survival. Additional information is needed to elucidate how primary care physicians and specialists should interact in the care of severely ill patients.

Aged↗
PubMed1996

A metaanalysis of predischarge risk stratification after acute myocardial infarction with stress electrocardiographic, myocardial perfusion, and ventricular function imaging.

We assessed the relation of abnormal predischarge non-invasive test results to outcomes in postmyocardial infarction patients. We included series published from 1980 to 1995 containing only myocardial infarction patients, enrolling most patients after 1980, testing within 6 weeks of infarction, having follow-up rates > 80%, and having 2 x 2 frequency outcome rates for test results, that were the latest of multiple reports. Sensitivity, specificity, and predictive values were calculated for test results for 1-year outcomes (cardiac death, cardiac death or reinfarction). Univariable and summary odds were calculated for test results. Reports (n = 54) included a total of 19,874 patients and were primarily retrospective (76%) and small series (35% of reports included < 5 deaths). One-year mortality ranged from 2.5% for pharmacologic stress echocardiography to 9.3% for exercise radionuclide angiography. Positive predictive values for most noninvasive risk markers were < 0.10 for cardiac death and < 0.20 for death or reinfarction. Electrocardiographic, symptomatic, and scintigraphic risk markers of ischemia (ST-segment depression, angina, a reversible defect) were less sensitive (< or = 44%) for identifying morbid and fatal outcomes than markers of left ventricular dysfunction or heart failure (exercise duration, impaired systolic blood pressure response, and peak left ventricular ejection fraction). The positive predictive value of predischarge noninvasive testing is low. Markers of left ventricular dysfunction appear to be better predictors than markers of ischemia. Limitations of the literature-small samples and widely varying event rates-impede our ability to discern the accuracy of pre-discharge noninvasive testing. More rigorous, controlled trials are required to elucidate the relative value of these tests for risk stratification.

Diagnostic Imaging↗
PubMed1996

Thrombolytic therapy for patients with prior percutaneous transluminal coronary angioplasty and subsequent acute myocardial infarction. GUSTO-I Investigators. Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries.

Our purpose was to evaluate the outcomes of patients with prior coronary angioplasty who underwent thrombolysis for new acute myocardial infarction (AMI) in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries-I trial. Baseline characteristics and clinical outcomes were compared between patients with (n = 1,647) and without (n = 39,150) previous angioplasty. The relations among prior angioplasty, clinical outcomes, and treatment effects were examined with logistic regression modeling. Patients with previous angioplasty tended to be younger and presented sooner after symptom onset, but had more multivessel disease and lower ejection fractions. Unadjusted mortality was significantly lower in the prior-angioplasty group at 24 hours (1.8% vs 2.7%, p = 0.03) and 30 days (5.6% vs 7.0%, p = 0.036). Although most of the survival advantage was due to low-risk characteristics in this group (lower age and heart rate and fewer anterior wall AMIs), prior angioplasty remained a weak but independent predictor of survival. Recurrent ischemia and reinfarction occurred more often in the prior-angioplasty group, as did bypass surgery (12.2% vs 8.5%) and repeat angioplasty (34.5% vs 21.4%). Patients with prior angioplasty and prior AMI had lower 30-day mortality than those with prior infarction alone (6.3% vs 12.6%, p < 0.01). Treatment effects on 30-day mortality were similar among patients with prior angioplasty (odds ratio 1.2 for accelerated tissue-plasminogen activator v. combined streptokinase arms, 95% confidence interval 0.73 to 1.9). Patients with prior angioplasty who present with AMI have fewer in-hospital adverse events and lower 30-day mortality than those without such a history.

Aged↗
PubMed1996

Relation of increased arterial blood pressure to mortality and stroke in the context of contemporary thrombolytic therapy for acute myocardial infarction. A randomized trial. GUSTO-I Investigators.

BACKGROUND: Despite concern that hypertension increases the risk for intracranial hemorrhage during thrombolysis for acute myocardial infarction, the exact nature of the risk remains unclear. OBJECTIVE: To assess the effects of previous hypertension and blood pressure at study entry on the outcomes of patients who had acute myocardial infarction and received thrombolysis. DESIGN: Randomized trial. SETTING: 1081 hospitals in 15 countries. PATIENTS: 41,021 patients who had myocardial infarction accompanied by ST-segment elevation and who presented to hospitals within 6 hours of symptom onset. INTERVENTION: One of four thrombolytic regimens. MAIN OUTCOME MEASURES: Mortality, stroke subtypes, and death plus disabling stroke in patients with previous hypertension and as functions of blood pressure at entry. Logistic regression analysis of relations among blood pressure at entry, baseline characteristics, and treatment effects. RESULTS: The incidence of total stroke and intracranial hemorrhage increased as systolic blood pressure at entry increased and was particularly high for systolic pressures of about 175 mm Hg or more (incidence of total stroke, 3.4% compared with 1.17% for pressures between 100 and 124 mm Hg). Patients who had systolic blood pressure of 175 mm Hg or more at entry and who received accelerated alteplase therapy had a lower rate of death within 30 days (4.3% compared with 7.8%; P = 0.044) and a lower rate of death plus disabling stroke (4.9% compared with 8.9%; P = 0.031) than patients treated with streptokinase, despite having higher rates of total and hemorrhagic stroke (incidence of hemorrhagic stroke, 2.3% compared with 1.5%). Assumptions based on previous trials and rates of stroke from the GUSTO-1 (Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries) trial suggest that in hypertensive patients with low risk for death from cardiac causes (no previous infarction, Killip class I), the risk-to-benefit ratio with thrombolysis is about unity, with about 13 lives saved per 1000 persons treated at the risk of about 13 intracranial hemorrhages. CONCLUSIONS: Patients with myocardial infarction and very elevated blood pressure who have thrombolysis and risk for stroke is higher in the former group. Future studies should assess 1) the risk-to-benefit ratio of thrombolysis in these patients, especially those at low risk for death from cardiac causes, and 2) whether decreasing elevated blood pressure before thrombolysis reduces the incidence of stroke without increasing mortality rates.

Aged↗
PubMed1996

A comparison of debulking versus dilatation of bifurcation coronary arterial narrowings (from the CAVEAT I Trial). Coronary Angioplasty Versus Excisional Atherectomy Trial-I.

We compared the effectiveness of percutaneous transluminal coronary angioplasty and directional coronary atherectomy for the management of bifurcation coronary lesions in 1,012 patients enrolled in the Coronary Angioplasty Versus Excisional Atherectomy Trial-I. Directional coronary atherectomy was associated with less angiographic residual stenosis, but with a higher rate of side-branch closure and non-Q-wave myocardial infarction.

Aged↗
PubMed1996

Relation between estrogen replacement therapy and restenosis after percutaneous coronary interventions.

OBJECTIVES: We attempted to determine the relation between estrogen replacement therapy and the rate of restenosis after coronary angioplasty and atherectomy. BACKGROUND: Although estrogen replacement therapy in women has been associated with a reduction in cardiovascular events and improvement in endothelial function, no study has examined whether estrogen reduces restenosis rates after percutaneous coronary interventions. METHODS: A total of 204 women enrolled in the Coronary Angioplasty Versus Excisional Atherectomy Trial with angiographic follow-up were contacted, and their menopausal and estrogen replacement status was determined. Late loss in minimal lumen diameter, late loss index, minimal lumen diameter, rate of restenosis > 50% and actual percent of stenosis were compared in estrogen users and nonusers by quantitative coronary angiography at 6-month follow-up. RESULTS: Late loss in minimal lumen diameter was significantly less in women using estrogen than in nonusers (-0.13 vs. -0.46 mm, p = 0.01). A regression analysis of the determinants of late loss in minimal lumen diameter revealed that estrogen use was the single most important predictor of subsequent late loss (F = 13.38, p = 0.0006). Formal testing revealed a highly significant interaction between the use of estrogen and intervention (angioplasty or atherectomy). Women undergoing atherectomy who received estrogen had a significantly lower late loss index (0.06 vs. -0.63, p = 0.002), less late loss (0.06 vs. -0.61 mm, p = 0.0006), larger minimal lumen diameter (p = 0.044) and lower restenosis rates (p = 0.038 for > 50% stenosis) than those not using estrogen. In contrast, estrogen had minimal effects on restenosis end points after angioplasty. CONCLUSIONS: This study demonstrates the potential for estrogen replacement therapy to reduce angiographic measures of restenosis in postmenopausal women after coronary intervention, particularly in those undergoing atherectomy.

Aged↗
PubMed1996

Effects of integrelin, a platelet glycoprotein IIb/IIIa receptor antagonist, in unstable angina. A randomized multicenter trial.

BACKGROUND: Although aspirin is beneficial in patients with unstable angina, it is a relatively weak inhibitor of platelet aggregation. The effect of Integrelin, which inhibits the platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa, on the frequency and duration of Holter ischemia was evaluated in 227 patients with unstable angina. METHODS AND RESULTS: Patients received intravenous heparin and standard ischemic therapy and were randomized to receive oral aspirin and placebo Integrelin; placebo aspirin and low-dose Integrelin. 45 micrograms/kg bolus followed by a 0.5 microgram.kg-1. min-1 continuous infusion; or placebo aspirin and high-dose Integrelin, 90 micrograms/kg bolus followed by a 1.0-microgram.kg-1, min-1 constant infusion. Study drug was continued for 24 to 72 hours, and Holter monitoring was performed. Patients randomized to high-dose Integrelin experienced 0.24 +/- 0.11 ischemic episodes (mean +/- SEM) on Holter lasting 8.41 +/- 5.29 minutes over 24 hours of study drug infusion. Patients randomized to aspirin experienced a greater number (1.0 +/- 0.33, P < .05) and longer duration (26.2 +/- 9.8 minutes, P = .01) of ischemic episodes than the high-dose Integrelin group. There was no evidence of rebound ischemia after withdrawal of study drug. In 46 patients, platelet aggregation was rapidly inhibited by Integrelin in a dose-dependent fashion. The number of clinical events was small, and there were no bleeding differences in the three treatment arms. CONCLUSIONS: Intravenous Integrelin is well tolerated, is a potent reversible inhibitor of platelet aggregation, and added to full-dose heparin reduces the number and duration of Holter ischemic events in patients with unstable angina compared with aspirin.

Adult↗
PubMed1996

Cardiac troponin T levels for risk stratification in acute myocardial ischemia. GUSTO IIA Investigators.

BACKGROUND: The prognosis of patients hospitalized with acute myocardial ischemia is quite variable. We examined the value of serum levels of cardiac troponin T, serum creatine kinase MB (CK-MB) levels, and electrocardiographic abnormalities for risk stratification in patients with acute myocardial ischemia. METHODS: We studied 855 patients within 12 hours of the onset of symptoms. Cardiac troponin T levels, CK-MB levels, and electrocardiograms were analyzed in a blinded fashion at the core laboratory. We used logistic regression to assess the usefulness of baseline levels of cardiac troponin T and CK-MB and the electrocardiographic category assigned at admission-ST-segment elevation, ST-segment depression, T-wave inversion, or the presence of confounding factors that impair the detection of ischemia (bundle-branch block and paced rhythms)-in predicting outcome. RESULTS: On admission, 289 of 801 patients with base-line serum samples had elevated troponin T levels (> 0.1 ng per milliliter). Mortality within 30 days was significantly higher in these patients than in patients with lower levels of troponin T (11.8 percent vs. 3.9 percent, P < 0.001). The troponin T level was the variable most strongly related to 30-day mortality (chi-square = 21, P < 0.001), followed by the electrocardiographic category (chi-square = 14, P = 0.003) and the CK-MB level (chi-square = 11, P = 0.004). Troponin T levels remained significantly predictive of 30-day mortality in a model that contained the electrocardiographic categories and CK-MB levels (chi-square = 9.2, P = 0.027). CONCLUSIONS: The cardiac troponin T level is a powerful, independent risk marker in patients who present with acute myocardial ischemia. It allows further stratification of risk when combined with standard measures such as electrocardiography and the CK-MB level.

Acute Disease↗
PubMed1996

Determinants of the use of coronary angiography and revascularization after thrombolysis for acute myocardial infarction.

BACKGROUND: Clinical trials and practice guidelines have identified clinical criteria for the use of coronary angiography and revascularization procedures after thrombolysis for acute myocardial infarction. The effect of these criteria on clinical practice has not been extensively evaluated. METHODS: We used classification-and-regression-tree (CART) and logistic-regression models to study the patients in the first Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries trial, to identify the variables that best predicted the use of angiography and revascularization procedures after thrombolysis. RESULTS: Among the 21,772 U.S. patients in the trial, 71 percent underwent coronary angiography before discharge from the hospital. Of these, 58 percent underwent revascularization (73 percent receiving angioplasty). The CART model for the use of angiography showed that age was the variable most predictive of angiography; only 53 percent of patients at least 73 years of age underwent angiography, as compared with 76 percent of those under 73. Among the older patients, age was again the most predictive factor; among the younger patients, the availability of angioplasty was a more important predictor (67 percent of patients in hospitals without angioplasty facilities underwent angiography, as compared with 83 percent in hospitals with such facilities). The next most important variable was recurrent ischemia, which was more predictive at hospitals without angioplasty facilities than at those with them. Both statistical models identified coronary anatomy as the most important predictor of the use and type of revascularization. CONCLUSIONS: More patients treated with thrombolysis underwent angiography and revascularization before discharge than might be expected. Younger age and the availability of the procedures appeared to be the major determinants of the use of coronary angiography, whereas coronary anatomy largely determined the use and type of revascularization. This process appeared to select low-risk patients for intervention rather than those at higher risk, who would be the most likely to benefit.

Age Factors↗
PubMed1996

Age and outcome with contemporary thrombolytic therapy. Results from the GUSTO-I trial. Global Utilization of Streptokinase and TPA for Occluded coronary arteries trial.

BACKGROUND: Elderly patients with acute myocardial infarction have much to gain from reperfusion with thrombolytic therapy but are also at increased risk of adverse events. We examined outcomes according to age of patients receiving thrombolysis in an international trial. METHODS AND RESULTS: Patients were randomized to streptokinase plus subcutaneous heparin, streptokinase plus intravenous heparin, accelerated tissue plasminogen activator (TPA) plus intravenous heparin, or streptokinase and TPA plus intravenous heparin. Clinical outcomes at 30 days (death, stroke, and nonfatal, disabling stroke) and 1-year mortality were summarized descriptively for patients aged < 65 (n = 24,708), 65 to 74 (n = 11,201), 75 to 85 (n = 4625), and > 85 years (n = 412) and assessed as continuous functions of age. Older patients had a higher-risk profile with regard to baseline clinical and angiographic characteristics. Mortality at 30 days increased markedly with age (3.0%, 9.5%, 19.6%, and 30.3% in the four groups, respectively), as did stroke, cardiogenic shock, bleeding, and reinfarction. Combined death or disabling stroke occurred less often with accelerated TPA in all but the oldest patients, who showed a weak trend toward a lower incidence with streptokinase plus subcutaneous heparin: odds ratio 1.13; 95% confidence interval 0.6, 2.1. Similarly, accelerated TPA treatment resulted in lower 1-year mortality in all but the oldest patients (47% TPA versus 40.3% streptokinase). CONCLUSIONS: Lower mortality and greater net clinical benefit were seen with accelerated TPA in patients aged < or = 85 years. Because data are limited for patients aged > 85 years, the relative superiority of a given thrombolytic regimen cannot be determined. The interactions of stroke and mortality with newer thrombolytic strategies must be examined explicitly in older patients.

Aged↗
PubMed1996

The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators.

OBJECTIVE: To examine the association between the use of right heart catheterization (RHC) during the first 24 hours of care in the intensive care unit (ICU) and subsequent survival, length of stay, intensity of care, and cost of care. DESIGN: Prospective cohort study. SETTING: Five US teaching hospitals between 1989 and 1994. SUBJECTS: A total of 5735 critically ill adult patients receiving care in an ICU for 1 of 9 prespecified disease categories. MAIN OUTCOME MEASURES: Survival time, cost of care, intensity of care, and length of stay in the ICU and hospital, determined from the clinical record and from the National Death Index. A propensity score for RHC was constructed using multivariable logistic regression. Case-matching and multivariable regression modeling techniques were used to estimate the association of RHC with specific outcomes after adjusting for treatment selection using the propensity score. Sensitivity analysis was used to estimate the potential effect of an unidentified or missing covariate on the results. RESULTS: By case-matching analysis, patients with RHC had an increased 30-day mortality (odds ratio, 1.24; 95% confidence interval, 1.03-1.49). The mean cost (25th, 50th, 75th percentiles) per hospital stay was $49 300 ($17 000, $30 500, $56 600) with RHC and $35 700 ($11 300, $20 600, $39 200) without RHC. Mean length of stay in the ICU was 14.8 (5, 9, 17) days with RHC and 13.0 (4, 7, 14) days without RHC. These findings were all confirmed by multivariable modeling techniques. Subgroup analysis did not reveal any patient group or site for which RHC was associated with improved outcomes. Patients with higher baseline probability of surviving 2 months had the highest relative risk of death following RHC. Sensitivity analysis suggested that a missing covariate would have to increase the risk of death 6-fold and the risk of RHC 6-fold for a true beneficial effect of RHC to be misrepresented as harmful. CONCLUSION: In this observational study of critically ill patients, after adjustment for treatment selection bias, RHC was associated with increased mortality and increased utilization of resources. The cause of this apparent lack of benefit is unclear. The results of this analysis should be confirmed in other observational studies. These findings justify reconsideration of a randomized controlled trial of RHC and may guide patient selection for such a study.

APACHE↗
PubMed1996

Depression and long-term mortality risk in patients with coronary artery disease.

Previous research has established that patients with coronary artery disease (CAD) have an increased risk of death if they are depressed at the time of hospitalization. Follow-up periods have been short in these studies; therefore, the present investigation examined this phenomenon over an extended period of time. Patients with established CAD (n = 1,250) were assessed for depression with the Zung Self-Rating Depression Scale (SDS) and followed for subsequent mortality. Follow-up ranged up to 19.4 years. SDS scores were associated with increased risk of subsequent cardiac death (p = 0.002) and total mortality (p < 0.001) after controlling for initial disease severity and treatment. Patients with moderate to severe depression had a 69% greater odds of cardiac death and a 78% greater odds of mortality from all causes than nondepressed patients. Increased risk was not confined to the initial months after hospitalization. Patients with high SDS scores at baseline still had a higher risk of cardiac death > 5 years later (p < 0.005). Compared with the nondepressed, patients with moderate to severe depression had an 84% greater risk 5 to 10 years later and a 72% greater risk after > 10 years. Patients with mild depression had intermediate levels of risk in all models. The heightened long-term risk of depressed patients suggests that depression may be persistent or frequently recurrent in CAD patients and is associated with CAD progression, triggering of acute events, or both.

Coronary Disease↗
PubMed1996

One-year results from the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial. GUSTO-I Investigators.

BACKGROUND: In the randomized Global Utilization of t-PA and Streptokinase for Occluded Coronary Arteries (GUSTO-I) trial, 41021 patients received one of four thrombolytic regimens. Patients treated with accelerated tissue plasminogen activator (TPA) had a lower 30-day mortality rate (6.3%) than those treated with the other regimens (7.3%, combined streptokinase groups). METHODS AND RESULTS: Each patient who was alive at 30 days was sent a return postcard to ascertain vital status at 1 year. If the postcard was not returned, the patient (or an alternate specified at randomization) was contacted by telephone. A locator service was used in the United States for patients who could not be located by these methods. Final follow-up was 96% worldwide. One-year mortality rates remained in favor of accelerated TPA (9.1%) over streptokinase with subcutaneous heparin (10.1%, P = .011) and streptokinase with intravenous heparin (10.1%, P = .009). Combination therapy had an intermediate 1-year mortality (9.9%); this outcome was statistically indistinguishable from that with streptokinase (P = .47) but was marginally different from that with accelerated TPA (P = .05). CONCLUSIONS: The 1-year results demonstrated a saving of 10 lives per 1000 patients treated with accelerated TPA versus streptokinase and subcutaneous or intravenous heparin. Combination thrombolytic therapy had an intermediate benefit but offered no advantage over accelerated TPA treatment alone.

Aged↗
PubMed1996

Prediction of the infarct-related artery in acute myocardial infarction by a scoring system using summary ST-segment and T-wave changes.

We developed a scoring system to predict the artery responsible for an acute myocardial infarction (AMI) using ST-segment and T-wave changes on the initial electrocardiogram (ECG) using data from 228 patients (development set) with symptoms compatible with AMI and tested in a similar group of 223 patients (test set) from the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI-5) Trial. Using stepwise logistic regression we were able to accurately predict the left anterior descending (LAD), right, or left circumflex (LC) coronary artery as the infarct-related artery using 2 variables: (1) the summation of the ST-segment elevation in leads V1 to V4; and (2) the summation of the T-wave negativity in leads I, aVL, and V5. In the development set, these 2 variables demonstrated respective sensitivity and specificity of 98% and 90% for LAD lesions, 82% and 85% for right narrowings, and 82% and 84% for LC narrowings. In the test set, the sensitivity and specificity were 97% and 95% for LAD lesions, 85% and 86% for right lesions, and 73% and 60% for LC coronary artery lesions. Information easily obtained on the ECG can accurately predict the likelihood of the LAD, right, or LC artery as the infarct-related artery. This may be useful in the decision to administer thrombolytic treatment.

Coronary Disease↗