Biomedical subjects

R J Simes

Publications and source records attributed to R J Simes.

At least 37 records · Page 2Linked to original sources

PubMed1999

A cardiovascular extension of the Health Measurement Questionnaire.

OBJECTIVE: To investigate the psychometric properties of a cardiovascular extension of an existing utility-based quality of life questionnaire (Health Measurement Questionnaire). The new instrument has been named the Utility Based Quality of life--Heart questionnaire, or UBQ-H. DESIGN: Explored the test-retest reliability, construct validity, and responsiveness of the UBQ-H. PATIENTS: A sample of 322 patients attending cardiac outpatient clinics were recruited from two large metropolitan teaching hospitals. A second sample of 1112 patients taking part in the LIPID trial was also used to investigate the validity and responsiveness of the UBQ-H. RESULTS: Ninety per cent of all UBQ-H questionnaires were returned, and item completion rates were high (median of less than 1% missing or N/A answers). Cronbach's alpha measure of internal consistency for the scales ranged between 0.79-0.91, and each item was also most strongly correlated with its hypothesised domain than alternative domains. The intra-class test-retest reliability of the UBQ-H scales ranged from 0.65 to 0.81 for patients with stable health. Results supported the construct validity of the UBQ-H. The UBQ-H was significantly correlated with other information on quality of life (for example, General Health Questionnaire) as anticipated. The instrument was able to distinguish between contrasted groups of patients (for example, with versus without symptoms of dyspnoea, prior myocardial infarction versus none, etc), and was responsive to changes in health associated with adverse events requiring hospitalisation. CONCLUSIONS: The modifications made to the Health Measurement Questionnaire has resulted in an assessment designed for cardiovascular patients that has proved to be both reliable and valid.

Cardiovascular Diseases↗

PubMed1998

Quality adjusted survival analysis with repeated quality of life measures.

One way of examining trade-offs between quantity and quality of life (QOL) is to combine them into a single measure such as quality-adjusted life year (QALY). If censoring occurs, then estimation presents some difficulties. One approach, known as Q-TWiST, is to define a series of health states, use a 'partitioned' survival analysis to calculate the average time in each state, and then weight each state according to its quality of life to calculate QALYs. Such health-state models, however, are unhelpful when the transitions between health states are unclear or if they do not adequately reflect variations in quality of life. We therefore examine an alternative analysis to be used when repeated measures of quality of life are available from individual patients in a clinical trial. The method proceeds by separating quality of life and survival, that is, dQALY/dt = S(t)Q(t), where S(t) is the survival curve, estimated from the standard Kaplan-Meier method, and Q(t) is the quality of life function, derived from individual repeated measures of quality of life. We derive single health-state (QALY) and multiple health-state (Q-TWiST) models and illustrate the approach by comparing different durations of adjuvant chemotherapy for breast cancer.

Adult↗

PubMed1998

Randomized comparison of direct thrombin inhibition versus heparin in conjunction with fibrinolytic therapy for acute myocardial infarction: results from the GUSTO-IIb Trial. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO-IIb) Investigators.

OBJECTIVES: We sought to show that hirudin might interact differently with streptokinase (SK) and tissue-type plasminogen activator (t-PA), which could reduce the incidence of death or reinfarction at 30 days. BACKGROUND: In a large-scale trial of patients with acute coronary syndromes, hirudin provided modest benefit compared with heparin. However, the interaction with thrombolytic agents was not specifically assessed. METHODS: Patients with symptoms of acute myocardial infarction and electrocardiographic ST segment elevation were treated with thrombolytic therapy and randomly assigned to receive hirudin or heparin. RESULTS: A total of 2,274 patients received t-PA, and 1,015 received SK. Baseline characteristics were balanced by antithrombin assignment. Among SK-treated patients, death or reinfarction at 30 days occurred more often in those treated with adjunctive heparin (14.4%) rather than hirudin (8.6%, odds ratio [OR] 1.78, 95% confidence interval [CI] 1.20 to 2.66, p = 0.004). Among t-PA-treated patients, the rates were 10.9% with heparin and 10.3% with hirudin (OR 1.06, 95% CI 0.81 to 1.38, p = 0.68; for treatment heterogeneity: chi-square 4.20, degrees of freedom [df] 1, p = 0.04). After adjustment for baseline differences between thrombolytic groups, the rates were 9.1% for SK with hirudin, 10.3% for t-PA with hirudin, 10.5% for t-PA with heparin and 14.9% for SK with heparin (for treatment heterogeneity: chi-square 4.5, df 1, p = 0.03), suggesting that the beneficial treatment effect of hirudin was limited to the SK-treated patients. CONCLUSIONS: Hirudin interacts favorably with SK but not t-PA, highlighting the importance of thrombin activity after SK therapy and the potential for simulating the effects of a more potent fibrinolytic agent through direct antithrombin therapy.

Aged↗

PubMed1998

Predicting patients' utilities from quality of life items: an improved scoring system for the UBQ-H.

The Utility-based Quality of Life--Heart Questionnaire (UBQ-H) is a cardiovascular extension of the Health Measurement Questionnaire. It is a multidimensional instrument that can be scored to yield a utility estimate using the Rosser Index and a classification algorithm developed for the Health Measurement Questionnaire. The aim of this study was to employ a statistical modelling approach to devise an improved scoring system. A sample of 201 cardiovascular patients completed the UBQ-H and assessed the utility of their own health state using standard gamble and time trade-off questions in an interview. Two new scoring methods were devised by regressing the UBQ-H data against patients' self-assessed utilities. The new methods gave utility estimates that correlated with angina/dyspnoea grades, life satisfaction scores and General Health Questionnaire (GHQ) scores. In a second sample of 1,112 cardiovascular patients, the UBQ-H utilities were able to distinguish between patients who had/had not experienced an adverse event (e.g. myocardial infarction) and were responsive to changes in health over time. The new scoring methods were not particularly more sensitive to quality of life effects than the original method based on the Rosser Index. However, they produced significantly lower estimates and more accurately reflected patients' self-assessed utilities.

Cardiovascular Diseases↗

PubMed1998

Intervention with PTCA and CABG following thrombolysis for acute myocardial infarction. Australian data from GUSTO 1 (1991-3) and International Study Group r-TPA-Streptokinase Mortality (1989) trials. Global Utilisation of Streptokinase and Tissue.

The patterns of revascularisation with percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft (CABG) surgery in the GUSTO 1 trial patients in Australia are described. In comparison with rates documented in earlier trials of thrombolytic therapy in Australia, the rates of revascularisation post-thrombolysis increased by 50%, primarily due to a doubling in the rate of use of PTCA. However, the rates were low by international comparisons. There were marked variations in the rates of revascularisation between States, but no correlation with differences in mortality between States. The main predictors of post thrombolysis PTCA were prior angina, mild infarction and access to PTCA facilities.

Aged↗

PubMed1997

Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review.

OBJECTIVE: To provide a quantitative review of the treatment effects of primary coronary angioplasty vs intravenous thrombolysis for acute myocardial infarction. DATA SOURCES: Ten randomized trials were identified through computerized bibliographic search of MEDLINE from January 1985 through March 1996 and by queries of principal investigators. STUDY SELECTION: Single-center and multicenter randomized trials comparing primary angioplasty with intravenous thrombolytic therapy among 2606 patients were included. Four trials compared angioplasty with streptokinase, 3 compared angioplasty with a 3- to 4-hour infusion of tissue-type plasminogen activator, and 3 compared angioplasty with "accelerated" administration of tissue-type plasminogen activator over 90 minutes. DATA EXTRACTION: Each investigator provided definitions and exact data for outcome events. Odds ratios (ORs), 95% confidence intervals (CIs), and P values were calculated using exact tests for categorical data. DATA SYNTHESIS: Mortality at 30 days or less was 4.4% for the 1290 patients treated with primary angioplasty compared with 6.5% for the 1316 patients treated with thrombolysis (34% reduction; OR, 0.66; 95% CI, 0.46-0.94; P=.02). The effect was similar among thrombolytic regimens, and no subgroup demonstrated a significant reduction in death. The rates of death or nonfatal reinfarction were 7.2% for angioplasty and 11.9% for thrombolytic therapy (OR, 0.58; 95% CI, 0.44-0.76; P<.001). Angioplasty was associated with a significant reduction in total stroke (0.7% vs 2.0%; P=.007) and hemorrhagic stroke (0.1% vs 1.1%; P<.001). CONCLUSIONS: Based on outcomes at hospital discharge or 30 days, primary angioplasty appears to be superior to thrombolytic therapy for treatment of patients with acute myocardial infarction, with the proviso that success rates for angioplasty are as good as those achieved in these trials. Data evaluating longer-term outcomes, operator experience, and time delay before treatment are needed before primary angioplasty can be universally recommended as the preferred treatment.

Angioplasty, Balloon, Coronary↗

PubMed1997

Publication bias: evidence of delayed publication in a cohort study of clinical research projects.

OBJECTIVES: To determine the extent to which publication is influenced by study outcome. DESIGN: A cohort of studies submitted to a hospital ethics committee over 10 years were examined retrospectively by reviewing the protocols and by questionnaire. The primary method of analysis was Cox's proportional hazards model. SETTING: University hospital, Sydney, Australia. STUDIES: 748 eligible studies submitted to Royal Prince Alfred Hospital Ethics Committee between 1979 and 1988. MAIN OUTCOME MEASURES: Time to publication. RESULTS: Response to the questionnaire was received for 520 (70%) of the eligible studies. Of the 218 studies analysed with tests of significance, those with positive results (P < 0.05) were much more likely to be published than those with negative results (P > or = 0.10) (hazard ratio 2.32 (95% confidence interval 1.47 to 3.66), P = 0.0003), with a significantly shorter time to publication (median 4.8 v 8.0 years). This finding was even stronger for the group of 130 clinical trials (hazard ratio 3.13 (1.76 to 5.58). P = 0.0001), with median times to publication of 4.7 and 8.0 years respectively. These results were not materially changed after adjusting for other significant predictors of publication. Studies with indefinite conclusions (0.05 < or = P < 0.10) tended to have an even lower publication rate and longer time to publication than studies with negative results (hazard ratio 0.39 (0.13 to 1.12), P = 0.08). For the 103 studies in which outcome was rated qualitatively, there was no clear cut evidence of publication bias, although the number of studies in this group was not large. CONCLUSIONS: This study confirms the evidence of publication bias found in other studies and identifies delay in publication as an additional important factor. The study results support the need for prospective registration of trials to avoid publication bias and also support restricting the selection of trials to those started before a common date in undertaking systematic reviews.

Biomedical Research↗

PubMed1997

Selection of thrombolytic therapy for individual patients: development of a clinical model. GUSTO-I Investigators.

We developed a logistic regression model with data from the GUSTO-I trial to predict mortality rate differences in individual patients who received accelerated tissue plasminogen activator (TPA) versus streptokinase treatment for acute myocardial infarction. A nomogram was developed from a reduced version of this model that approximated the underlying risk of patients treated with streptokinase, and thus the benefit of TPA. The 30-day mortality rate with accelerated TPA was 0.063 versus 0.073 with streptokinase and subcutaneously administered heparin and 0.074 with streptokinase and intravenously administered heparin. No baseline patient characteristics were significantly associated with a different relative effect of TPA. Older patients and those with anterior infarction, higher Killip classification (except Killip class IV), lower blood pressure, and increased heart rate had the greatest absolute benefit with accelerated TPA. Patients with acute myocardial infarction who had more high-risk characteristics derived a greater absolute benefit from treatment with accelerated TPA versus streptokinase.

Age Factors↗

PubMed1997

Design of a cost-effectiveness study within a randomized trial: the LIPID Trial for Secondary Prevention of IHD. Long-term Intervention with Pravastatin in Ischemic Heart disease.

The Long-term Intervention with Pravastatin in Ischemic Heart Disease (LIPID) trial is a double-blind, randomized, placebo-controlled trial evaluating the long-term effect of pravastatin on coronary mortality in patients with a previous myocardial infarction or unstable angina-ischemic heart disease (IHD). It is planned to run for at least five years with 9014 patients from 85 centers in Australia and New Zealand. The trial will monitor cause-specific mortality and major clinical events associated with each treatment. Running in parallel with the main study is a prospective economic analysis, the objectives of which are (1) to estimate the effectiveness of pravastatin compared with placebo in terms of survival, quality of life (QOL), and quality-adjusted life-years (QALY); (2) to estimate the resource usage associated with pravastatin compared with placebo-in particular, to study whether it alters resource usage through prevention of disease progression; and (3) to use this information for a cost-utility analysis with cost per quality-adjusted life-year as the unit of analysis. A novel aspect of the design is the use of a preliminary cost-effectiveness analysis, based on "best-guess" values, and a sensitivity analysis over plausible ranges to guide the choice of subsample size. Some data, such a mortality, days spent in hospital, major clinical events, and drug use, are being collected within the main LIPID trial. However, additional subsamples for the cost-effectiveness study will include information on quality of life, time off work, and resources used, such as time in hospital, procedures, and medications taken. The methods and sample sizes for these substudies have been a crucial issue in validity and feasibility.

Absenteeism↗

PubMed1997

Improved quality of life with megestrol acetate in patients with endocrine-insensitive advanced cancer: a randomised placebo-controlled trial. Australasian Megestrol Acetate Cooperative Study Group.

PURPOSE: To investigate the effect of two doses of megestrol acetate (MA) compared with placebo on quality of life (QoL) and nutritional status (NS) in patients with advanced endocrine-insensitive cancer. PATIENTS AND METHODS: Two hundred forty patients were randomised to double-blind MA 480 mg/day, MA 160 mg/day, or matching placebo for 12 weeks. Nutritional status (including weight, skinfold thickness and midarm circumference) and QoL (using 6 linear analogue self-assessment (LASA) scales) were assessed at randomisation and after four, eight and 12 weeks. A QoL ranking incorporating QoL and death was also used ranging from 1 = dead to 5 = much better QoL. RESULTS: One hundred seventy-four patients were assessable at week four, 136 at week eight and 103 patients at week 12. Patients receiving MA reported substantially better appetite (P = 0.001), mood (P = 0.001) and overall quality of life (P < 0.001), and possibly less nausea and vomiting (P = 0.08) than patients receiving placebo, based on a test for trend. A larger benefit was seen with the higher dose which (unlike the lower dose) was significantly better in pairwise comparisons with placebo for appetite, mood and overall QoL (each P < or = 0.001). Despite some missing data on QoL scores, QoL ranking was available on 227 (95%) of patients with significantly higher QoL ranking associated with MA (P = 0.002). Improvements in QoL occurred early within four weeks and were sustained. No statistically significant differences were observed in NS measurements, including weight (P = 0.29). Side effects of therapy were minor and did not differ significantly across treatments. CONCLUSION: Megestrol acetate given at 480 mg/day is useful palliation in patients with endocrine-insensitive advanced cancer. It improves appetite, mood and overall quality of life in these patients, although not through a direct effect on nutritional status.

Aged↗

PubMed1997

Medroxyprogesterone acetate addition or substitution for tamoxifen in advanced tamoxifen-resistant breast cancer: a phase III randomized trial. Australian-New Zealand Breast Cancer Trials Group.

PURPOSE: To determine whether a strategy of adding medroxyprogesterone acetate (MPA) to tamoxifen (TAM) is superior to the substitution of MPA for TAM among women with advanced breast cancer and disease progressing on TAM. To assess the patterns or response and subsequent progression in sites and tissues according to prior involvement and treatment. PATIENTS AND METHODS: Two-hundred-fifteen postmenopausal women with advanced breast cancer progressing on TAM after receiving TAM for at least six months were randomized: 109 to add MPA 500 mg/day orally (TAM + MPA), and 106 to stop TAM and to substitute MPA. RESULTS: There were no significant differences between the groups with respect to complete plus partial response rates: TAM + MPA 10%, MPA 9%, median time to progression TAM + MPA 3.0 months, MPA 4.5 months, or median overall survival, TAM + MPA 17.2 months, MPA 18.4 months. In a multivariate model, prognostic factors significant for a shorter time to disease progression were worse for performance status, involvement of more than one tissue, prior radiotherapy, and shorter time from recurrence after primary therapy to randomization. Adjusting for these factors, treatment with TAM + MPA was associated with a higher relative risk for disease progression, with a hazards ratio of 1.31, but this was not significant (95% confidence interval, 0.98 to 1.74; P = .067). However, in an exploratory analysis, the time to disease progression, among patients with progesterone receptor positive (PR+) tumors, was 6.3 months with MPA versus 2.9 months with TAM + MPA, with a hazards ratio of 1.92 (95% confidence interval, 1.12 to 3.32; P = .02). There was a significant interaction, P = .04, between PR status and treatment, indicating an advantage to treatment substitution for those who have PR+ tumors. Tumor response occurred in 14% of assessed metastatic sites. Subsequent progression occurred in a new tissue alone in 13% of patients, in both new and previously involved (old) tissues in 76%, and in old tissues only in 11%. In 23% of patients, progression occurred only at a new site, in 50% at both old and new sites, and in 27% only at old sites. No significant differences in the patterns of response or progression were seen in the different treatment groups. CONCLUSION: Among women with breast cancer whose disease is progressing after at least six months of treatment with TAM, there is no advantage to maintaining TAM when MPA is to be given. An overall effect of treatment on the pattern of failure at old sites or at new sites or tissues cannot be discerned.

Aged↗

PubMed1996

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

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

Aged↗

PubMed1996

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

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

Aged↗

PubMed1996

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↗

PubMed1995

Prospective meta-analysis of cholesterol-lowering studies: the Prospective Pravastatin Pooling (PPP) Project and the Cholesterol Treatment Trialists (CTT) Collaboration.

Meta-analyses of randomized trials evaluating cholesterol-lowering therapy have demonstrated clear reductions in coronary events and coronary mortality. However, the treatment impact on total mortality has been less certain. With the variable selection of trials and treatment questions, results of meta-analyses have sometimes given conflicting conclusions regarding the magnitude of treatment effects and the populations to whom benefits might accrue. Prospective meta-analysis can avoid these problems by clearly specifying the research questions, eligible studies, analysis plans, and outcome definitions in advance of trial results publication. This approach has been adopted in 2 major prospective meta-analyses of cholesterol-lowering treatments: the Prospective Pravastatin Pooling (PPP) project and the Cholesterol Treatment Trialists (CTT) collaboration. The PPP project is a prospectively planned combined analysis of 3 large-scale pravastatin trials comparing pravastatin against placebo over a minimum 5-year period. The analysis will contain data for > 19,500 patients and should have the power to examine the effects of treatment on total mortality, coronary mortality, and incidence of cancers as well as the ability to look at total coronary events in important subgroups underrepresented in previous trials. The CTT collaboration is a planned prospective meta-analysis of 12 major ongoing or planned randomized trials evaluating therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, a fibrate, or dietary modification. The trials were prospectively registered and the CTT protocols became final in November 1994. By the year 2000, the CTT collaboration is projected to have information on about 65,000 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion. Importance of early and complete infarct artery reperfusion. GUSTO-I Investigators.

BACKGROUND: The Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial was designed to test whether thrombolytic strategies achieving more complete, early, sustained coronary artery patency would lead to further reductions in mortality in patients with acute myocardial infarction. An angiographic substudy within GUSTO-I provided a unique opportunity to examine the relation between mortality and degrees of patency among the regimens. METHODS AND RESULTS: Four thrombolytic strategies were compared in 41,021 patients in GUSTO-I: streptokinase with subcutaneous or intravenous heparin, accelerated tissue plasminogen activator (TPA) with intravenous heparin, and combination streptokinase plus TPA with intravenous heparin. Accelerated TPA was associated with lower 30-day mortality (6.3%) than the other strategies (7.2%, 7.4%, and 7.0%, respectively). Among the 1210 patients in the angiographic substudy randomized to angiography 90 minutes after starting treatment, there was improved patency, particularly Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, with accelerated TPA over the other regimens (P < .0001). Coronary artery perfusion (TIMI grade 3) at 90 minutes was also a significant predictor of 30-day survival (P < .01). To determine whether differences in mortality among the four strategies matched differences in 90-minute patency, a model was developed for predicting mortality differences in the main trial from the angiographic substudy. The model assumed that any differences in treatment effects on 30-day mortality were mediated through differences in 90-minute patency for the four treatments. The predicted rates were then compared with observed mortality rates of the remaining patients in the main trial for each treatment group. The predicted and observed 30-day mortality rates of the four treatments were streptokinase with subcutaneous heparin, 7.46% versus 7.28%; streptokinase with intravenous heparin, 7.26% versus 7.39%; accelerated TPA, 6.31% versus 6.37%; and streptokinase plus TPA, 6.98% versus 6.96%. The correlation between predicted and observed results was .97, and the proportion of squared error explained (R2) was .92. CONCLUSIONS: The close relation between the predicted and observed 30-day mortality rates supports the concept that an important mechanism for improved survival with thrombolytic therapy is achievement of early, complete perfusion. The close match provides a strong biological explanation for the mortality differences seen in GUSTO-I and a sound rationale for the additional survival advantage of the accelerated TPA regimen. Irrespective of which treatment is used, early and complete restoration of infarct artery perfusion represents an essential goal of myocardial reperfusion therapy.

Coronary Angiography↗

PubMed1994

Quality of life six months after myocardial infarction treated with thrombolytic therapy. AUS-TASK Group. Australian arm of International tPA/SK Mortality Trial.

OBJECTIVE: To assess and compare quality of life of patients six months after an acute myocardial infarction treated with one of two thrombolytic agents, streptokinase (SK) or recombinant tissue plasminogen activator (tPA). DESIGN: A cohort study of consecutive patients randomly allocated to thrombolytic therapy and treated in hospitals participating in the Australian arm of the International tPA/SK Mortality Trial (AUS-TASK). PATIENTS AND SETTING: 776 patients with acute myocardial infarction were asked to complete questionnaires at their follow-up clinic visit six months after the infarct. MAIN OUTCOME MEASURES: Two measures were used: (i) the York Health Measurement Questionnaire, which measures activities and distress and provides basic descriptors of quality of life; and (ii) a time trade-off question about the number of years a person would be willing to give up in exchange for returning to full health. RESULTS: The quality of life of the 714 respondents (92%) was generally high, with a mean index of 0.98. The five main areas causing distress were: lack of energy; breathlessness; anxiety; difficulty sleeping; and pain. In the time trade-off question, the mean number of years respondents were willing to forgo, out of 15 years, was 0.87 years; while 76% did not think it worthwhile to forgo any time. The 8% of patients who declined to answer the questionnaire were in significantly poorer health (New York Heart Association classification, P = 0.01; and Karnofsky index, P < 0.001). There were no significant differences in quality of life or time trade-off answers between patients allocated to streptokinase or tPA (P = 0.96 and 0.73, respectively). CONCLUSIONS: Quality of life six months after myocardial infarction is generally high, and most patients are able to return to normal activities. However, it is significantly impaired in a small group of patients, mainly those with a subsequent stroke or re-infarction. There was no significant difference in quality of life between those treated with tPA and those with streptokinase.

Activities of Daily Living↗

PubMed1994

Low cholesterol and risk of non-coronary mortality.

Based on a systematic review of over 20 cohort studies, a clear association exists, for both men and women, between particularly low cholesterol levels and the rate of non-coronary mortality. The excess in women appears mainly confined to non-cancer causes, particularly respiratory and digestive diseases, while there is also an excess of deaths from cancer seen in men with low cholesterol levels. Higher mortality rates from trauma, haemorrhagic stroke and cirrhosis have also been observed. Much of this association is known to be as a consequence of the disease with a fall in cholesterol levels seen after developing a variety of inflammatory diseases. However, the excess risk of non-coronary heart disease deaths is still apparent by excluding deaths within five years suggesting that effect-cause is not the only explanation. Confounding still remains the most likely explanation for the association with an underlying chronic disease or risk factor causing both the low cholesterol and the fatal event. However, there is still the possibility that some of the increased risk is due to the low cholesterol. This makes it important that appropriately controlled trials of both drug and dietary interventions demonstrate net clinical benefit among those with low levels of coronary risk before cholesterol-lowering strategies are adopted more widely in these groups.

Cholesterol↗