http://repub.eur.nl/res/aut/4816/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/4835/ 2001-05-10T00:00:00Z OBJECTIVES: This study sought to establish whether the early favorable results in the Benestent-I randomized trial comparing elective Palmaz-Schatz stent implantation with balloon angioplasty in 516 patients with stable angina pectoris are maintained at 5 years. BACKGROUND: The size of the required sample was based on a 40% reduction in clinical events in the stent group. Seven months and one-year follow-up in this trial showed a decreased incidence of restenosis and clinical events in patients randomized to stent implantation. METHODS: Data at five years were collected by outpatient visit, via telephone and via the referring cardiologist. Three patients in the stent group and one in the percutaneous transluminal coronary angioplasty (PTCA) group were lost to follow-up at five years. Major clinical events, anginal status and use of cardiac medication were recorded according to the intention to treat principle. RESULTS: No significant differences were found in anginal status and use of cardiac medication between the two groups. In the PTCA group, 27.3% of patients underwent target lesion revascularization (TLR) versus 17.2% of patients in the stent group (p = 0.008). No significant differences in mortality (5.9% vs. 3.1%), cerebrovascular accident (0.8% vs. 1.2%), myocardial infarction (9.4% vs. 6.3%) or coronary bypass surgery (11.7% vs. 9.8%) were found between the stent and PTCA groups, respectively. At five years, the event-free survival rate (59.8% vs. 65.6%; p = 0.20) between the stent and PTCA groups no longer achieved statistical significance. CONCLUSIONS: The original 10% absolute difference in TLR in favor of the stent group has remained unchanged at five years, emphasizing the long-term stability of the stented target site. http://repub.eur.nl/res/pub/12815/ 1999-11-19T00:00:00Z BACKGROUND: The CAPTURE study (c 7E3 A nti P latelet T herapy in U nstable Re fractory angina) was designed to assess outcome in patients with refractory angina undergoing angioplasty, receiving either abciximab or placebo. METHODS: One thousand two hundred and sixty-five patients with refractory unstable angina, defined as recurrent myocardial ischaemia despite medical treatment including heparin and nitrates were enrolled. After angiography, patients received an infusion of abciximab or placebo over 18-24 h preceding angioplasty, continuing until 1 h after the procedure. In 1197 patients undergoing angioplasty the angiographic committee centrally reviewed the baseline as well as the procedural angiograms. Coronary flow and lesion characteristics were assessed in the baseline angiogram as well as before intervention. Angiographic outcome, reason for failure as well as complications were assessed after angioplasty. RESULTS: At 30 days follow-up, patients receiving abciximab (n=595) compared with placebo (n=602) had a 30% reduction in the composite primary end-point death, myocardial infarction or urgent (re)intervention: 10.8% vs 15.4% (P=0.017). Baseline demographics were identical in the angiogram available group compared with the total study group. At 30 days, the non-angiogram available patients showed a higher incidence of events compared to those in whom the angiogram was reviewed: 19.4 vs 13.1% (P=ns). Lesion characteristics and coronary flow were not different at baseline between the placebo and abciximab groups. A primary end-point was reached in 9.6% of both placebo and abciximab patients with type A or B(1)lesions, in 17.0% vs 12.0% with type B(2)lesions, and in 19.1% vs 11.5% with type >B(2)or C lesions. Sixty-one percent of placebo and abciximab patients had TIMI 3 flow at baseline angiography. Pre-angioplasty TIMI 3 flow was observed in 69% and 72% respectively. The thrombus was resolved between the angiograms in 22% and 43% respectively, in the placebo and abciximab groups (P=0. 033). Angiographic success of the procedure was achieved in 88% and 94% in the placebo and abciximab patients, respectively (P<0.001). Stents were implanted in the ischaemia-related artery in 56 and 60 patients, respectively. However, failure of the stent procedure was more frequent in the placebo group than in the abciximab group, nine vs no patients (P=0.003). CONCLUSION: More frequent thrombus resolution was observed and a higher angiographic success rate was achieved in patients treated with abciximab before and during angioplasty compared with placebo. Patients with complex lesions as the underlying pathology reached fewer end-points if treated with abciximab before and during angioplasty. http://repub.eur.nl/res/pub/5047/ 1996-01-01T00:00:00Z Background The purpose of the Benestent-II Pilot Study was to evaluate the safety of delaying and eliminating anticoagulant therapy in patients receiving a heparin-coated stent in conjunction with antiplatelet drugs. Methods and Results The study consisted of three initial phases (I, II, III) during which resumption of heparin therapy after sheath removal was progressively deferred by 6, 12, and 36 hours. In phase IV, coumadin and heparin were replaced by 250 mg ticlopidine and 100 mg aspirin. Of the 207 patients with stable angina pectoris and a de novo lesion in whom heparin-coated stent implantation was attempted, implantation was successful in 202 patients (98%). Stent thrombosis did not occur during all four phases, and the overall clinical success rate at discharge was 99%. Bleeding complications requiring blood transfusion or surgery fell from 7.9% in phase I to 5.9%, 4%, and 0% in the three following phases. Hospital stay was 7.4, 6.1, 7.2, and 3.1 days for the consecutive phases. The restenosis rate for the combined four phases was 13% (15% in phase I, 20% in phase II, 11% in phase III, and 6% in phase IV). The overall rate of reintervention for the four phases was 8.9%. At 6 months, 84%, 75%, 94%, and 92% of the patients of phases I to IV, respectively, were event free. For the four phases, the event-free rate was 86%, which compares favorably with the rate observed in the Benestent-I study (80%; relative risk, 0.68 [0.45 to 1.04]). Conclusions The implantation of stents coated with polyamine and end-point–attached heparin in stable patients with one significant de novo coronary lesion is well tolerated, is associated with no (sub)acute stent thrombosis, and results in a favorable event-free survival after 6 months. http://repub.eur.nl/res/pub/4616/ 1994-01-01T00:00:00Z BACKGROUND. Balloon-expandable coronary-artery stents were developed to prevent coronary restenosis after coronary angioplasty. These devices hold coronary vessels open at sites that have been dilated. However, it is unknown whether stenting improves long-term angiographic and clinical outcomes as compared with standard balloon angioplasty. METHODS. A total of 520 patients with stable angina and a single coronary-artery lesion were randomly assigned to either stent implantation (262 patients) or standard balloon angioplasty (258 patients). The primary clinical end points were death, the occurrence of a cerebrovascular accident, myocardial infarction, the need for coronary-artery bypass surgery, or a second percutaneous intervention involving the previously treated lesion, either at the time of the initial procedure or during the subsequent seven months. The primary angiographic end point was the minimal luminal diameter at follow-up, as determined by quantitative coronary angiography. RESULTS. After exclusions, 52 patients in the stent group (20 percent) and 76 patients in the angioplasty group (30 percent) reached a primary clinical end point (relative risk, 0.68; 95 percent confidence interval, 0.50 to 0.92; P = 0.02). The difference in clinical-event rates was explained mainly by a reduced need for a second coronary angioplasty in the stent group (relative risk, 0.58; 95 percent confidence interval, 0.40 to 0.85; P = 0.005). The mean (+/- SD) minimal luminal diameters immediately after the procedure were 2.48 +/- 0.39 mm in the stent group and 2.05 +/- 0.33 mm in the angioplasty group; at follow-up, the diameters were 1.82 +/- 0.64 mm in the stent group and 1.73 +/- 0.55 mm in the angioplasty group (P = 0.09), which correspond to rates of restenosis (diameter of stenosis, > or = 50 percent) of 22 and 32 percent, respectively (P = 0.02). Peripheral vascular complications necessitating surgery, blood transfusion, or both were more frequent after stenting than after balloon angioplasty (13.5 vs. 3.1 percent, P < 0.001). The mean hospital stay was significantly longer in the stent group than in the angioplasty group (8.5 vs. 3.1 days, P < 0.001). CONCLUSIONS. Over seven months of follow-up, the clinical and angiographic outcomes were better in patients who received a stent than in those who received standard coronary angioplasty. However, this benefit was achieved at the cost of a significantly higher risk of vascular complications at the access site and a longer hospital stay. http://repub.eur.nl/res/pub/5475/ 1994-01-01T00:00:00Z BACKGROUND: Patients with unstable angina despite intensive medical therapy, ie, refractory angina, are at high risk for developing thrombotic complications: myocardial infarction or coronary occlusion during percutaneous transluminal coronary angioplasty (PTCA). Chimeric 7E3 (c7E3) Fab is an antibody fragment that blocks the platelet glycoprotein (GP) IIb/IIIa receptor and potently inhibits platelet aggregation. METHODS AND RESULTS: To evaluate whether potent platelet inhibition could reduce these complications, 60 patients with dynamic ST-T changes and recurrent pain despite intensive medical therapy were randomized to c7E3 Fab or placebo. After initial angiography had demonstrated a culprit lesion suitable for PTCA, placebo or c7E3 Fab was administered as 0.25 mg/kg bolus injection followed by 10 micrograms/min for 18 to 24 hours until 1 hour after completion of second angiography and PTCA. During study drug infusion, ischemia occurred in 9 c7E3 Fab and 16 placebo patients (P = .06). During hospital stay, 12 major events occurred in 7 placebo patients (23%), including 1 death, 4 infarcts, and 7 urgent interventions. In the c7E3 Fab group, only 1 event (an infarct) occurred (3%, P = .03). Angiography showed improved TIMI flow in 4 placebo and 6 c7E3 Fab patients and worsening of flow in 3 placebo patients but in none of the c7E3 Fab patients. Quantitative analysis showed significant improvement of the lesion in the patients treated with c7E3 Fab, which was not observed in the placebo group, although the difference between the two treatment groups was not significant. Measurement of platelet function and bleeding time demonstrated > 90% blockade of GPIIb/IIIa receptors, > 90% reduction of ex vivo platelet aggregation to ADP, and a significantly prolonged bleeding time during c7E3 Fab infusion, without excess bleeding. CONCLUSIONS: Combined therapy with c7E3 Fab, heparin, and aspirin appears safe. These pilot study results support the concept that effective blockade of the platelet GPIIb/IIIa receptors can reduce myocardial infarction and facilitate PTCA in patients with refractory unstable angina. http://repub.eur.nl/res/pub/4522/ 1993-07-01T00:00:00Z Major, adverse cardiac events (death, myocardial infarction, bypass surgery and reintervention) occur in 4 to 7% of all patients undergoing coronary balloon angioplasty. Prospectively collected clinical data, and angiographic quantitative and qualitative lesion morphologic assessment and procedural factors were examined to determine whether the occurrence of these events could be predicted. Of 1,442 patients undergoing balloon angioplasty for native primary coronary disease in 2 European multicenter trials, 69 had major, adverse cardiac procedural or in-hospital complications after ≥1 balloon inflation and were randomly matched with patients who completed an uncomplicated in-hospital course after successful angioplasty. No quantitative angiographic variable was associated with major adverse cardiac events in univariate and multivariate analyses. Univariate analysis showed that major adverse cardiac events were associated with the following preprocedural variables: (1) unstable angina (odds ratio [OR] 3.11; p < 0.0001), (2) type C lesion (OR 2.53; p < 0.004), (3) lesion location at a bend >45 ° (OR 2.34; p < 0.004), and (4) stenosis located in the middle segment of the artery dilated (OR 1.88; p < 0.03); and with the following postprocedural variable: angiographically visible dissection (OR 5.39; p < 0.0001). Muttivariate logistic analysis was performed to identify variables independently correlated with the occurrence of major adverse cardiac events. The preprocedural multivariate model entered unstable angina (OR 3.77; p < 0.0003), lesions located at a bend >45 ° (OR 2.87; p < 0.0005), and stenosis located in the middle portion of the artery dilated (OR 1.95; p < 0.04). If all variables were included, then angiographically visible dissection (OR 6.58; p < 0.0001), unstable angina (OR 3.46; p < 0.002) and lesions located at a bend >45 ° (OR 2.54; p < 0.006) were independent predictors of major adverse cardiac events. http://repub.eur.nl/res/pub/4532/ 1993-01-01T00:00:00Z Background. The renarrowing process after successful percutaneous transluminal coronary angioplasty (PTCA) is now believed to be caused by a response-to-injury vessel wall reaction. The magnitude of this process can be assessed by the change in minimal lumen diameter (MLD) at follow-up angiography. The aim of the present study was to find independent patient-related, lesion-related, and procedure-related risk factors for this luminal narrowing process. A model that accurately predicts the amount of luminal narrowing could be an aid in patient or lesion selection for the procedure, and it could improve assessment of medium-term (6 months) prognosis. Modification or control of the identified risk factors could reduce overall restenosis rates, and it could assist in the selection of patients at risk for a large loss in lumen diameter. This population could then constitute the target population for pharmacological intervention studies. Methods and Results. Quantitative angiography was performed on 666 successfully dilated lesions at angioplasty and at 6-month follow-up. Multivariate linear regression analysis was performed to obtain variables with an independent contribution to the prediction of the absolute change in minimal lumen diameter. Diabetes mellitus, duration of angina <2.3 months, gain in MLD at angioplasty, pre-PTCA MLD, lesion length 26.8 mm, and thrombus after PTCA were independently predictive of change in MLD. Overall prediction of the model was poor, however, percentage-correct classification for a predicted change between -0.1 to -0.4 mm was approximately 10%. Lesions showing no change or regression (change > -0.1 mm) and lesions showing large progression (< -0.4 mm) were more predictable (correct classification, 59.5% and 49.7%, respectively). Conclusions. Renarrowing after successful PTCA as determined with contrast angiography is a process that cannot be accurately predicted by simple clinical, morphological, and lesion characteristics. http://repub.eur.nl/res/pub/4540/ 1993-01-01T00:00:00Z BACKGROUND. Enhanced thrombin activity has been associated with acute and long-term complications following balloon angioplasty (percutaneous transluminal coronary angioplasty (PTCA). We evaluated, in a 2-to-1 randomized, double-blind trial, the effects of recombinant hirudin, CGP 39 393, relative to unfractionated sodium heparin on periprocedural events, bleeding, early angiographic outcome, and coagulation in 113 patients with stable angina undergoing PTCA. METHODS AND RESULTS. Prior to PTCA, 20 mg CGP 39 393 was administered as a bolus, followed by continuous infusion at a rate of 0.16 mg.kg-1 x h-1, or 10,000 IU sodium heparin was administered as a bolus and continued at a rate of 12 IU.kg-1 x h-1 for 24 hours. Infusion was adjusted to activated partial thromboplastin time (APTT) levels. ST segment was monitored for 24 hours, and angiograms were analyzed with quantitative technique (QCA). In 74 CGP 39 393- and 39 heparin-treated patients, 132 lesions were dilated. Myocardial infarction and/or emergency coronary bypass surgery occurred in 1 (1.4%) CGP 39 393 patient compared with 4 (10.3%) heparin patients (relative risk, 7.6; 95% confidence interval, 0.9, 65.6). At 24 hours, complete perfusion was present in 91% heparin and 100% CGP 39 393 patients. Significant ST segment displacement was found in 11% of heparin versus 4% of CGP 39 393 subjects. Bleeding occurred only at the puncture site in 4 CGP 39 393-treated patients. QCA did not reveal significant differences between the groups. APTT values were more often in the target range and more stable in CGP 39 393 patients. Levels of thrombin-antithrombin III complexes, prothrombin fragment F1+2, and fibrinopeptide A indicated that CGP 39 393 was an effective inhibitor of thrombin activity. CONCLUSIONS. CGP 39 393 can safely be administered to patients undergoing elective PTCA for stable anginal symptoms and may have a more favorable anticoagulant profile than heparin. http://repub.eur.nl/res/pub/4545/ 1993-01-01T00:00:00Z Because of the unavoidable occurrence of vessel disruption after successful coronary balloon angioplasty, the reliability of quantitative angiographic analysis in that setting has been questioned. For this reason and the suggested occurrence of delayed elastic recoil, repeat angiography at 24 hours has been advocated in clinical interventional trials. In this study, these issues are confronted by performing comprehensive quantitative analysis (Cardiovascular Angiographic Analysis System) of coronary angiograms, acquired in multiple identical projections immediately after and 24 hours after angioplasty, in 102 patients with 110 successfully dilated lesions. Vasomotion was controlled by intracoronary nitrate before angiography and all patients were fully anticoagulated (activated partial thromboplastin time 85 to 120 seconds) for > 24 hours. Paired Student's t tests applied to angiographic measurements revealed that there was no significant deterioration in minimal luminal diameter or cross-sectional area from immediately after angioplasty to 24 hours later. It can thus be inferred that there is no phenomenon of delayed elastic recoil, at least during this time period. Measurement accuracy and precision of the Cardiovascular Angiographic Analysis System from the postangioplasty angiogram are highly acceptable, at < 0.01 and +/- 0.20 mm, respectively. Therefore, it is concluded that routine repeat 24-hour angiography is not indicated after successful angioplasty. A highly significant increase (p < 0.001) in reference diameter (+0.11 +/- 0.18 mm) was responsible for the apparent increase in percent diameter stenosis (2.4 +/- 7%), a finding that demonstrates the potential for error by selective application of percent diameter stenosis measurements alone. Preferential use of absolute luminal measurements is thus strongly recommended for clinical trials with angiographic monitoring. http://repub.eur.nl/res/pub/4548/ 1993-01-01T00:00:00Z BACKGROUND. Ketanserin is a serotonin S2-receptor antagonist that inhibits the platelet activation and vasoconstriction induced by serotonin and also inhibits the mitogenic effect of serotonin on vascular smooth muscle cells. METHODS AND RESULTS. We conducted a randomized, double blind, placebo-controlled trial to assess the effect of ketanserin in restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received either ketanserin (loading dose, 40 mg 1 hour before PTCA; maintenance dose, 40 mg bid for 6 months) or matched placebo. In addition, all patients received aspirin for 6 months. Coronary angiograms before PTCA, after PTCA, and at 6 months were quantitatively analyzed. Six hundred fifty-eight patients were entered into the intention-to-treat analysis. The primary clinical end point of the study was the occurrence between PTCA and 6 months of any one of the following: cardiac death, myocardial infarction, the need for repeat angioplasty, or bypass surgery. It also included the need for revascularization actuated by findings at 6-month follow-up angiography. The primary clinical end point was reached by 92 (28%) patients in the ketanserin group and 104 (32%) in the placebo group (RR, 0.89; 95% CI, 0.70, 1.13; P = .38). Quantitative angiography after PTCA and at follow-up was available in 592 patients (ketanserin, 287; control, 305). The mean difference in minimal lumen diameter between post-PTCA and follow-up angiogram (primary angiographic end point) was 0.27 +/- 0.49 mm in the ketanserin group and 0.24 +/- 0.52 mm in the control group (difference, 0.03 mm; 95% CI, -0.05, 0.11; P = .50). CONCLUSIONS. Ketanserin at the dose administered in this trial failed to reduce the loss in minimal lumen diameter during follow-up after PTCA and did not significantly improve the clinical outcome. http://repub.eur.nl/res/pub/4488/ 1992-01-01T00:00:00Z Abstract OBJECTIVES: The safety and long-term results of directional coronary atherectomy in stented coronary arteries were determined. In addition, tissue studies were performed to characterize the development of restenosis. METHODS: Directional coronary atherectomy was performed in restenosed stents in nine patients (10 procedures) 82 to 1,179 days after stenting. The tissue was assessed for histologic features of restenosis, smooth muscle cell phenotype, markers of cell proliferation and cell density. A control (no stenting) group consisted of 13 patients treated with directional coronary atherectomy for restenosis 14 to 597 days after coronary angioplasty, directional coronary atherectomy or laser intervention. RESULTS: Directional coronary atherectomy procedures within the stent were technically successful with results similar to those of the initial stenting procedure (2.31 +/- 0.38 vs. 2.44 +/- 0.35 mm). Of five patients with angiographic follow-up, three had restenosis requiring reintervention (surgery in two and repeat atherectomy followed by laser angioplasty in one). Intimal hyperplasia was identified in 80% of specimens after stenting and in 77% after coronary angioplasty or atherectomy. In three patients with stenting, 70% to 76% of the intimal cells showed morphologic features of a contractile phenotype by electron microscopy 47 to 185 days after coronary intervention. Evidence of ongoing proliferation (proliferating cell nuclear antigen antibody studies) was absent in all specimens studied. Although wide individual variability was present in the maximal cell density of the intimal hyperplasia, there was a trend toward a reduction in cell density over time. CONCLUSIONS: Although atherectomy is feasible for the treatment of restenosis in stented coronary arteries and initial results are excellent, recurrence of restenosis is common. Intimal hyperplasia is a nonspecific response to injury regardless of the device used and accounts for about 80% of cases of restenosis. Smooth muscle cell proliferation and phenotypic modulation toward a contractile phenotype are early events and largely completed by the time of clinical presentation of restenosis. Restenotic lesions may be predominantly cellular, matrix or a combination at a particular time after a coronary procedure. http://repub.eur.nl/res/pub/4435/ 1991-01-01T00:00:00Z BACKGROUND. GR32191B is a novel thromboxane A2-receptor antagonist with potent antiagregational and antivasoconstrictive properties. We have conducted a randomized, double-blind placebo-controlled trial to study its usefulness in restenosis prevention. METHODS AND RESULTS. Patients received either GR32191B (80 mg orally before angioplasty and 80 mg/day orally for 6 months) or 250 mg i.v. aspirin before angioplasty and placebo for 6 months. Coronary angiograms before angioplasty, after angioplasty, and at 6-month follow-up were quantitatively analyzed. Angioplasty was attempted in 697 patients. For efficacy analysis, quantitative angiography at follow-up was available in 522 compliant patients (261 in each group). Baseline clinical and angiographic parameters did not differ between the two treatment groups. The mean difference in coronary diameter between postangioplasty and follow-up angiogram (primary end point) was -0.31 +/- 0.54 mm in the control group and -0.31 +/- 0.55 mm in the GR32191B group. Clinical events during 6-month follow-up, analyzed on intention-to-treat basis, were ranked according to the highest category on a scale ranging from death (control, six; GR32191B, four) to nonfatal infarction (control, 22; GR32191B, 18), bypass grafting (control, 19; GR32191B, 22) and repeat angioplasty (control, 52; GR32191B, 48). No significant difference in ranking was detected. Six months after angioplasty, 75% of patients in the GR32191B group and 72% of patients in the control group were symptom free. CONCLUSIONS. Long-term thromboxane A2-receptor blockade with GR32191B does not prevent restenosis and does not favorably influence the clinical course after angioplasty. http://repub.eur.nl/res/pub/4138/ 1985-01-01T00:00:00Z Of 652 consecutive patients referred for coronary angioplasty between September 1980 and March 1984, 49 patients presented with total or functional 'occlusion' of the involved vessel. Total vessel occlusion was defined as absent anterograde filling beyond the lesion. Functional occlusion was defined as faint, late anterograde opacification of the distal segment in the absence of a discernible luminal continuity. In 39 patients, the total or functional occlusion represented a progression, without acute myocardial infarction, of a previously diagnosed stenotic lesion. The maximal potential duration of occlusion was estimated to be 4 weeks or less in 21 patients, more than 4 to 8 weeks in 12, and more than 8 weeks in 16. Dilation of the occluded artery was attempted in the left anterior descending coronary artery in 30 patients, in the right coronary artery in 8, in the circumflex coronary in 7 and in 4 jumpgrafts. For the whole group, angioplasty was successful in 28 patients (57%). The primary success rate with the functionally occluded vessel (81%) was significantly higher than with the total occlusion (45%). In 33 patients with an occlusion estimated to be of 8 weeks or less, angioplasty was successful in 65%. In the 16 patients with an occlusion estimated to be of 8 weeks or less, angioplasty was successful in 65%. In the 16 patients with an occlusion estimated to be of more than 8 weeks duration, dilation was successful in 44%. Of the 21 patients in whom angioplasty was unsuccessful, 11 required surgery (1 urgent with persistent pain and ST elevation and 10 elective). Ten patients were maintained on medical treatment. Of the 28 patients in whom angioplasty was successful, 10 patients had recurrence of symptoms during follow-up (1-42 months). Four were kept on medical therapy, three required bypass surgery and three underwent repeat percutaneous transluminal coronary angioplasty (PTCA). After primary success, late angiographic studies obtained in 20 out of 28 patients showed reocclusion in 8. In conclusion, elective PTCA of totally occluded coronary arteries is feasible but the primary success rate is lower (57%) than that associated with conventional lesions. The long-term clinical results following successful angioplasty are satisfactory (64%), but the incidence of reocclusion is higher (40%).