Malcolm Maclure

Analysis of possible triggers of acute myocardial infarction (the MILIS study).

Recent documentation of a circadian variation in acute myocardial infarction (AMI) suggests that AMI is not a random event, but may frequently result from identifiable triggering activities. The possible triggers reported by 849 patients enrolled in the Multicenter Investigation of Limitation of Infarct Size were analyzed. Possible triggers were identified by 48.5% of the population; the most common were emotional upset (18.4%) and moderate physical activity (14.1%). Multiple possible triggers were reported by 13% of the population. Younger patients, men and those without diabetes mellitus were more likely to report a possible trigger than were older patients, women and those with diabetes. The likelihood of reporting a trigger was not affected by infarct size. This study suggests that potentially identifiable triggers may play an important role in AMI. Because potential triggering activities are common in persons with coronary artery disease, yet infrequently result in AMI, further studies are needed to identify (1) the circumstances in which a potential trigger may cause an event, (2) the specific nature of potential triggering activites, (3) the frequency of such activities in individuals who do not develop AMI and (4) the presence or absence of identifiable triggers in various subgroups of patients with infarction.

Commitment to change statements can predict actual change in practice

Introduction: Statements of commitment to change are advocated both to promote and to assess continuing education interventions. However, most studies of commitment to change have used self‐reported outcomes, and self‐reports may significantly overestimate actual performance. As part of an educational randomized controlled trial, this study documented changes that family physicians committed to make in their prescribing and then used third‐party data to examine actual changes. Method: Following participation in a continuing medical education program using interactive small groups, physicians were asked to identify changes that they planned to make in their practices. For prescribing changes related to four conditions, data from a provincial pharmacy registry were analyzed for 6‐month periods before and after the educational intervention. Results: A total of 207 physicians participated in the project, which involved monthly meetings of 30 peer learning groups. Ninety‐nine physicians received experimental case‐based educational modules ± personal prescribing feedback, and 91 of these indicated that they planned to make at least one change in practice. Of the 209 intended changes, 71% were directly related to the prescribing messages in the materials. Discussion: In three of four indicator conditions, physicians who expressed a commitment to change were significantly more likely to change their actual prescribing for the target medications in the following 6 months. The percentage of physicians who did change their prescribing varied significantly by condition. Further study of the process of translating commitment to change into real practice change is needed.

When should case-only designs be used for safety monitoring of medical products?

To assess case‐only designs for surveillance with administrative databases.

Influences of educational interventions and adverse news about calcium-channel blockers on first-line prescribing of antihypertensive drugs to elderly people in British Columbia

BACKGROUND The way in which dissemination of evidence changes medical practice needs to be better understood. Controversy about calcium-channel blockers (CCB) in the past 3 years has provided a natural experiment, enabling assessment of the impact of media stories, a national warning letter, a teleconference, small group workshops, and newsletters on first-line prescribing of antihypertensive drugs. METHODS We included all physicians (4403) in British Columbia who prescribed a thiazide diuretic, beta-blocker, inhibitor of angiotensin-converting enzyme (ACE), or CCB as the first antihypertensive agent for 36,507 residents aged 66 years and over, with no previous or concurrent sign of underlying cardiovascular disease. We used a database covering all prescriptions to elderly people to measure the change in proportion of newly treated patients who received each class of drug as first-line therapy. We used a matched cohort design for assessment of the teleconference and workshops, a randomised community design for the newsletters, and time-series analysis for the media impacts. FINDINGS The proportion of patients who received a CCB as first-line therapy declined gradually from 22% in early 1994 to 15% in late 1996. This proportion was not affected by two waves of adverse news about CCBs in 1995, but fell by 5% for 5 months and by 3% for 1 month after two waves in 1996. The proportion of patients who received either a CCB or an ACE inhibitor as first-line therapy, contrary to guidelines, was still 42% overall in 1996. The workshops and newsletters were followed by shifts from first-line CCB to first-line thiazide prescribing. INTERPRETATION Changes in prescribing practices occur gradually with the accumulation of small impacts from educational interventions and lay media attention.

Design considerations in an active medical product safety monitoring system

Active medical product monitoring systems, such as the Sentinel System, will utilize electronic healthcare data captured during routine health care. Safety signals that arise from these data may be spurious because of chance or bias, particularly confounding bias, given the observational nature of the data. Applying appropriate monitoring designs can filter out many false‐positive and false‐negative associations from the outset. Designs can be classified by whether they produce estimates based on between‐person or within‐person comparisons. In deciding which approach is more suitable for a given monitoring scenario, stakeholders must consider the characteristics of the monitored product, characteristics of the health outcome of interest (HOI), and characteristics of the potential link between these. Specifically, three factors drive design decisions: (i) strength of within‐person and between‐person confounding; (ii) whether circumstances exist that may predispose to misclassification of exposure or misclassification of the timing of the HOI; and (iii) whether the exposure of interest is predominantly transient or sustained. Additional design considerations include whether to focus on new users, the availability of appropriate active comparators, the presence of an exposure time trend, and the measure of association of interest. When the key assumptions of self‐controlled designs are fulfilled (i.e., lack of within‐person, time‐varying confounding; abrupt HOI onset; and transient exposure), within‐person comparisons are preferred because they inherently avoid confounding by fixed factors. The cohort approach generally is preferred in other situations and particularly when timing of exposure or outcome is uncertain because cohort approaches are less vulnerable to biases resulting from misclassification. Copyright

Relation of outbursts of anger and risk of acute myocardial infarction.

The aim of the present study was to explore the association between outbursts of anger and acute myocardial infarction (AMI) risk. Outbursts of anger are associated with an abrupt increase in cardiovascular events; however, it remains unknown whether greater levels of anger intensity are associated with greater levels of AMI risk or whether potentially modifiable factors can mitigate the short-term risk of AMI. We conducted a case-crossover analysis of 3,886 participants from the multicenter Determinants of Myocardial Infarction Onset Study, who were interviewed during the index hospitalization for AMI from 1989 to 1996. We compared the observed number and intensity of anger outbursts in the 2 hours preceding AMI symptom onset with its expected frequency according to each patients control information, defined as the number of anger outbursts in the previous year. Of the 3,886 participants in the Determinants of Myocardial Infarction Onset Study, 1,484 (38%) reported outbursts of anger in the previous year. The incidence rate of AMI onset was elevated 2.43-fold (95% confidence interval 2.01 to 2.90) within 2 hours of an outburst of anger. The association was consistently stronger with increasing anger intensities (p trend <0.001). In conclusion, the risk of experiencing AMI was more than twofold greater after outbursts of anger compared with at other times, and greater intensities of anger were associated with greater relative risks. Compared with nonusers, regular β-blocker users had a lower susceptibility to heart attacks triggered by anger, suggesting that some drugs might lower the risk from each anger episode.

Rosiglitazone and Myocardial Infarction in Patients Previously Prescribed Metformin

Objective Rosiglitazone was found associated with approximately a 43% increase in risk of acute myocardial infarction (AMI) in a two meta-analyses of clinical trials. Our objective is to estimate the magnitude of the association in real-world patients previously treated with metformin. Research Design and Methods We conducted a nested case control study in British Columbia using health care databases on 4.3 million people. Our cohort consisted of 158,578 patients with Type 2 diabetes who used metformin as first-line drug treatment. We matched 2,244 cases of myocardial infarction (AMI) with up to 4 controls. Conditional logistic regression models were used to estimate matched odds ratios for AMI associated with treatment with rosiglitazone, pioglitazone and sulfonylureas. Results In our cohort of prior metformin users, adding rosiglitazone for up to 6 months was not associated with an increased risk of AMI compared to adding a sulfonylurea (odds ratio [OR] 1.38; 95% confidence interval [CI], 0.91–2.10), or compared to adding pioglitazone (OR for rosi versus pio 1.41; 95% CI, 0.74–2.66). There were also no significant differences between rosiglitazone, pioglitazone and sulfonylureas for longer durations of treatment. Though not significantly different from sulfonylureas, there was a transient increase in AMI risk associated with the first 6 months of treatment with a glitazone compared to not using the treatment (OR 1.53; 95% CI, 1.13–2.07) Conclusions In our British Columbia cohort of patients who received metformin as first-line pharmacotherapy for Type 2 diabetes mellitus, further treatment with rosiglitazone did not increase the risk of AMI compared to patients who were treated with pioglitazone or a sulfonylurea. Though not statistically significantly different compared from each other, an increased risk of AMI observed after starting rosiglitazone or sulfonylureas is a matter of concern that requires more research.

Case‐crossover study design in pharmacoepidemiology: systematic review and recommendations

The purpose of this study is to systematically identify and review articles that use the case‐crossover study design in the area of pharmacoepidemiology.

Explaining pragmatic trials to pragmatic policy-makers

Successful policy-makers value pragmatism. As politics is “the art of the possible,” pragmatism is the art of the practical and workable. It entails getting more results sooner through flexibility rather than slavish adherence to rigid preconceptions. This requires experience with the trade-offs

Tea consumption and infarct-related ventricular arrhythmias: the determinants of myocardial infarction onset study.

Background: Tea consumption is associated with lower post-infarct mortality among patients with acute myocardial infarction. We previously found preliminary evidence that tea consumption may also be associated with lower risk of infarct-related ventricular arrhythmias. Methods: Between 1989 and 1996, 3882 subjects with AMI were enrolled in the two phases of the Determinants of Myocardial Infarction Onset Study a median of four days after admission. Trained interviewers assessed self-reported usual tea and coffee consumption during the year prior to infarction with a standardized questionnaire. We examined the prevalence of ventricular arrhythmias in the two phases of the study separately and together. Results: Among the 1912 patients with complete information in the first phase, the prevalence of ventricular arrhythmias was 16% among abstainers from tea, 11% among moderate tea drinkers (<14 cups per week), and 14% among heavier tea drinkers (≥14 cups per week) (p homogeneity = 0.03). Among the 1791 patients with comparable information in the second phase, the corresponding prevalence rates were 11%, 8%, and 8%, respectively (p = 0.06). When the phases were combined, the adjusted odds ratios for VA were 0.7 (95% confidence interval, 0.6–0.9) among moderate tea drinkers and 0.9 (95% confidence interval, 0.7–1.2) among heavier tea drinkers. The findings were of similar direction for both ventricular tachycardia and fibrillation. In contrast, there was higher risk of VA with increasing coffee intake (odds ratio for >14 cups per week 1.3; 95% confidence interval, 1.0–1.7; p trend 0.02). Conclusions: Moderate tea intake is associated with a lower prevalence, and higher coffee intake with a slightly higher prevalence, of ventricular arrhythmias among patients hospitalized with acute myocardial infarction. If the association with tea intake is confirmed, it may suggest new approaches to prevention of ischemia-related arrhythmias.