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Biomedical subjects

Robert M Califf

Publications and source records attributed to Robert M Califf.

At least 19 recordsLinked to original sources
PubMed2026

Regulating cell and xeno-transplants: learning from medical device oversight.

The widespread availability of genetically engineered cellular products and organs for xenotransplantation could address the persistent shortage of human donor organs, but the current regulatory paradigm, which was originally designed for discrete molecular entities, is poorly suited to the paradigm of innovation in this field. The Food and Drug Administration requires sponsors to file investigational new drug applications and pursue a Biologics License Application built around a binary, one-time approval decision. This is fundamentally misaligned with cell- and xenotransplant development, which advances through cumulative incremental change in genomic edits, preservation techniques, and optimized immunosuppression. We argue that the FDA should adopt a risk-adapted framework that combines the strengths of the current biologics paradigm with lessons from medical device oversight, including early feasibility studies, evidence requirements proportionate to product risk and prior knowledge, evolving endpoints, manufacturing standards calibrated to whole organs and cellular preparations rather than mass-produced biologics, pre-negotiated change control plans, and active postmarket surveillance built on existing transplant registry infrastructure.

cellular transplants↗
PubMed2007

Bleeding complications in patients with acute coronary syndrome undergoing early invasive management can be reduced with radial access, smaller sheath sizes, and timely sheath removal.

OBJECTIVES: Our objective was to analyze the impact of arterial access site, sheath size, timing of sheath removal, and use of access site closure devices on high-risk patients with acute coronary syndromes (ACS). BACKGROUND: In the SYNERGY trial, 9,978 patients with ACS were randomly assigned to receive enoxaparin or unfractionated heparin. METHODS: This analysis includes 9,404 patients for whom sheath access information was obtained for the first PCI procedure or diagnostic catheterization. Comparisons of baseline, angiographic, and procedural characteristics were carried out according to access site and sheath size. RESULTS: Overall, 9,404 (94%) patients underwent angiography at a median of 21 hr (25th and 75th percentiles: 5, 42) and 4,687 (50%) underwent PCI at a median of 23 hr (6,49) of enrollment. The access site was femoral for 94.9% of cases, radial for 4.4%, and brachial for 0.7%. Radial access was associated with fewer transfusions than femoral access (0.9% vs. 4.8%, P=0.007). For femoral access, the rates of noncoronary artery bypass grafting (CABG)-related TIMI major bleeding by sheath size was 1.5% for 4 or 5 French (Fr), 1.6% for 6 Fr, 3.3% for 7 Fr, and 3.8% for >or=8 Fr (P<0.0001). After adjustment for baseline characteristics, femoral access site, larger sheath size, and delayed sheath removal were independent predictors of need for transfusion. CONCLUSIONS: Smaller sheaths, radial access, and timely sheath removal may mitigate the bleeding risk associated with potent antithrombotic/platelet therapy and early catheterization.

Aged↗
PubMed2007

Benefit assessment of therapeutic products: the Centers for Education and Research on Therapeutics.

The ability to manage risk depends critically on an understanding of the degree to which a known risk is balanced by the probability of a clinical benefit. Despite the massive emphasis on risk and risk management in the past few years and the long-term focus on defining benefit in the regulatory system, considerable uncertainty remains about the methods of defining benefit and how to operationalize this knowledge. In this 'think tank,' part of a larger series on risk management, issues were divided into those that can be identified before a study is initiated, those that commonly arise after a study is completed, biomarkers and surrogates, use of benefit findings in defining quality and performance indicators, implementation of findings into health systems and formularies, and methods of comparative trials. Key categories for the establishment of a research agenda to fill in gaps in our understanding of assessing benefit were developed by the group.

Drug Industry↗
PubMed2006

Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation.

CONTEXT: Recent studies of drug-eluting intracoronary stents suggest that current antiplatelet regimens may not be sufficient to prevent late stent thrombosis. OBJECTIVE: To assess the association between clopidogrel use and long-term clinical outcomes of patients receiving drug-eluting stents (DES) and bare-metal stents (BMS) for treatment of coronary artery disease. DESIGN, SETTING, AND PATIENTS: An observational study examining consecutive patients receiving intracoronary stents at Duke Heart Center, a tertiary care medical center in Durham, NC, between January 1, 2000, and July 31, 2005, with follow-up contact at 6, 12, and 24 months through September 7, 2006. Study population included 4666 patients undergoing initial percutaneous coronary intervention with BMS (n = 3165) or DES (n = 1501). Landmark analyses were performed among patients who were event-free (no death, myocardial infarction [MI], or revascularization) at 6- and 12-month follow-up. At these points, patients were divided into 4 groups based on stent type and self-reported clopidogrel use: DES with clopidogrel, DES without clopidogrel, BMS with clopidogrel, and BMS without clopidogrel. MAIN OUTCOME MEASURES: Death, nonfatal MI, and the composite of death or MI at 24-month follow-up. RESULTS: Among patients with DES who were event-free at 6 months (637 with and 579 without clopidogrel), clopidogrel use was a significant predictor of lower adjusted rates of death (2.0% with vs 5.3% without; difference, -3.3%; 95% CI, -6.3% to -0.3%; P = .03) and death or MI (3.1% vs 7.2%; difference, -4.1%; 95% CI, -7.6% to -0.6%; P = .02) at 24 months. However, among patients with BMS (417 with and 1976 without clopidogrel), there were no differences in death (3.7% vs 4.5%; difference, -0.7%; 95% CI, -2.9% to 1.4%; P = .50) and death or MI (5.5% vs 6.0%; difference, -0.5%; 95% CI, -3.2% to 2.2%; P = .70). Among patients with DES who were event-free at 12 months (252 with and 276 without clopidogrel), clopidogrel use continued to predict lower rates of death (0% vs 3.5%; difference, -3.5%; 95% CI, -5.9% to -1.1%; P = .004) and death or MI (0% vs 4.5%; difference, -4.5%; 95% CI, -7.1% to -1.9%; P<.001) at 24 months. However, among patients with BMS (346 with and 1644 without clopidogrel), there continued to be no differences in death (3.3% vs 2.7%; difference, 0.6%; 95% CI, -1.5% to 2.8%; P = .57) and death or MI (4.7% vs 3.6%; difference, 1.0%; 95% CI, -1.6% to 3.6%; P = .44). CONCLUSIONS: The extended use of clopidogrel in patients with DES may be associated with a reduced risk for death and death or MI. However, the appropriate duration for clopidogrel administration can only be determined within the context of a large-scale randomized clinical trial.

Aged↗
PubMed2006

Predictors of stroke within 30 days in patients with non-ST-segment elevation acute coronary syndromes.

AIMS: Stroke is an uncommon but serious complication after non-ST-segment elevation acute coronary syndrome (NSTE-ACS). We aimed to identify predictors of stroke within 30 days in patients who suffered NSTE-ACS. METHODS AND RESULTS: We pooled data from six trials (n=31 402) that randomized NSTE-ACS patients either to platelet glycoprotein (GP) IIb/IIIa receptor blockers or to placebo/control therapy. Potential predictors of stroke included treatment, demographic, and clinical characteristics. We identified predictors using univariable and multivariable logistic models, and their performance was evaluated with calibration (Hosmer-Lemeshow test) and discrimination (c-statistic). We found 228 (0.7%) all-cause strokes: 155 (0.5%) non-haemorrhagic, 20 (0.06%) haemorrhagic, and 53 without computed tomography (CT) confirmation. Patients with any type of stroke had a 30-day mortality of 25%. Randomization to GP IIb/IIIa receptor blockers was not significantly associated with all-cause stroke [OR (95% CI) 1.08 (0.83-1.41)]. Older age [OR per 10-year increase 1.5 (1.3-1.7)], prior stroke [2.1 (1.4-3.1)], and elevated heart rate [per 10-beat increase 1.1 (1.0-1.2)] were the strongest predictors of 30-day all-cause stroke. Similar predictors were found for non-haemorrhagic and haemorrhagic strokes. Smoking, previous myocardial infarction, diabetes, and hypertension were not independent predictors of all-cause stroke. The multivariable model to predict all-cause stroke was well calibrated, but its discrimination was only moderate [c-statistic 0.69 (0.65-0.72)]. CONCLUSION: Stroke is a rare complication occurring early after NSTE-ACS, but is associated with high mortality. We found no evidence that GP IIb/IIIa receptor blockers increase stroke risks. A few clinical characteristics predicted higher stroke risks. Thus, incident strokes in NSTE-ACS patients remain largely unexplained.

Adult↗
PubMed2006

Effects of platelet glycoprotein IIb/IIIa receptor blockers in non-ST segment elevation acute coronary syndromes: benefit and harm in different age subgroups.

OBJECTIVE: To investigate whether the beneficial and harmful effects of platelet glycoprotein IIb/IIIa receptor blockers in non-ST elevation acute coronary syndromes (NSTE-ACS) depend on age. METHODS: A meta-analysis of six trials of platelet glycoprotein IIb/IIIa receptor blockers in patients with NSTE-ACS (PRISM, PRISM-PLUS, PARAGON-A, PURSUIT, PARAGON-B, GUSTO IV-ACS; n = 31 402) was performed. We applied multivariable logistic regression analyses to evaluate the drug effects on death or non-fatal myocardial infarction at 30 days, and on major bleeding, by age subgroups (<60, 60-69, 70-79, > or =80 years). We quantified the reduction of death or myocardial infarction as the number needed to treat (NNT), and the increase of major bleeding as the number needed to harm (NNH). RESULTS: Subgroups had 11 155 (35%), 9727 (31%), 8468 (27%) and 2049 (7%) patients, respectively. The relative benefit of platelet glycoprotein IIb/IIIa receptor blockers did not differ significantly (p = 0.5) between age subgroups (OR (95% CI) for death or myocardial infarction: 0.86 (0.74 to 0.99), 0.90 (0.80 to 1.02), 0.97 (0.86 to 1.10), 0.90 (0.73 to 1.16); overall 0.91 (0.86 to 0.99). ORs for major bleeding were 1.9 (1.3 to 2.8), 1.9 (1.4 to 2.7), 1.6 (1.2 to 2.1) and 2.5 (1.5-4.1). Overall NNT was 105, and overall NNH was 90. The oldest patients had larger absolute increases in major bleeding, but also had the largest absolute reductions of death or myocardial infarction. Patients > or =80 years had half of the NNT and a third of the NNH of patients <60 years. CONCLUSIONS: In patients with NSTE-ACS, the relative reduction of death or non-fatal myocardial infarction with platelet glycoprotein IIb/IIIa receptor blockers was independent of patient age. Larger absolute outcome reductions were seen in older patients, but with a higher risk of major bleeding. Close monitoring of these patients is warranted.

Adult↗
PubMed2006

The impact of anthropomorphic indices on clinical outcomes in patients with acute ST-elevation myocardial infarction.

AIMS: Multiple studies have focused on the relationship of body anthropometric measures with clinical events in ST-elevation myocardial infarction (STEMI) patients, highlighting the 'obesity paradox'. However, the relative prognostic importance of these measures over other baseline variables is less known. METHOD AND RESULTS: We performed a retrospective analysis of 94,108 STEMI patients from seven clinical trials evaluating various reperfusion strategies to study the relationship and prognostic importance of height, weight, body mass index (BMI), and body surface area (BSA) with 30-day death and in-hospital cardiogenic shock, major bleeding, and stroke. Main outcome measures of interest included 30-day death and in-hospital cardiogenic shock, major bleeding, and stroke. Weight, BMI, and BSA were inversely and independently related to all clinical events. Despite being statistically significant (P<0.0001), the prognostic information contributed by weight beyond that conferred by baseline clinical factors was minimal (<1% of total prognostic information) making it of limited clinical relevance for predicting 30-day death and cardiogenic shock. In contrast, weight accounted for 8.4% and 4.3% of the prognostic information in the logistic regression models for major bleeding and for stroke. BMI or BSA added little incremental value over simple measure of weight. CONCLUSION: Although statistically significantly related to most outcomes in patients with STEMI including death and shock, body weight provided clinically relevant prognostic information only for the risk of major bleeding and of stroke. Furthermore, BMI or BSA contributed little incremental prognostic information beyond that provided by weight alone. Thus, the existing large body of information concerning the strong prognostic importance of anthropometric measures with outcomes after STEMI should be interpreted in the context of other more important risk factors.

Body Height↗
PubMed2006

Recent trends in the care of patients with non-ST-segment elevation acute coronary syndromes: insights from the CRUSADE initiative.

BACKGROUND: The extent to which national health quality improvement initiatives have altered reported treatment gaps among patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) is unknown. We sought to determine recent trends in adherence to guideline-based therapies for NSTE ACS. METHODS: We evaluated the treatment of patients with high-risk (positive cardiac markers and/or ischemic ST-segment changes) NSTE ACS enrolled in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA (American College of Cardiology/American Heart Association) Guidelines (CRUSADE) Quality Improvement Initiative from 2002 through 2004 (a total of 113 595 patients over 11 calendar quarters). We analyzed adherence to guideline-recommended therapies, including medications used in the acute care period (<24 hours after presentation), invasive procedures, in-hospital outcomes, and discharge therapies and interventions. RESULTS: The use of each class I guideline recommendation, as well as overall adherence to the guidelines, improved significantly (P<.001) during the study period. In the acute care setting, the use of antiplatelet agents increased by 5% and beta-blockers by 12%; at hospital discharge, the use of antiplatelet agents increased by 3% and beta-blockers by 8%. Heparin use in the acute care period increased by 6%, largely owing to a 9% increase in the use of low-molecular-weight heparin. Use of glycoprotein IIb/IIIa inhibitors in the acute care period also increased by more than 13%. At discharge, clopidogrel use increased by 22%, lipid-lowering agents by 11%, and angiotensin-converting enzyme inhibitors by 5%. While adherence improved, many patients still failed to receive 100% indicated treatments at the end of the study period. CONCLUSIONS: During the 4 years since the initial release of the ACC/AHA guidelines for NSTE ACS, adherence to class I recommendations has significantly improved among hospitals participating in CRUSADE. Still, further improvements are needed for optimal implementation of the these guidelines.

Adrenergic beta-Antagonists↗
PubMed2006

Peer-reviewed publication of clinical trials completed for pediatric exclusivity.

CONTEXT: Much of pediatric drug use is off-label because appropriate pediatric studies have not been conducted and the drugs have not been labeled by the US Food and Drug Administration (FDA) for use in children. In 1997, Congress authorized the FDA to grant extensions of marketing rights known as "pediatric exclusivity" if FDA-requested pediatric trials were conducted. As a result, there have been over 100 product labeling changes. The publication status of studies completed for pediatric exclusivity has not been evaluated. OBJECTIVE: To quantify the dissemination of results of studies conducted for pediatric exclusivity into the peer-review literature. DESIGN: Cohort study of all trials conducted for pediatric exclusivity between 1998 and 2004 as determined by MEDLINE and EMBASE searches through 2005, the subsequent labeling changes, and the publication of those studies in peer-reviewed journals. We categorized any labeling changes resulting from the studies as positive or negative for the drug under study. We then evaluated aspects of the studies and product label changes that were associated with subsequent publication in peer-reviewed medical journals. MAIN OUTCOME MEASURES: Publication of the trial data in peer-reviewed journals. RESULTS: Between 1998 and 2004, 253 studies were submitted to the FDA for pediatric exclusivity: 125 (50%) evaluated efficacy, 51 (20%) were multi-dose pharmacokinetic, 34 (13%) were single-dose pharmacokinetic, and 43 (17%) were safety studies. Labeling changes were positive for 127/253 (50%) of studies; only 113/253 (45%) were published. Efficacy studies and those with a positive labeling change were more likely to be published. CONCLUSIONS: The pediatric exclusivity program has been successful in encouraging drug studies in children. However, the dissemination of these results in the peer-reviewed literature is limited. Mechanisms to more widely disperse this information through publication warrant further evaluation.

Clinical Trials as Topic↗
PubMed2006

A subgroup analysis of the impact of prerandomization antithrombin therapy on outcomes in the SYNERGY trial: enoxaparin versus unfractionated heparin in non-ST-segment elevation acute coronary syndromes.

OBJECTIVES: The purpose of this study was to compare the effect of receiving pretreatment with antithrombin before randomization as well as overall efficacy and safety of enoxaparin versus unfractionated heparin (UFH) in the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) trial. BACKGROUND: The SYNERGY trial results demonstrated noninferiority in outcomes with enoxaparin compared with UFH. Randomized treatment was independent of prerandomization treatment. METHODS: Analyses were first performed on the 4 prerandomization subgroups: patients who received no antithrombin therapy and those who were treated with enoxaparin or UFH or both. Then, we focused on the subgroup of patients who received no pretreatment or were pretreated with and randomized to the same drug. Of the 9,978 patients, 2,440 did not receive prerandomization therapy and 6,138 received consistent therapy through randomization. The primary end point was the composite of death and nonfatal myocardial infarction (MI) at 30 days. RESULTS: After adjustment for differences among the subgroups, no significant difference in the association between the 4 pretreatment groups and death or MI remained (p = 0.171). The randomized treatment effect on 30-day death or MI tended to vary with pretreatment (p = 0.055 for interaction test after adjustment). Patients who received consistent therapy with enoxaparin had significantly less death or MI than patients randomized to UFH (adjusted p = 0.041) with a trend toward increased bleeding. CONCLUSIONS: Treatment with antithrombin therapy before randomization had potential impact on comparison of study drug effects. After adjustment for differences in baseline characteristics between subgroups, consistent therapy with enoxaparin might be superior to UFH in reducing death or nonfatal MI, with a modest excess in bleeding.

Aged↗
PubMed2006

Short- and long-term risk stratification in acute coronary syndromes: the added value of quantitative ST-segment depression and multiple biomarkers.

OBJECTIVES: The purpose of this study was to develop 30-day and 1-year risk stratification models for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients that incorporate quantitative ST-segment depression and novel biomarkers. BACKGROUND: Several novel biomarkers have changed the risk profile of ACS; thus, the reassessment of traditional indicators such as ST-segment depression in this new context is warranted. METHODS: Multivariable logistic regression was used to identify significant predictors of 30-day death and death/myocardial infarction (MI) and 1-year mortality in 7,800 NSTE-ACS patients enrolled in the GUSTO-IV (Global Utilization of Strategies to Open Occluded Arteries-IV ACS) trial between 1998 and 2000. RESULTS: Among all other predictors, the degree of ST-segment depression had the highest prognostic value for 30-day death, 30-day death/MI, and 1-year death. Troponin T (TnT), creatinine clearance, N-terminal pro-brain natriuretic peptide (NT-proBNP), heart rate, and age were also highly influential on adverse outcomes. Unlike TnT and NT-proBNP, C-reactive protein was only predictive of long-term death. In contrast to mortality, the contribution of TnT to predicting 30-day death/MI increased, whereas NT-proBNP's role was attenuated. The discriminatory power was excellent (c-index [adjusted for over-optimism]: 0.82 [30-day death]; 0.72 [30-day death/MI]; 0.81 [1-year]). CONCLUSIONS: In this large contemporary study of NSTE-ACS patients, novel insights into risk stratification were observed-in particular, the utility of quantitative ST-segment depression and multiple biomarkers. Collection of these indicators in future NSTE-ACS populations is recommended to evaluate generalizability and clinical application of these findings.

Aged↗
PubMed2006

Evaluation of the National Cholesterol Education Program Adult Treatment Panel III algorithm for selecting candidates for statin therapy: insights from the A to Z trial.

The National Cholesterol Education Program Adult Treatment Panel III recommends an algorithm to integrate iterative risk-stratification information with low-density lipoprotein (LDL) cholesterol levels to identify candidates for statin therapy. We used the Aggrastat to Zocor (A to Z) trial, in which all patients presented with an acute coronary syndrome (ACS) event in the absence of previous statin therapy, to evaluate the performance of this algorithm. Of 1,750 patients with ACS included in this analysis, 1,126 (64%) had an indication for statin therapy before enrollment and 624 (36%) did not have a statin indication before enrollment. We estimate that initiating statin therapy at moderate dosages (decreasing LDL by 1 mmol/L) according to the National Cholesterol Education Program Adult Treatment Panel III guidelines would have prevented approximately 15% of the ACS events leading to enrollment in the A to Z trial, whereas more intensive statin therapy (decreasing LDL by 1.5 mmol/L) would have prevented >21% of events. Aspirin use before enrollment was reported in only 38% of subjects with a statin indication. In conclusion, these observations represent missed opportunities for primary and secondary prevention and highlight the need for assessment of patient risk and better adherence to existing prevention guidelines.

Aged↗
PubMed2006

Clinical relevance of C-reactive protein during follow-up of patients with acute coronary syndromes in the Aggrastat-to-Zocor Trial.

BACKGROUND: Elevated levels of high-sensitivity C-reactive protein (hsCRP) are associated with higher risk of adverse outcomes in patients at risk for or with established coronary artery disease. Retrospective analyses suggest that this risk may be modified with statin therapy. However, a role for hsCRP in monitoring the success of therapy remains uncertain. METHODS AND RESULTS: We measured the serum concentration of hsCRP at 30 days (n=3813) and 4 months in patients with non-ST-elevation or ST-elevation acute coronary syndrome randomly assigned to an early intensive versus delayed conservative simvastatin strategy in the Aggrastat-to-Zocor Trial. Patients with hsCRP >3 mg/L at 30 days had significantly higher 2-year mortality rates than those with hsCRP 1 to 3 mg/L or hsCRP <1 mg/L (6.1% versus 3.7% versus 1.6%, P<0.0001). Results were similar with hsCRP measured at 4 months. After adjusting for age, gender, diabetes, smoking, cardiovascular history, index event, lipid levels, and randomly assigned treatment, patients with hsCRP >3 mg/L were at more than 3-fold higher risk of death (HR, 3.7; 95% CI, 1.9 to 7.2) compared with those with hsCRP <1 mg/L. "Average" levels of hsCRP (1 to 3 mg/L) were also associated with increased risk compared with those with hsCRP <1 mg/L (HR, 2.3; 95% CI, 1.2 to 4.6). Patients allocated to early intensive statin therapy were more likely to achieve hsCRP levels <1 mg/L at 30 days (P=0.028) and 4 months (P<0.0001). CONCLUSIONS: Achieved levels of hsCRP at 30 days and 4 months after acute coronary syndrome are independently associated with long-term survival. Patients treated with more aggressive statin therapy are more likely to achieve lower levels of hsCRP.

Acute Disease↗
PubMed2006

Impact of internal mammary artery conduit on long-term outcomes after percutaneous intervention of saphenous vein graft.

BACKGROUND: The influence of an internal mammary artery (IMA) graft on long-term outcomes after percutaneous saphenous vein graft (SVG) intervention is currently unknown. METHODS AND RESULTS: To examine the impact of IMA on outcomes in patients undergoing SVG interventions, we analyzed 2119 patients from the Duke Cardiovascular Disease Database (1986-2003) with prior coronary artery bypass surgery undergoing cardiac catheterization who had at least 1 SVG graft. Patients were categorized into 4 groups: group I, SVG intervention and patent IMA; group II, no SVG intervention and patent IMA; group III, SVG intervention without patent IMA; and group IV, no SVG intervention without patent IMA. At a median follow-up of 4.8 years (interquartile range, 2.1 to 8.8 years), adjusted survival rates in groups I, II, III, and IV were 72.8%, 72.3%, 64.5%, and 58.9%, respectively. Multivariate Cox proportional hazards modeling showed similar survival for groups I and II (P=0.63) and for groups III and IV (P=0.33). The presence of IMA graft was related to lower long-term mortality (adjusted hazard ratio [HR], 0.69; 95% CI, 0.58 to 0.82), whereas SVG intervention was not associated with long-term mortality (adjusted HR, 0.94; 95% CI, 0.81 to 1.10). In contrast, the adjusted event-free rates for nonfatal myocardial infarction were lower in the SVG intervention groups (groups I and III) than in the non-SVG intervention groups (groups II and IV) (HR for SVG intervention versus no SVG intervention, 3.19; 95% CI, 2.18 to 4.66), with the presence of patent IMA conferring no significant benefit on this outcome (HR, 1.37; 95% CI, 0.91 to 2.08). CONCLUSIONS: In patients undergoing SVG interventions, survival, but not nonfatal myocardial infarction, is favorably influenced by the presence of patent IMA. In contrast, SVG intervention had no measurable survival benefit but was associated with an increased risk of nonfatal myocardial infarction.

Aged↗
PubMed2006

International variation in invasive care of the elderly with acute coronary syndromes.

AIMS: To explore variations in invasive care of the elderly with acute coronary syndromes across international practice. METHODS AND RESULTS: Using combined populations from the SYMPHONY and 2nd SYMPHONY trials, we describe 30-day cardiac catheterization in elderly (> or = 75 years; n = 1794) vs. younger patients (< 75 years; n = 14,043) after multivariable adjustment and by region of enrolment. The use of cardiac catheterization and revascularization were not protocol-specified. Elderly patients (median age 78 years) were more often female and more frequently had hypertension, diabetes, prior myocardial infarction, and prior coronary bypass surgery. Overall, they underwent less cardiac catheterization than younger patients [53 vs. 63%; adjusted OR 0.53 (0.46, 0.60)]. The absolute rate of cardiac catheterization in the elderly varied from 77% (vs. 91% in younger patients) in the US cohort to 27% (vs. 41% in younger patients) in the non-US cohort. Revascularization of elderly who underwent cardiac catheterization was also higher in US than non-US cohorts (71.3 vs. 53.6%). There was a significant interaction between the patient age and the use of catheterization across US and non-US regions of enrolment, as well as differences in the predictors of catheterization in the elderly. Despite these findings, after adjustment, 90-day rates of death and death or myocardial infarction (MI) were not significantly different in elderly who underwent catheterization compared with those who did not. CONCLUSION: Although older age is universally predictive of lower use of cardiac catheterization, marked variation in catheterization of the elderly exists across international practice. Demonstrated differences in patterns of use suggest a lack of consensus regarding optimal use of an invasive strategy in the elderly.

Acute Disease↗
PubMed2006

Statin use and sex-specific stroke outcomes in patients with vascular disease.

BACKGROUND AND PURPOSE: Although statins reduce the risk of stroke in patients with coronary heart disease, possible differing effects of statins on stroke outcomes based on sex remain uncertain. We investigated the relationships between statin use and sex-specific stroke incidence, severity, and mortality. METHODS: Data from 3 trials of oral glycoprotein IIb/IIIa inhibitors (first and second Sibrafiban versus aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes [SYMPHONY] and Blockade of the glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion [BRAVO]) were pooled and stroke outcomes compared among 8191 baseline statin users versus 14,752 nonusers. Time-to-event data were modeled with proportional hazards regression. Stroke severity was assessed retrospectively with the Canadian Neurological Scale (CNS) based on records with scoreable neurological examinations. RESULTS: A total of 217 subjects had strokes (0.95%). Statin users had a lower risk of stroke in unadjusted (hazard ratio [HR], 0.69; 95% CI, 0.51 to 0.92) and risk-adjusted models (HR, 0.72; 95% CI, 0.53 to 0.97). There was no difference in stroke mortality with statin use (P=0.8). CNS scores could be assigned to 106 of the subjects, with no difference in severity among statin users and nonusers (median CNS=10.5 in users versus CNS=9.75 in nonusers; P=0.14). Women had more severe strokes than men (median CNS=10.5 in men versus 9.5 in women; Poisson regression P=0.035). Women had more severe strokes after adjustment for statin use (P=0.03) and the combination of statin use, atrial fibrillation, and age (P=0.03). CONCLUSIONS: In patients included in these clinical trials of oral glycoprotein IIb/IIIa inhibitors, statin use is associated with a reduced risk of stroke but not severity or mortality. Women had more severe strokes than men, a difference that was not explained by baseline characteristics or statin use.

Aged↗