Failure of epoprostenol (prostacyclin, PGI2) to inhibit platelet aggregation and to prevent restenosis after coronary angioplasty: results of a randomised placebo controlled trial.

OBJECTIVE--To study the effect of epoprostenol (prostacyclin, PGI2) given before, during, and for 36 h after coronary angioplasty on restenosis at six months and to evaluate the transcardiac gradient of platelet aggregation before and after percutaneous transluminal coronary angioplasty (PTCA) in treated and placebo groups. DESIGN--Double blind placebo controlled randomised study. PATIENTS--135 patients with successful coronary angioplasty. METHODS--Intravenous infusion of PGI2 (4 ng/kg/ml) or buffer was started before balloon angioplasty and continued for 36 hours. Platelet aggregation was measured in blood from the aorta and coronary sinus before and after PTCA in each group. Routine follow up was at six months with repeat angiography and there was quantitative assessment of all angiograms (those undertaken within the follow up period and at routine follow up). PRESENTATION OF RESULTS--Restenosis rates in treated and placebo groups determined according to the National Heart, Lung and Blood Institute definition IV. Comparison at follow up between the effect of treatment on mean absolute luminal diameter and mean absolute follow up diameter in the placebo group. Comparison of acute gain and late loss between groups. RESULTS--Of 125 patients available for assessment 23 were re-admitted because of angina within the follow up period. Quantitative angiography showed restenosis in 15 (10 in the PGI2 group and five in the placebo group). Of 105 patients evaluated at six month angiography there was restenosis in nine more in the PGI2 group and 18 more in the placebo group. Total restenosis rates (for patients) were 29.2% for PGI2 and 38.3% for placebo (NS). The mean absolute gain in luminal diameter was 1.84 (0.76) mm in the PGI2 group and 1.58 (0.56) mm in the placebo group (p = 0.04); the late loss in the PGI2 group was also greater (0.65 (0.94) mm vs 0.62 (0.89) mm (NS) and there was no significant difference in final luminal diameter at follow up between the two groups (1.83 (0.88) mm v 1.59 (0.60) mm). The transcardiac gradient of quantitative platelet aggregation increased after PTCA in both groups, indicating that PGI2 in this dose did not affect angioplasty-induced platelet activation. Mean (SD) platelet activation indices in the PGI2 group were pre PTCA aorta 8.4 (4.1) v coronary sinus 8.8 (4.0) (p = 0.001) and post PTCA aorta 8.9(3.0) v coronary sinus 12.9 (5.7) (p = 0.001). In the placebo group the values were pre PTCA aorta 7.6 (3.3) v coronary sinus 7.4 (3.6) (p = 0.001) and post PTCA aorta 7.6(2.8) v coronary sinus 11.2(4.3) (p = 0.001). CONCLUSION--The dose of PGI2 given was designed to limit side effects and as a short-term infusion did not significantly decrease the six month restenosis rate after PTCA. The sample size, which was determined by the original protocol and chosen because of the potency of the agent being tested, would have detected only a 50% reduction in restenosis rate. There was, however, no effect in the treated patients on the increased platelet aggregation seen in placebo group as a result of angioplasty. Angioplasty is a powerful stimulus to blood factor activation. Powerful agents that prevent local platelet adhesion and aggregation are likely to be required to reduce restenosis.     

Establishing a Research Agenda on Mobile Health Technologies and Later-Life Pain Using an Evidence-Based Consensus Workshop Approach

The rapid growth of mobile health (mHealth) devices holds substantial potential for improving care and care outcomes in all patient populations, including older adults with pain. However, existing research reflects a substantial gap in knowledge about how to design, evaluate, and disseminate devices to optimally address the many challenges associated with managing pain in older persons. Given these knowledge gaps, we sought to develop a set of practice-based research priorities to facilitate innovation in this field. We employed the Cornell Research-Practice Consensus Workshop Model, an evidence-based approach to generating research priorities. Sixty participants attended the conference, where stakeholder groups included older adults with pain and their caregivers, behavioral and social scientists, healthcare providers, pain experts, and specialists in mHealth and health policy. Participants generated 13 recommendations classified into 2 categories: 1) implications for designing research on mHealth among older adults (eg, conduct research on ways to enhance accessibility of mHealth tools among diverse groups of older adults with pain, expand research on mHealth sensing applications), and 2) implementation of mHealth technology into practice and associated regulatory issues (eg, promote research on ways to initiate/sustain patient behavior change, expand research on mHealth cybersecurity and privacy issues).

Carotid ultrasonography--the new "gold standard". Surgical and angiographic correlation

Atherosclerotic plaques and high grade stenosis in the carotid circulation are responsible for symptoms of cerebral and retinal ischemia. Identification of these lesions by angiography has been the "gold standard" for which the decision of endarterectomy depended. The recent introduction of high resolution carotid ultrasonography has allowed us to compare thirty-seven surgical specimens with the results of preoperative screening with angiography. UCI had a 97% correlation whereas angiography was accurate only 70%. More importantly there were ten negative angiograms in patients with clinically active ulcerative plaque disease. If surgery were based solely on the angiographic appearance of ulcerative plaques or high grade stenosis, then less than half of the patients have received the correct treatment. UCI deserves to be considered the new reference standard.     

Assessment of left ventricular performance during percutaneous transluminal coronary angioplasty: a study by intravenous digital subtraction ventriculography.

Left ventricular performance during percutaneous transluminal coronary angioplasty was assessed in 52 patients by intravenous digital subtraction ventriculography. After injection of contrast into the right atrium ventriculograms were obtained before and during balloon inflation. In 37 patients they were also obtained after the procedure. A 12 lead electrocardiogram was monitored throughout. During balloon inflation the left ventricular ejection fraction fell (from 73% to 57%) in all but one patient; the decreases in patients with single vessel or multivessel disease were similar. The fall in left ventricular ejection fraction during percutaneous transluminal coronary angioplasty of the left anterior descending artery (19%) was significantly greater than that during balloon inflation in the right coronary (10%) or circumflex (8%) coronary arteries. It also reduced anterobasal, anterior, and apical segmental shortening while right coronary percutaneous transluminal coronary angioplasty affected inferior and apical segments. In 33 (63%) patients the ST segment was altered during balloon inflation. The fall in left ventricular ejection fraction correlated significantly with the magnitude of both ST segment elevation (r = 0.637) and ST depression (r = 0.396). Left ventricular ejection fraction and regional wall motion returned to baseline values after the procedure. Balloon inflation during percutaneous transluminal coronary angioplasty produces considerable abnormalities of global and regional left ventricular performance and this indicates the presence of myocardial ischaemia, which may not be apparent on electrocardiographic monitoring. Intravenous digital subtraction ventriculography is useful for monitoring left ventricular performance during controlled episodes of coronary occlusion produced by balloon inflation.     

Identification of a high risk subgroup of patients with silent ischaemia after myocardial infarction: a group for early therapeutic revascularisation?

Asymptomatic ("silent") ischaemia has been shown to be of prognostic significance in patients with stable and unstable angina and more recently in patients recovering after myocardial infarction. No therapeutic regimen has yet been shown to improve the prognosis of patients with silent ischaemia after infarction, which can be found in as many as a third of these patients. Attempts to achieve therapeutic revascularisation in all these patients may be undesirable, but early revascularisation could be especially beneficial in some selected high risk patients. Two hundred and fifty consecutive clinically stable survivors of myocardial infarction who had predischarge submaximal exercise tests were followed up for a year. Silent ischaemia was found in 27% of these patients; 15% had symptomatic ischaemia. Patients with a positive exercise test were prescribed a beta blocker before discharge. Mortality in patients with silent (9.4%) and symptomatic (5.4%) ischaemia in the first year after infarction was not significantly different. Patients with symptomatic ischaemia were more likely to have undergone coronary artery bypass grafting in the first year. Patients with silent ischaemia were, however, significantly more likely to die than patients with a negative exercise test (relative odds 12:1). Patients with silent ischaemia and an abnormal blood pressure response or who could not complete a submaximal exercise protocol were at particularly high risk, being 32 times more likely to die than those with a negative test (95% confidence interval from 3.3 to 307 times more likely). First year mortality in this group was 22%. The benefits of therapeutic revascularisation in this high risk group need to be studied.