Long-term outcome of percutaneous catheter intervention for de novo coronary bifurcation lesions with drug-eluting stents or bare-metal stents.

BACKGROUND: The purpose of this study was to assess the long-term risks and benefits of drug-eluting stents (DESs) compared with bare-metal stents (BMSs) for treatment of coronary bifurcation lesions. METHODS: Our registry comprised 1,038 patients treated for coronary bifurcation lesion according to the provisional T-stenting strategy who were followed up for 3 years. RESULTS: Target lesion revascularization rates were 24.3% for BMSs (n = 337), 15.6% for sirolimus-eluting stents (SESs, n = 422), and 17.3% for paclitaxel-eluting stents (PESs, n = 279) (P = .003 BMSs vs DESs, P = .54 SESs vs PESs). The respective incidences were 11.4%, 9.5%, and 14.8% (P = .65, P = .13) for death and myocardial infarction and 9.9%, 6.5%, and 10.6% (P = .72, P = .19) for death. Propensity score adjusted hazard ratios (95% CI) for DESs versus BMSs were 0.49 (0.35-0.68, P < .001) for target lesion revascularization, 0.94 (0.64-1.40, P = .078) for death and myocardial infarction, and 0.85 (0.55-1.32, P = .47) for death. We did not find any significant differences between SESs and PESs, except for an increased risk of death after PESs compared with SESs (but not BMSs) in the subgroup receiving a side-branch stent (adjusted hazard ratio 2.45, 95% CI 1.05-5.73, P = .035). CONCLUSIONS: Compared with BMSs, both PESs and SESs substantially reduced the long-term need for repeated revascularization but did not increase the risk of death and myocardial infarction.

Variation in the human soluble epoxide hydrolase gene and risk of restenosis after percutaneous coronary intervention.

BACKGROUND: Restenosis represents the major limiting factor for the long-term efficacy of percutaneous coronary intervention (PCI). Several genetic factors involved in the regulation of the vascular system have been described to play a role in the pathogenesis of restenosis. We investigated whether the EPHX2 K55R polymorphism, previously linked to significantly higher risk for coronary heart disease (CHD), was associated with the occurrence of restenosis after PCI. The association with incident CHD should have been confirmed and a potential correlation of the EPHX2 K55R variant to an increased risk of hypertension was analysed. METHODS: An overall cohort of 706 patients was studied: This cohort comprised of 435 CHD patients who had undergone successful PCI. Follow-up coronary angiography in all patients was performed 6 months after intervention. Another 271 patients in whom CHD had been excluded by coronary angiography served as controls. From each patient EDTA-blood was drawn at the baseline ward round. Genomic DNA was extracted from these samples and genotyping was performed by real-time PCR and subsequent melting curve analysis. RESULTS: In CHD patients 6 month follow-up coronary angiography revealed a restenosis rate of 29.4%, classified as late lumen loss as well as lumen re-narrowing >or= 50%.Statistical analysis showed an equal genotype distribution in restenosis patients and non-restenosis patients (A/A 82.0% and A/G + G/G 18.0% versus A/A 82.1% and A/G + G/G 17.9%). Moreover, neither a significant difference in the genotype distribution of CHD patients and controls nor an association with increased risk of hypertension was found. CONCLUSION: The results of the present study indicate that the EPHX2 K55R polymorphism is not associated with restenosis after PCI, with incidence of CHD, or with an increased risk of hypertension and therefore, can not serve as a predictor for risk of CHD or restenosis after PCI.

Randomized trial on routine vs. provisional T-stenting in the treatment of de novo coronary bifurcation lesions.

AIMS: We investigated whether routine T-stenting reduces restenosis of the side branch as compared with provisional T-stenting in patients with de novo coronary bifurcation lesions. METHODS AND RESULTS: Our randomized study assigned 101 patients with a coronary bifurcation lesion to routine T-stenting with sirolimus-eluting stents (SES) in both branches and 101 patients to provisional T-stenting with SES placement in the main branch followed by kissing-balloon angioplasty and provisional SES placement in the side branch only for inadequate results. Primary endpoint was per cent diameter stenosis of the side branch at 9 month angiographic follow-up. Angiographic follow-up in 192 (95%) patients revealed a per cent stenosis of the side branch of 23.0 +/- 20.2% after provisional T-stenting (19% with side-branch stent) and of 27.7 +/- 24.8% (P = 0.15) after routine T-stenting (98.2% with side-branch stent). The corresponding binary restenosis rates were 9.4 and 12.5% (P = 0.32), prompting re-intervention in 5.0 and 7.9% (P = 0.39), respectively. In the main branch, binary restenosis rates were 7.3% after provisional and 3.1% after routine T-stenting (P = 0.17). The overall 1 year incidence of target lesion re-intervention was 10.9% after provisional and 8.9% after routine T-stenting (P = 0.64). CONCLUSIONS: Routine T-stenting with SES did not improve the angiographic outcome of percutaneous coronary intervention of coronary bifurcation lesions as compared with stenting of the main branch followed by kissing-balloon angioplasty and provisional side-branch stenting.

Impact of cytochrome P450 3A4-metabolized statins on the antiplatelet effect of a 600-mg loading dose clopidogrel and on clinical outcome in patients undergoing elective coronary stent placement.

Early studies suggested interactions between statins and clopidogrel. Based on the outcome and platelet data, there is now huge evidence of no interactions between statins and 75 to 300 mg clopidogrel; however, data with 600-mg loading are lacking. In a pre-specified analysis of the EXCELSIOR cohort, we investigated the interaction between statins, especially cytochrome P4503A4-metabolized atorvastatin and simvastatin, and the antiplatelet effects of a 600-mg loading dose of clopidogrel. We analyzed 1,395 patients scheduled for coronary angiography (CA). Patients received clopidogrel 600 mg at least two hours before CA and 75 mg daily thereafter in case of percutaneous coronary intervention (PCI). Statin medication on admission was continued unaltered until discharge. Platelet function was assessed by optical aggregometry and flow cytometry of adenosine diphosphate (ADP)-stimulated surface expression of CD62P, CD63 and PAC-1 before clopidogrel and immediately before CA. Residual platelet aggregation (RPA) after addition of ADP 5 muM was similar irrespective of statin treatment at baseline (p = 0.968). RPA at CA was 46.2 +/- 16.8% in patients without statin (n = 682), 45.5 +/- 17.0% in patients with atorvastatin (n = 255), 45.8 +/- 16.3% with simvastatin (n = 335), 47.3 +/- 14.9% with fluvastatin (n = 42) and 45.9 +/- 16.2% with pravastatin (n = 81; p = 0.962). Consistent results were obtained by flow cytometry. In patients with PCI (n = 553), the one-year incidence of death, myocardial infarction and target lesion reintervention did not differ between cohorts stratified according to statin co-medication (p = 0.645). Thus, peri-interventional atorvastatin and simvastatin had no effect on the antiplatelet activity of a loading dose of clopidogrel 600 mg and did not affect clinical outcome after PCI.

Time dependence of platelet inhibition after a 600-mg loading dose of clopidogrel in a large, unselected cohort of candidates for percutaneous coronary intervention.

BACKGROUND: Pretreatment with clopidogrel can reduce the risks associated with percutaneous coronary intervention (PCI). To shorten the time for clopidogrel to become effective, a 600-mg loading dose has been used. We sought to validate this regimen in a large cohort and investigated the time dependence of the antiplatelet effect of 600 mg of clopidogrel. METHODS AND RESULTS: Our study included 1001 patients who were scheduled for cardiac catheterization as potential candidates for PCI. We obtained blood samples before administration of 600 mg of clopidogrel and at the time of catheterization, which varied according to logistic needs. We assessed platelet aggregation by optical aggregometry and surface expression of P-selectin and activated glycoprotein IIb/IIIa by flow cytometry. Platelet aggregation induced by 5 micromol/L ADP was 51+/-14% when catheterization was performed at <1 hour, 41+/-14% at 1 to <2 hours, 37+/-15% at 2 to <4 hours, 36+/-13% at 4 to <6 hours, and 35+/-14% at > or =6 hours after clopidogrel administration. After 2 hours (n=718), the level of platelet aggregation and the surface expression of P-selectin and activated glycoprotein IIb/IIIa did not change significantly with time after clopidogrel (P>0.24 by univariate or multivariate regression). Comedication with CYP3A4 metabolized statins did not significantly affect platelet aggregation after clopidogrel (P=0.62). Among the 428 patients undergoing PCI, the 30-day composite rate of major adverse cardiac events was 1.9%, with no significant difference between patients undergoing PCI within 2 hours after clopidogrel loading and those undergoing PCI at a later time point. CONCLUSIONS: After loading with 600 mg of clopidogrel, the full antiplatelet effect of the drug is achieved after 2 hours. Statins do not interfere with the level of platelet inhibition after this dose.

Randomized evaluation of the effects of filter-based distal protection on myocardial perfusion and infarct size after primary percutaneous catheter intervention in myocardial infarction with and without ST-segment elevation.

BACKGROUND: In acute myocardial infarction, distal embolization of debris during primary percutaneous catheter intervention may curtail microvascular reperfusion of the infarct region. Our randomized trial investigated whether distal protection with a filter device can improve microvascular perfusion and reduce infarct size after primary percutaneous catheter intervention. METHODS AND RESULTS: We enrolled 200 patients who had angina within 48 hours after onset of pain plus at least 1 of 3 additional criteria: ST-segment elevation, elevated myocardial marker proteins, and angiographic evidence of thrombotic occlusion. Among the patients included (83% men; mean age, 62+/-12 years), 100 were randomly assigned to the filter-wire group and 100 to the control group. The primary end point was the maximal adenosine-induced Doppler flow velocity in the recanalized infarct artery; the secondary end point was infarct size estimated by the volume of delayed enhancement on nuclear MRI. ST-segment elevation myocardial infarction was present in 68.5% of the patients; the median time from onset of pain was 6.9 hours. In the filter-wire group, maximal adenosine-induced flow velocity was 34+/-17 compared with 36+/-20 cm/s in the control group (P=0.46). Infarct sizes, assessed in 82 patients in the filter-wire group and 78 patients in the control group, were 11.8+/-9.3% of the left ventricular mass in the filter-wire group and 10.4+/-9.4% in the control group (P=0.33). Thirty-day mortality was 2% in filter-wire group and 3% in the control group. CONCLUSIONS: The filter wire as an adjunct to primary percutaneous catheter intervention in myocardial infarction with and without ST-segment elevation did not improve reperfusion or reduce infarct size.

Predictors of improved renal function after percutaneous stent-supported angioplasty of severe atherosclerotic ostial renal artery stenosis.

BACKGROUND: Percutaneous stent-supported angioplasty is a treatment option for atherosclerotic ostial renal artery stenosis. Improvement of renal function by such intervention, however, is controversial and thought to be limited to specific subsets, such as nondiabetic patients and bilateral stenoses. In this prospective study, we investigated predictors for improvement of renal function and blood pressure after renal artery stent placement. METHODS AND RESULTS: The study included 215 consecutive patients with ostial renal artery stenosis of > or =70% diameter stenosis undergoing stent-supported angioplasty. The primary end point was decrease in serum creatinine concentration at 1 year; the secondary end point, decrease in average mean arterial blood pressure assessed by 24-hour monitoring. One-year follow-up was complete in 191 surviving patients. In 52% (99/191) of the patients, serum creatinine concentration decreased during 1-year follow-up. Median serum creatinine concentration dropped significantly from 1.21 mg/dL (quartiles: 0.92, 1.60 mg/dL) at baseline to 1.10 mg/dL (quartiles: 0.88, 1.50 mg/dL) at 1 year (P=0.047). On average, mean arterial blood pressure decreased significantly, from 102+/-12 mm Hg (mean+/-SD) at baseline to 92+/-10 mm Hg at 1 year (P<0.001). Significant independent predictors of improved renal function were baseline serum creatinine (odds ratio [95% CI], 2.58 [1.35 to 4.94], P=0.004) and left ventricular function (OR 1.51 [1.04 to 2.21], P=0.032). Female sex, high baseline mean blood pressure, and normal renal parenchymal thickness were independent predictors for decreased mean blood pressure. CONCLUSIONS: Stent-supported angioplasty for severe ostial renal artery stenosis improves renal function and blood pressure in a broader spectrum of patients than previously thought.

Evaluation of the effect of oral verapamil on clinical outcome and angiographic restenosis after percutaneous coronary intervention: the randomized, double-blind, placebo-controlled, multicenter Verapamil Slow-Release for Prevention of Cardiovascular Events After Angioplasty (VESPA) Trial.

OBJECTIVES: We investigated the effect of oral verapamil on clinical outcome and angiographic restenosis after percutaneous coronary intervention (PCI). BACKGROUND: Thus far, there is no established systemic pharmacologic approach for the prevention of restenosis after PCIs. Five small studies reported encouraging results for calcium channel blockers. METHODS: Our randomized double-blind trial included 700 consecutive patients with successful PCI of a native coronary artery. Patients received the calcium channel blocker verapamil, 240 mg twice daily for six months, or placebo. Primary clinical end point was the composite rate of death, myocardial infarction, and target vessel revascularization (TVR) during one-year follow-up; the angiographic end point was late lumen loss at the six-month follow-up angiography. RESULTS: We obtained complete clinical follow-up in 95% of the patients, and scheduled angiography was performed in 94%. The proportion of patients treated with stents was 83%. The primary clinical end point was reached in 67 (19.3%) patients on verapamil and in 103 (29.3%) patients on placebo (relative risk [RR] 0.66 [95% confidence interval (CI) 0.48 to 0.89]; p = 0.002). This difference between the groups was driven by TVR (17.5% with verapamil vs. 26.2% with placebo; RR 0.67 [95% CI 0.49 to 0.93]; p = 0.006). Late lumen loss was 0.74 +/- 0.70 mm with verapamil and 0.81 +/- 0.75 mm with placebo (p = 0.11). Compared with placebo, verapamil reduced the rate of restenosis > or =75% (7.8% vs. 13.7%; RR 0.57 [95% CI 0.35 to 0.92]; p = 0.014). CONCLUSIONS: Verapamil compared with placebo improves long-term clinical outcome after PCI of native coronary arteries by reducing the need for TVR. This was caused by a reduction in the rate of high-grade restenosis.

Operator experience and long term outcome after percutaneous coronary intervention.

OBJECTIVES: To investigate the impact of operator experience on long term outcome of patients undergoing percutaneous coronary intervention (PCI). METHODS: Two hundred and fifty consecutive patients with 334 lesions undergoing elective PCI by three highly experienced (greater than 600 PCI, mean 1100) and three less experienced (fewer than 400 PCI, mean 250) high volume operators at a single tertiary care centre were prospectively studied. Quantitative assessment of the six-month angiography was possible in 273 lesions (82%). Clinical follow-up at 24 months was complete in all patients. RESULTS: Baseline characteristics of the 159 lesions treated by the highly experienced operators were comparable with the 175 lesions treated by the less experienced operators. Six months following PCI, the minimal lumen diameter at the lesion site was similar for both more experienced and less experienced operators (1.68+/-0.95 mm versus 1.63+/-0.89 mm, P=0.66), as was net lumen gain (0.97+/-1.02 mm versus 0.98+/-0.93 mm, P=0.96) and the rate of restenosis (33% versus 32%, P=0.87). By multivariate analysis, lower operator experience was not a predictor of restenosis (odds ratio 0.97, 95% CI 0.75 to 1.25, P=0.81). In addition, 24-month clinical follow-up did not reveal any relevant difference in the combined end point of death, myocardial infarction or clinically driven revascularization between more experienced (29 events in 116 patients) and less experienced operators (35 events in 134 patients; 25% versus 26%, P=0.84). CONCLUSIONS: Less experienced high volume operators seem to achieve similar long term results as more experienced high volume operators.

Evaluation of prolonged antithrombotic pretreatment ("cooling-off" strategy) before intervention in patients with unstable coronary syndromes: a randomized controlled trial.

CONTEXT: In unstable coronary syndromes, catheter intervention is frequently preceded by antithrombotic treatment to reduce periprocedural risk; however, evidence from clinical trials to support antithrombotic pretreatment is sparse. OBJECTIVE: To test the hypothesis that prolonged antithrombotic pretreatment improves the outcome of catheter intervention in patients with acute unstable coronary syndromes compared with early intervention. DESIGN, SETTING, AND PATIENTS: Randomized controlled trial conducted from February 27, 2000, to April 8, 2002, and including patients admitted to 2 German tertiary care centers with symptoms of unstable angina plus either ST-segment depression or elevation of cardiac troponin T levels. INTERVENTIONS: Patients were randomly allocated to antithrombotic pretreatment for 3 to 5 days or to early intervention after pretreatment for less than 6 hours. In both groups, antithrombotic pretreatment consisted of intravenous unfractionated heparin (60-U/kg bolus followed by infusion adjusted to maintain partial thromboplastin time of 60 to 85 seconds), aspirin (500-mg intravenous bolus followed by 100-mg twice-daily oral dose), oral clopidogrel (600-mg loading dose followed by 75-mg twice-daily dose), and intravenous tirofiban (10- microg/kg bolus followed by continuous infusion of 0.10 microg/kg per min). MAIN OUTCOME MEASURE: Composite 30-day incidence of large nonfatal myocardial infarction or death from any cause. RESULTS: Of the 410 patients enrolled, 207 were allocated to receive prolonged antithrombotic pretreatment and 203 to receive early intervention. Elevated levels of cardiac troponin T were present in 274 patients (67%), while 268 (65%) had ST-segment depression. The antithrombotic pretreatment and the early intervention groups were well matched with respect to major baseline characteristics and definitive treatment (catheter revascularization: 133 [64.3%] vs 143 [70.4%], respectively; coronary artery bypass graft surgery: 16 [7.7%] vs 16 [7.9%]). The primary end point was reached in 11.6% (3 deaths, 21 infarctions) of the group receiving prolonged antithrombotic pretreatment and in 5.9% (no deaths, 12 infarctions) of the group receiving early intervention (relative risk, 1.96 [95% confidence interval, 1.01-3.82]; P =.04). This outcome was attributable to events occurring before catheterization; after catheterization, both groups incurred 11 events each (P =.92). CONCLUSION: In patients with unstable coronary syndromes, deferral of intervention for prolonged antithrombotic pretreatment does not improve the outcome compared with immediate intervention accompanied by intense antiplatelet treatment.