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Biomedical subjects

W Douglas Weaver

Publications and source records attributed to W Douglas Weaver.

At least 19 recordsLinked to original sources
PubMed2006

Effects of selective matrix metalloproteinase inhibitor (PG-116800) to prevent ventricular remodeling after myocardial infarction: results of the PREMIER (Prevention of Myocardial Infarction Early Remodeling) trial.

OBJECTIVES: We sought to determine whether matrix metalloproteinase (MMP) inhibitor, PG-116800, reduced left ventricular (LV) remodeling after myocardial infarction (MI). BACKGROUND: PG-116800 is an oral MMP inhibitor with significant antiremodeling effects in animal models of MI and ischemic heart failure. METHODS: In an international, randomized, double-blind, placebo-controlled study, 253 patients with first ST-segment elevation MI and ejection fraction between 15% and 40% were enrolled 48+/- 24 h after MI and treated with placebo or PG-116800 for 90 days. Major efficacy end points were changes in LV volumes as determined by serial echocardiography, and clinical and safety outcomes were also collected. RESULTS: In total, 203 patients (80%) completed 90 days of treatment and had evaluable baseline and 90-day echocardiograms. The proportion of patients with anterior MI (78% vs. 81%) and primary percutaneous coronary intervention (90% vs. 91%) along with baseline LV ejection fraction (35.5% vs. 36.8%) did not differ between PG-116800-treated and placebo-treated patients. There was no difference in the change in LV end-diastolic volume index from days 0 to 90 with PG-116800 versus placebo (5.09 +/- 1.45 ml/m(2) vs. 5.48 +/- 1.41 ml/m2, p = 0.42). Changes in LV diastolic volume, LV systolic volume, LV ejection fraction, sphericity index, plus rates of death or reinfarction were not significantly improved with PG-116800. PG-116800 was well tolerated; however, there was increased incidence of arthralgia and joint stiffness without significant increase in overall musculoskeletal adverse events (21% vs. 15%, p = 0.33). CONCLUSIONS: Matrix metalloproteinase inhibition with PG-116800 failed to reduce LV remodeling or improve clinical outcomes after MI.

Angioplasty, Balloon, Coronary↗
PubMed2006

Prognostic significance of the change in glucose level in the first 24 h after acute myocardial infarction: results from the CARDINAL study.

AIMS: In acute myocardial infarction (AMI), baseline hyperglycaemia predicts adverse outcomes, but the relation between subsequent change in glucose levels and outcomes is unclear. We evaluated the prognostic significance of baseline glucose and the change in glucose in the first 24 h following AMI. METHODS AND RESULTS: We analysed 1469 AMI patients with baseline and 24 h glucose data from the CARDINAL trial database. Baseline glucose and the 24 h change in glucose (24 h glucose level subtracted from baseline glucose) were included in multivariable models for 30- and 180-day mortality. By 30 and 180 days, respectively, 45 and 74 patients had died. In the multivariable 30-day mortality model, neither baseline glucose nor the 24 h change in glucose predicted mortality in diabetic patients (n=250). However, in nondiabetic patients (n=1219), higher baseline glucose predicted higher mortality [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.04-1.20, per 0.6 mmol/L increase], and a greater 24 h change in glucose predicted lower mortality (HR 0.91, 95% CI 0.86-0.96, for every 0.6 mmol/L drop in glucose in the first 24 h) at 30 days. Baseline glucose and the 24 h change in glucose remained significant multivariable mortality predictors at 180 days in nondiabetic patients. CONCLUSION: Both higher baseline glucose and the failure of glucose levels to decrease in the first 24 h after AMI predict higher mortality in nondiabetic patients.

Adolescent↗
PubMed2006

Angiotensin-converting enzyme inhibitors in coronary artery disease and preserved left ventricular systolic function: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This study sought to assess the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in patients with coronary heart disease and preserved left ventricular (LV) function. BACKGROUND: The ACEIs have been shown to improve outcomes in patients with heart failure and myocardial infarction (MI). However, there is conflicting evidence concerning the benefits of ACEIs in patients with coronary artery disease (CAD) and preserved LV systolic function. METHODS: An extensive search was performed to identify randomized, placebo-controlled trials of ACEI use in patients with CAD and preserved LV systolic function. Of 61 potentially relevant articles screened, 6 trials met the inclusion criteria. They were reviewed to determine cardiovascular mortality, nonfatal MI, all-cause mortality, and revascularization rates. We performed random-effect model meta-analyses and quantified between-studies heterogeneity with I(2). RESULTS: There were 16,772 patients randomized to ACEI and 16,728 patients randomized to placebo. Use of ACEIs was associated with a decrease in cardiovascular mortality (relative risk [RR] 0.83, 95% confidence interval [CI] 0.72 to 0.96, p = 0.01), nonfatal MI (RR 0.84, 95% CI 0.75 to 0.94, p = 0.003), all-cause mortality (RR 0.87, 95% CI 0.81 to 0.94, p = 0.0003), and revascularization rates (RR 0.93, 95% CI 0.87 to 1.00, p = 0.04). There was no significant between-studies heterogeneity. Treatment of 100 patients for an average duration of 4.4 years prevents either of the adverse outcomes (one death, or one nonfatal myocardial infarction, or one cardiovascular death or one coronary revascularization procedure). CONCLUSIONS: The cumulative evidence provided by this meta-analysis shows a modest favorable effect of ACEIs on the outcome of patients with CAD and preserved LV systolic function.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

ST-segment elevation myocardial infarction: recommendations on triage of patients to heart attack centers: is it time for a national policy for the treatment of ST-segment elevation myocardial infarction?

Despite substantial progress in the diagnosis and treatment of acute ST-segment elevation myocardial infarction (STEMI), implementation of this knowledge into routine clinical practice has been variable. It has become increasing clear that primary percutaneous coronary intervention (PCI) is the preferred method of reperfusion if it can be performed in a timely manner. Recent European data suggest that transfer for direct PCI may also be preferable to fibrinolytic therapy. We believe it is time to establish a national policy for treatment of patients with STEMI to develop a coordinated system of care similar to that of the level 1 trauma system.

Electrocardiography↗
PubMed2006

The cost of acute myocardial infarction in the new millennium: evidence from a multinational registry.

BACKGROUND: Although geographic variation in the treatment of acute myocardial infarction (AMI) has been recognized, the impact of evidence-based international treatment guidelines on such variation is unclear. We sought to characterize resource use and cost of initial hospitalization for AMI in 9 countries and compare the contribution of length of stay (LOS) and procedure use to cost. METHODS: We applied country-specific cost estimates to data from the international AMI registry associated with the VALIANT trial. The registry includes demographic, medical history, treatment, and discharge information for 5573 patients with AMI admitted to 84 sites in 9 countries from November 1999 to June 2001. Hospitalization cost was estimated by imputed discharge diagnosis-related group code and adjusted for the LOS and procedures. Generalized linear regression was used to adjust cost by country; the contribution of LOS and procedures to cost was assessed by ordinary least squares regression. RESULTS: Unadjusted mean cost for initial AMI hospitalization was 9993 dollars (95% CI 9702 dollars-10,228 dollars). After adjustment for baseline patient-level variation, the lowest average cost was 1605 dollars (Argentina) and the highest was 9196 dollars (United States). Length of stay explained more of the variation in cost (50.7%) than did procedure intensity (31.9%). CONCLUSIONS: International differences in the cost of AMI persist, reflecting variations in procedure use and especially LOS. Relative differences in resource costs and incentives inherent in the provision and financing of health care likely contribute to treatment and cost variation and limit the widespread adoption of international practice guidelines.

Aged↗
PubMed2006

Concerning the mechanism of pexelizumab's benefit in acute myocardial infarction.

BACKGROUND: The COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial previously demonstrated an unexpected dose-dependent reduction in 90-day mortality after bolus/infusion of pexelizumab despite no reduction in the primary end point of myocardial infarction (MI) size. We examined whether the mortality benefit was related to established modulators of clinical benefit such as baseline demographics, time to treatment from symptom onset, myocardial perfusion post-percutaneous coronary intervention (PCI), and extent of ST resolution. METHODS AND RESULTS: Eight hundred fourteen patients were randomized into 3 groups; (1) placebo, (2) pexelizumab bolus 2.0 mg/kg and placebo infusion for 20 hours, and (3) pexelizumab bolus 2.0 and 0.05 mg/kg per hour infusion for 20 hours commencing 4 hours after the bolus. Subjects presented with ST elevation MI within 6 hours of symptom onset and underwent PCI, creatine kinase (CK), and CK-MB measurements taken sequentially to define CK-MB area under the curve (AUC) and sequential ECG's defined ST resolution and QRS infarct size. Whereas mortality for both placebo and bolus pexelizumab groups rose during later time after presentation, it remained low and did not change appreciably during the 6-hour randomization window when patients received pexelizumab bolus infusion. Amplification of the mortality benefit was evident in patients with the highest quartile of hemodynamic compromise, that is, heart rate > or = 90 beat/min and systolic blood pressure < or = 118 mm Hg (3.2% vs 11.3% P = .004). A significant interaction between treatment assignment and hemodynamic status (P = .013) existed after adjusting for age, race, and MI location. Clinical benefit was not related to infarct size, extent of ST elevation, or evidence of angiographic or electrocardiographic reperfusion. CONCLUSIONS: These data raise the possibility that the clinical benefit of pexelizumab is mediated through novel pathways such as reduction in apoptosis or other mechanisms.

Adolescent↗
PubMed2006

Extent of coronary artery disease as a predictor of outcomes in acute myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.

BACKGROUND: Left ventricular systolic dysfunction (LVSD) and heart failure (HF) are powerful predictors of poor outcome after acute myocardial infarction (MI). It is not known, however, whether the extent of coronary artery disease (CAD) independently influences cardiovascular (CV) outcomes in these high-risk patients. METHODS: In the VALIANT, 14703 patients were randomly assigned to receive either captopril monotherapy, valsartan monotherapy, or a valsartan and captopril combination between 0.5 and 10 days after acute MI complicated by LVSD, HF, or both. Cox proportional hazards models were used to evaluate the relation between the extent of CAD (the number of diseased vessels as assessed by angiography) and a range of CV outcomes and all-cause mortality. RESULTS: Coronary angiography data were available on 5742 (40%) of the 14703 randomized patients. Single-vessel disease was reported in 1955 patients (34%), 2-vessel disease in 1598 (28%), and 3-vessel disease in 2189 (38%). For all CV outcomes, the risk increased with the severity of CAD (P for trend < .002). A comparison of single-, 2-, and 3-vessel disease showed that, after adjusting for all known covariates, including revascularization and ejection fraction, 2-vessel disease was associated with a 40% increased hazard (P = .008) and 3-vessel disease was associated with an 85% increased hazard (P < .001) for all-cause mortality. The fully adjusted hazard ratios for death and other CV outcomes increased significantly with increasing extent of CAD. CONCLUSIONS: Increasing extent of CAD, as detected by angiography, is a significant and independent risk factor for adverse CV outcomes after MI complicated by HF, LVSD, or both. The observed risk was apparent even after excluding patients who had undergone revascularization.

Aged↗
PubMed2006

Initial experience with an intravenous P2Y12 platelet receptor antagonist in patients undergoing percutaneous coronary intervention: results from a 2-part, phase II, multicenter, randomized, placebo- and active-controlled trial.

BACKGROUND: Platelet-initiated acute thrombosis and coronary embolization are fundamental in the pathophysiology of complications during percutaneous coronary intervention (PCI). Cangrelor (formerly AR-C69931MX) is a novel, rapidly acting, intravenous, specific antagonist of platelet aggregation via binding to the adenosine diphosphate (ADP) P2Y12 receptor subtype. The primary aims of this study were to assess the initial safety and pharmacodynamics of cangrelor in patients undergoing PCI. METHODS: In part 1, patients undergoing PCI were randomized to an 18- to 24-hour of either placebo, 1-, 2-, or 4-microg/kg per minute cangrelor in addition to aspirin and heparin beginning before PCI. In part 2, patients were randomized to receive either cangrelor (4 microg/kg per minute) or abciximab before PCI. The primary end point was the composite incidence of major and minor bleeding through 7 days. Secondary end points included the occurrence of major adverse coronary events (death, MI, and unplanned repeat coronary intervention) through 30 days plus ex vivo platelet aggregation and bleeding times. RESULTS: Two hundred patients (3 dosage groups and placebo) were studied in part 1, and 199 additional patients were then randomized in the second part, comparing 1 dose of cangrelor and abciximab. Combined major and minor bleeding occurred in 13% of those receiving cangrelor and in 8% in those randomized to placebo (P = non significant [NS]) during part 1 and in 7% receiving cangrelor compared with 10% randomized to abciximab (P = NS), during part 2. The 30-day composite incidence of adverse cardiac events was similar between those receiving cangrelor and those receiving abciximab during part 2 (7.6% vs 5.3%, respectively, P = NS). Mean inhibition of ex vivo platelet aggregation in response to 3 micromol/L ADP at steady state was 100% for both cangrelor 4 microg/kg per minute and abciximab groups in part 2. After termination of infusion, platelet aggregation returned to baseline response more rapidly with cangrelor compared with abciximab. There was a trend toward longer bleeding time prolongation and lower platelet count with abciximab compared with cangrelor. CONCLUSIONS: This initial experience with intravenous cangrelor during PCI suggests an acceptable risk of bleeding and adverse cardiac events while achieving rapid, reversible inhibition of platelet aggregation via competitive binding to the ADP P2Y12 platelet receptor with less prolongation of bleeding time then the glycoprotein IIb/IIIa receptor antagonist abciximab.

Abciximab↗
PubMed2005

Mortality and morbidity remain high despite captopril and/or Valsartan therapy in elderly patients with left ventricular systolic dysfunction, heart failure, or both after acute myocardial infarction: results from the Valsartan in Acute Myocardial Infarction Trial (VALIANT).

BACKGROUND: The elderly constitute an increasing proportion of acute myocardial infarction patients and have disproportionately high mortality and morbidity. Those with heart failure or impaired left ventricular left ventricular function after acute myocardial infarction have high complication and mortality rates. Little is known about outcomes with contemporary therapies in these patients. METHODS AND RESULTS: The Valsartan in Acute Myocardial Infarction Trial (VALIANT) randomized 14,703 patients with heart failure and/or left ventricular ejection fraction <40% to receive captopril, valsartan, or both. Mortality and a composite end point, including cardiovascular mortality, readmission for heart failure, reinfarction, stroke, and resuscitated cardiac arrest, were compared for the age groups of <65 (n=6988), 65 to 74 (n=4555), 75 to 84 (n=2777), and > or =85 (n=383) years. With increasing age, 3-year mortality almost quadrupled (13.4%, 26.3%, 36.0%, and 52.1%, respectively), composite end-point events more than doubled (25.2%, 41.0%, 52.3%, and 66.8%), and hospital admissions for heart failure almost tripled (12.0%, 23.1%, 31.3%, and 35.4%). Outcomes did not differ between the 3 study treatments in any age group. Adverse events associated with captopril and valsartan were more common in the elderly and in patients receiving combination therapy. With increasing age, use of aspirin, beta-blockers, and statins declined, and use of digoxin, calcium-channel blockers, and non-potassium-sparing diuretics increased. On 3-year multivariable analysis, each 10-year age increase was associated with a hazard ratio of 1.49 (95% CI, 1.426 to 1.557; P<0.0001) for mortality and an odds ratio of 1.38 (95% CI, 1.31 to 1.46; P<0.0001) for readmission with heart failure. CONCLUSIONS: Outcomes remained poor in elderly patients with heart failure and/or impaired left ventricular systolic function after acute myocardial infarction, although most received beta-blockers and all received an ACE inhibitor and/or an angiotensin receptor blocker. Better therapies and increased use of aspirin, beta-blockers, and statins are needed in this important and increasing patient group.

Age Factors↗
PubMed2005

Enzyme estimates of infarct size correlate with functional and clinical outcomes in the setting of ST-segment elevation myocardial infarction.

BACKGROUND: Cardiac biomarkers are routinely obtained in the setting of suspected myocardial ischemia and infarction. Evidence suggests these markers may correlate with functional and clinical outcomes, but the strength of this correlation is unclear. The relationship between enzyme measures of myocardial necrosis and left ventricular performance and adverse clinical outcomes were explored. METHODS: Creatine kinase (CK) and CK-MB data were analyzed, as were left ventricular ejection fraction (LVEF) by angiogram, and infarct size by single-photon emission computed tomography (SPECT) imaging in patients in 2 trials: Prompt Reperfusion In Myocardial-infarction Evolution (PRIME), and Efegatran and Streptokinase to Canalize Arteries Like Accelerated Tissue plasminogen activator (ESCALAT). Both trials evaluated efegatran combined with thrombolysis for treating acute ST-segment elevation myocardial infarction (STEMI). RESULTS: Peak CK and CK area-under-the-curve (AUC) correlated significantly with SPECT-determined infarct size 5 to 10 days after enrollment. Peak CK had a statistically significant correlation with LVEF, but CK-AUC and LVEF correlation were less robust. Statistically significant correlations exist between SPECT-determined infarct size and peak CK-MB and CK-MB AUC. However, there was no correlation with LVEF for peak CK-MB and CK-MB AUC. The combined outcome of congestive heart failure and death were significantly associated with CK AUC, CK-MB AUC, peak CK, and peak CK-MB measurements. CONCLUSION: Peak CK and CK-MB values and AUC calculations have significant correlation with functional outcomes (LVEF- and SPECT-determined infarct size) and death or CHF outcomes in the setting of STEMI. Cardiac biomarkers provide prognostic information and may serve as valid endpoint measurements for phase II clinical trials.

Journal Article↗
PubMed2005

Relation of chronic and acute glycemic control on mortality in acute myocardial infarction with diabetes mellitus.

Acute hyperglycemia during myocardial infarction predicts adverse short-term outcomes and mortality in diabetic patients. Conversely, chronic hyperglycemia is associated with an increased incidence of long-term cardiovascular complications, although its effect on acute hyperglycemic response and mortality after acute myocardial infarction is unknown. We investigated the prognostic relation of the glucose concentration at admission and the baseline average glycohemoglobin on acute myocardial infarction mortality. Of 808 consecutive diabetic patients with acute myocardial infarction, the most significant independent predictor of in-hospital mortality was the glucose concentration at admission. Baseline glycohemoglobin strongly correlated with admission hyperglycemia but did not predict mortality independently.

Acute Disease↗
PubMed2005

Bundle branch block patterns, age, renal dysfunction, and heart failure mortality.

BACKGROUND: The determinants of bundle block patterns and their relationship to mortality in heart failure patients is not completely understood. METHODS: We evaluated 2907 consecutive patients admitted to an intensive care unit with decompensated heart failure over 8 years. Clinical and echocardiographic factors were analyzed using multivariate techniques. All-cause mortality was available on greater than 99.0% of patients at a median of 23 months after discharge. RESULTS: Right and left bundle branch blocks occurred in 211 (7.3%) and 386 (13.2%), p<0.0001. Older age, decreased left ventricular ejection fraction, and renal dysfunction were all found to be independently associated with bundle branch block patterns. Mortality rates for the subgroups of QRS<120 ms, right bundle branch block and left bundle branch block, over a mean follow-up of 23.4+/-2.6 months were 46.1%, 56.8% and 57.7%, p<0.0001 for comparison of QRS<120 ms versus either bundle pattern. Cox proportional hazards model adjusting for age, sex, ejection fraction, and renal function demonstrated graded decrements in survival in those with QRS<120 ms, right bundle branch block and left bundle branch block, p=0.03. CONCLUSIONS: In patients hospitalized with severe heart failure, age, left ventricular dysfunction, and renal dysfunction are associated with bundle branch block patterns. When controlling for these factors, bundle branch block patterns are independently associated with slightly higher all cause mortality after discharge.

Age Factors↗
PubMed2005

Characterization of myocardial infarction as an end point in two large trials of acute coronary syndromes.

Myocardial infarction (MI) is a key component of composite end points in trials that evaluate new therapies in non-ST-segment elevation acute coronary syndromes. Types of MI events in these trials have not been well characterized. A similar clinical-events classification process adjudicated all suspected MI end points in the PURSUIT and PARAGON B trials. All MI end points were classified as nonprocedural, related to percutaneous coronary intervention, or related to coronary artery bypass grafting. A total of 16,173 patients was enrolled in the 2 trials, and 1,802 MI end points occurred during a 30-day follow-up. Nearly 66% of MI end points were not related to percutaneous coronary intervention or coronary artery bypass grafting. Patients who had MI compared with those who did not had higher 30-day mortality rates (13.6% vs 2.3%, p <0.001) and 6-month mortality rates (18.4% vs 4.4%, p <0.001). Patients who had been randomized to glycoprotein IIb/IIIa inhibition showed trends toward fewer MI events regardless of type. Two-thirds of MI end points in 2 large trials of acute coronary syndrome were not related to procedure. All MI types were associated with worse short- and long-term outcomes. Characterization of the type of MI provides an opportunity for more informed interpretation of clinical trial results and improved planning for future trials.

Angioplasty, Balloon, Coronary↗
PubMed2005

Prognostic usefulness of white blood cell count and temperature in acute myocardial infarction (from the CARDINAL Trial).

White blood cell (WBC) count and temperature are 2 global measures of inflammation that are systematically gathered and easily identifiable in a clinical setting, unlike many other markers of inflammation being investigated in patients with coronary artery disease. The prognostic usefulness of the WBC count and temperature were evaluated in a large acute myocardial infarction trial, the Complement And ReDuction of INfarct size after Angioplasty or Lytics program. Baseline and serial measurements of WBC counts and temperature were correlated with infarct size and clinical outcome.

Angioplasty↗
PubMed2005

Prevalence and management of hypertension in acute coronary syndrome patients varies by sex: observations from the Sibrafiban versus aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes (SYMPHONY) randomized clinical trials.

BACKGROUND: Hypertension affects 1 billion individuals worldwide and is an independent risk factor for death after acute coronary syndromes (ACS). METHODS: We examined the prevalence and medical treatment of hypertension among 15,904 ACS patients randomized in the SYMPHONY and 2nd SYMPHONY trials. Analyses were performed overall and according to sex for the United States and across international practice. Multivariable models identified factors associated with use of antihypertensive medication classes and examined the association of hypertension and sex with mortality. RESULTS: In the United States, hypertension was more prevalent in women than in men, overall (63% vs 50%) and within every decile of age. Hypertensive women more often received calcium-channel blockers (35% vs 30%) and diuretics (33% vs 19%) and less often received beta-blockers (51% vs 57%). Angiotensin-converting enzyme inhibitor use was similar (35% vs 34%). Women received multiple agents more frequently than did men: 2 agents, 35% vs 30%; > or = 3 agents, 16% vs 13%. Female sex independently predicted drug-class use only for diuretics. Mortality was higher in hypertensive women than in hypertensive men; after multivariable adjustment, mortality was similar without evidence of a differential association between hypertension and mortality according to sex. Although there was international variation in the use of individual classes of agents, the overall findings by sex were similar across regions. CONCLUSION: Hypertension is more prevalent in women than in men with ACS, and its medical management varies by sex, but its association with mortality is similar. Opportunities exist to improve medical therapy and outcomes in women with hypertension.

Acute Disease↗