Efficacy and safety of zotarolimus-eluting and sirolimus-eluting coronary stents in routine clinical care (SORT OUT III): a randomised controlled superiority trial.

BACKGROUND: In low-risk patients, the zotarolimus-eluting stent has been shown to reduce rates of restenosis without increasing the risk of stent thrombosis. We compared the efficacy and safety of the zotarolimus-eluting stent versus the sirolimus-eluting stent in patients with coronary artery disease who were receiving routine clinical care with no direct follow-up. METHODS: We did a single-blind, all-comer superiority trial in adult patients with chronic stable coronary artery disease or acute coronary syndromes, and at least one target lesion. Patients were treated at one of five percutaneous coronary intervention centres between January, 2006, and August, 2007. Computer-generated block randomisation and a telephone allocation service were used to randomly assign patients to receive the zotarolimus-eluting or the sirolimus-eluting stent. Data for follow-up were obtained from national Danish administrative and health-care registries. The primary endpoint was a composite of major adverse cardiac events within 9 months: cardiac death, myocardial infarction, and target vessel revascularisation. Intention-to-treat analyses were done at 9-month and 18-month follow-up. This trial is registered with ClinicalTrials.gov, number NCT00660478. FINDINGS: 1162 patients (1619 lesions) were assigned to receive the zotarolimus-eluting stent, and 1170 patients (1611 lesions) to receive the sirolimus-eluting stent. 67 patients (72 lesions) had stent failure, and six patients were lost to follow-up. All randomly assigned patients were included in analyses at 9-month follow-up; 2200 patients (94%) had completed 18-month follow-up by the time of our assessment. At 9 months, the primary endpoint had occurred in a higher proportion of patients treated with the zotarolimus-eluting stent than in those treated with the sirolimus-eluting stent (72 [6%] vs 34 [3%]; HR 2.15, 95% CI 1.43-3.23; p=0.0002). At 18-month follow-up, this difference was sustained (113 [10%] vs 53 [5%]; 2.19, 1.58-3.04; p<0.0001). For patients receiving the zotarolimus-eluting stent and those receiving the sirolimus-eluting stent, all cause-mortality was similar at 9-month follow-up (25 [2%] vs 18 [2%]; 1.40, 0.76-2.56; p=0.28), but was significantly different at 18-month follow-up (51 [4%] vs 32 [3%]; 1.61, 1.03-2.50; p=0.035). INTERPRETATION: The sirolimus-eluting stent is superior to the zotarolimus-eluting stent for patients receiving routine clinical care. FUNDING: Cordis and Medtronic.

Small dense LDL particles--a predictor of coronary artery disease evaluated by invasive and CT-based techniques: a case-control study.

BACKGROUND: Coronary angiography is the current standard method to evaluate coronary atherosclerosis in patients with suspected angina pectoris, but non-invasive CT scanning of the coronaries are increasingly used for the same purpose. Low-density lipoprotein (LDL) cholesterol and other lipid and lipoprotein variables are major risk factors for coronary artery disease. Small dense LDL particles may be of particular importance, but clinical studies evaluating their predictive value for coronary atherosclerosis are few. METHODS: We performed a study of 194 consecutive patients with chest pain, a priori considered of low to intermediate risk for significant coronary stenosis (>50% lumen obstruction) who were referred for elective coronary angiography. Plasma lipids and lipoproteins were measured including the subtype pattern of LDL particles, and all patients were examined by coronary CT scanning before coronary angiography. RESULTS: The proportion of small dense LDL was a strong univariate predictor of significant coronary artery stenosis evaluated by both methods. After adjustment for age, gender, smoking, and waist circumference only results obtained by traditional coronary angiography remained statistically significant. CONCLUSION: Small dense LDL particles may add to risk stratification of patients with suspected angina pectoris.

Long-term effects of invasive treatment in patients with a post-thrombolytic Q-wave myocardial infarction.

OBJECTIVES: The aim of the present study was to assess the effect of a deferred invasive treatment strategy on long-term outcome in patients with a post-thrombolytic Q-wave myocardial infarction and inducible myocardial ischemia. DESIGN: Patients (N=751) with post-thrombolytic Q-wave myocardial infarction and inducible ischemia (angina pectoris or silent myocardial ischemia) were randomized to a deferred invasive treatment (balloon angioplasty or coronary bypass surgery) or medical treatment. Vital status and non-fatal cardiac events defined as hospitalization caused by acute cardiac events were recorded for a median of 11.4 years. RESULTS: Survival was significantly improved in patients receiving invasive treatment compared to patients treated medically (hazard ratio 0.85 (95% confidence limits 0.73-0.99), p=0.034). Subgroup analysis showed a reduction of non-fatal cardiac events and improved survival among the patients with post-infarction angina pectoris and not among the patients with silent myocardial ischemia. CONCLUSIONS: A deferred invasive treatment strategy improves survival compared to medical treatment in patients with inducible myocardial ischemia after a post-thrombolytic Q-wave myocardial infarction.

Clinical reinfarction according to infarct location and reperfusion modality in patients with ST elevation myocardial infarction. A DANAMI-2 long-term follow-up substudy.

OBJECTIVES: To evaluate clinical reinfarction during a 3-year follow-up after randomization to primary angioplasty versus fibrinolysis in anterior and non-anterior ST elevation myocardial infarction (STEMI). METHODS: Clinical reinfarction was prospectively assessed by an endpoint committee blinded to the study treatment. RESULTS: At 30 days, primary angioplasty compared with fibrinolysis reduced the reinfarction rate both in anterior STEMI patients (n = 823; 2.5 vs. 5.6%, p = 0.02) and in non-anterior STEMI patients (n = 743; 0.8 vs. 7.4%, p < 0.001). After 3 years, the reduction in reinfarction rate was no longer present in anterior STEMI patients (11.2 vs. 11.2%, p = 0.86), but persisted in non-anterior STEMI patients (5.2 vs. 13.5%, p < 0.001). Reinfarction after anterior STEMI carried a higher mortality than reinfarction after non-anterior STEMI (37.6 vs. 15.3%, p = 0.01). Independent predictors of death were: age [hazard ratio (HR) per 1-year increase in age = 1.08 (1.07-1.09)], clinical reinfarction [HR = 5.15 (3.57-7.43)], anterior index STEMI [HR = 1.65 (1.24-2.19)], and Killip class > or =2 [HR = 1.42 (1.01-2.00)]. The additional late reinfarctions after angioplasty for anterior STEMI were located within the angioplasty-treated target segment. Anterior STEMI patients had smaller mean target vessel diameter, which was associated with reinfarction. CONCLUSIONS: Clinical reinfarction is an independent predictor of death. The early superiority of primary angioplasty over fibrinolysis on reinfarction rate after anterior STEMI diminished during long-term follow-up.

The Danish multicentre randomized study of fibrinolytic therapy vs. primary angioplasty in acute myocardial infarction (the DANAMI-2 trial): outcome after 3 years follow-up.

BACKGROUND: The DANAMI-2 trial showed that in patients with ST-elevation myocardial infarction (STEMI), a strategy of inter-hospital transfer for primary angioplasty was superior to on-site fibrinolysis at 30 days follow-up. This paper reports on the pre-specified long-term composite endpoint at 3 years follow-up in DANAMI-2. METHODS AND RESULTS: We randomized 1572 patients with STEMI to primary angioplasty or intravenous alteplase; 1129 patients were enrolled at 24 referral hospitals and 443 patients at 5 angioplasty centres. Ninety-six percent of inter-hospital transfers for angioplasty were completed within 2 h. No patients were lost to follow-up. The composite endpoint (death, clinical re-infarction, or disabling stroke) was reduced by angioplasty when compared with fibrinolysis at 3 years (19.6 vs. 25.2%, P =0.006). For patients transferred to angioplasty compared with those receiving on-site fibrinolysis, the composite endpoint occurred in 20.1 vs. 26.7% (P = 0.007), death in 13.6 vs. 16.4% (P = 0.18), clinical re-infarction in 8.9 vs. 12.3% (P = 0.05), and disabling stroke in 3.2 vs. 4.7% (P = 0.23). CONCLUSION: The benefit of transfer for primary angioplasty based on the composite endpoint was sustained after 3 years. For patients with characteristics as those in DANAMI-2, primary angioplasty should be the preferred treatment strategy when inter-hospital transfer can be completed within 2 h.

Comparison of stent thrombosis, myocardial infarction, and mortality following drug-eluting versus bare-metal stent coronary intervention in patients with diabetes mellitus.

The aim of this study was to examine outcomes subsequent to implantation of drug-eluting stents (DESs) and bare-metal stents (BMSs) in patients with diabetes. From January 2002 to June 2005, data from all percutaneous coronary interventions performed in Western Denmark were prospectively recorded. A total of 1,423 consecutive diabetic patients treated with stent implantation (2,094 lesions) were followed up for 15 months. Of these, 871 patients (1,180 lesions) were treated with a BMS, and 552 patients (914 lesions) were treated with a DES. Dual antiplatelet therapy was recommended for 12 months in both treatment groups. Data for death and myocardial infarction (MI) were ascertained from national health care databases. Use of DESs was not associated with increased risk of definite stent thrombosis (adjusted relative risk [RR] 0.76, 95% confidence interval [CI] 0.10 to 3.26) or MI (adjusted RR 0.90, 95% CI 0.53 to 1.52). In the DES group compared with the BMS group, adjusted RRs of target-lesion revascularization (adjusted RR 0.48, 95% CI 0.33 to 0.71), total mortality (adjusted RR 0.66, 95% CI 0.44 to 0.99), and cardiac mortality (adjusted RR 0.53, 95% CI 0.31 to 0.90) decreased by 52%, 34%, and 47%, respectively. In conclusion, use of DESs reduced target-lesion revascularization in diabetic patients receiving routine clinical care. This result was obtained without increased risk of death, stent thrombosis, or MI.

Comparison of paclitaxel- and sirolimus-eluting stents in everyday clinical practice: the SORT OUT II randomized trial.

CONTEXT: Approval of drug-eluting coronary stents was based on results of relatively small trials of selected patients; however, in routine practice, stents are used in a broader spectrum of patients. OBJECTIVE: To compare the first 2 commercially available drug-eluting stents-sirolimus-eluting and paclitaxel-eluting-for prevention of symptom-driven clinical end points, using a study design reflecting everyday clinical practice. DESIGN, SETTING, AND PATIENTS: Randomized, blinded trial conducted August 2004 to January 2006 at 5 university hospitals in Denmark. Patients were 2098 men and women (mean [SD] age, 63.6 [10.8] years) treated with percutaneous coronary intervention (PCI) and randomized to receive either sirolimus-eluting (n = 1065) or paclitaxel-eluting (n = 1033) stents. Indications for PCI included ST-segment elevation myocardial infarction (STEMI), non-STEMI or unstable angina pectoris, and stable angina. MAIN OUTCOME MEASURES: The primary end point was a composite clinical end point of major adverse cardiac events, defined as either cardiac death, acute myocardial infarction, target lesion revascularization, or target vessel revascularization. Secondary end points included individual components of the composite end point, all-cause mortality, and stent thrombosis. RESULTS: The sirolimus- and the paclitaxel-eluting stent groups did not differ significantly in major adverse cardiac events (98 [9.3%] vs 114 [11.2%]; hazard ratio, 0.83 [95% confidence interval, 0.63-1.08]; P = .16) or in any of the secondary end points. The stent thrombosis rates were 27 (2.5%) and 30 (2.9%) (hazard ratio, 0.87 [95% confidence interval, 0.52-1.46]; P = .60), respectively. CONCLUSION: In this practical randomized trial, there were no significant differences in clinical outcomes between patients receiving sirolimus- and paclitaxel-eluting stents. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00388934.

Routine thrombectomy in percutaneous coronary intervention for acute ST-segment-elevation myocardial infarction: a randomized, controlled trial.

BACKGROUND: Distal embolization during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction may result in reduced myocardial perfusion, infarct extension, and impaired prognosis. METHODS AND RESULTS: In a prospective randomized trial, we studied the effect of routine thrombectomy in 215 patients with ST-segment-elevation myocardial infarction lasting <12 hours undergoing primary PCI. Patients were randomized to thrombectomy pretreatment or standard PCI. The primary end point was myocardial salvage measured by sestamibi SPECT, calculated as the difference between area at risk and final infarct size determined after 30 days (percent). Secondary end points included final infarct size, ST-segment resolution, and troponin T release. Baseline variables, including ST-segment elevation and area at risk, were similar. Salvage was not statistically different in the thrombectomy and control groups (median, 13% [interquartile range, 9% to 21%] and 18% [interquartile range, 7% to 25%]; P=0.12), but 24 patients in the thrombectomy group and 12 patients in the control group did not have an early SPECT scan, mainly because of poor general or cardiac condition (P=0.04). In the thrombectomy group, final infarct size was increased (median, 15%; [interquartile range, 4% to 25%] versus 8% [interquartile range, 2% to 18%]; P=0.004). CONCLUSIONS: Thrombectomy performed as routine therapy in primary PCI for ST-elevation myocardial infarction does not increase myocardial salvage. The study suggests a possible deleterious effect of thrombectomy, resulting in an increased final infarct size, and does not support the use of thrombectomy in unselected primary PCI patients.

A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction.

BACKGROUND: For the treatment of myocardial infarction with ST-segment elevation, primary angioplasty is considered superior to fibrinolysis for patients who are admitted to hospitals with angioplasty facilities. Whether this benefit is maintained for patients who require transportation from a community hospital to a center where invasive treatment is available is uncertain. METHODS: We randomly assigned 1572 patients with acute myocardial infarction to treatment with angioplasty or accelerated treatment with intravenous alteplase; 1129 patients were enrolled at 24 referral hospitals and 443 patients at 5 invasive-treatment centers. The primary study end point was a composite of death, clinical evidence of reinfarction, or disabling stroke at 30 days. RESULTS: Among patients who underwent randomization at referral hospitals, the primary end point was reached in 8.5 percent of the patients in the angioplasty group, as compared with 14.2 percent of those in the fibrinolysis group (P=0.002). The results were similar among patients who were enrolled at invasive-treatment centers: 6.7 percent of the patients in the angioplasty group reached the primary end point, as compared with 12.3 percent in the fibrinolysis group (P=0.05). Among all patients, the better outcome after angioplasty was driven primarily by a reduction in the rate of reinfarction (1.6 percent in the angioplasty group vs. 6.3 percent in the fibrinolysis group, P<0.001); no significant differences were observed in the rate of death (6.6 percent vs. 7.8 percent, P=0.35) or the rate of stroke (1.1 percent vs. 2.0 percent, P=0.15). Ninety-six percent of patients were transferred from referral hospitals to an invasive-treatment center within two hours. CONCLUSIONS: A strategy for reperfusion involving the transfer of patients to an invasive-treatment center for primary angioplasty is superior to on-site fibrinolysis, provided that the transfer takes two hours or less.

Revascularization compared to medical treatment in patients with silent vs. symptomatic residual ischemia after thrombolyzed myocardial infarction--the DANAMI study.

AIMS: The aim was to compare the effect of revascularization to conservative treatment in patients with residual silent and with residual symptomatic ischemia following acute myocardial infarction (AMI). The study was a subanalysis of the DANAMI (DANish AMI) randomized study of invasive vs. conservative treatment in patients with inducible ischemia after thrombolysis in AMI. METHODS AND RESULTS: One thousand and eight patients were randomized to invasive or conservative treatment, stratified by the type of ischemia: silent, i.e. ST depression during an exercise test prior to discharge in 56%, or symptomatic, i.e. chest pain occurring either spontaneously during admission or during the exercise test, with or without ST changes, in 44%. Compared to a conservative strategy, invasive treatment reduced the incidence of nonfatal reinfarction, after in median 2.4 years, in both symptomatic patients (13.3-7.2%, p < 0.006) and patients with silent ischemia (10.1 vs. 5.7%, p < 0.05), and of admissions with unstable angina in symptomatic (44.5-27.6%, p < 0.0001) and silent ischemia (21.6-13.3%, p < 0.0006). CONCLUSIONS: Compared to conservative strategy, invasive treatment reduces the risk of nonfatal reinfarction and hospital admissions for unstable angina in thrombolyzed post-AMI patients with silent as well as symptomatic exercise-induced ischemia.

[Percutaneous coronary intervention in Denmark from 1989 to 1998. Results from the Danish PTCA registry]. / Perkutan koronar intervention i Danmark fra 1989 til 1998. Resultater fra Dansk PTCA register.

INTRODUCTION: During the ten-year period 1989 to 1998, all percutaneous coronary interventions (PCI) in Denmark were recorded in the Danish PTCA Registry. The purpose was quality control based on treatment activity, severity of illness, technique employed, success rate, and complications. MATERIAL AND METHODS: For each PCI procedure a number of 144 parameters were recorded in a national database. The present analysis of these data was carried out using parametric statistics and logistic regression analysis. RESULTS: From 1989 to 1998 the annual number of PCI procedures increased from 240 to 3840. The database contains 13,868 procedures of which 10,804 are first time interventions. Men accounted for three fourths of the patients. The mean age was 60.7 years for women and 57.9 years for men. During the ten-year period a rise of two years on average was seen for both sexes with a doubling of patients being older than 70 years. More patients with acute coronary syndrome and multivessel disease had PCI. The use of coronary stents increased from 2.0% in 1992 to 90.7% in 1998 and the primary success rate rose from 81% to 90%. Serious complications decreased from 5.4% to 3.0%, mainly due to a significant fall in procedurally related acute bypass surgery. Mortality remained unchanged around 0.6%. Age was found to be the only independent predictor for major procedurally related complications. DISCUSSION: From 1989 to 1998 a sixteenfold increase in the number of PCI was observed. In parallel to this was seen an increase in the use of coronary stents and in the procedural success rate, while the frequency of serious complications decreased. This progress is similar to that of several other European countries.

Smokers with ST-segment elevation myocardial infarction and short time to treatment have equal effects of PCI and fibrinolysis.

OBJECTIVES: The purpose of this study was to examine the effect of primary percutaneous coronary intervention (PCI) compared to fibrinolysis in smokers and non-smokers with ST-segment elevation myocardial infarction (STEMI). Smokers seem to have less atherosclerosis but are more prone to thrombotic disease. Compared to non-smokers, they have higher rates of early, complete reperfusion when treated with fibrinolysis for MI. METHODS AND RESULTS: In the Second Danish Multicenter Trial in Acute Myocardial Infarction (DANAMI-2), a total of 1572 patients with STEMI were randomized to either fibrinolysis or PCI (1129 patients were enrolled at 24 referral hospitals and 443 patients at 5 invasive treatment centers). The primary endpoint for this substudy was death by any cause. Secondary endpoints were a composite of death by any cause, clinical re-infarction or disabling stroke. Follow-up was 3 years. The effect of PCI is reported according to time to treatment and smoking status. Data on smoking habits were available for 1534 patients (895 smokers and 639 non-smokers). Smokers with short time to treatment (<3 hours) benefited equally from PCI and fibrinolysis with a trend toward higher mortality in the PCI group (mortality [hazard ratio, 1.64 (0.79-3.41); P=.18], composite endpoint [hazard ratio, 1.06 (0.65-1.71); P=.82]). In non-smokers with short time to treatment PCI was superior to fibrinolysis (mortality [hazard ratio, 0.46 (0.22-0.93); P=.02], combined endpoint [hazard ratio, 0.45 (0.26- 0.79); P=.004]). Patients with >3 hours to treatment all showed a tendency toward a superior effect of PCI irrespective of smoking habits. CONCLUSIONS: PCI and fibrinolysis are equally beneficial in smokers with STEMI and short time to treatment.

Outcome of sirolimus-eluting versus zotarolimus-eluting coronary stent implantation in patients with and without diabetes mellitus (a SORT OUT III Substudy).

Diabetes is associated with an increased risk of major adverse cardiac events after percutaneous coronary intervention. We compared clinical outcomes in patients with and without diabetes mellitus treated with the second-generation Endeavor zotarolimus-eluting stent (ZES) or the first-generation Cypher Select+ sirolimus-eluting stent (SES). We randomized 2,332 patients to treatment with ZESs (n = 1,162, n = 169 diabetics) or SESs (n = 1,170, n = 168 diabetics) and followed them for 18 months. Randomization was stratified by presence/absence of diabetes. The primary end point was major adverse cardiac events defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization. Secondary end points included these individual end points plus all-cause mortality and target lesion revascularization. In diabetic patients, use of ZES compared to SES was associated with an increased risk of major adverse cardiac events (18.3% vs 4.8%, hazard ratio 4.05, 95% confidence interval 1.86 to 8.82), myocardial infarction (4.7% vs 0.6%, hazard ratio 8.09, 95% confidence interval 1.01 to 64.7), target vessel revascularization (14.2% vs 3.0%, hazard ratio 4.99, 95% confidence interval 1.90 to 13.1), and target lesion revascularization (12.4% vs 1.2%, hazard ratio 11.0, 95% confidence interval 2.59 to 47.1). In patients without diabetes differences in absolute risk decrease were smaller but similarly favored SES. In conclusion, implantation of ZESs compared to SESs is associated with a considerable increased risk of adverse events in patients with diabetes at 18-month follow-up.

[Detection of stenoses in the coronary arteries using 64-slice computed tomography]. / Stenoser i koronararterierne påvist med 64-slice-computertomografi.

INTRODUCTION: The purpose of the present study was to assess the diagnostic value of 64-slice computed tomography of the coronary arteries (CTCA) with invasive coronary angiography (CA) as reference. MATERIAL AND METHODS: We studied 194 patients (mean age: 62.7 ± 9.5 years, males: 97) with symptoms suggesting angina who had been referred for CA according to usual criteria. We excluded patients with known ischaemic heart disease and patients with an unstable heart rhythm. CTCA was analysed without knowledge of CA and vice versa. Stenoses > 50% were considered significant. The effective radiation (mSv) was measured with both methods. RESULTS: In 17 patients (8.8%), the CT-angiogram was not assessable. In 177 patients (91.2%) with assessable CT-angiogram, the sensitivity of CTCA was 97%, the specificity 63%, the predictive value of a positive test 58%, and the predictive value of a negative test 97%. In the 174 patients in whom CTCA was performed using retrospective technique, the effective radiation was 14.0 ± 2.3, versus 4.9 ± 2.6 at CA (p < 0.0005). In the 20 patients in whom CTCA was performed using prospective technique, the effective radiation was 5.4 ± 1.2 versus 5.9 ± 3.6 at CA (non-significant) CONCLUSION: CTCA with 64-slice scanner has a high sensitivity for demonstration coronary artery stenoses.

Long-term outcomes after percutaneous coronary intervention in patients with and without diabetes mellitus in Western Denmark.

Patients with diabetes mellitus have worse outcomes after percutaneous coronary intervention than patients without diabetes mellitus. We compared the risk of stent thrombosis, myocardial infarction, death, and target lesion revascularization in diabetic and nondiabetic patients after implantation of drug-eluting stents or bare metal stents. In the Western Denmark Heart Registry, 12,347 consecutive patients (1,575 with and 10,772 without diabetes) were identified and followed up for 2 years. The 2-year risk of definite stent thrombosis was 0.52% in patients with diabetes mellitus and 0.71% in nondiabetic patients (adjusted relative risk [RR] 0.74, 95% confidence interval [CI] 0.41 to 1.34, p = 0.321). The 2-year risk of myocardial infarction was greater in the diabetic patients (6.9%) than in the nondiabetic patients (3.6%; adjusted RR 1.96, 95% CI 1.58 to 2.43; p <0.001). The all-cause 2-year mortality rate was almost twice as great for the diabetic patients compared to the nondiabetic patients (12.4% vs 6.7%; adjusted RR 1.91, 95% CI 1.63 to 2.23; p <0.001). The 2-year risk of target lesion revascularization was 8.5% in the diabetic patients and 6.8% in the nondiabetic patients (adjusted RR 1.28, 95% CI 1.10 to 1.49; p <0.001). In conclusion, 2 years after drug-eluting stent or bare metal stent implantation, diabetic patients had a greater risk than nondiabetic patients of myocardial infarction and death. Drug-eluting stent treatment reduced the risk of target lesion revascularization compared to bare metal stent treatment, regardless of diabetes status.

2-year clinical outcomes after implantation of sirolimus-eluting, paclitaxel-eluting, and bare-metal coronary stents: results from the WDHR (Western Denmark Heart Registry).

OBJECTIVES: This registry study assessed the safety and efficacy of the 2 types of drug-eluting stents (DES), sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES), compared with bare-metal stents (BMS). BACKGROUND: Drug-eluting stents may increase the risk of stent thrombosis (ST), myocardial infarction (MI), and death. METHODS: A total of 12,395 consecutive patients with coronary intervention and stent implantation recorded in the Western Denmark Heart Registry from January 2002 through June 2005 were followed up for 2 years. Data on death and MI were ascertained from national medical databases. We used Cox regression analysis to control for confounding. RESULTS: The 2-year incidence of definite ST was 0.64% in BMS patients, 0.79% in DES patients (adjusted relative risk [RR]: 1.09; 95% confidence interval [CI]: 0.72 to 1.65), 0.50% in SES patients (adjusted RR: 0.63, 95% CI: 0.35 to 1.15), and 1.30% in PES patients (adjusted RR: 1.82, 95% CI: 1.13 to 2.94). The incidence of MI was 3.8% in BMS-treated patients, 4.5% in DES-treated patients (adjusted RR: 1.24, 95% CI: 1.02 to 1.51), 4.1% in SES-treated patients (adjusted RR: 1.15, 95% CI: 0.91 to 1.47), and 5.3% in PES-treated patients (adjusted RR: 1.38, 95% CI: 1.06 to 1.81). Whereas overall 2-year adjusted mortality was similar in the BMS and the 2 DES stent groups, 12- to 24-month mortality was higher in patients treated with PES (RR 1.46, 95% CI: 1.02 to 2.09). Target lesion revascularization was reduced in both DES groups. CONCLUSIONS: During 2 years of follow-up, patients treated with PES had an increased risk of ST and MI compared with those treated with BMS and SES. Mortality after 12 months was also increased in PES patients.

Effects of pentoxifylline on the vascular response to injury after angioplasty in rabbit iliac arteries.

Pentoxifylline (PTX) inhibits the effects of several cytokines and reduces injury-related collagen accumulation. The aim of the present study was to investigate the effect of PTX on the vascular response to injury. We treated rabbits with PTX (100 mg/kg/day) or placebo (saline) subcutaneously from 2 days before angioplasty of an iliac artery until euthanasia 7 or 28 days later. At 7 days after injury, PTX treatment was associated with a more differentiated (less proliferation, more smoothelin-positive) intimal smooth muscle cell phenotype. Furthermore, PTX reduced myofibroblast accumulation in adventitia. At 28 days after injury, PTX-treated rabbits had a 48.5% larger lumen area (P = 0.03) and a 28.1% larger area within the external elastic lamina (P = 0.04). There were no significant differences between PTX-treated rabbits and the placebo group with regard to neointima and media area. Angioplasty induced marked neoadventitial hyperplasia, which was reduced by 20.5% (P = 0.01) in the PTX-treated group. Finally, PTX reduced collagen density in all three arterial layers. We conclude that PTX treatment induces less proliferation within the vessel wall early after angioplasty and increases late lumen size after angioplasty by a positive effect on vascular remodeling.

Clinical outcome after primary percutaneous coronary intervention with drug-eluting and bare metal stents in patients with ST-segment elevation myocardial infarction.

BACKGROUND: The use of drug-eluting stents (DESs) versus bare metal stents (BMSs) in primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction is a matter of debate. Therefore, we examined the risk of target lesion revascularization (TLR), stent thrombosis, myocardial infarction, and death after the implantation of DES or BMS in primary PCI patients in Western Denmark. METHODS AND RESULTS: A total of 3756 consecutive patients with ST-segment elevation myocardial infarction treated with primary PCI and stent implantation, recorded in the Western Denmark Heart Registry from January 2002 through June 2005, were followed up for 2 years. We used Cox regression analysis to control for confounding. The 2-year incidence of definite stent thrombosis was 1.9% in the DES group and 1.1% in the BMS group (adjusted relative risk [RR]=1.53; 95% CI=0.84 to 2.78; P=0.17). Very late definite stent thrombosis (> or =12 months) was seen in 0.4% in the DES group and 0.06% in the BMS group (adjusted RR=6.74; 95% CI=1.23 to 37.00; P=0.03). The 2-year incidence of myocardial infarction was similar in the 2 groups, 5.2% in the DES group versus 6.3% in the BMS group (P=0.28; adjusted RR=1.13; 95% CI=0.81 to 1.59; P=0.47). All-cause 2-year mortality was 7.8% in the DES group and 11.4% in BMS group (P<0.004; adjusted RR=0.79; 95% CI=0.60 to 1.04; P=0.09). The 2-year incidence of target lesion revascularization was 7.2% in the DES group and 8.7% in the BMS group (P=0.09; adjusted RR=0.70; 95% CI=0.52 to 0.92; P=0.012). CONCLUSIONS: In ST-segment elevation myocardial infarction patients treated with primary PCI, target lesion revascularization was reduced by 30% in patients treated with a DES. The risk of very late definite stent thrombosis was low but increased in patients treated with DES. DES was not associated with increased risk of myocardial infarction or death, when compared with BMS.

Target lesion revascularisation in patients treated with a sirolimus-eluting or paclitaxel-eluting stent.

OBJECTIVE: To identify risk factors for clinical-driven target lesion revascularisation (TLR) in patients treated with sirolimus-eluting (Cypher) or paclitaxel-eluting (Taxus) stents in a real-world scenario. DESIGN: From 1 January 2003 to 18 May 2005, all patients treated with a Cypher or Taxus stent were consecutively registered and followed for 9 months. Re-intervention was driven by clinical symptoms. SETTING: Western Denmark Heart Registry. PATIENTS: 4432 patients with 6102 lesions treated with a Cypher (n = 3791 lesions) or Taxus (n = 2311 lesions) stent. INTERVENTIONS: Percutaneous coronary intervention. MAIN OUTCOME MEASURES: TLR, defined as either new percutaneous coronary intervention or coronary artery bypass graft operation of the target lesion, within 9 months from the index procedure. RESULTS: TLR within 9 months was performed in 2.5% of lesions treated with the Cypher stent and in 3.3% of lesions treated with the Taxus stent (OR 1.36, 95% CI 1.00 to 1.84). After adjustment by multivariate logistic regression, Taxus stent implantation was an independent predictor of TLR (OR 1.43, 95% CI 1.05 to 1.95). Implantation of >1 stent per lesion (OR 1.62, 95% CI 1.13 to 2.33) and reference diameter <2.8 mm (OR 1.42, 95% CI 1.00 to 2.02) were also identified as independent predictors of TLR. CONCLUSIONS: These data from the registry reflect a real-world clinical scenario with operator-driven use of drug-eluting stents and symptom-driven re-intervention. In this setting, use of the Taxus stent, implantation of multiple stents per lesion and stent implantation in small vessels were independent predictors of TLR.

One year clinical follow-up of the XIENCE V Everolimus-eluting stent system in the treatment of patients with de novo native coronary artery lesions: the SPIRIT II study.

AIMS: The SPIRIT II study randomised 300 patients in a ratio of 3:1 to receive either a XIENCE V or a TAXUS stent. The six month clinical and angiographic results have previously been reported. This paper presents the clinical follow-up of these patients to one year. METHODS AND RESULTS: As a continuation in the assessment of the safety and performance of the XIENCE V Everolimus-Eluting Coronary Stent System (EECSS) enrolled patients were requested to return for clinical follow-up one year following the procedure to assess the occurrence of ischaemia driven major adverse cardiac events (MACE).Of the 300 patients recruited at 28 sites in Europe, New Zealand and India, 223 were randomised to receive an EECSS stent and 77 a TAXUS paclitaxel eluting coronary stent system (PECSS). One-year clinical follow-up was obtained in 220 of the 223 patients in the EECSS group (98.7%) with one withdrawal prior to 180 days and two non-cardiac deaths (pulmonary malignancy and pneumonia) between six and 12 months, and in 76 of 77 (98.7%) PECSS group of patients (one patient had a missed 270-day and 1-year visit). Between six and 12 months there were no new occurrences of late stent thrombotic events in either group. There were no additional MACE events in the EECSS compared to, two, both ischaemia driven target lesion revascularisations (TLR) in the PECSS group. CONCLUSIONS: The clinical safety of the XIENCE V EECSS stent observed at six months was sustained at one year. There were no additional thrombotic or MACE events in the EECSS group. Although not a primary endpoint, there was a significant difference in MACE favouring the EECSS compared to PECSS (2.7% versus 9.2%, P=0.04).