Comparing health expenditure.
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Health Expenditures↗
Biomedical subjects
H D White
Publications and source records attributed to H D White.
One-year results from the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial. GUSTO-I Investigators.
BACKGROUND: In the randomized Global Utilization of t-PA and Streptokinase for Occluded Coronary Arteries (GUSTO-I) trial, 41021 patients received one of four thrombolytic regimens. Patients treated with accelerated tissue plasminogen activator (TPA) had a lower 30-day mortality rate (6.3%) than those treated with the other regimens (7.3%, combined streptokinase groups). METHODS AND RESULTS: Each patient who was alive at 30 days was sent a return postcard to ascertain vital status at 1 year. If the postcard was not returned, the patient (or an alternate specified at randomization) was contacted by telephone. A locator service was used in the United States for patients who could not be located by these methods. Final follow-up was 96% worldwide. One-year mortality rates remained in favor of accelerated TPA (9.1%) over streptokinase with subcutaneous heparin (10.1%, P = .011) and streptokinase with intravenous heparin (10.1%, P = .009). Combination therapy had an intermediate 1-year mortality (9.9%); this outcome was statistically indistinguishable from that with streptokinase (P = .47) but was marginally different from that with accelerated TPA (P = .05). CONCLUSIONS: The 1-year results demonstrated a saving of 10 lives per 1000 patients treated with accelerated TPA versus streptokinase and subcutaneous or intravenous heparin. Combination thrombolytic therapy had an intermediate benefit but offered no advantage over accelerated TPA treatment alone.
Aged↗
Comparison of aspirin with a thromboxane antagonist for patients with prolonged chest pain and ST segment depression.
AIM: To compare a thromboxane antagonist (GR3219) with aspirin in patients with prolonged chest pain and ST segment depression to see if the frequency of attacks of chest pain was reduced. METHODS: The trial was part of a study comparing GR3219 with aspirin, and streptokinase with placebo and comprised the GR3219/aspirin leg. Thirty one patients were randomly assigned to GR3219 80 mg twice daily and 28 to aspirin 300 mg daily. The patients were under the age of 76 and admitted to a coronary care unit within 6 hours of continuous chest pain. The ECG showed at least 1 mm of flat or down-going ST segment. The patients kept diaries of their pain over the subsequent 31 days. RESULTS: Seventy percent of patients developed further chest pain. There was no difference between the pattern of recurrent chest pain according to which drug was used. CONCLUSIONS: The hypothesis that specific thromboxane A blockade with GR3219 would be more efficacious than aspirin was not supported by these results.
Aged↗
Prospective evaluation of eligibility for thrombolytic therapy in acute myocardial infarction.
OBJECTIVES: To determine the proportion of patients presenting with acute myocardial infarction who are eligible for thrombolytic therapy. DESIGN: Cohort follow up study. SETTING: The four coronary care units in Auckland, New Zealand. SUBJECTS: All 3014 patients presenting to the units with suspected myocardial infarction in 1993. MAIN OUTCOME MEASURES: Eligibility for reperfusion with thrombolytic therapy (presentation within 12 hours of the onset of ischaemic chest pain with ST elevation > or = 2 mm in leads V1-V3, ST elevation > or = 1 mm in any other two contiguous leads, or new left bundle branch block); proportions of (a) patients eligible for reperfusion and (b) patients with contraindications to thrombolysis; death (including causes); definite myocardial infarction. RESULTS: 948 patients had definite myocardial infarction, 124 probable myocardial infarction, and nine ST elevation but no infarction; 1274 patients had unstable angina and 659 chest pain of other causes. Of patients with definite or probable myocardial infarction, 576 (53.3%) were eligible for reperfusion, 39 had definite contraindications to thrombolysis (risk of bleeding). Hence 49.7% of patients (537/1081) were eligible for thrombolysis and 43.5% (470) received this treatment. Hospital mortality among patients eligible for reperfusion was 11.7% (55/470 cases) among those who received thrombolysis and 17.0% (18/106) among those who did not. CONCLUSIONS: On current criteria about half of patients admitted to coronary care units with definite or probable myocardial infarction are eligible for thrombolytic therapy. Few eligible patients have definite contraindications to thrombolytic therapy. Mortality for all community admissions for myocardial infarction remains high.
Age Factors↗
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↗
Activated partial thromboplastin time and outcome after thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I trial.
BACKGROUND: Although intravenous heparin is commonly used after thrombolytic therapy, few reports have addressed the relationship between the degree of anticoagulation and clinical outcomes. We examined the activated partial thromboplastin time (aPTT) in 29,656 patients in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial and analyzed the relationship between the aPTT and both baseline patient characteristics and clinical outcomes. METHODS AND RESULTS: Intravenous heparin was administered as a 5000-U bolus followed by an initial infusion of 1000 U/h, with dose adjustment to achieve a target aPTT of 60 to 85 seconds. aPTTs were collected 6, 12, and 24 hours after thrombolytic administration. Higher aPTT at 24 hours was strongly related to lower patient weight (P < .00001) as well as older age, female sex, and lack of cigarette smoking (all PT< .0001). At 12 hours, the aPTT associated with the lowest 30-day mortality, stroke, and bleeding rates was 50 to 70 seconds. There was an unexpected direct relationship between the aPTT and the risk of subsequent reinfarction. There was a clustering of reinfarction in the first 10 hours after discontinuation of intravenous heparin. CONCLUSIONS: Although the relationship between aPTT and clinical outcome was confounded to some degree by the influence of baseline prognostic characteristics, aPTTs higher than 70 seconds were found to be associated with higher likelihood of mortality, stroke, bleeding, and reinfarction. These findings suggest that until proven otherwise, we should consider the aPTT range of 50 to 70 seconds as optimal with intravenous heparin after thrombolytic therapy.
Adult↗
Failure of implementation of the National Heart Foundation of New Zealand guidelines for the management of dyslipidaemia.
AIMS: We examined the outcome of patients at high absolute risk of coronary events who had been discharged from the Green Lane Hospital risk factor clinic before publication of the 1993 National Heart Foundation of New Zealand (NHF) guidelines for management of dyslipidaemia. METHODS: Consecutive patients who had been discharged >12 months previously were followed up by general practitioner and patient questionnaires. Patients were categorised according to risk of a coronary event over 10 years. Ideal lipid levels (cholesterol <5.2 mmol/L, high-density lipoprotein (HDL) cholesterol >1 mmol/L, total:HDL cholesterol ratio <5) and 'acceptable' lipid levels (cholesterol <6.5 mmol/L for high risk, <7.5 for moderate risk, <8 in men and <8.5 in women at mild or low risk) were defined according to the NHF guidelines. RESULTS: Of the 270 patients, 55.6% were at very high risk, 25.5% at high risk, 10.4% at moderate risk, 3.8% at mild risk and 0.7% at low risk. Twenty-four percent of patients were managed on diet alone at clinic discharge and 18% at follow up of 32+/-12 months. Total cholesterol (6.39 mmol/L), HDL cholesterol (1.22 mmol/L) and the total:HDL cholesterol ratio (5.71) were unchanged from discharge. In the very high risk group ideal lipid levels were achieved in only 12% at discharge and 7% at follow up. The corresponding figures for achievement of acceptable lipids at discharge compared with follow up were 48% and 39% for the high risk group, 88% and 79% for the moderate risk group and 93% and 93% for the mild risk group. The corresponding figures for achievement of ideal lipids were 4% and 8% for the high risk group, 0% and 5% for the moderate risk group and 7% and 7% for the mild risk group. CONCLUSIONS: Lipid levels achieved during clinic visits were maintained long term, but there were no improvements following publication of the NHF guidelines. Continued efforts are needed to increase awareness and implementation of the guidelines, particularly in patients at high risk. Removal of the restrictions on prescription of lipid modifying agents by general practitioners and improved interchange between general practitioners and specialists should greatly improve these outcomes.
Family Practice↗
Different mechanisms for Ca2+ dissociation from complexes of calmodulin with nitric oxide synthase or myosin light chain kinase.
We have determined the stoichiometry and rate constants for the dissociation of Ca2+ ion from calmodulin (CaM) complexes with rabbit skeletal muscle myosin light chain kinase (skMLCK), rat brain nitric oxide synthase (nNOS) or with the respective peptides (skPEP and nPEP) representing the CaM-binding domains in these enzymes. Ca2+ dissociation kinetics determined by stopped-flow fluorescence using the Ca2+ chelator quin-2 MF are as follows. 1) Two sites in the CaM-nNOS and CaM-nPEP complexes have a rate constant of 1 s-1. 2) The remaining two sites have a rate constant of 18 s-1 for CaM-nPEP and > 1000 s-1 for CaM-nNOS. 3) Three sites have a rate constant of 1.6 s-1 for CaM-skMLCK and 0.15 s-1 for CaM-skPEP. 4) The remaining site has a rate constant of 2 s-1 for CaM-skPEP and > 1000 s-1 for CaM-skMLCK. Comparison of these rate constants with those determined for complexes between the peptides and tryptic fragments representing the C- or N-terminal lobes of CaM indicate a mechanism for Ca2+ dissociation from CaM-nNOS of 2C slow + 2N fast and from CaM-skMLCK of (2C + 1N) slow + 1N fast. Ca2+ removal inactivates CaM-nNOS and CaM-skMLCK activities with respective rate constants of > 10 s-1 and 1 s-1. CaM-nNOS inactivation is fit by a model in which rapid Ca2+ dissociation from the N-terminal lobe of CaM is coupled to enzyme inactivation and slower Ca2+ dissociation from the C-terminal lobe is coupled to dissociation of the CaM-nNOS complex. CaM-skMLCK inactivation is fit by a model in which the three slowly dissociating Ca(2+)-binding sites are coupled to both dissociation of the complex and enzyme inactivation.
Amino Acid Sequence↗
The effect of transcutaneous electrical nerve stimulation on coronary and systemic haemodynamics in syndrome X.
BACKGROUND: Neurostimulation techniques have been shown to be beneficial in patients with angina and syndrome X but the mechanism remains unclear. We examined the effect of transcutaneous electrical nerve stimulation (TENS) on coronary artery blood flow in a group of patients with syndrome X. METHODS: Coronary blood flows were measured in 11 patients with angiographically normal coronary arteries, positive results from exercise tests and angina (syndrome X) using intracoronary Doppler catheters combined with quantitative coronary angiography. RESULTS: The mean coronary flow velocity did not increase in any patient during TENS therapy; in fact, there was a fall from 5.2 +/- 2.8 to 4.3 +/- 1.9 cm/s (P = 0.02) and the coronary blood flow index fell from 47 +/- 22 to 38 +/- 16 cm/s per mm2 (P = 0.007). This was associated with a fall in the rate x pressure product from 0.92 +/- 0.22 to 0.83 +/- 0.18 mmHg/min (P = 0.038). The coronary vascular resistance rose from 2.4 +/- 1.1 to 3.0 +/- 1.6 mmHg/cm per s per mm2 (P = 0.041). There were no major changes in the epicardial coronary artery diameter during TENS and there was no significant effect on the response to the cold-pressor test. CONCLUSIONS: In this group of patients with syndrome X, TENS produced a small but significant fall in coronary artery blood flow associated with a reduction in the rate x pressure product. TENS had no significant effect on coronary vasomotion during sympathetic stimulation by the cold-pressor test. Thus, TENS is unlikely to have a direct effect on coronary artery vasomotion or haemodynamics in syndrome X but reduces the rate x pressure product and thus myocardial oxygen consumption.
Blood Flow Velocity↗
Evidence-based assessment of the benefit of revascularisation in coronary disease: beyond the randomised trials.
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Adult↗
New insights into the pathogenesis, prevention and management of acute coronary syndromes.
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Angioplasty, Balloon, Coronary↗
Non-invasive diagnosis of infarct artery patency after acute myocardial infarction by use of serial plasma troponin T concentrations: importance of measurement of peak levels.
OBJECTIVE: To confirm the validity of a previously described method for assessment of infarct artery patency involving serial measurements of creatine kinase activity by use of troponin T concentration as an independent plasma marker. DESIGN: Streptokinase (1.5 x 10(6) units) was given intravenously to 60 patients within 6 h of onset of prolonged chest pain and ST segment elevation, and blood was taken for measurement of troponin T concentration at baseline and at 1, 2, 3, 4, 8, 12, 16, 20, and 24 h after starting treatment. Coronary arteriography was performed at 2.6 (SD 0.3) h. Plasma troponin T concentration was assessed by two methods: (1) as the absolute rise between 0 and 3 h; and (2) as the proportion of the total rise (from baseline to peak) over the same period. Accuracy for prediction of infarct artery patency, assessed by receiver operating characteristic curves, was compared for both methods of assessment using troponin T and was in turn compared with previously reported results on the same patients using serial measurements of creatine kinase activity. RESULTS: Sufficient values for prediction of patency using troponin T were available in 53 patients. A rise in troponin T between 0 and 3 h to > or = 9% of peak concentration predicted angiographic patency with sensitivity of 94% and specificity of 100%. By contrast, at the optimum cutoff for absolute rate of rise (0.5 micrograms/l/h) sensitivity was only 66% and specificity 86%. Comparable figures for creatine kinase were 92% and 91% (> or = 20% of peak by 3 h) and 62% and 78% (150 IU/l/h). Receiver operating curves confirmed better predictive accuracy for proportions over absolute rates of rise for both markers (P < 0.01). CONCLUSIONS: For accurate diagnosis of infarct artery patency using plasma markers it is necessary to express the rate of rise as a proportion of the peak level. Analysed in this way, both creatine kinase and troponin T are suitable for use in randomised trials of new thrombolytic or adjuvant drugs.
Adult↗
Is thrombolytic therapy really better than conventional treatment in acute inferior myocardial infarct.
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Humans↗
Thrombolytic therapy in the elderly. Pharmacoeconomic considerations.
Elderly patients have the highest absolute risk of death following an acute myocardial infarction (MI); 16.1% for those aged between 65 and 74 years, and 25.3% for those older than 75 years. Therefore, this age-group potentially may benefit most from the use of thrombolytic therapy. Cost-effectiveness analysis of streptokinase therapy has estimated that in patients aged 70 to 80 years, the cost per life-year saved is between $US21,200 and $US22,400 (1990 dollars) compared with placebo treatment. Additional mortality benefits have been shown for accelerated alteplase compared with streptokinase-treated patients (30-day mortality for alteplase and streptokinase was 6.3% and 7.3%, respectively; p = 0.001). A prospective cost-effectiveness study for all age groups concluded that the cost of an additional year of life saved with alteplase compared with streptokinase was $US32,678 (1993 dollars). This extra cost of alteplase treatment declined to $US13,410 and $US16,246 with patients older than 75 years with anterior and inferior MI, respectively. In patients aged 40 years or younger with an anterior or inferior MI, and for those aged up to 60 years with an inferior infarction, the accepted cost-effectiveness ratio of $US50,000 was exceeded. Alteplase appears to be a cost-effective therapy for the treatment of elderly patients with acute MI.
Aged↗
Stroke after thrombolysis. Mortality and functional outcomes in the GUSTO-I trial. Global Use of Strategies to Open Occluded Coronary Arteries.
BACKGROUND: Stroke is the most feared complication of thrombolysis for acute myocardial infarction because of the resulting mortality and disability. We analyzed the incidence, timing, and outcomes of stroke in an international trial. METHODS AND RESULTS: Patients were randomly assigned to one of four thrombolytic strategies. Neurological events were confirmed clinically and anatomically and were adjudicated by a blinded committee. Stroke survivors, categorized by residual deficit and disability, assessed their quality of life with a time trade-off technique. Multivariable regression identified patient characteristics associated with intracranial hemorrhage. Over-all, 1.4% of the patients had a stroke (93% anatomic documentation). The risk ranged from 1.19% with streptokinase/subcutaneous heparin therapy to 1.64% with combination thrombolytic therapy (P = .007). Primary intracranial hemorrhage rates ranged from 0.46% with streptokinase/subcutaneous heparin to 0.88% with combination therapy (P < .001). Of all strokes, 41% were fatal, 31% were disabling, and 24% were nondisabling, with no significant treatment-related differences. Stroke subtype affected prognosis: 60% of patients with primary intracranial hemorrhage died and 25% were disabled versus 17% dead and 40% disabled with nonhemorrhagic infarctions. Patients with moderate or severe residual deficits showed significantly decreased quality of life. Advanced age, lower weight, prior cerebrovascular disease or hypertension, systolic and diastolic blood pressures, randomization to tissue plasminogen activator, and an interaction between age and hypertension were significant predictors of intracranial hemorrhage. CONCLUSIONS: Stroke remains a rare but catastrophic complication of thrombolysis. Additional studies should assess the net clinical benefit of thrombolysis in high-risk subgroups, particularly the elderly and patients with prior cerebrovascular events.
Aged↗
Angioplasty versus bypass surgery.
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Aged↗
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↗