Jacques Lespérance

Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty.

To examine the role of antiplatelet therapy in the prevention of arterial restenosis after percutaneous transluminal coronary angioplasty (PTCA), we conducted a randomized, double-blind, placebo-controlled study in 376 patients. The active treatment consisted of an oral aspirin-dipyridamole combination (330 mg-75 mg) given three times daily, beginning 24 hours before PTCA. Eight hours before PTCA, the oral dipyridamole was replaced with intravenous dipyridamole at a dosage of 10 mg per hour for 24 hours, and oral aspirin was continued. Sixteen hours after PTCA, the initial combination was reinstituted. Treatment was continued in patients with a successfully dilated vessel until follow-up angiography four to seven months after PTCA--or earlier, if symptoms dictated. Of 249 patients who underwent follow-up angiography, 37.7 percent of patients receiving the active drug had restenosis in at least one segment, as compared with 38.6 percent of patients taking placebo (P not significant). The number of stenotic segments was virtually the same in the two groups. Among the 376 randomized patients, there were 16 periprocedural Q-wave myocardial infarctions--13 in the placebo group and 3 in the active-drug group (6.9 percent vs. 1.6 percent, P = 0.0113). Although the use of this antiplatelet regimen before and after PTCA did not reduce the six-month rate of restenosis after successful coronary angioplasty, it markedly reduced the incidence of transmural myocardial infarction during or soon after PTCA. Thus, the short-term use of antiplatelet agents in relation to PTCA can be recommended.

Probucol and Multivitamins in the Prevention of Restenosis after Coronary Angioplasty

BACKGROUNDnOxidizing metabolites generated at the site of coronary angioplasty can induce chain reactions that may lead to restenosis. Antioxidants may counter oxidative stress and modify neointimal formation and vascular remodeling. Experimental data and small clinical studies have suggested that antioxidants may prevent restenosis after angioplasty. In a double-blind, randomized trial, we studied whether drugs with antioxidant properties decrease the incidence and severity of restenosis after angioplasty.nnnMETHODSnOne month before angioplasty, 317 patients were randomly assigned to receive one of four treatments: placebo, probucol (500 mg), multivitamins (30,000 IU of beta carotene, 500 mg of vitamin C, and 700 IU of vitamin E), or both probucol and multivitamins-all given twice daily. Patients were treated for four weeks before and six months after angioplasty. Patients received an extra 1000 mg of probucol, 2000 IU of vitamin E, both probucol and vitamin E, or placebo 12 hours before angioplasty, according to their treatment assignments. Base-line and follow-up angiograms were interpreted by blinded investigators using a quantitative approach.nnnRESULTSnThe mean (+/-SD) reduction in luminal diameter six months after angioplasty was 0.12 +/- 0.41 mm in the probucol group, 0.22 +/- 0.46 mm in the combined-treatment group, 0.33 +/- 0.51 in the multivitamin group, and 0.38 +/- 0.50 mm in the placebo group (P = 0.006 for those receiving vs. those not receiving probucol, and P = 0.70 for those receiving vs. those not receiving vitamins. Restenosis rates per segment were 20.7 percent in the probucol group, 28.9 percent in the combined-treatment group, 40.3 percent in the multivitamin group, and 38.9 percent in the placebo group (P = 0.003 for probucol vs. no probucol). The rates of repeat angioplasty were 11.2 percent. 16.2 percent, 24.4 percent, and 26.6 percent, respectively (P = 0.009 for probucol vs. no probucol).nnnCONCLUSIONSnThe antioxidant probucol is effective in reducing the rate of restenosis after balloon coronary angioplasty.

Unstable Angina and Progression of Coronary Atherosclerosis

We studied the progression of atherosclerotic coronary lesions in 38 patients who had previously undergone angiography and were later hospitalized for an episode of unstable angina pectoris, and in 38 matched patients with stable angina who had also undergone prior catheterization. Patients with unstable angina and those with stable angina were similar in terms of age (mean, 49 and 50 years, respectively), number of risk factors (1.5 per patient in both groups), interval between studies (mean +/- S.D., 44 +/- 31 and 35 +/- 31 months, respectively), number of diseased vessels on the first angiogram (1.52 in both groups), and initial ejection fraction (65 and 63 per cent, respectively). Progression of coronary lesions was demonstrated in 29 of the 38 patients with unstable angina, as compared with 12 of the 38 with stable angina (P less than 0.0005). Progression to 70 per cent or more stenosis was recorded in 21 of the patients with unstable angina but in only 5 of those with stable angina (P less than 0.0005). Also more frequent in the patients with unstable angina were multifocal progression (11 vs. 2, P less than 0.01) and progression of the left main or preseptal left anterior descending artery or both (9 vs. 1, P less than 0.01). Thus, we have demonstrated by angiography that unstable angina is associated with progression in the extent and severity of coronary atherosclerosis.

Effects of AGI-1067 and Probucol After Percutaneous Coronary Interventions

Background—AGI-1067, a metabolically stable modification of probucol, is an equipotent antioxidant to probucol but is pharmacologically distinct. In a multicenter trial, we studied whether AGI-1067 reduces restenosis assessed by intravascular ultrasound (IVUS) after percutaneous coronary intervention (PCI) compared with placebo and probucol used as a positive control. Methods and Results—Two weeks before PCI, 305 patients were randomly assigned to 1 of 5 treatment groups: placebo, probucol 500 mg BID, or AGI-1067 70, 140, or 280 mg once daily. Patients were treated for 2 weeks before and 4 weeks after PCI. Baseline and 6-month follow-up IVUS were interpreted by a blinded core laboratory. Stents were used in 85% of patients. Luminal area at the PCI site at follow-up was 2.66±1.58 mm2 for placebo, 3.69±2.69 mm2 for probucol, 2.75±1.76 mm2 for AGI-1067 70 mg, 3.17±2.26 mm2 for AGI-1067 140 mg, and 3.36±2.12 mm2 for AGI-1067 280 mg (P =0.02 for the dose-response relationship;P ≤0.05 for AGI-1067 280 mg and probucol versus placebo). There was a mean narrowing of 5.3 mm3 of reference segment lumen in the placebo group and an enlargement in the AGI-1067 140- and 280-mg groups at follow-up (P =0.05 for 140 mg). An increase in QTc interval >60 ms occurred in 4.8% of placebo patients, 17.4% of probucol patients, and 4.8%, 2.4%, and 2.5% of patients in the AGI-1067 groups (P =0.02). Conclusions—AGI-1067 and probucol reduce restenosis after PCI. In contrast to probucol, AGI-1067 did not cause prolongation of the QTc interval and improved lumen dimensions of reference segments, suggestive of a direct effect on atherosclerosis.

Noninvasive diagnostic test choices for the evaluation of coronary artery disease in women: a multivariate comparison of cardiac fluoroscopy, exercise electrocardiography and exercise thallium myocardial perfusion scintigraphy

Several diagnostic noninvasive tests to detect coronary and multivessel coronary disease are available for women. However, all are imperfect and it is not yet clear whether one particular test provides substantially more information than others. The aim of this study was to evaluate clinical findings, exercise electrocardiography, exercise thallium myocardial scintigraphy and cardiac fluoroscopy in 92 symptomatic women without previous infarction and determine which tests were most useful in determining the presence of coronary disease and its severity. Univariate analysis revealed two clinical, eight exercise electrocardiographic, seven myocardial scintigraphic and seven fluoroscopic variables predictive of coronary or multivessel disease with 70% or greater stenosis. The multivariate discriminant function analysis selected a reversible thallium defect, coronary calcification and character of chest pain syndrome (p less than 0.05) as the variables most predictive of presence or absence of coronary disease. The ranked order of variables most predictive of multivessel disease were cardiac fluoroscopy score, thallium score and extent of ST segment depression in 14 electrocardiographic leads. Each provided statistically significant information to the model. The estimate of predictive accuracy was 89% for coronary disease and 97% for multivessel coronary disease. The results suggest that cardiac fluoroscopy or thallium scintigraphy provide significantly more diagnostic information than exercise electrocardiography in women over a wide range of clinical patient subsets.

Prognostic significance of angiographically documented left ventricular aneurysm from the Coronary Artery Surgery Study (CASS)

In order to evaluate the prognosis of medically treated patients with angiographically defined left ventricular aneurysm the data available from 1,136 patients with aneurysm (7.6 percent) from 15,019 patients with coronary artery disease in the Coronary Artery Surgery Study (CASS) registry were analyzed. Prior myocardial infarction, reduced ejection fraction, absence of angina and evidence of congestive heart failure were more commonly present in patients with aneurysm. The cumulative survival rates of medically treated patients at 1, 2, 3 and 4 years were 90, 84, 79 and 71 percent, respectively. The Cox analysis of survival indicated that the following variables predicted outcome: age, residual left ventricular function as assessed with angiography, left ventricular end-diastolic pressure, functional impairment due to congestive heart failure, number of vessels diseased, mitral regurgitation and S3 gallop. When survival was stratified for similar degrees of left ventricular dysfunction and functional impairment there was no difference between the survival of patients with aneurysm and that of registry patients without aneurysm. The data from this large population study indicate that the survival of patients with left ventricular aneurysm is better than previously recognized. The mortality in this group is primarily related to age, left ventricular function and clinical severity of heart failure. The presence of an aneurysm does not independently alter survival.

Left main coronary artery stenosis: angiographic determination.

Reliability of angiographic assessment of the left main coronary artery segment was evaluated by review of 106 coronary cineangiograms from the Coronary Artery Surgery Study. The films were interpreted by three groups of angiographers: those at a clinical site, those at a quality control site, and those on a study census panel. Among the readings of these three groups, there was 41% to 59% agreement on the severity of the lesion, with 80% agreement on whether the lesion was greater or less than 50%. The severity of lesion, its location, or presence of ectasia or calcium did not affect the discrepancy rate, whereas segments that were unusually short, diffusely diseased, or obscured by overlapping vessels were especially difficult to interpret.

Incidence and clinical characteristics of the metabolic syndrome in patients with coronary artery disease.

Background and objectives Several studies suggested that the insulin resistance‐associated metabolic syndrome (MS) is a major risk factor for coronary artery disease (CAD), but the criteria to identify MS were only recently standardized by the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III. Methods We evaluated the incidence of the newly defined MS in patients with documented CAD and compared the characteristics of patients with and without this syndrome. Results In a Canadian population with CAD (793 men and 315 women, age 58.1 ±9.8 years) 51% had MS. As compared to patients without the MS syndrome, these patients had significantly higher waist circumference, blood pressure levels and fasting glucose and triglyceride, but lower high‐density lipoprotein (HDL)‐cholesterol levels. Their homeostatic model assessment (HOMA) insulin resistance index was significantly higher, with indicators of highly atherogenic, small low‐density lipoprotein (LDL) and HDL particles. Family history of diabetes and the use of hypoglycemic agents, &bgr;‐blockers and thiazides were more frequent, but physical exercise and alcohol consumption were less frequent in MS positive patients. Cumulative coronary stenosis score and the frequency of patients with > 50% coronary artery narrowing were higher and there was a strong tendency for higher rates of previous myocardial infarction in MS positive patients. Conclusions In a CAD population documented in 1991‐1992, 51% of participants had MS and in several respects a more advanced coronary disease than those without the syndrome. These results support the view of NCEP ATP III, that in CAD prevention, beyond lowering LDL‐cholesterol levels, interventions concerning the constituents of MS should be important. Coron Artery Dis 14:207‐212

Effects of Cholesterol Lowering on the Progression of Coronary Atherosclerosis in Women A Canadian Coronary Atherosclerosis Intervention Trial (CCAIT) Substudy

BACKGROUNDnAlthough coronary disease is the leading cause of death in women and its clinical features differ from those in men, very few women have been included in angiographic trials of cholesterol lowering.nnnMETHODS AND RESULTSnSixty-two women with diffuse but not necessarily severe coronary atherosclerosis documented on a recent angiogram and with fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a double-blind, placebo-controlled trial. More than one half had a history of hypertension, approximately one quarter were diabetics, and one third were current smokers. All women received dietary counseling. Lovastatin or placebo was begun at 20 mg/d and was titrated if necessary to 40 and then to 80 mg during the first 16 weeks to attain a fasting LDL cholesterol < or = 130 mg/dL. The mean lovastatin dose was 34 mg/d. Total and LDL cholesterol decreased by 24% and 32%, respectively, in lovastatin-treated women but by < 3% in women receiving placebo. Coronary arteriography was repeated after 2 years in 54 women (87%), and their 394 lesions were measured blindly on pairs of film with an automated computerized quantitative system. Progression, defined as a worsening in minimum diameter of one or more stenoses by > or = 0.4 mm, occurred in 7 of 25 lovastatin-treated women and 17 of 29 placebo-treated women (28% versus 59%, P = .031). New coronary lesions developed in 1 lovastatin-treated woman and 13 placebo-treated women (4% versus 45%, P < .001). The outcome for each of the angiographic end points was not significantly different between the women and the 245 men who completed the trial.nnnCONCLUSIONSnLovastatin slows the progression of coronary atherosclerosis and prevents the development of new coronary lesions in women.

A life table and Cox regression analysis of patients with combined proximal left anterior descending and proximal left circumflex coronary artery disease: non-left main equivalent lesions (CASS).

Combined proximal left anterior descending and proximal left circumflex artery stenoses greater than or equal to 70% have been referred to as left main equivalent lesions. We compared the survival rates of medically treated patients who have this type of coronary anatomic characteristics with the survival rates of patients who have left main coronary artery stenoses greater than or equal to 70% by use of a stratified life table approach and a Cox regression model. Comparison of the patients with left main coronary artery stenoses with those who have left main equivalent lesions by use of life table analysis and three different calculations of patient exposure time revealed a poorer prognosis for the patients who had left main coronary artery disease (p less than or equal to .04 for all three methods). The stepwise Cox analysis also determined that patients who had left main artery stenoses had a significantly poorer prognosis than patients who had left main equivalent coronary disease (p = .002), even after consideration of important baseline variables known to affect survival rates. We then compared the patients who had combined proximal left anterior descending and proximal left circumflex artery disease with patients who had combined stenoses greater than or equal to 70% in the nonproximal left anterior descending stenosis influenced survival rates. The 5 year to determine if location of the left anterior descending stenosis influenced survival rates. The 5 year survival rate was not as high for the patients who had proximal left anterior descending artery disease (55% vs 70%, p = .001). In conclusion, combined proximal left anterior descending and proximal left circumflex artery disease identifies a high-risk (as determined by angiography) patient subset.(ABSTRACT TRUNCATED AT 250 WORDS)