What should be done about asymptomatic hypercholesterolaemia?
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Biomedical subjects
Publications and source records attributed to C D Naylor.
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A meta-analysis of randomized clinical trials of fibrinolysis was performed, examining the interaction between aspirin and fibrinolysis in treating patients with acute myocardial infarction. Reductions in the odds of death up to 35 days were assessed for patients receiving tissue plasminogen activator or streptokinase up to 6 hours after the onset of symptoms. No significant difference in effectiveness between tissue plasminogen activator and streptokinase was demonstrated. The overall reduction in odds of death due to fibrinolytic therapy was 28%. However, there was a significant difference between the odds reduction of 24% when fibrinolysis is compared to placebo, and 40% when fibrinolysis and aspirin combined are compared to aspirin alone (p = 0.02). This difference indicates that there exists a synergistic interaction between coronary fibrinolysis and aspirin rather than independence of their beneficial effects, as is generally believed. These results illustrate the perils of assessing drug efficacy, even in an overview of all relevant trials, without consideration of identifiable sources of heterogeneity such as the interaction between the treatment of interest and co-interventions. They also demonstrate the potential application of logistic regression diagnostic techniques to meta-analyses.
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In light of lengthy waiting lists for coronary surgery in Canada, a panel of 16 cardiologists and cardiac surgeons was convened to derive guiding principles for ranking how urgently diverse patients with angiographically proven coronary disease require revascularization. Factors likely to affect urgency were agreed upon by the panelists and incorporated into a case scenario questionnaire. Each panelist then rated 438 case scenarios with respect to maximum acceptable waiting time on a scale with seven time frames ranging from emergency surgery ('level 1') to delays of up to six months ('level 7'). The scenario rating process facilitated attainment of a panel consensus. The purpose of the principles is to assist in assigning priorities to patients according to both symptoms and risk of death or additional morbidity from ischemic events. The pattern or severity of the patient's anginal symptoms and the response of those symptoms to medical therapy emerged as the single most important determinant of the level of urgency. Anatomy and noninvasive tests of ischemic risk were the other key determinants of priority. All other factors were less important, and operated largely within a given level of urgency on the seven-point scale. The principles, including explicit ranking criteria divided according to angina class, are outlined in this final report. The panel specifically cautioned that adoption of such principles is not designed to countenance delays in treatment, but if necessary, should help form more rational queues for coronary revascularization.
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Evidence of the potential impact of intravenous thrombolytic therapy on short-term revascularization rates among patients with acute myocardial infarction was sought. Because nonrandomized comparisons with conventional treatment would be subject to various confounders, a meta-analysis of randomized controlled trials was performed. Seven trials were included, applying standard doses of either tissue plasminogen activator or streptokinase without an aggressive revascularization protocol. Follow-up ranged from 14 to 30 days. The revascularization rates among treated patients in all trials were lower than in the conservative arm of the Thrombolysis in Myocardial Infarction Phase II trial, which established the current procedural benchmarks for postthrombolysis management. However, the aggregate volume of bypass surgery and angioplasty in patients treated with tissue plasminogen activator was more than double that of controls (odds ratio, 2.25; 95% confidence interval, 1.31 to 3.94), with a smaller but still significant increase for streptokinase-treated patients (odds ratio, 1.66; 95% confidence interval, 1.08 to 2.59). Combining all trials, the increase in mechanical revascularization was 80% (95% confidence interval, 33% to 144%). Thus, for patterns of practice currently accepted in North America, intravenous thrombolysis for myocardial infarction leads to a significant short-term increase in clinical and angiographic indications for revascularization as compared with conventional treatment.
The Ontario Medical Association (OMA) guidelines for intravenous thrombolysis in acute myocardial infarction were released in March 1988 and contributed to a government decision against special per-case funding to assist hospitals using tissue-type plasminogen activator (tPA). In October 1988, 1512 cardiologists, internists and physician-administrators who were OMA members were mailed a questionnaire seeking their views on the OMA guidelines and related issues. Of the 419 questionnaires (28%) that were returned, 392 contained usable responses. Among the respondents 268 (68%) had used thrombolytic drugs in the preceding 12 months; the mean number of cases was 10.6 (standard deviation 12.9). A strong or a mild preference for tPA over streptokinase was registered by 64% of the respondents; 28% had no preference. However, the self-reported ratio of actual streptokinase:tPA use was about 3:1, and 73% indicated that the government's funding policy had limited the availability of tPA in their hospital. The respondents were almost equally divided as to whether the policy should be changed. The guidelines were deemed helpful by 85% of the noncardiologists, as opposed to 52% of the cardiologists (p less than 0.005). OMA involvement in developing and circulating such guidelines was supported by 74% of the respondents and opposed by 18%; opposition was more likely to come from those who found the guidelines unhelpful (p less than 0.001). Support for involvement by the College of Physicians and Surgeons of Ontario was much weaker (supported by 32%, opposed by 62%). Overwhelming opposition to government involvement was evident.
To develop guidelines for ranking the urgency with which patients with angiographically proven coronary disease need revascularisation procedures, factors that a panel of cardiac specialists agreed were likely to affect urgency were incorporated into 438 fictitious case-histories. Each panelist then rated the cases on a 7-point scale based on maximum acceptable waiting time for surgery; 1 on the scale represented emergency surgery and 7 delays of up to 6 months. For only 1% of cases was there agreement on a single rating by at least 12/16 panelists. Results of this ranking exercise were used by the panel to draw up triage guidelines. The three main urgency determinants were severity and stability of symptoms of angina, coronary anatomy from angiographic studies, and results of non-invasive tests for risk of ischaemia. Together these three factors generally gave an urgency rating for any given case to within less than 0.25 scale points of the value predicted with all factors. A numerical scoring system was derived to permit rapid estimation of the panel's recommended ratings.
In recent years the Ontario government has been concerned that the proportion of public expenditures devoted to health care is at an all-time high. In addition, the media have devoted considerable attention to specific incidents that may represent inadequate funding of hospital services. To shed light on the debate on health care expenditures we analysed the trend in expenditures of Ontario's hospital sector in the 1980s in terms of the amount of inputs (e.g., labour) used to produce hospital services (e.g., a patient-day or admission) and after adjustment for general inflation. As in the 1970s the number of inputs grew relatively slowly during the 1980s. Inputs per patient-day grew at an annual rate of 0.46% and inputs per admission at an annual rate of 2.4%. Cost increases were largely accounted for by hospital wage increases; this could have been due to Ontario's rapidly expanding economy. These findings indicate that Ontario has continued to be successful in containing the number of inputs used in the hospital sector. However, after two decades of substantial success with publicly acceptable cost control, the government faces increased scrutiny as the media and the public focus attention on several areas of perceived inadequate funding in health care services.
Ontario's universal health insurance system has placed few constraints on the clinical and economic autonomy of medical doctors. Although fees are standardized, most physicians remain in private fee-for-service practice and thereby retain control of the mix and volume of services. Utilization review is minimal. While organized medicine has argued that health care is 'under-funded', the government is pressing for better use of extant resources through firmer management of the medical services sector. The Ontario Medical Association (OMA), the major bargaining agent for doctors in the province, has accordingly sought to protect professional autonomy by developing voluntary self-regulatory approaches that obviate the need for external controls over physician practice patterns. Part of this strategy is promulgation of practice guidelines. Tissue plasminogen activator (t-PA), a clot-lysing drug for myocardial infarction, was released in late 1987, and, at C$2950 per treatment, constituted an unforeseen add-on cost for hospitals. The OMA subsequently convened an expert panel to develop guidelines for thrombolysis in myocardial infarction. Among the unanticipated results was the conclusion that insufficient evidence had accumulated to recommend routine use of t-PA instead of streptokinase, an older drug costing C$290. The OMA panel's guidelines were approved by the OMA executive, and led the government to reject special add-on funding for hospitals purchasing t-PA. The OMA's position and government decision provoked negative reactions from the OMA's own cardiology section. Indicative of clinicians' feelings, a follow-up survey of cardiologists and internists showed that only 28% of respondents were indifferent between t-PA and streptokinase, while 64% preferred t-PA. On the other hand, 74% supported clinical policy development by the OMA, while 94% opposed direct government involvement in guideline-setting. The case of the OMA thrombolysis guidelines illustrates a strategic conundrum facing Canadian organized medicine. Professional activism in guideline-setting may in theory protect the individual practitioner's autonomy by offering a voluntary alternative to utilization management by government, and is likely to strengthen the collective influence of organized medicine. However, among the risks are alienation of practitioners who see professional guidelines and government control as two sides of the same regulatory coin, and the transmogrification of voluntary guidelines into parameters for cost control and utilization management by government or hospitals. Future initiatives will depend on how these benefits and risks are weighed.
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A panel of 16 cardiologists and cardiac surgeons rated 438 case scenarios for the maximum acceptable delay prior to revascularization, using a scale with seven interventional time frames and two nodes for designating dubious or inappropriate cases. If consensus was defined as agreement by 12 or more panelists, only 1.4 percent of the case scenarios showed consensus on a single rating. Dividing the scale into three broad clinical categories (revascularize promptly, place on a waiting list, or no intervention), 11.4 percent of scenarios showed all 16 panelists agreeing on a single category, rising to 59.4 percent of scenarios if agreement by 12 panelists was accepted as a consensus. The mean difference between the panelists' highest and lowest urgency ratings yielded waiting time differences of two weeks for scenarios of very unstable angina, and more than three months for those with stable angina. However, in a regression model, individual panelist factors on average had less effect than clinical features such as severity and stability of angina, or stenosis of major coronary arteries. These findings strongly support the need for consensus criteria to ensure that triage practices are consistent and fair, and also suggest that widespread adoption of a standardized approach to revascularization priorities may be feasible.
Hospital medical records staff enter diagnostic codes on charts using the International Classification of Diseases (Clinically Modified), Ninth Revision (ICD-9-CM). In a downtown Toronto tertiary hospital, 209 consecutive charts coded for acute myocardial infarction as the primary diagnosis in 1987-88 were reviewed. Criteria for documentation of acute myocardial infarction included symptomatic, electrocardiographic and enzymatic elements. Forty-three (21%) false-positives, ie, charts coded acute myocardial infarction where criteria were not fulfilled, were found (95% confidence interval 15 to 26%). Physician diagnosis of acute myocardial infarction appeared on the face sheet of 30 of the false-positive cases. Common reasons for false-positive face sheet entries and chart coding were acute myocardial infarction within the previous eight weeks with transfer or readmission for coronary angiography and other procedures; and presumed acute myocardial infarction on admission subsequently unproven or disproved. The false-positive proportion was similar to a Canadian study drawing on charts from hospitals of various sizes in 1977, lower than in recent reports from various American tertiary teaching hospitals (P less than 0.0001), and higher than in five Boston area community hospitals (P = 0.0005) where procedure-related transfers or readmissions of previous acute myocardial infarction patients were less likely. This audit lends credence to arguments that changes are needed in ICD-9-CM codes for acute myocardial infarction and in the assignation of reasons for hospitalization.
A simple model was developed to project the potential effect of intravenous thrombolytic therapy on the caseloads of revascularization early after acute myocardial infarction. Published data were used to estimate the proportion of infarct patients eligible for thrombolytic treatment and their subsequent rates of percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass surgery (CABS) within 2 weeks and up to 6 to 12 weeks after treatment. Toronto regional caseload data were obtained from registries and hospital discharge records. Our primary projections, based only on coronary angiography for evidence of spontaneous or exercise-induced ischemia, suggest a 165% increase in the post-thrombolysis use of PTCA within 2 weeks of infarction and even greater increases 6 to 12 weeks after infarction. Adding in selective use of salvage PTCA for some patients with persisting pain despite thrombolysis increases the overall PTCA caseload within 2 weeks by 242%. Data on the current caseload of post-thrombolysis CABS are unavailable. However, our projected caseload for the 30% of infarct patients treated with thrombolytic drugs equals or exceeds the current number of CABS procedures performed on all infarct patients within a month of the event. All these projections are conservative, in that they consider neither procedures 3 to 12 months after infarction nor restenosis after PTCA. This analysis illustrates that current approaches to revascularization after thrombolytic therapy could have a substantial effect on PTCA and CABS caseloads. Further studies with improved caseload data are needed to validate these preliminary projections.
A consensus group convened under the auspices of the Ontario Medical Association produced guidelines for the use of intravenous thrombolytic agents in acute myocardial infarction. The guidelines, updated to December 1988, include the following points. 1) Any hospital that routinely accepts the responsibility for looking after patients with acute myocardial infarction could offer thrombolytic therapy if monitoring facilities are available and if the staff are experienced in the treatment of cardiac rhythm disturbances. 2) Before treatment, all patients must be carefully screened for factors predisposing to hemorrhagic complications. 3) A physician should be clearly designated as responsible for the care of the patient receiving an infusion and be available in the event of problems. 4) For the two approved agents the usual dosages are as follows: streptokinase, 1.5 million units given over 1 hour; and tissue-type plasminogen activator (tPA), 100 mg over 3 hours, delivered as 60 mg in the first hour (of which 6 to 7 mg should be given as a bolus in the first 1 to 2 minutes) and then an infusion of 20 mg/h over the next 2 hours. 5) Intravenous thrombolytics should be considered for any patient with presumed acute myocardial infarction, as suggested by prolonged chest pain or other appropriate symptoms and typical electrocardiographic changes. Expeditious treatment is critical, since myocardial necrosis occurs within hours. 6) Emergency angiography is indicated for patients with hemodynamic compromise and no apparent response to streptokinase or tPA and in those with recurrent chest pain suggestive of acute myocardial infarction despite an apparent response to intravenous thrombolysis. Angiography before discharge is recommended for patients with postinfarction angina or evidence from noninvasive testing of significant residual ischemic risk. 7) There is insufficient evidence to choose between streptokinase and tPA on the basis of the two most important outcome measures: patient survival and myocardial preservation. More conclusive evidence comparing tPA, streptokinase and another promising agent, acylated plasminogen-streptokinase activator complex, will be available in 1989-90.