Persantine-aspirin reinfarction study. Part II. Secondary coronary prevention with persantine and aspirin

In the Persantine-Aspirin Reinfarction Study, Part II (PARIS II), 3,128 persons who had recovered from myocardial infarction, suffered from 4 weeks to 4 months previously, were randomized into two groups: dipyridamole (Persantine) plus aspirin (n = 1,563) and placebo (n = 1,565). The average length of follow-up was 23.4 months. Prespecified primary end points were coronary incidence (definite nonfatal myocardial infarction plus death due to recent or acute cardiac event), coronary mortality (death due to recent or acute cardiac event) and total mortality, each at 1 year of patient follow-up and at the end of the study.Coronary incidence in the Persantine plus aspirin group was significantly lower than in the placebo group, both at 1 year (30% reduction) and at the end of the study (24% reduction). The statistically significant differences in coronary incidence, at 1 year and at the end of the study, in favor of the combination treatment remained after adjustment for multiple baseline variables and adjustment for multiple testing (three end points for two time periods). Although there were reductions for other end points, these differences were not statistically significant. Coronary mortality was 20% lower in the Persantine plus aspirin group compared with the placebo group at 1 year, and 6% lower overall. Total mortality in the treated group compared with the placebo group was 11% lower at I year and 3 % lower overall. The reduced rates of coronary incidence largely reflected lower rates of definite nonfatal myocardial infarction in the Persantine plus aspirin group.Several subgroups were defined a priori and at the end of the study. The beneficial effect of Persantine plus aspirin compared with placebo for coronary incidence tended to be greater for the following groups of patients: those who had a non-Q wave infarct; those who were not taking digitalis; those who were receiving beta-receptor blocking drugs at baseline; those who were in New York Heart Association functional class I; those who had had only one myocardial infarction; or those who were enrolled in the study early, that is within 85 days of the qualifying myocardial infarction

Prognostic significance of nonfatal reinfarction during 3-year follow-up: Results of the thrombolysis in myocardial infarction (TIMI) phase II clinical trial

Objectives.This study sought to assess the independent contribution of nonfatal reinfarction to the risk of subsequent death in patients with acute myocardial infarction undergoing thrombolytic therapy.Background.A composite of “unsatisfactory outcomes” as an end point has increased statistical power and facilitated evaluation of evolving treatment regimens in acute myocardial infarction. The significance of nonfatal reinfarction as a component of a composite end point has not been evaluated in the thrombolytic era.Methods.Event rate of nonfatal reinfarction over 3-year follow-up was evaluated in patients with acute myocardial infarction entered into the Thrombolysis in Myocardial Infarction Phase II trial. The independent risk of nonfatal reinfarction for subsequent death within various time intervals of follow-up was determined. The mortality rate after nonfatal reinfarction was compared with that of a matched control group.Results.During 3-year follow-up, 349 of 3,339 patients had a nonfatal reinfarction. Univariate predictors were history (antedating the index event) of angina (p = 0.01), hypertension (p = 0.01), multivessel disease (p = 0.007) and not a current smoker (p = 0.003); the latter was an independent predictor (relative risk [RR] 1.3, 99% confidence interval [CI]1.0 to 1.8). Forty-three of the 349 patients with a nonfatal reinfarction died: RR for death (vs. patients without a nonfatal reinfarction) was 1.9 (99% CI 1.1 to 3.2) if reinfarction occurred within 42 days of study entry, 6.2 (99% CI 3.0 to 12.9) if reinfarction occurred between 43 and 365 days and 2.9 (99% CI 0.6 to 13.4) if reinfarction occurred between 366 days and 3 years. The cumulative 3-year death rate was 14.1% in patients with a nonfatal reinfarction compared with 7.9% (p < 0.01) in a matched control group. Univariate predictors of death after nonfatal reinfarction were age ≥65 years (p < 0.001), not low risk category (p = 0.015) and history of heart failure before the index event (p < 0.001). Age ≥65 years was the only independent predictor (RR 5.4, 99% CI 2.3 to 12.4).Conclusions.Nonfatal reinfarction is a strong and independent predictor for subsequent death. It represents a powerful component for a composite end point in patients who received thrombolytic therapy after acute myocardial infarction

994-99 Can Late Saphenous Vein Graft Closure Be Predicted by Quantitative Angiographic Analysis Before the Clinical Event?

Angiographic parameters predicting the likelihood of late occlusion of saphenous vein grafts (SVG) have been infrequently described. The Post-CABG Study, a 5-year trial aimed at reducing SVG closure in minimally symptomatic patients 1–11 years Post-CABG, offers a unique view into this event since this study requires an angiogram to document baseline graft patency. In this preliminary study we performed quantitative angiographic analysis (QAA Reiber) comparing the baseline Post-CABG study angiogram to an unscheduled “clinically driven” angiogram. Of 1253 enrolled patients with at least one patent SVG, 35 developed MI or unstable angina associated angiographically with a changed SVG lesion and either total or subtotal occlusion. Average patient age was 58±2 (SEM)years; 97% were male. Years since SVG placement to baseline angiogram averaged 6.5±0.4 (range 2–14). Time from the baseline to the unscheduled angiogram was 22±2 mo (range 3–47). In 28 patients the involved graft was single and in 7 sequential. The SVG insertion segments involved the LCX in 17, RCA in 15 and LAD in 10.ResultsThe initial lesion diameter at the site of the subsequent inciting lesion for all 35 patients averaged 2.58±0.17 mm, or 29.5±3.6% diam. stenosis. (This was defined as the most severe stenosis in any part of the graft in patients with subsequent total graft occlusion, and the exactly matched graft site in those with subtotal occlusion.) In 8 patients the baseline SVG was entirely normal. The initial lesion was &gt;50% stenosis in only 4 patients. At the time of the clinical event, the lesion had progressed to 87±2.6% diam stenosis (N=35). In 16 patients the causal lesion was subtotal, while in 19 the SVG was totally occluded. The mean native vessel — responsible graft anastomotic diameter was 2.33±0.12mm.ConclusionQAA of SVG in asymptomatic patients may not predict subsequent graft closure associated with acute coronary syndromes. The initial site of the lesion is typically of mild-moderate severity, and only later exhibits rapid progression to occlusion

Asymptomatic cardiac ischemia pilot (ACIP) study: Effects of coronary angioplasty and coronary artery bypass graft surgery on recurrent angina and ischemia

ObjectivesThe Asymptomatic Cardiac Ischemia Pilot (ACIP) study showed that revascularization is more effective than medical therapy in suppressing cardiac ischemia at 12 weeks. This report compares the relative efficacy of coronary angioplasty or coronary artery bypass graft surgery in suppressing ambulatory electrocardiographic (ECG) and treadmill exercise cardiac ischemia between 2 and 3 months after revascularization in the ACIP study.BackgroundPrevious studies have shown that coronary angioplasty and bypass surgery relieve angina early after the procedure in a high proportion of selected patients. However, alleviation of ischemia on the ambulatory ECG and treadmill exercise test have not been adequately studied prospectively after revascularization.MethodsIn patients randomly assigned to revascularization in the ACIP study, the choice of coronary angioplasty or bypass surgery was made by the clinical unit staff and the patient.ResultsPatients assigned to bypass surgery (n = 78) had more severe coronary disease (p = 0.001) and more ischemic episodes (p = 0.01) at baseline than those assigned to angioplasty (n = 92). Ambulatory ECG ischemia was no longer present 8 weeks after revascularization (12 weeks after enrollment) in 70% of the bypass surgery group versus 46% of the angioplasty group (p = 0.002). ST segment depression on the exercise ECG was no longer present in 46% of the bypass surgery group versus 23% of the angioplasty group (p = 0.005). Total exercise time in minutes on the treadmill exercise test increased by 2.4 min after bypass surgery and by 1.4 min after angioplasty (p = 0.02). Only 10% of the bypass surgery group versus 32% of the angioplasty group still reported angina in the 4 weeks before the 12-week visit (p = 0.001).ConclusionsAngina and ambulatory ECG ischemia are relieved in a high proportion of patients early after revascularization. However, ischemia can still be induced on the treadmill exercise test, albeit at higher levels of exercise, in many patients. Bypass surgery was superior to coronary angioplasty in suppressing cardiac ischemia despite the finding that patients who underwent bypass surgery had more severe coronary artery disease

Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials

Background: Statin therapy has been shown to reduce major vascular events and vascular mortality in a wide range of individuals, but there is uncertainty about its efficacy and safety among older people. We undertook a meta-analysis of data from all large statin trials to compare the effects of statin therapy at different ages. Methods: In this meta-analysis, randomised trials of statin therapy were eligible if they aimed to recruit at least 1000 participants with a scheduled treatment duration of at least 2 years. We analysed individual participant data from 22 trials (n=134 537) and detailed summary data from one trial (n=12 705) of statin therapy versus control, plus individual participant data from five trials of more intensive versus less intensive statin therapy (n=39 612). We subdivided participants into six age groups (55 years or younger, 56–60 years, 61–65 years, 66–70 years, 71–75 years, and older than 75 years). We estimated effects on major vascular events (ie, major coronary events, strokes, and coronary revascularisations), cause-specific mortality, and cancer incidence as the rate ratio (RR) per 1·0 mmol/L reduction in LDL cholesterol. We compared proportional risk reductions in different age subgroups by use of standard χ2 tests for heterogeneity when there were two groups, or trend when there were more than two groups. Findings: 14 483 (8%) of 186 854 participants in the 28 trials were older than 75 years at randomisation, and the median follow-up duration was 4·9 years. Overall, statin therapy or a more intensive statin regimen produced a 21% (RR 0·79, 95% CI 0·77–0·81) proportional reduction in major vascular events per 1·0 mmol/L reduction in LDL cholesterol. We observed a significant reduction in major vascular events in all age groups. Although proportional reductions in major vascular events diminished slightly with age, this trend was not statistically significant (ptrend=0·06). Overall, statin or more intensive therapy yielded a 24% (RR 0·76, 95% CI 0·73–0·79) proportional reduction in major coronary events per 1·0 mmol/L reduction in LDL cholesterol, and with increasing age, we observed a trend towards smaller proportional risk reductions in major coronary events (ptrend=0·009). We observed a 25% (RR 0·75, 95% CI 0·73–0·78) proportional reduction in the risk of coronary revascularisation procedures with statin therapy or a more intensive statin regimen per 1·0 mmol/L lower LDL cholesterol, which did not differ significantly across age groups (ptrend=0·6). Similarly, the proportional reductions in stroke of any type (RR 0·84, 95% CI 0·80–0·89) did not differ significantly across age groups (ptrend=0·7). After exclusion of four trials which enrolled only patients with heart failure or undergoing renal dialysis (among whom statin therapy has not been shown to be effective), the trend to smaller proportional risk reductions with increasing age persisted for major coronary events (ptrend=0·01), and remained non-significant for major vascular events (ptrend=0·3). The proportional reduction in major vascular events was similar, irrespective of age, among patients with pre-existing vascular disease (ptrend=0·2), but appeared smaller among older than among younger individuals not known to have vascular disease (ptrend=0·05). We found a 12% (RR 0·88, 95% CI 0·85–0·91) proportional reduction in vascular mortality per 1·0 mmol/L reduction in LDL cholesterol, with a trend towards smaller proportional reductions with older age (ptrend=0·004), but this trend did not persist after exclusion of the heart failure or dialysis trials (ptrend=0·2). Statin therapy had no effect at any age on non-vascular mortality, cancer death, or cancer incidence. Interpretation: Statin therapy produces significant reductions in major vascular events irrespective of age, but there is less direct evidence of benefit among patients older than 75 years who do not already have evidence of occlusive vascular disease. This limitation is now being addressed by further trials. Funding: Australian National Health and Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, and British Heart Foundation

Examination of the analytic quality of behavioral health randomized clinical trials

Adoption of evidence-based practice (EBP) policy has implications for clinicians and researchers alike. In fields that have already adopted EBP, evidence-based practice guidelines derive from systematic reviews of research evidence. Ultimately, such guidelines serve as tools used by practitioners. Systematic reviews of treatment efficacy and effectiveness reserve their strongest endorsements for treatments that are supported by high-quality randomized clinical trials (RCTs). It is unknown how well RCTs reported in behavioral science journals fare compared to quality standards set forth in fields that pioneered the evidence-based movement. We compared analytic quality features of all behavioral health RCTs (n = 73) published in three leading behavioral journals and two leading medical journals between January 2000 and July 2003. A behavioral health trial was operationalized as one employing a behavioral treatment modality to prevent or treat an acute or chronic physical disease or condition. Findings revealed areas of weakness in analytic aspects of the behavioral health RCTs reported in both sets of journals. Weaknesses were more pronounced in behavioral journals. The authors offer recommendations for improving the analytic quality of behavioral health RCTs to ensure that evidence about behavioral treatments is highly weighted in systematic reviews