Meier, B.

The Impact of Body Mass Index on the One Year Outcomes of Patients Treated by Percutaneous Coronary Intervention With Biolimus- and Sirolimus-Eluting Stents (from the LEADERS Trial) (Article)

2010-02-15T00:00:00Z

The aim of this analysis was to assess the effect of body mass index (BMI) on 1-year outcomes in patients enrolled in a contemporary percutaneous coronary intervention trial comparing a sirolimus-eluting stent with a durable polymer to a biolimus-eluting stent with a biodegradable polymer. A total of 1,707 patients who underwent percutaneous coronary intervention were randomized to treatment with either biolimus-eluting stents (n = 857) or sirolimus-eluting stents (n = 850). Patients were assigned to 1 of 3 groups according to BMI: normal (<25 kg/m(2)), overweight (25 to 30 kg/m(2)), or obese (>30 kg/m(2)). At 1 year, the incidence of the composite of cardiac death, myocardial infarction, and clinically justified target vessel revascularization was assessed. In addition, rates of clinically justified target lesion revascularization and stent thrombosis were assessed. Cox proportional-hazards analysis, adjusted for clinical differences, was used to develop models for 1-year mortality. Forty-five percent of the patients (n = 770) were overweight, 26% (n = 434) were obese, and 29% (n = 497) had normal BMIs. At 1-year follow-up, the cumulative rate of cardiac death, myocardial infarction, and clinically justified target vessel revascularization was significantly higher in the obese group (8.7% in normal-weight, 11.3% in overweight, and 14.5% in obese patients, p = 0.01). BMI (hazard ratio 1.47, 95% confidence interval 1.02 to 2.14, p = 0.04) was an independent predictor of stent thrombosis. Stent type had no impact on the composite of cardiac death, myocardial infarction, and clinically justified target vessel revascularization at 1 year in the 3 BMI groups (hazard ratio 1.08, 95% confidence interval 0.63 to 1.83, p = 0.73). In conclusion, BMI was an independent predictor of major adverse cardiac events at 1-year clinical follow-up. The higher incidence of stent thrombosis in the obese group may suggest the need for a weight-adjusted dose of clopidogrel.

Incidence and Correlates of Drug-Eluting Stent Thrombosis in Routine Clinical Practice. 4-Year Results From a Large 2-Institutional Cohort Study (Article)

2008-09-30T00:00:00Z

Objectives: We sought to determine the risk of late stent thrombosis (ST) during long-term follow-up beyond 3 years, searched for predictors, and assessed the impact of ST on overall mortality. Background: Late ST was reported to occur at an annual rate of 0.6% up to 3 years after drug-eluting stent (DES) implantation. Methods: A total of 8,146 patients underwent percutaneous coronary intervention with a sirolimus-eluting stent (SES) (n = 3,823) or paclitaxel-eluting stent (PES) (n = 4,323) and were followed up to 4 years after stent implantation. Dual antiplatelet treatment was prescribed for 6 to 12 months. Results: Definite ST occurred in 192 of 8,146 patients with an incidence density of 1.0/100 patient-years and a cumulative incidence of 3.3% at 4 years. The hazard of ST continued at a steady rate of 0.53% (95% confidence interval [CI]: 0.44 to 0.64) between 30 days and 4 years. Diabetes was an independent predictor of early ST (hazard ratio [HR]: 1.96; 95% CI: 1.18 to 3.28), and acute coronary syndrome (HR: 2.21; 95% CI: 1.39 to 3.51), younger age (HR: 0.97; 95% CI: 0.95 to 0.99), and use of PES (HR: 1.67; 95% CI: 1.08 to 2.56) were independent predictors of late ST. Rates of death and myocardial infarction at 4 years were 10.6% and 4.6%, respectively. Conclusions: Late ST occurs steadily at an annual rate of 0.4% to 0.6% for up to 4 years. Diabetes is an independent predictor of early ST, whereas acute coronary syndrome, younger age, and PES implantation are associated with late ST.

Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial (Article)

2008-09-01T00:00:00Z

Background: A novel stent platform eluting biolimus, a sirolimus analogue, from a biodegradable polymer showed promising results in preliminary studies. We compared the safety and efficacy of a biolimus-eluting stent (with biodegradable polymer) with a sirolimus-eluting stent (with durable polymer). Methods: We undertook a multicentre, assessor-blind, non-inferiority study in ten European centres. 1707 patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes were centrally randomised by a computer-generated allocation sequence to treatment with either biolimus-eluting (n=857) or sirolimus-eluting (n=850) stents. The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation within 9 months. Analysis was by intention to treat. 427 patients were randomly allocated to angiographic follow-up, with in-stent percentage diameter stenosis as principal outcome measure at 9 months. The trial is registered with ClinicalTrials.gov, number NCT00389220. Findings: We analysed all randomised patients. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents for the primary endpoint at 9 months (79 [9%] patients vs 89 [11%], rate ratio 0·88 [95% CI 0·64-1·19], p for non-inferiority=0·003, p for superiority=0·39). Frequency of cardiac death (14 [1·6%] vs 21 [2·5%], p for superiority=0·22), myocardial infarction (49 [5·7%] vs 39 [4·6%], p=0·30), and clinically-indicated target vessel revascularisation (38 [4·4%] vs 47 [5·5%], p=0·29) were similar for both stent types. 168 (79%) patients in the biolimus-eluting group and 167 (78%) in the sirolimus-eluting group had data for angiographic follow-up available. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents in in-stent percentage diameter stenosis (20·9% vs 23·3%, difference -2·2% [95% CI -6·0 to 1·6], p for non-inferiority=0·001, p for superiority=0·26). Interpretation: Our results suggest that a stent eluting biolimus from a biodegradable polymer represents a safe and effective alternative to a stent eluting sirolimus from a durable polymer in patients with chronic stable coronary artery disease or acute coronary syndromes. Funding: Biosensors Europe SA, Switzerland.

Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study (Article)

2007-02-24T00:00:00Z

Background: Stent thrombosis is a safety concern associated with use of drug-eluting stents. Little is known about occurrence of stent thrombosis more than 1 year after implantation of such stents. Methods: Between April, 2002, and Dec, 2005, 8146 patients underwent percutaneous coronary intervention with sirolimus-eluting stents (SES; n=3823) or paclitaxel-eluting stents (PES; n=4323) at two academic hospitals. We assessed data from this group to ascertain the incidence, time course, and correlates of stent thrombosis, and the differences between early (0-30 days) and late (>30 days) stent thrombosis and between SES and PES. Findings: Angiographically documented stent thrombosis occurred in 152 patients (incidence density 1·3 per 100 person-years; cumulative incidence at 3 years 2·9%). Early stent thrombosis was noted in 91 (60%) patients, and late stent thrombosis in 61 (40%) patients. Late stent thrombosis occurred steadily at a constant rate of 0·6% per year up to 3 years after stent implantation. Incidence of early stent thrombosis was similar for SES (1·1%) and PES (1·3%), but late stent thrombosis was more frequent with PES (1·8%) than with SES (1·4%; p=0·031). At the time of stent thrombosis, dual antiplatelet therapy was being taken by 87% (early) and 23% (late) of patients (p<0·0001). Independent predictors of overall stent thrombosis were acute coronary syndrome at presentation (hazard ratio 2·28, 95% CI 1·29-4·03) and diabetes (2·03, 1·07-3·83). Interpretation: Late stent thrombosis was encountered steadily with no evidence of diminution up to 3 years of follow-up. Early and late stent thrombosis were observed with SES and with PES. Acute coronary syndrome at presentation and diabetes were independent predictors of stent thrombosis.

Clinical and angiographic outcome of patients with mild coronary lesions treated with balloon angioplasty or coronary stenting. Implications for mechanical plaque sealing (Article)

2003-03-01T00:00:00Z

AIMS: To investigate the clinical and angiographic outcome of patients with mild coronary lesions treated with balloon angioplasty or coronary stenting (coronary plaque sealing, i.e. dilatation of angiographically non-significant lesions) compared to moderate and severe stenoses. METHODS AND RESULTS: Patients with chronic stable angina and a single de novo lesion in a native coronary vessel scheduled to undergo percutaneous coronary intervention (PCI) were selected from 14 different studies. Off-line analysis of angiographic outcomes was assessed in all patients using identical and standardised methods of data acquisition, analysis and definitions. Clinical endpoints were adjudicated by independent clinical events committees. All quantitative coronary angiographic (QCA) analyses were performed in the same core laboratory. Stenosis severity prior to PCI was categorised into three groups: <50% diameter stenosis (DS), 50-99%DS and >99%DS pre. A total of 3812 patients were included in this study; 1484 patients (39%) were successfully treated with balloon angioplasty (BA) only and stented angioplasty was performed in 2328 patients (61%).One-year mortality and rate of non-fatal myocardial infarction (MI) (Kaplan-Meier) did not differ between BA and stented angioplasty for any of the stenosis severity categories. Following BA, the combined event rate (death and non-fatal MI) was 4.8, 4.6 and 0% in the <50, 50-99 and >99%DS categories, respectively. Following stented angioplasty, the combined event rate was 3.1, 4.4 and 4.8% in the same categories. The need for repeat revascularisation corrected for stenosis severity in the Cox proportional-hazards regression model was reduced by 20% after stented angioplasty (hazard ratio (HR) 0.80, 95%CI 0.69-0.93). CONCLUSION: The concept of plaque sealing is appealing from the theoretical point of view. However, with current technology, plaque sealing cannot prevent death and future non-fatal MIs in the long-term because 1-year event rates after PCI of non-significant stenoses remain unacceptably elevated when compared with the estimated 1-year probability of a non-fatal MI in lesions with a <50%DS. Moreover, major adverse cardiac events at 1-year after PCI are not directly related to the degree of pre-procedural stenosis severity.

Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial (Article)

2002-01-01T00:00:00Z

CONTEXT: Percutaneous coronary intervention (PCI) is associated with excellent short-term improvements in ischemic symptoms, yet only three fifths of PCI patients at 5 years and one third of patients at 10 years remain free of major adverse cardiac events (MACE). OBJECTIVE: To determine whether treatment with fluvastatin reduces MACE in patients who have undergone PCI. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial conducted at 77 referral centers in Europe, Canada, and Brazil. PATIENTS: A total of 1677 patients (aged 18-80 years) recruited between April 1996 and October 1998 with stable or unstable angina or silent ischemia following successful completion of their first PCI who had baseline total cholesterol levels between 135 and 270 mg/dL (3.5-7.0 mmol/L), with fasting triglyceride levels of less than 400 mg/dL (4.5 mmol/L). INTERVENTIONS: Patients were randomly assigned to receive treatment with fluvastatin, 80 mg/d (n = 844), or matching placebo (n = 833) at hospital discharge for 3 to 4 years. MAIN OUTCOME MEASURE: Survival time free of MACE, defined as cardiac death, nonfatal myocardial infarction, or reintervention procedure, compared between the treatment and placebo groups. RESULTS: Median time between PCI and first dose of study medication was 2.0 days, and median follow-up was 3.9 years. MACE-free survival time was significantly longer in the fluvastatin group (P =.01). One hundred eighty-one (21.4%) of 844 patients in the fluvastatin group and 222 (26.7%) of 833 patients in the placebo group had at least 1 MACE (relative risk [RR], 0.78; 95% confidence interval [CI], 0.64-0.95; P =.01). This result was independent of baseline total cholesterol levels (above [RR, 0.76; 95% CI, 0.56-1.04] vs below [RR, 0.77; 95% CI, 0.57-1.02] the median). In subgroup analysis, the risk of MACE was reduced in patients with diabetes (n = 202; RR, 0.53; 95% CI, 0.29-0.97; P =.04) and in those with multivessel disease (n = 614; RR, 0.66; 95% CI, 0.48-0.91; P =.01) who received fluvastatin compared with those who received placebo. There were no instances of creatine phosphokinase elevations 10 or more times the upper limit of normal or rhabdomyolysis in the fluvastatin group. CONCLUSION: Fluvastatin treatment in patients with average cholesterol levels undergoing their first successful PCI significantly reduces the risk of major adverse cardiac events.

Total occlusion trial with angioplasty by using laser guidewire. The TOTAL trial. (Article)

2000-01-01T00:00:00Z

AIMS: A randomized trial was performed to assess the safety and efficacy of a laser guidewire, in the treatment of chronic coronary occlusions. METHODS AND RESULTS: In 18 European centres, 303 patients with a chronic coronary occlusion were randomized to treatment with either the laser guidewire (n=144) or conventional guidewires (mechanical guidewire, n=159). The primary end-point of the study was treatment success, defined as reaching the true lumen distal to the occlusion by the allocated wire within 30 min of fluoroscopic time: laser guidewire vs mechanical guidewire; 52.8% (n=76) vs 47.2% (n=75), P=0.33. Serious adverse events following the initial guidewire attempt were 0% (laser guidewire) and 0.6% (mechanical guidewire), respectively. Angioplasty (performed following successful guidewire crossing) was successful in 179 patients (91%, laser guidewire n=79, mechanical guidewire n=100), followed by stent implantation in 149 (79%). At the 6-month angiographic follow-up, the difference in binary restenosis rate (laser guidewire vs mechanical guidewire; 45.5% vs 38.3 %, P=0.72) or reocclusion rate (25.8% vs 16.1%, P=0.15) did not reach statistical significance. At 1, 6 and 12 months, angina and event-free survival were 69%, 35% and 24% (laser guidewire) vs 74%, 40% and 31% (mechanical guidewire). CONCLUSION: Although laser guidewire technology was safe, the increase in crossing success did not reach statistical significance.

Quantitative angiographic follow-up of the coronary wallstent in native vessels and bypass grafts (European experience - March 1986 to March 1990) (Article)

1992-01-01T00:00:00Z

The coronary stent has been investigated as an adjunct to percutaneous transluminal coronary angioplasty to obviate the problems of early occlusion and late restenosis. From March 1986 to March 1990, 265 patients (308 lesions) were implanted with the coronary Wallstent in 6 European centers. For this study, the patients were analyzed according to date of implantation (group 1, March 1986 to January 1988; group 2, February 1988 to March 1990) and vessel type (native arteries versus bypass grafts). Quantitative angiographic follow-up was performed in 82% of the study patients. The early in-hospital occlusion rate in the overall group was 15%. Group 1 patients had a 20% rate in contrast to 12% rate in group 2 (p = not significant [NS]). The early occlusion rate in native vessels and bypass grafts was 19 and 8%, respectively (p = 0.019). Restenosis was determined by 2 criteria (criterion 1, greater than or equal to 0.72 mm loss in minimal luminal diameter from poststent to follow-up; criterion 2, greater than or equal to 50% diameter stenosis at follow-up) within the stent and in the segments immediately proximal and distal to the stent. The restenosis rate with criterion 1 was 43% in the overall group of patients, 35% in group 1 versus 49% in group 2 (p = NS), and 34% in native vessels versus 54% in bypass grafts (p = 0.016). The second criterion was met by 27% of patients in the overall group, 21% in group 1 versus 32% in group 2 (p = NS), and 18% in native vessel versus 39% in bypass grafts (p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiographic follow-up after placement of a self-expanding coronary artery stent (Article)

1991-01-01T00:00:00Z

BACKGROUND. The placement of stents in coronary arteries after coronary angioplasty has been investigated as a way of treating abrupt coronary-artery occlusion related to the angioplasty and of reducing the late intimal hyperplasia responsible for gradual restenosis of the dilated lesion. METHODS. From March 1986 to January 1988, we implanted 117 self-expanding, stainless-steel endovascular stents (Wallstent) in the native coronary arteries (94 stents) or saphenous-vein bypass grafts (23 stents) of 105 patients. Angiograms were obtained immediately before and after placement of the stent and at follow-up at least one month later (unless symptoms required angiography sooner). The mortality after one year was 7.6 percent (8 patients). Follow-up angiograms (after a mean [+/- SD] of 5.7 +/- 4.4 months) were obtained in 95 patients with 105 stents and were analyzed quantitatively by a computer-assisted system of cardiovascular angiographic analysis. The 10 patients without follow-up angiograms included 4 who died. RESULTS. Complete occlusion occurred in 27 stents in 25 patients (24 percent); 21 occlusions were documented within the first 14 days after implantation. Overall, immediately after placement of the stent there was a significant increase in the minimal luminal diameter and a significant decrease in the percentage of the diameter with stenosis (changing from a mean [+/- SD] of 1.88 +/- 0.43 to 2.48 +/- 0.51 mm and from 37 +/- 12 to 21 +/- 10 percent, respectively; P less than 0.0001). Later, however, there was a significant decrease in the minimal luminal diameter and a significant increase in the stenosis of the segment with the stent (1.68 +/- 1.78 mm and 48 +/- 34 percent at follow-up). Significant restenosis, as indicated by a reduction of 0.72 mm in the minimal luminal diameter or by an increase in the percentage of stenosis to greater than or equal to 50 percent, occurred in 32 percent and 14 percent of patent stents, respectively. CONCLUSIONS. Early occlusion remains an important limitation of this coronary-artery stent. Even when the early effects are beneficial, there are frequently late occlusions or restenosis. The place of this form of treatment for coronary artery disease remains to be determined.

Relative risk analysis of angiographic predictors of restenosis within the coronary Wallstent (Article)

1991-01-01T00:00:00Z

BACKGROUND. Late angiographic narrowing has been observed following coronary implantation of the Wallstent. To identify the angiographic variables that predict restenosis within the stented segment, a retrospective study of data from the European Wallstent core laboratory was performed. METHODS AND RESULTS. Follow-up angiograms (excluding patients with in-hospital occlusions) were analyzed for 214 lesions in 176 patients (78% restudy rate). The incidence of restenosis within the stented segment was 35% by lesion and 35% by patient for criterion 1 (greater than or equal to 0.72 mm loss in minimal luminal diameter) and 24% by lesion and 24% by patient for criterion 2 (diameter stenosis greater than or equal to 50% at follow-up). The association between 16 variables and restenosis was determined by a relative risk ratio assessment. Variables with significant risk ratios for restenosis with criterion 1 were use of multiple stents/lesion (relative risk, 1.56; 95% confidence interval [CI], 1.08-2.25) and oversized (unconstrained stent diameter exceeding reference diameter greater than 0.7 mm) stents (relative risk, 1.64; 95% CI, 1.10-2.45), and for criterion 2, oversizing by more than 0.70 mm (relative risk, 1.93; 95% CI, 1.13-3.31), bypass grafts (relative risk, 1.62; 95% CI, 0.98-2.66), use of multiple stents/lesion (relative risk, 1.61; 95% CI, 0.97-2.67) and residual diameter stenosis more than 20% post stenting (relative risk, 1.51; 95% CI, 0.91-2.50). CONCLUSIONS. It is concluded that several angiographic variables are significantly associated with late angiographic narrowing after stenting in the coronary arteries. We suggest that stent operators avoid excessive oversizing in the selection of stent diameter and the use of multiple stents per lesion to lessen the risk of late restenosis.

Assessment of the "long sheath" technique for percutaneous aortic balloon valvuloplasty (Article)

1990-01-01T00:00:00Z

A 100 cm-long 16.5 F valvuloplasty catheter introducer was assessed as an adjunct for percutaneous transluminal aortic valvuloplasty (PTAV) via the femoral artery in 31 patients with severe aortic stenosis. Observed improvements in peak systolic gradient (81.6 +/- 29.9 mm Hg vs. 35.5 +/- 16.0 mm Hg, P less than 0.000001) and aortic valve area (0.6 +/- 0.4 cm2 vs. 1.0 +/- 0.6 cm2, P less than 0.00001) were similar to those achieved in a control group (C) of 17 patients in which no femoral sheath was used. However, a shorter procedure duration (211 +/- 81 min vs. 117 +/- 30 min, P less than 0.001) and a reduced rate of vascular complications at the femoral puncture site (41% vs. 6.5%) were observed in patients in whom the long sheath (LS) technique was used. The frequency of other PTAV-related complications was comparable (C = 35%, LS = 29%, P = n.s.). Other technical advantages of this device are: 1) prevention of looping and bending of the balloon catheter in tortuous vessels and easy positioning of the balloon across the aortic orifice provided by the LS trackability, 2) stabilisation of the balloon during inflation, 3) monitoring of supravalvular aortic pressure provided by the side-arm of the LS and reliable measurement of systolic gradient, and 4) the ability to perform aortograms without the need of another catheter in the ascending aorta. Thus, in our experience, the long sheath technique is a valuable adjunct for PTAV.

Thrombolysis with tissue plasminogen activator in acute myocardial infarction: no additional benefit from immediate percutaneous coronary angioplasty (Article)

1988-01-30T00:00:00Z

A randomised trial of 367 patients with acute myocardial infarction was performed to determine whether an invasive strategy combining thrombolysis with recombinant tissue-type plasminogen activator (rTPA), heparin, and acetylsalicylic acid, and immediate percutaneous transluminal coronary angioplasty (PTCA) would be superior to a noninvasive strategy with the same medical treatment but without immediate angiography and PTCA. Intravenous infusion of 100 mg rTPA was started within 5 h after onset of symptoms (median 156 min). Angiography was performed 6-165 min later in 180 out of 183 patients allocated to the invasive strategy; 184 patients were allocated to the non-invasive strategy. Immediate PTCA reduced the percentage stenosis of the infarct-related segment, but this was offset by a high rate of transient (16%) and sustained (7%) reocclusion during the procedure and recurrent ischaemia during the first 24 h (17%). The clinical course was more favourable after non-invasive therapy, with a lower incidence of recurrent ischaemia within 24 h (3%), bleeding complications, hypotension, and ventricular fibrillation. Mortality at 14 days was lower in patients allocated to non-invasive treatment (3%) than in the group allocated to invasive treatment (7%). No difference between the treatment groups was observed in infarct size estimated from myocardial release of alpha-hydroxybutyrate dehydrogenase or in left ventricular ejection fraction after 10-22 days. Since immediate PTCA does not provide additional benefit there seems to be no need for immediate angiography and PTCA in patients with acute myocardial infarction treated with rTPA.

Thrombolysis with rt-PA in acute myocardial infarction: no additional benefit of immediate PTCA (Miscellaneous)

1988-01-30T00:00:00Z