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R G Wilcox

Publications and source records attributed to R G Wilcox.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prior aspirin use predicts worse outcomes in patients with non-ST-elevation acute coronary syndromes. PURSUIT Investigators. Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy.

Aspirin is beneficial in the prevention and treatment of cardiovascular events, but patients who have events while taking aspirin may have worse outcomes than those not on aspirin. We investigated the association between prior aspirin use and clinical outcomes in 9,461 patients with non-ST-elevation acute coronary syndromes enrolled in the Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, before and after adjustment for baseline factors. We also examined whether eptifibatide has a differential treatment effect in prior aspirin users. Prior aspirin users were less likely to have an enrollment myocardial infarction (MI) (vs unstable angina) (43.9% vs 48.8%, p = 0.001) but more likely to have death or MI at 30 days (16.1% vs 13.0%, p = 0.001) and at 6 months (19.9% vs 15.9%, p = 0.001). After adjustment, prior aspirin users remained less likely to have an enrollment MI (odds ratio 0.88, 95% confidence interval 0.79 to 0.97) and more likely to have death or MI at 30 days (odds ratio 1.16, 95% confidence interval 1.00 to 1.33) but not at 6 months (odds ratio 1.14, 95% confidence interval 0.98 to 1.33). In a multivariable model, eptifibatide did not have a different treatment effect in prior aspirin users compared with nonusers (p = 0.534). Prior aspirin users had fewer enrollment MIs but worse long-term outcomes than nonusers. We found no evidence for a different treatment effect of eptifibatide in prior aspirin users.

Acute Disease↗
PubMed1999

Comparison of antiplatelet activity of microencapsulated aspirin 162.5 Mg (Caspac XL), with enteric coated aspirin 75 mg and 150 mg in patients with atherosclerosis.

AIMS: A new formulation, low dose microencapsulated aspirin, permits slow absorption of aspirin and presystemic acetylation of platelet cyclo-oxygenase within the portal circulation, potentially avoiding deleterious effects on gastric and systemic prostaglandin synthesis. The objective of this study was to determine whether the administration of microencapsulated aspirin was as effective as enteric coated (EC) aspirin as an inhibitor of platelet function in patients with atherosclerosis. METHODS: One hundred and four patients were enrolled and randomised after a run in period of at least 14 days on aspirin EC 75 mg (day 0), to receive either microencapsulated aspirin 162.5 mg (n=34), aspirin EC 150 mg (n=36) or continue on aspirin EC 75 mg (n=34) for 28 days. Serum thromboxane B2 and collagen-induced platelet aggregation and release of 5-hydroxytryptamine (EC50 values) were measured on days 0 and 28. Aggregation/release EC50s were then repeated in the presence of a large dose of aspirin added in vitro to determine the EC50 at the maximum level of platelet inhibition. RESULTS: Median thromboxane B2 levels were low after 14 days run-in therapy with aspirin EC 75 mg, but significant further reductions were seen on day 28 in patients randomised to microencapsulated aspirin 162.5 mg (P=0.0368) and aspirin EC 150 mg (P=0.0004) compared with those remaining on aspirin EC 75 mg. Median EC50 s on day 28 showed small but significant increases from baseline (day 0) in aggregation in patients randomised to microencapsulated aspirin 162.5 mg (0.62-0.85, P=0.0482) and in both aggregation and release in patients randomised to aspirin EC 150 mg (0.95-1.20, P=0.0002, 8.4-11.7, P<0. 0001, respectively) signifying enhanced antiplatelet activity. No changes were seen in patients continuing on aspirin EC 75 mg. Results following addition of high dose aspirin in vitro suggest that mechanisms other than thromboxane synthesis may be operative in the long term effects of microencapsulated aspirin 162.5 mg and aspirin EC 150 mg over aspirin EC 75 mg. CONCLUSIONS: The results show good inhibition of thromboxane B2 synthesis and subsequent platelet activity by all preparations of aspirin, although both microencapsulated aspirin 162.5 mg and aspirin EC 150 mg are slightly more effective than aspirin EC 75 mg. A randomised trial is now required to determine whether microencapsulated aspirin is associated with fewer gastric side-effects.

Arteriosclerosis↗
PubMed1999

Relevance of clinical trial results in myocardial infarction to medical practice: comparison of four year outcome in participants of a thrombolytic trial, patients receiving routine thrombolysis, and those deemed ineligible for thrombolysis.

OBJECTIVE: To assess the medium to long term outcome of patients ineligible for thrombolysis compared to those enrolled in a clinical trial of thrombolysis and patients receiving non-trial thrombolysis. DESIGN: Cohort study based on the Nottingham heart attack register. SETTING: Two district general hospitals serving a defined urban/rural population. SUBJECTS: All patients admitted with a confirmed acute myocardial infarction during 1992 categorised as either participants of a thrombolytic trial (group A, n = 140), receiving non-trial thrombolysis (group B, n = 329), or deemed ineligible for lytic treatment (group C, n = 431). MAIN OUTCOME MEASURES: Background characteristics, inhospital treatment, patterns of follow up, referrals to cardiologists, revascularisation rates, and short and long term survival. RESULTS: Clinical trial recruits were younger by almost 10 years, were less likely to have a previous history of myocardial infarction, and more likely to be in Killip class 1 on admission than those ineligible for thrombolysis. Cardiology follow up was mandatory for all surviving trial participants but 22% of patients in group B and 31% of patients in group C received no follow up, and during four years less than 50% ever saw a cardiologist. Revascularisation was performed in 17.2% of patients in group A, 13.6% of patients in group B, and 7.5% of patients in group C. Cumulative mortality at a median of four years was 24.3% in group A, 36.8% in B, and 59.6% in group C. Adjusting for age, sex, previous myocardial infarction, type of infarction, and Killip class in a logistic regression model the odds ratios (OR) of death at four years for groups B and C were 1.60 (95% confidence intervals (CI) 0.97 to 2.63, p = 0.065) and 2.64 (95% CI 1.61 to 4. 32, p < 0.001), respectively, when compared to group A (OR 1). CONCLUSIONS: Patients enrolled into thrombolytic trials are at low risk. Patients deemed ineligible for thrombolysis are high risk, receive less surveillance, are less likely to be revascularised or receive trial proven treatments, have a poor long term outcome not entirely explained by increased age or severity of infarction, and deserve further evaluation.

Aftercare↗
PubMed1999

A whole blood assay of inhibition of platelet aggregation by glycoprotein IIb/IIIa antagonists: comparison with other aggregation methodologies.

We have used a whole blood single-platelet counting assay (WB-SPC) that is sensitive to microaggregation for monitoring GPIIb/IIIa antagonists and have compared this with other methodologies. In vitro effects of the GPIIb/IIIa antagonist fradafiban on ADP-induced platelet aggregation were determined using WBSPC and PRP turbidimetry, comparing citrate and hirudin anticoagulation. Fradafiban was a more potent inhibitor of aggregation assessed by PRP turbidimetry compared to WBSPC. Citrate showed only a trend towards enhancing fradafiban potency (p = 0.087). Citrated blood from 8 patients with unstable angina, randomised to receive oral lefradafiban (the oral prodrug of fradafiban) or placebo, was studied before and during treatment using WBSPC, PRP turbidimetry, impedance aggregometry and Rapid Platelet Function Assay (RPFA, Accumetrics). RPFA, PRP turbidimetry and WBSPC measurements correlated well. Impedance aggregometry responses were oversensitive to GPIIb/IIIa blockade. WBSPC was most discriminating at high levels of inhibition and offered a rapid means of monitoring GPIIb/IIIa antagonist effect within the therapeutic range of inhibition.

Adolescent↗
PubMed1998

Differential effects of glycoprotein IIb/IIIa antagonists on platelet microaggregate and macroaggregate formation and effect of anticoagulant on antagonist potency. Implications for assay methodology and comparison of different antagonists.

BACKGROUND: Citrated platelet-rich plasma (PRP) turbidimetry is used for assessing pharmacodynamic effects of glycoprotein (GP) IIb/IIIa antagonists in clinical trials. However, citrate can enhance the potency of at least eptifibatide (Integrilin), and turbidimetry is insensitive to microaggregate formation. We compared PRP turbidimetry, as a measure of macroaggregate formation, with single-platelet counting in both whole blood and PRP as a measure of microaggregate formation, using both citrate and hirudin anticoagulation. METHODS AND RESULTS: Three GP IIb/IIIa antagonists, eptifibatide, MK-0852, and GR144053, were compared in PRP (turbidimetry) and whole blood (platelet counting with an Ultra-Flo 100 Platelet Counter), with ADP and collagen used as agonists. Compared with hirudin, citrate enhanced the potency of eptifibatide by up to 4-fold in both PRP and whole blood (P<0.0005), modestly enhanced MK-0852 potency (P=0.001), and had no effect on GR144053. Potency measured in PRP was 2- to 3-fold greater compared with whole blood for MK-0852 and GR144053 but 3- to 4-fold greater for eptifibatide. Simultaneous turbidimetry and platelet counting performed in PRP indicated that this is because GP IIb/IIIa antagonists are more potent inhibitors of in vitro macroaggregation than microaggregation, this effect being greater for eptifibatide in hirudinized PRP compared with GR144053 (P=0.032). CONCLUSIONS: GP IIb/IIIa antagonist potency is variably enhanced by citrate. Macroaggregation is inhibited more effectively than microaggregation, most markedly in the case of eptifibatide in hirudinized blood. These observations have implications for the interpretation and comparison of pharmacodynamic assays and possibly for the risk/benefit ratio of different agents.

Adenosine Diphosphate↗
PubMed1998

Prospective use of glycoprotein IIb/IIIa receptor blockers in the emergency department setting.

Platelets play a pivotal role in the pathophysiology of acute coronary syndromes (ACS) and thus are logical therapeutic targets for treatment of this disease process. Platelet glycoprotein (GP) IIb/IIIa receptor antagonists, which interrupt the final common pathway of platelet aggregation, have been proved to reduce the 30-day incidence of death, acute myocardial infarction (MI), and urgent revascularization in both high-risk and low-risk patients undergoing percutaneous intervention procedures. Three-year follow-up has indicated that these benefits appear durable. Recent large-scale randomized trials have demonstrated the value of GP IIb/IIIa receptor inhibitors in reducing the risk of death and MI in patients with unstable angina or those with MI with non-Q-wave abnormalities who are receiving pharmacologic management. In addition, emerging evidence suggests a future role for GP IIb/IIIa receptor inhibitors as an adjunct to low-dose fibrinolytic therapy in patients with acute MI. As the list of indications for GP IIb/IIIa receptor antagonists expands to encompass the full spectrum of ACS, there is increasing interest in the potential use of these agents in the emergency department setting. The integration of GP IIb/IIIa receptor inhibitors into ED protocols will ultimately depend largely on whether these drugs prove to be safe and effective regardless of the direction of ST-segment deviation, and irrespective of whether definitive therapy will be invasive or conservative.

Acute Disease↗
PubMed1998

Prospective use of platelet glycoprotein IIb/IIIa receptor blockers in the emergency department setting.

Platelets play a pivotal role in the pathophysiology of acute coronary syndromes (ACS) and thus are logical therapeutic targets for treatment of this disease process. Platelet glycoprotein (GP IIb/IIIa receptor antagonists, which interrupt the final common pathway of platelet aggregation, have been proven to reduce the 30-day incidence of death, acute myocardial infarction (MI), and urgent revascularization in both high-risk and low-risk patients undergoing percutaneous intervention procedures. Three-year follow-up has indicated that these benefits appear durable. Recent large-scale randomized trials have demonstrated the value of GP IIb/IIIa receptor inhibitors in reducing the risk of death and MI in unstable angina/non-Q-wave MI patients receiving pharmacologic management. And, emerging evidence suggests a future role for GP IIb/IIIa receptor inhibitors as an adjunct to low-dose fibrinolytic therapy in patients with acute MI. As the list of indications for GP IIb/IIIa receptor antagonists expands to encompass the full spectrum of ACS, there is increasing interest in the potential use of these agents in the emergency department setting. The integration of GP IIb/IIIa receptor inhibitors into emergency department protocols will ultimately depend largely on whether these drugs prove to be safe and effective regardless of the direction of ST-segment deviation, and irrespective of whether definitive therapy will be invasive or conservative.

Algorithms↗
PubMed1997

Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. GUSTO-I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

OBJECTIVES: This study was undertaken to define and better understand the characteristics and outcomes of patients with diabetes treated for acute myocardial infarction with contemporary thrombolysis. BACKGROUND: Although thrombolysis has substantially improved survival of patients with myocardial infarction, diabetes mellitus remains an independent predictor for a poor prognosis. METHODS: We characterized the contemporary relation between diabetes and outcome after myocardial infarction treated with thrombolytic agents from a large international cohort. Of 41,021 patients randomized to receive accelerated tissue-type plasminogen activator (t-PA), streptokinase or a combination of both agents in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries study, there were 5,944 patients with diabetes and 34,888 patients without diabetes. RESULTS: Patients with diabetes were older and more likely to be female, to present with anterior wall infarction, to receive thrombolysis later and to have triple-vessel coronary artery disease. Mortality at 30 days was highest among diabetic patients treated with insulin (12.5%) compared with non-insulin-treated diabetic (9.7%) and nondiabetic (6.2%) patients (p < 0.001). Mortality was lowest among those with diabetes receiving accelerated t-PA, which is consistent with the results of the overall patient cohort. Although stroke occurred more frequently among diabetic (1.9%) than nondiabetic patients (1.4%, p < 0.001), there was no significant difference in the rates of intracranial hemorrhage. Cardiac failure, shock, atrioventricular block and atrial flutter/ fibrillation were more common among diabetic patients. The proportion of patients undergoing revascularization was similar between patients with and without diabetes, although diabetic patients were more likely to undergo coronary artery bypass graft surgery (10.4% vs. 8.3%). Diabetes remained an independent predictor for mortality at 1-year follow-up (14.5% vs. 8.9%, p < 0.001). CONCLUSIONS: Diabetes, alone and in association with its comorbidities, portends a substantially worse 30-day and 1-year prognosis for patients with myocardial infarction.

Aged↗
PubMed1996

Clinical trials in thrombolytic therapy: what do they tell us? INJECT 6-month outcomes data.

Numerous controlled clinical trials have documented the efficacy of thrombolytic agents in reducing the risk of mortality after myocardial infarction (MI). As a result, it is no longer ethical to test a new thrombolytic regimen against placebo. Rather, promising new therapies must be compared with proven treatments. This has been the direction taken in trials of reteplase, a new recombinant plasminogen activator. Initial studies of double-bolus reteplase demonstrated its superior ability to produce. TIMI grade 2 or 3 flow at 90 minutes when compared with accelerated alteplase. A subsequent randomized, double-blind, 9-country study, the International Joint Efficacy Comparison of Thrombolytics (INJECT) trial was designed to determine whether the efficacy of reteplase is at least equivalent to that of streptokinase. The 2 treatments were associated with similar frequencies of inhospital cardiac events, bleeding, and strokes. Likewise, no significant difference was apparent between the reteplase and streptokinase groups with regard to 35-day mortality (the primary endpoint), the combined endpoint of 35-day mortality plus continuing disability from inhospital stroke, or 6-month mortality. Unadjusted data from the 3 countries that contributed the majority of patients seemed to indicate a survival benefit, irrespective of treatment allocation, among patients who underwent interventional procedures. However, no such benefit was apparent when the data were adjusted for differences in the baseline characteristics of the patients enrolled in the different countries. Rather, intervention within the first 3 days post-MI was found to place patients at a substantially higher risk of 35-day mortality. Further insights into the relative efficacy of reteplase should emerge from the ongoing third Global Utilization of Strategies to Open Occluded Coronary Arteries (GUSTO-III) trial.

Cerebrovascular Disorders↗
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

Comparisons of characteristics and outcomes among women and men with acute myocardial infarction treated with thrombolytic therapy. GUSTO-I investigators.

OBJECTIVE: To compare baseline characteristics, complications, and treatment-specific outcomes of women and men with acute myocardial infarction treated with thrombolytic therapy. DESIGN: Randomized controlled trial. PATIENTS AND SETTING: A total of 10315 women and 30706 men with acute myocardial infarction treated in 1081 hospitals in 15 countries as part of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I). INTERVENTION: One of four thrombolytic regimens: (1) streptokinase with subcutaneous heparin; (2) streptokinase with intravenous heparin; (3) streptokinase plus alteplase (tissue-type plasminogen activator) with intravenous heparin; or (4) accelerated alteplase with intravenous heparin. MAIN OUTCOME MEASURES: Mortality, stroke, and nonfatal complications during 30-day follow-up. RESULTS: Women were on average 7 years older than men and delayed 18 minutes (median) longer after symptom onset before presenting to the hospital. After adjustment for age, women more often had a history of diabetes, hypertension, and smoking than men. Time to treatment was significantly longer in women (1.2 vs 1.0 hours; P<.001). Women had more nonfatal complications after treatment, including shock (9% vs 5%; P<.001), congestive heart failure (22% vs 14%; P<.001), serious bleeding (15% vs 7%; P<.001), and reinfarction (5.1% vs 3.6%; P<.001). Women had twice as many total strokes as men (2.1% vs 1.2%; P<.001), secondary to their older age at presentation. The unadjusted mortality rate was twice as high in women as men (11.3% vs 5.5%; P<.001); the relative risk (RR) of death was greater among women than men after adjustment for differences in baseline characteristics (RR=1.15; 95% confidence interval, 1.0 to 1.31). Although women and men underwent angiography at similar rates, there were small but significant differences in their rates of revascularization procedures (angioplasty: 35% of women and 32% of men; bypass surgery: 7% of women and 9% of men; P<.001 for both). The higher rate of stroke in women after treatment with alteplase (2.0% vs 1.9% with streptokinase and intravenous heparin) was offset by a greater relative reduction in mortality (10.3% vs 11.1%). CONCLUSION: Women who received thrombolytic therapy for treatment of acute myocardial infarction were at greater risk for both fatal and nonfatal complications than men.

Aged↗
PubMed1996

Late assessment of thrombolytic efficacy (LATE) study: prognosis in patients with non-Q wave myocardial infarction. (LATE Study Investigators)

OBJECTIVES: We examined the impact of thrombolytic therapy and the prognosis of patients with non-Q wave myocardial infarction in a randomized placebo-controlled trial known as the Late Assessment of Thrombolytic Efficacy (LATE) study. BACKGROUND: Patients with non-Q wave as compared with Q wave myocardial infarction in the era before thrombolytic therapy were traditionally thought to have a higher rate of reinfarction and death between hospital discharge and 1 year such that the overall prognosis for outcome at 1 year was similar in the two groups. METHODS: The study patients began treatment with either recombinant tissue-type plasminogen activator (rt-PA) or matching placebo, 6 to 24 h after the onset of chest pain. Post hoc analysis of mortality and reinfarction was carried out by comparing rt-PA and placebo in various subsets of patients based on the presenting electrocardiogram (ECG) and the evolution of the ECG with respect to the development of Q waves. RESULTS: Among 5,711 participants, 4,759 had a confirmed myocardial infarction, including 1,309 classified as having a non-Q wave infarction at hospital discharge. Irrespective of treatment assignment, all patients with non-Q wave versus Q wave infarction had a lower 1-year mortality rate (13.3% vs. 17.1%, p = 0.001) and a similar 1-year reinfarction rate (8.6% vs. 7.9%, p = 0.7). Of the 4,759 patients with confirmed myocardial infarction, 2,973 presented with ST segment elevation or bundle branch block, 528 with ST depression and 1,258 with neither ST elevation nor depression. No overall benefit from rt-PA versus placebo with respect to mortality rate at 1 year was seen among patients presenting with ST elevation (21.2% vs. 22.4%, p = 0.5 [90% power to detect 20% relative difference]). Patients with ST elevation who were treated with rt-PA versus placebo <3 h after hospital admission had a lower mortality rate at 1 year (15.8% vs. 19.6%, p = 0.028) than did those treated after 3 h (17.6% vs. 13.0%, p = 0.055). Patients presenting initially with ST depression >2 mm had significant benefit from treatment with rt-PA with respect to 1 year mortality rate (20.1% vs. 31.9%, p = 0.006). CONCLUSIONS: Patients with non-Q wave myocardial infarction constitute a heterogeneous group of patients. Although the observations presented here are limited by post hoc analysis, it is apparent that patients classified as having a non-Q wave infarction after thrombolytic therapy have a better prognosis than do those given placebo. Late admission of thrombolytic therapy (after 6 h) may also be beneficial in patients presenting with ST depression >2 mm and confirmed myocardial infarction. These hypotheses require prospective testing in a larger number of patients.

Electrocardiography↗
PubMed1995

Evaluation of paradoxic beneficial effects of smoking in patients receiving thrombolytic therapy for acute myocardial infarction: mechanism of the "smoker's paradox" from the GUSTO-I trial, with angiographic insights. Global Utilization of Streptokinase and Tissue-Plasminogen Activator for Occluded Coronary Arteries.

OBJECTIVES: Our purpose was to evaluate the relation between smoking and the outcomes of patients receiving thrombolysis for acute myocardial infarction. BACKGROUND: A paradoxic beneficial effect has been observed in smokers with a myocardial infarction. We analyzed outcomes and baseline characteristics of 11,975 nonsmokers, 11,117 ex-smokers and 17,507 current smokers in a multinational trial of thrombolysis for acute myocardial infarction. METHODS: Patients were randomized to one of four thrombolytic protocols. An angiographic substudy in 2,431 patients evaluated reperfusion, reocclusion and ventricular function. Effects of smoking were evaluated by logistic regression analysis after adjustment for age and gender. A mortality model evaluated the simultaneous effect of baseline characteristics on the prognostic importance of smoking. These processes were performed with data from both the main trial and the angiographic substudy; then angiographic factors (coronary anatomy, patency and ejection fraction) were added to the model. RESULTS: Smokers were significantly younger by a mean of 11 years) and had less comorbidity or severe coronary artery disease than nonsmokers. Nonsmokers had significantly higher hospital and 30-day mortality rates (9.9% and 10.3%, respectively) than smokers (3.7% vs. 4%, respectively, both p < 0.001) and more in-hospital complications. The unadjusted odds ratio for 30-day mortality in nonsmokers was 3.36 (95% confidence interval [CI] 2.08 to 5.41), 1.21 (95% CI 0.71 to 2.08) after adjustment for age and gender and 1.08 (95% CI 0.59 to 1.96) after adjustment for all clinical baseline characteristics. CONCLUSIONS: Smokers receiving thrombolysis for acute myocardial infarction presented 11 years earlier than nonsmokers, which generally accounted for their better outcome. When other differences in clinical and angiographic baseline factors and therapeutic responses were evaluated, no significant difference in mortality was seen between smokers and nonsmokers.

Adult↗
PubMed1995

Cardiac rupture associated with thrombolytic therapy: impact of time to treatment in the Late Assessment of Thrombolytic Efficacy (LATE) study.

OBJECTIVES: This prospective ancillary study was conducted to determine the association between the time from symptom onset to treatment and cardiac rupture in patients with acute myocardial infarction. BACKGROUND: There is strong evidence that the time window for thrombolytic therapy should be extended to at least 12 h; however, many clinicians are concerned that late treatment may cause an excessive occurrence of death from cardiac rupture. Because up to 30% of patients with acute myocardial infarction arrive in the hospital > 6 h from symptom onset, resolving this issue is of paramount clinical importance. METHODS: A total of 5,711 patients with acute myocardial infarction were randomized to receive intravenous recombinant tissue-type plasminogen activator (rt-PA) (100 mg over 3 h) or matching placebo, within 6 and 24 h from symptom onset. Both groups received immediate oral aspirin, and a majority of patients received intravenous heparin during the initial 48 h. RESULTS: By 35 days, 177 patients had died, with the cause of death specified as cardiac rupture (53 patients), electromechanical dissociation (42 patients) or asystole (82 patients). An additional 370 patients had died of other causes. In patients treated within 12 h, the proportion of rupture deaths in the group given rt-PA was higher than that observed in those who received placebo, but the difference was not statistically significant. In patients treated after 12 h, there was no evidence of an increased incidence of rupture with rt-PA, and the proportion of deaths due to rupture in this group was lower than that in patients given placebo. However, there was evidence of a difference between rt-PA and placebo with respect to the time that rupture became clinically manifest (treatment by time to death interaction, p = 0.03). CONCLUSIONS: This study provides unequivocal evidence that late treatment (6 to 24 h after symptom onset) with rt-PA is not associated with an increased risk of cardiac rupture. However, for reasons that are unclear, coronary thrombolysis appears to accelerate rupture events, typically to within 24 h of treatment.

Aged↗
PubMed1995

Effects of ticlopidine administered to healthy volunteers on platelet function in whole blood.

Ticlopidine is thought to be a selective inhibitor of ADP-induced platelet function. Here we have investigated the effects of ticlopidine on platelet function in whole blood induced by ADP and by other platelet agonists. Whole blood was used because it was considered that ADP derived from red cells might act synergistically with other platelet agonists to enhance platelet responses, and that ticlopidine might interfere with this process. Measurements were performed using blood from 16 healthy volunteers before ticlopidine administration, after taking ticlopidine 250 mg daily for 10 days, after taking ticlopidine 250 mg twice daily for a further 10 days, and after 14 days off treatment. Ticlopidine proved to be a very effective inhibitor of the platelet aggregation induced by ADP; it was most effective in enhancing the reversibility of the aggregation response. The drug modestly but significantly reduced streptokinase, adrenaline, collagen, sodium arachidonate, PAF and U46619 - induced platelet aggregation. The drug significantly reduced the extent of the release reaction (14C-5HT release) induced by ADP, streptokinase, PAF, ristocetin and sodium arachidonate, and also reduced the extent of the synergistic 14C-5HT release induced by combinations of ADP and PAF, ADP and adrenaline and PAF and adrenaline. The various inhibitory effects of ticlopidine were evident after treatment with 250 mg daily but were more pronounced after 250 mg twice daily. All values had returned to normal after 14 days off treatment. Ticlopidine had no effect on serum thromboxane B2 production nor on several parameters of coagulation and fibrinolysis. We conclude that ticlopidine is an effective inhibitor of ADP-induced platelet aggregation and also the platelet aggregation and 14C-5HT release induced in whole blood by a number of platelet agonists and combinations of agonists. These latter effects are probably mainly via a selective effect on ADP. The inhibitory effects of the drug are dose-related.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Gallopamil slow release: a double blind study of twice daily versus once daily treatment in chronic stable angina.

The clinical efficacy of a new slow release preparation of the calcium antagonist gallopamil was assessed in 20 patients by diary cards and treadmill exercise tests. A single blind phase of two week periods of placebo, gallopamil 100 mg o.d. and gallopamil 100 mg b.i.d., blinded to the patient, was followed in 18 patients by a double blind comparison of gallopamil 100 mg od versus 100 mg b.i.d. Angina frequency and trinitrin consumption per week were both significantly less on high dose (2.7 and 1.7) than on low dose (5.4 and 3.4) respectively. Treadmill total exercise time was longer on high dose (523s) than low dose (449s). Other exercise test parameters showed similar improvements on high dose treatment. Gallopamil was well tolerated. PR interval correlated best with plasma gallopamil level, while exercise test parameters correlated best with the log plasma level of its major metabolite nor-gallopamil.

Adult↗