http://repub.eur.nl/res/aut/2742/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39443/ 2013-03-21T00:00:00Z Objectives: This study sought to analyze stroke rates in the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial's randomized and registry cohorts of patients being treated with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) for treatment of complex coronary artery disease. Background: The SYNTAX trial compared PCI to CABG in patients with de novo 3-vessel and/or left main coronary disease. Methods: The SYNTAX randomized trial was conducted at 85 U.S. and European sites (n = 1,800). All strokes (up to 4 years) were independently adjudicated by a clinical events committee that included a neurologist. An additional 1,077 (of which 644 were followed for 5 years) and 198 patients were included in the CABG and PCI registries, respectively. Results: In the randomized cohort, 31 CABG and 19 PCI patients experienced 33 and 20 strokes post-randomization at 4-year follow-up, respectively (p = 0.062). Three strokes occurred pre-procedurally but following randomization in CABG-treated patients. After CABG, a large proportion of strokes occurred acutely (0 to 30 days: 9 of 33), whereas in the PCI arm, most strokes occurred >30 days after the procedure (18 of 20). Stroke resulted in death in 3 patients in both the PCI and CABG groups. Of the patients who developed stroke, 68% (21 of 31) in the CABG group had residual deficits at discharge; in the PCI group, 47% (9 of 19) had residual deficits. In a multivariate analysis, treatment with CABG was not significantly associated with increased stroke rates (odds ratio: 1.67, 95% confidence interval: 0.93 to 3.01, p = 0.089). The incidence and outcomes of stroke were similar in the randomized trial and registries. Conclusions: There is a higher risk of periprocedural stroke in patients undergoing CABG versus PCI; however, the risk converges over the first 4 years of follow-up. (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery [SYNTAX]; NCT00114972). http://repub.eur.nl/res/pub/20145/ 2010-06-22T00:00:00Z BACKGROUND-: The prospective, multinational, randomized Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial was designed to assess the optimal revascularization strategy between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), for patients with left main (LM) and/or 3-vessel coronary disease. METHODS AND RESULTS-: This observational hypothesis-generating analysis reports the results of a prespecified powered subgroup of 705 randomized patients who had LM disease among the 1800 patients with de novo 3-vessel disease and/or LM disease randomized to PCI with paclitaxel-eluting stents or CABG in the SYNTAX trial. Major adverse cardiac and cerebrovascular event rates at 1 year in LM patients were similar for CABG and PCI (13.7% versus 15.8%; Δ2.1% [95% confidence interval-3.2% to 7.4%]; P=0.44). At 1 year, stroke was significantly higher in the CABG arm (2.7% versus 0.3%; Δ-2.4% [95% confidence interval-4.2% to-0.1%]; P=0.009]), whereas repeat revascularization was significantly higher in the PCI arm (6.5% versus 11.8%; Δ5.3% [95% confidence interval 1.0% to 9.6%]; P=0.02); there was no observed difference between groups for other end points. When patients were scored for anatomic complexity, those with higher baseline SYNTAX scores had significantly worse outcomes with PCI than did patients with low or intermediate SYNTAX scores; outcomes for patients with CABG did not correlate with baseline SYNTAX score, but baseline EuroSCORE significantly predicted outcomes for both treatments. CONCLUSIONS-: Patients with LM disease who had revascularization with PCI had safety and efficacy outcomes comparable to CABG at 1 year; longer follow-up is required to determine whether these 2 revascularization strategies offer comparable medium-term outcomes in this group of complex patients. http://repub.eur.nl/res/pub/28713/ 2010-01-01T00:00:00Z Objectives: We explore the bifurcation angle (BA) parameters of the left main coronary artery (LM), the effect of percutaneous coronary intervention (PCI) on this angulation, and the impact of BA on clinical outcome. Background: The BA is emerging as a predictor of outcome after PCI of bifurcation lesions. Three-dimensional (3D) quantitative coronary angiography (QCA) overcomes the shortcomings of 2-dimensional analysis and provides reliable data. Methods: This is a substudy of the SYNTAX (SYNergy Between Percutaneous Coronary Intervention With TAXus and Cardiac Surgery) trial. The cineangiograms of the 354 patients who underwent PCI of their LM stem were analyzed with 3D QCA software (CardiOp-B, Paieon Medical, Ltd., Rosh Ha'ayin, Israel). The proximal BA (between LM and left circumflex [LCX]) and the distal BA (between left anterior descending and LCX) were computed in end-diastole and end-systole, both before and after PCI. The cumulative major adverse cardiac and cardiovascular event (MACCE) rates throughout the 12-month period after randomization were stratified across pre-PCI distal BA values and compared accordingly. Results: Complete analysis was feasible in 266 (75.1%) patients. Proximal and distal BA had mean pre-PCI end-diastolic values of 105.9 ± 21.7° and 95.6 ± 23.6°, respectively, and were inversely correlated (r = -0.75, p < 0.001). During systolic motion of the heart there was an enlargement of the proximal angle and a reduction of the distal angle (ΔBA -8.2° and 8.5°, respectively, p < 0.001 for both). The PCI resulted in a mean decrease in the distal BA (ΔBA 4.5°, p < 0.001). The MACCE rates did not differ across distal BA values; freedom from MACCE at 12 months was 82.8%, 85.4%, and 81.1% (p = 0.74) for diastolic values (first through third tertile). Conclusions: Left main BA analysis with 3D QCA is feasible. Both proximal and distal angles are affected by cardiac motion; PCI modifies the distal angle. There is no clear difference in event rates across pre-PCI distal BA values. http://repub.eur.nl/res/pub/18230/ 2009-03-05T00:00:00Z BACKGROUND Percutaneous coronary intervention (PCI) involving drug-eluting stents is increasingly used to treat complex coronary artery disease, although coronary-artery bypass grafting (CABG) has been the treatment of choice historically. Our trial compared PCI and CABG for treating patients with previously untreated three-vessel or left main coronary artery disease (or both). METHODS We randomly assigned 1800 patients with three-vessel or left main coronary artery disease to undergo CABG or PCI (in a 1:1 ratio). For all these patients, the local cardiac surgeon and interventional cardiologist determined that equivalent anatomical revascularization could be achieved with either treatment. A noninferiority comparison of the two groups was performed for the primary end point - a major adverse cardiac or cerebrovascular event (i.e., death from any cause, stroke, myocardial infarction, or repeat revascularization) during the 12-month period after randomization. Patients for whom only one of the two treatment options would be beneficial because of anatomical features or clinical conditions, were entered into a parallel, nested CABG or PCI registry. Results Most of the preoperative characteristics were similar in the two groups. Rates of major adverse cardiac or cerebrovascular events at 12 months were significantly higher in the PCI group (17.8%, vs. 12.4% for CABG; P=0.002), in large part because of an increased rate of repeat revascularization (13.5% vs. 5.9%, P<0.001); as a result, the criterion for noninferiority was not met. At 12 months, the rates of death and myocardial infarction were similar between the two groups; stroke was significantly more likely to occur with CABG (2.2%, vs. 0.6% with PCI; P = 0.003). CONCLUSIONS CABG remains the standard of care for patients with three-vessel or left main coronary artery disease, since the use of CABG, as compared with PCI, resulted in lower rates of the combined end point of major adverse cardiac or cerebrovascular events at 1 year. (CIinicaITriaIs.gov number, NCT00114972.). http://repub.eur.nl/res/pub/9972/ 2002-01-01T00:00:00Z BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) is a major problem affecting 15% to 30% of patients after stent placement. No oral agent has shown a beneficial effect on restenosis or on associated major adverse cardiovascular events. In limited trials, the oral agent tranilast has been shown to decrease the frequency of angiographic restenosis after PCI. METHODS AND RESULTS: In this double-blind, randomized, placebo-controlled trial of tranilast (300 and 450 mg BID for 1 or 3 months), 11 484 patients were enrolled. Enrollment and drug were initiated within 4 hours after successful PCI of at least 1 vessel. The primary end point was the first occurrence of death, myocardial infarction, or ischemia-driven target vessel revascularization within 9 months and was 15.8% in the placebo group and 15.5% to 16.1% in the tranilast groups (P=0.77 to 0.81). Myocardial infarction was the only component of major adverse cardiovascular events to show some evidence of a reduction with tranilast (450 mg BID for 3 months): 1.1% versus 1.8% with placebo (P=0.061 for intent-to-treat population). The primary reason for not completing treatment was > or =1 hepatic laboratory test abnormality (11.4% versus 0.2% with placebo, P<0.01). In the angiographic substudy composed of 2018 patients, minimal lumen diameter (MLD) was measured by quantitative coronary angiography. At follow-up, MLD was 1.76+/-0.77 mm in the placebo group, which was not different from MLD in the tranilast groups (1.72 to 1.78+/-0.76 to 80 mm, P=0.49 to 0.89). In a subset of these patients (n=1107), intravascular ultrasound was performed at follow-up. Plaque volume was not different between the placebo and tranilast groups (39.3 versus 37.5 to 46.1 mm(3), respectively; P=0.16 to 0.72). CONCLUSIONS: Tranilast does not improve the quantitative measures of restenosis (angiographic and intravascular ultrasound) or its clinical sequelae. http://repub.eur.nl/res/pub/5739/ 2000-01-01T00:00:00Z BACKGROUND: Studies have shown that cigarette smokers constitute a substantial proportion of patients with acute coronary syndromes (ACS) and have platelet-rich coronary thrombi. We characterized the influence of smoking status on outcome of patients with ACS without persistent ST-segment elevation and tested the hypothesis that selective inhibition of the platelet glycoprotein IIb/IIIa receptor with eptifibatide would improve outcomes among cigarette smokers. METHODS: The study population included patients enrolled in the PURSUIT trial (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) with known smoking status presenting with ischemic chest pain </=24 hours and having either ischemic electrocardiographic changes without persistent ST-segment elevation or elevated creatine kinase MB levels. Patients were randomly assigned to receive a bolus and infusion of either eptifibatide or placebo in addition to standard therapy. The primary end point was a composite of death or nonfatal myocardial infarction within 30 days. RESULTS: Of the 9406 patients with known smoking status, 2677 were current smokers, 3086 were former smokers, and 3643 were nonsmokers. Cigarette smokers had better 30-day outcomes (12.3%, 16.8%, and 15.4% for smokers, former smokers, and nonsmokers, respectively; P =.001). However, after adjusting for differences in baseline clinical variables, smoking status was not a predictor of 30-day outcome (P =.45). There was a reduction in the composite end point overall with eptifibatide compared with placebo (14.3% vs 15. 7%, P =.054) but no interaction between smoking status and treatment strategy (P =.68). CONCLUSIONS: Among patients with ACS without persistent ST-segment elevation, cigarette smokers had better short-term outcomes because of their more favorable clinical profile. Although prior studies have suggested that smokers more commonly have platelet-rich thrombi than nonsmokers, eptifibatide did not result in more improvement in their outcome compared with former smokers or nonsmokers. http://repub.eur.nl/res/pub/4938/ 1998-12-01T00:00:00Z Controversy continues regarding the mechanism of coronary restenosis. While neointimal thickening was initially considered the major cause, recent studies suggest that changes in arterial size, or remodeling, plays an important or even dominant role in late lumen loss. Moreover, neointimal thickness and remodeling may be interrelated. The field has been complicated by the fact that remodeling analyses have not used consistent definitions or methods. In this editorial we thus describe a quantitative paradigm for remodeling analyses: as arterial plaque or neointima forms in an artery, it is accompanied by luminal encroachment, artery expansion or gradations of either. In this manner, remodeling is generally defined as any arterial size change (enlargement or contraction), independent or dependent of neointimal thickening. Standardization of definitions and quantitative methods may improve understanding of the components of restenosis resulting from artery size changes, neointimal thickening and their impact on lumen size. http://repub.eur.nl/res/pub/5538/ 1997-01-20T00:00:00Z BACKGROUND: Use of aggressive and invasive interventions is more common in the USA than in other countries. We have compared use of resources for patients with cardiogenic shock after myocardial infarction in the USA and in other countries, and assessed the association between use of resources and clinical outcomes. METHODS: We analysed data for patients with cardiogenic shock after myocardial infarction who were enrolled in the GUSTO-I trial (1891 treated in the USA, 1081 treated in other countries). Patients were randomly assigned combinations of streptokinase, heparin, and accelerated tissue-plasminogen activator (t-PA), then decisions about further interventions were left to the discretion of the attending physician. The interventions included in our analysis were: pulmonary-artery catheterisation, cardiac catheterisation, intravenous inotropic agents, ventilatory support, intra-aortic balloon counterpulsation (IABP), percutaneous transluminal coronary angioplasty (PTCA), and coronary bypass graft surgery (CABG). The primary outcome measure was death from any cause at 30 days of follow-up. FINDINGS: Patients who were treated in the USA were significantly younger than those treated elsewhere (median 68 [IQR 59-75] vs 70 [62-76], p < 0.001), a smaller proportion had anterior infarction (49 vs 53%, p < 0.001), and they had a shorter time to treatment (mean 3.1 vs 3.3 h, p < 0.001). Aggressive diagnostic and therapeutic procedures were used more commonly in the USA than in the other countries: cardiac catheterisation (58 vs 23%); IABP (35 vs 7%); right-heart catheterisation (57 vs 22%); and ventilatory support (54 vs 38%). 483 (26%) of the patients treated in the USA underwent PTCA, compared with 82 (8%) patients in other countries. Patients who underwent revascularisation had better survival in all countries. Adjusted 30-day mortality was significantly lower among patients treated in the USA than among those treated elsewhere (50 vs 66%, p < 0.001). The difference in mortality remained at 1 year-56% of patients treated in the USA died versus 70% of patients treated elsewhere (hazard ratio 0.69 [95% CI 0.63-0.75], p < 0.001). INTERPRETATION: 30-day and 1-year mortality was significantly lower among patients treated in the USA than among those treated in other countries. This difference in mortality may be due to the greater use of invasive diagnostic and therapeutic interventions in the USA. http://repub.eur.nl/res/pub/4969/ 1997-01-01T00:00:00Z BACKGROUND: Coronary artery bypass surgery (CABG) has been considered the therapy of choice for patients with unprotected left main (ULMT) coronary stenoses. Selected single-center reports suggest that the results of percutaneous intervention may now approach those of CABG. METHODS AND RESULTS: To assess the results of percutaneous ULMT treatment from a wide variety of experienced interventional centers, we requested data on consecutive patients treated after January 1, 1994, from 25 centers. One hundred seven patients were identified who were treated either electively (n=91) or for acute myocardial infarction (n=16). Of patients treated electively, 25% were considered inoperable, and 27% were considered high risk for bypass surgery. Primary treatment included stents (50%), directional atherectomy (24%), and balloon angioplasty (20%). Follow-up was 98.8% complete at 15+/-8 months. Results varied considerably, depending on presentation and treatment. For patients with acute myocardial infarction, technical success was achieved in 75%, and survival to hospital discharge was 31%. For elective patients, technical success was achieved in 98.9%, and in-hospital survival was strongly correlated with left ventricular ejection fraction (P=.003). Longer-term event (death, infarction, or bypass surgery) -free survival was correlated with ejection fraction (P<.001) and was inversely related to presentation with progressive or rest angina (P<.001). Surgical candidates with ejection fractions > or = 40% had an in-hospital survival of 98% and a 9-month event-free survival of 86+/-5%, whereas patients with ejection fractions < 40% had 67% and 22+/-12% in-hospital and 9-month event-free survivals, respectively. Nine hospital survivors (10.6%) experienced cardiac death within 6 months of hospital discharge. CONCLUSIONS: While results for selected patients appear promising, until early post-hospital discharge cardiac death can be better understood and minimized, percutaneous revascularization of ULMT stenosis should not be considered an alternative to bypass surgery for most patients. When percutaneous revascularization of ULMT is required, directional atherectomy and stenting appear to be the preferred techniques, and follow-up angiography 6 to 8 weeks after treatment is probably advisable. http://repub.eur.nl/res/pub/5054/ 1996-01-01T00:00:00Z OBJECTIVES: This study sought to compare the frequency of restenosis, reocclusion and adverse cardiovascular events after angioplasty of occluded versus nonoccluded coronary arteries. BACKGROUND: Angioplasty of chronically occluded coronary arteries is believed to be associated with a higher frequency of restenosis and reocclusion than angioplasty of subtotal stenoses. Whether this leads to adverse cardiovascular events is unknown. METHODS: The Multicenter American Research Trial With Cilazapril After Angioplasty to Prevent Restenosis (MARCATOR) was a placebo-controlled trial with angiographic follow-up to determine the effect of the angiotensin-converting enzyme inhibitor cilazapril on the frequency of restenosis. In this trial, restenosis was defined as 1) angiographic reduction of minimal lumen diameter > or = 0.72 mm between angioplasty and the follow-up visit; and 2) > 50% diameter stenosis on the follow-up angiogram. We identified 139 patients with successful angioplasty of a coronary occlusion (Group 1) and compared the frequency of restenosis, reocclusion and adverse cardiovascular events with that in 1,295 patients with successful angioplasty of a subtotal stenosis (Group 2). RESULTS: Restenosis occurred in 36 patients with occluded arteries (29%) versus 264 with nonoccluded arteries (23%, p = 0.177) by definition 1 and in 62 patients with occluded arteries (49%) versus 478 with nonoccluded arteries (42%, p = 0.119) by definition 2. Occlusion was present in 24 Group 1 patients (19%) compared with 74 Group 2 patients (7%) (p < 0.001). During the 6 month follow-up period, two Group 1 patients (1.4%) and six Group 2 patients (0.5%) died; no Group 1 patients and 10 Group 2 patients (0.8%) developed severe congestive heart failure; nonfatal myocardial infarction occurred in 4 Group 1 patients (2.9%) and 31 Group 2 patients (2.4%); repeat coronary angioplasty or bypass surgery was performed in 29 Group 1 patients (21%) and 232 Group 2 patients (18%); and angina was present in 18 Group 1 and 163 Group 2 patients (13% for both). Eighty-six Group 1 patients (62%) and 853 Group 2 patients (66%) remained free of these adverse events during the 6-month follow-up period (p = 0.513). CONCLUSIONS: The frequency of restenosis was slightly but not significantly greater after successful angioplasty of an occluded artery than after angioplasty of a subtotal stenosis. Although reocclusion was more frequent, occurring in 19% of patients, the net clinical benefit of angioplasty in such patients was similar to that in patients with subtotal stenoses over the 6-month follow-up period. http://repub.eur.nl/res/pub/5496/ 1995-01-01T00:00:00Z BACKGROUND: The Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial was designed to test whether thrombolytic strategies achieving more complete, early, sustained coronary artery patency would lead to further reductions in mortality in patients with acute myocardial infarction. An angiographic substudy within GUSTO-I provided a unique opportunity to examine the relation between mortality and degrees of patency among the regimens. METHODS AND RESULTS: Four thrombolytic strategies were compared in 41,021 patients in GUSTO-I: streptokinase with subcutaneous or intravenous heparin, accelerated tissue plasminogen activator (TPA) with intravenous heparin, and combination streptokinase plus TPA with intravenous heparin. Accelerated TPA was associated with lower 30-day mortality (6.3%) than the other strategies (7.2%, 7.4%, and 7.0%, respectively). Among the 1210 patients in the angiographic substudy randomized to angiography 90 minutes after starting treatment, there was improved patency, particularly Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, with accelerated TPA over the other regimens (P < .0001). Coronary artery perfusion (TIMI grade 3) at 90 minutes was also a significant predictor of 30-day survival (P < .01). To determine whether differences in mortality among the four strategies matched differences in 90-minute patency, a model was developed for predicting mortality differences in the main trial from the angiographic substudy. The model assumed that any differences in treatment effects on 30-day mortality were mediated through differences in 90-minute patency for the four treatments. The predicted rates were then compared with observed mortality rates of the remaining patients in the main trial for each treatment group. The predicted and observed 30-day mortality rates of the four treatments were streptokinase with subcutaneous heparin, 7.46% versus 7.28%; streptokinase with intravenous heparin, 7.26% versus 7.39%; accelerated TPA, 6.31% versus 6.37%; and streptokinase plus TPA, 6.98% versus 6.96%. The correlation between predicted and observed results was .97, and the proportion of squared error explained (R2) was .92. CONCLUSIONS: The close relation between the predicted and observed 30-day mortality rates supports the concept that an important mechanism for improved survival with thrombolytic therapy is achievement of early, complete perfusion. The close match provides a strong biological explanation for the mortality differences seen in GUSTO-I and a sound rationale for the additional survival advantage of the accelerated TPA regimen. Irrespective of which treatment is used, early and complete restoration of infarct artery perfusion represents an essential goal of myocardial reperfusion therapy. http://repub.eur.nl/res/pub/4519/ 1993-01-01T00:00:00Z BACKGROUND. Directional coronary atherectomy is a new technique of coronary revascularization by which atherosclerotic plaque is excised and retrieved from target lesions. With respect to the rate of restenosis and clinical outcomes, it is not known how this procedure compares with balloon angioplasty, which relies on dilation of the plaque and vessel wall. We compared the rate of restenosis after angioplasty with that after atherectomy. METHODS. At 35 sites in the United States and Europe, 1012 patients were randomly assigned to either atherectomy (512 patients) or angioplasty (500 patients). The patients underwent coronary angiography at base line and again after six months; the paired angiograms were quantitatively assessed at one laboratory by investigators unaware of the treatment assignments. RESULTS. Stenosis was reduced to 50 percent or less more often with atherectomy than with angioplasty (89 percent vs. 80 percent; P < 0.001), and there was a greater immediate increase in vessel caliber (1.05 vs. 0.86 mm, P < 0.001). This was accompanied by a higher rate of early complications (11 percent vs. 5 percent, P < 0.001) and higher in-hospital costs ($11,904 vs $10,637; P = 0.006). At six months, the rate of restenosis was 50 percent for atherectomy and 57 percent for angioplasty (P = 0.06). However, the probability of death or myocardial infarction within six months was higher in the atherectomy group (8.6 percent vs. 4.6 percent, P = 0.007). CONCLUSIONS. Removing coronary artery plaque with atherectomy led to a larger luminal diameter and a small reduction in angiographic restenosis, the latter being confined largely to the proximal left anterior descending coronary artery. However, atherectomy led to a higher rate of early complications, increased cost, and no apparent clinical benefit after six months of follow-up.