Eulogio García

Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomised controlled trial (E-SIRIUS)

BACKGROUND Sirolimus-eluting stents have been developed to prevent restenosis in the treatment of coronary artery disease. We investigated the risk of restenosis with use of sirolimus-eluting stents compared with bare-metal stents to assess possible differences. METHODS We enrolled 352 patients in whom one coronary artery required treatment, with diameter 2.5-3.0 mm and lesion length 15-32 mm. We randomly assigned patients sirolimus-eluting stents (n=175) or bare-metal stents (control, n=177). At 8 months we assessed differences in minimum lumen diameter and binary restenosis within the lesion (restenosis of > or =50% diameter, including 5 mm vessel segments proximal and distal to stented segment). Patients were also followed up for 9 months for major adverse cardiac events. Analysis was by intention to treat. FINDINGS Stent implantation was successful in 100% of sirolimus-stent patients and 99.4% of controls. The mean diameter of treated coronary arteries was 2.55 mm (SD 0.37) and mean lesion length was 15.0 mm (6.0). Multiple stents were implanted in 170 (48%) patients. At 8 months, minimum lumen diameter was significantly higher with sirolimus-eluting stents than with control stents (2.22 vs 1.33 mm, p<0.0001). The rate of binary restenosis was significantly reduced with sirolimus-eluting stents compared with control stents (5.9 vs 42.3%, p=0.0001). Significantly fewer patients with sirolimus-eluting stents had major adverse cardiac events at 9 months than did controls (8.0 vs 22.6%, p=0.0002), due mainly to a lower need for target-lesion revascularisations (4.0 vs 20.9%, p<0.0001). INTERPRETATION Sirolimus-eluting stents are better than bare-metal stents for treatment of single long atherosclerotic lesions in a coronary vessel smaller than 3 mm in diameter.

Coronary Angioplasty with or without Stent Implantation for Acute Myocardial Infarction

Background Coronary-stent implantation is frequently performed for treatment of acute myocardial infarction. However, few studies have compared stent implantation with primary angioplasty alone. Methods We designed a multicenter study to compare primary angioplasty with angioplasty accompanied by implantation of a heparin-coated Palmaz–Schatz stent. Patients with acute myocardial infarction underwent emergency catheterization and angioplasty. Those with vessels suitable for stenting were randomly assigned to undergo angioplasty with stenting (452 patients) or angioplasty alone (448 patients). Results The mean (±SD) minimal luminal diameter was larger after stenting than after angioplasty alone (2.56±0.44 mm vs. 2.12±0.45 mm, P<0.001), although fewer patients assigned to stenting had grade 3 blood flow (according to the classification of the Thrombolysis in Myocardial Infarction trial) (89.4 percent, vs. 92.7 percent in the angioplasty group; P=0.10). After six months, fewer patients in the stent group tha...

Randomised comparison of implantation of heparin-coated stents with balloon angioplasty in selected patients with coronary artery disease (Benestent II)

BACKGROUND The multicentre, randomised Benestent-II study investigated a strategy of implantation of a heparin-coated Palmar-Schatz stent plus antiplatelet drugs compared with the use of balloon angioplasty in selected patients with stable or stabilised unstable angina, with one or more de-novo lesions, less than 18 mm long, in vessels of diameter 3 mm or more. METHODS 827 patients were randomly assigned stent implantation (414 patients) or standard balloon angioplasty (413 patients). The primary clinical endpoint was event-free survival at 6 months, including death, myocardial infarction, and the need for revascularisation. The secondary endpoints were the restenosis rate at 6 months and the cost-effectiveness at 12 months. There was also one-to-one subrandomisation to either clinical and angiographic follow-up or clinical follow-up alone. Analyses were by intention to treat. FINDINGS Four patients (one stent group, three angioplasty group) were excluded from analysis since no lesion was found. At 6 months, a primary clinical endpoint had occurred in 53 (12.8%) of 413 patients in the stent group and 79 (19.3%) of 410 in the angioplasty group (p=0.013). This significant difference in clinical outcome was maintained at 12 months. In the subgroup assigned angiographic follow-up, the mean minimum lumen diameter was greater in the stent group than in the balloon-angioplasty group, (1.89 [SD 0.65] vs 1.66 [0.57] mm, p=0.0002), which corresponds to restenosis rates (diameter stenosis > or =50%) of 16% and 31% (p=0.0008). In the group assigned clinical follow-up alone, event-free survival rate at 12 months was higher in the stent group than the balloon-angioplasty group (0.89 vs 0.79, p=0.004) at a cost of an additional 2085 Dutch guilders (US

Impact of Renal Insufficiency in Patients Undergoing Primary Angioplasty for Acute Myocardial Infarction

1020) per patient. INTERPRETATION Over 12-month follow-up, a strategy of elective stenting with heparin-coated stents is more effective but also more costly than balloon angioplasty.

Gender Differences in Outcomes After Primary Angioplasty Versus Primary Stenting With and Without Abciximab for Acute Myocardial Infarction Results of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Trial

Background—The prognostic importance of renal insufficiency (RI) in patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) has not been well characterized. Methods and Results—PCI was performed in 2082 AMI patients without shock presenting within 12 hours of symptom onset in a prospective, multicenter randomized trial. RI was defined as a calculated (Cockroft-Gault) creatinine clearance (CrCl) ≤60 mL/min. RI at baseline was present in 18% of patients. Compared with patients without RI, patients with RI were older and were more likely to be female; to have hypertension, peripheral vascular disease, or cerebrovascular disease; and to present in heart failure. Mortality was markedly increased in patients with versus without baseline RI both at 30 days (7.5% versus 0.8%, P <0.0001) and at 1 year (12.7% versus 2.4%, P <0.0001). Mortality rates increased incrementally for every 10-mL/min decrease in baseline CrCl. By multivariate analysis, reduced baseline CrCl was a powerful independent predictor of 30-day mortality (hazard ratio, 5.77; P <0.0001) and remained associated with reduced survival at 1 year (hazard ratio, 1.98; P =0.08). Hemorrhagic complications and transfusion requirements were also increased more than 2-fold in patients with RI, as were severe restenosis (diameter stenosis ≥70%; 20.6% versus 11.8%, P =0.024) and infarct artery reocclusion (14.7% versus 7.3%, P =0.02). Conclusions—Baseline RI in patients with AMI undergoing primary PCI is associated with a markedly increased risk of mortality, as well as bleeding and restenosis. Novel approaches are needed to improve the otherwise poor prognosis of patients with RI and AMI.

Randomized comparison of coronary stent implantation and balloon angioplasty in the treatment of de novo coronary artery lesions (START): a four-year follow-up.

Background—Women with acute myocardial infarction (AMI) undergoing primary angioplasty have higher rates of morbidity and mortality than do men. Whether contemporary interventional treatment strategies have improved outcomes for women compared with men is unknown. Methods and Results—In the CADILLAC trial, 2082 patients (27% women) with AMI within 12 hours of symptom onset were randomized to balloon angioplasty (PTCA; n=518), PTCA+abciximab (n=528), stenting (n=512), and stenting+abciximab (n=524). As compared with men, women had a lower body surface area; had a greater prevalence of diabetes, hypertension, and hyperlipidemia; experienced significant delays to treatment; and had better baseline and final TIMI grade 3 flows. Unadjusted 1-year event rates were higher for women, including death (7.6% versus 3.0%, P<0.001), ischemic target-vessel revascularization (TVR; 16.7% versus 12.1%, P=0.006), and major adverse cardiac events (MACE; 23.9% versus 15.3%, P<0.001). Female gender was an independent predictor of MACE and bleeding complications, although comorbid risk factors and body surface area but not gender predicted 1-year death. For women, primary stenting resulted in a reduction in 1-year MACE from 28.1% to 19.1% (P=0.01) and in ischemic TVR from 20.4% to 10.8% (P=0.002) compared with PTCA. The addition of abciximab to primary stenting significantly reduced the 30-day ischemic TVR without increasing bleeding or stroke rates. Conclusions—The higher mortality rate in women compared with men after interventional treatment for AMI may be explained by differences in body size and clinical risk factors, although female gender remains an important independent determinant of overall adverse outcomes. For women in the CADILLAC trial, the addition of abciximab reduced 30-day TVR without increasing bleeding risk, and primary stenting reduced 1-year TVR and MACE rates compared with PTCA.

Benefits and Risks of Abciximab Use in Primary Angioplasty for Acute Myocardial Infarction The Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Trial

OBJECTIVE The purpose of this study was to test the hypothesis that stent implantation in de novo coronary artery lesions would result in lower restenosis rates and better long-term clinical outcomes than balloon angioplasty. BACKGROUND Placement of an intracoronary stent, as compared with balloon angioplasty, has proven to reduce the rate of restenosis. However, the long-term clinical benefit of stenting over angioplasty has not been assessed in large randomized trials. METHODS We randomly assigned 452 patients with either stable (129 patients) or unstable (323 patients) angina pectoris to elective stent implantation (229 patients) or standard balloon angioplasty (223 patients). Coronary angiography was performed at baseline, immediately after the procedure and six months later. End points were the rate of restenosis at six months and a composite of death, myocardial infarction (MI) and target vessel revascularization over four years of follow-up. RESULTS Procedural success rate was achieved in 84% and 95% (balloon angioplasty vs. stent, respectively). The increase in the minimal luminal diameter was greater in the stent group both after the intervention (2.02 +/- 0.6 mm vs. 1.43 +/- 0.6 mm in the angioplasty group; p < 0.0001), and at six-month follow-up (1.98 +/- 0.7 mm vs. 1.63 +/- 0.7 mm; p < 0.001). The corresponding restenosis rates were 22% and 37%, respectively (p < 0.002). After four years, no differences in mortality (2.7% vs. 2.4%) and nonfatal MI (2.2% vs. 2.8%) were found between the stent and the angioplasty groups, respectively. However, the requirement for further revascularization procedures of the target lesions was significantly reduced in the stent group (12% vs. 25% in the angioplasty group; relative risk 0.49, 95% confidence interval 0.32 to 0.75, p = 0.0006); most of the repeat procedures (84%) were carried out within six months of entry into the study. CONCLUSIONS Patients who received an intracoronary stent showed a lower rate of restenosis than those treated with conventional balloon angioplasty. The benefit of stenting was maintained four years after implantation, as manifested by a significant reduction in the need for repeat revascularization.

Angiographic and clinical characteristics associated with increased in-hospital mortality in elderly patients with acute myocardial infarction undergoing percutaneous intervention (a pooled analysis of the primary angioplasty in myocardial infarction trials).

Background—Trials of platelet glycoprotein IIb/IIIa inhibitors as adjuncts to primary percutaneous coronary intervention for acute myocardial infarction (MI) have shown improved early clinical and angiographic outcomes with treatment. However, variations in trial designs, modest sample sizes, and limited long-term follow-up have precluded these studies from being definitive. Methods and Results—As a prespecified secondary analysis of the CADILLAC trial, we compared early and late outcomes by abciximab assignment among 2082 patients randomized in an open-label, 2×2 factorial-design trial of primary stenting versus angioplasty and abciximab treatment (n=1052) versus no abciximab treatment (n=1030). Baseline characteristics were balanced between groups. Abciximab treatment was associated with a significant reduction in the composite end point of death, MI, ischemia-driven target-vessel revascularization (TVR), or disabling stroke at 30 days (4.6% versus 7.0%; relative risk, 0.65; 95% CI, 0.46 to 0.93; P =0.01). Subacute thrombosis also was significantly reduced with abciximab treatment. At 12 months, however, rates of the composite end point did not differ significantly (18.4% for controls versus 16.9% for abciximab-treated patients; relative risk, 0.92; 95% CI, 0.76 to 1.10; P =0.29), reflecting a decrease in the relative difference in TVR rates (ie, no effect of abciximab on reducing restenosis). In an angiographic substudy (n=656), myocardial salvage, restenosis, and infarct-artery reocclusion at 7 months were unaffected by abciximab treatment. There was no significant interaction between stenting and abciximab treatment. Conclusions—Adjunctive abciximab treatment during primary percutaneous coronary intervention significantly enhanced 30-day event-free survival, predominantly by reducing ischemia-driven TVR. Abciximab treatment did not affect the composite end point at 1 year, reflecting a lack of effect on restenosis.

Primary angioplasty versus systemic thrombolysis in anterior myocardial infarction.

Advanced age is associated with increased mortality in acute myocardial infarction (AMI) but the mechanism remains unclear. We performed a pooled analysis of 3,032 patients from the Primary Angioplasty in Myocardial Infarction (PAMI)-2, Stent-PAMI, and PAMI-No Surgery On Site trials to determine which clinical, hemodynamic, and angiographic characteristics in the elderly were associated with in-hospital death. There were 452 patients aged >/=75 years and 2,580 patients aged <75 years. Older patients had a lower number of risk factors for coronary artery disease but more comorbidities. Acute catheterization demonstrated more 3-vessel disease, higher left ventricular (LV) end-diastolic pressure, lower LV ejection fraction, and higher initial rates of Thrombolysis In Myocardial Infarction (TIMI) trial 2 or 3 flow. Elderly patients were equally likely to undergo percutaneous intervention but had a lower procedural success rate and lower rates of final TIMI 3 flow, and older patients were more likely to have post-AMI complications. In-hospital mortality was 10.2% and 1.8%, respectively (p = 0.001). Cardiac and noncardiac mortality was higher in elderly patients, and no significant differences in causes of death were identified. Multivariate analysis revealed that the strongest predictors of death were age >/=75 years, lower LV ejection fraction, lower final TIMI flow, higher Killip class, need for an intra-aortic balloon pump (IABP), and post-AMI stroke/transient ischemic attack, or significant arrhythmia. Despite avoiding thrombolysis, elderly patients remain at increased risk of bleeding, stroke, and other post-AMI complications, and death. Cardiac risk factor analysis and acute catheterization offer prognostic information but do not completely explain the mechanism of increased in-hospital mortality in the elderly.

Importance of time to reperfusion on outcomes with primary coronary angioplasty for acute myocardial infarction (results from the Stent Primary Angioplasty in Myocardial Infarction Trial).

OBJECTIVES This study compares the efficacy of primary angioplasty and systemic thrombolysis with t-PA in reducing the in-hospital mortality of patients with anterior AMI. BACKGROUND Controversy still exists about the relative benefit of primary angioplasty over thrombolysis as treatment for AMI. METHODS Two-hundred and twenty patients with anterior AMI were randomly assigned in our institution to primary angioplasty (109 patients) or systemic thrombolysis with accelerated t-PA (111 patients) within the first five hours from the onset of symptoms. RESULTS Baseline characteristics were similar in both groups. Primary angioplasty was independently associated with a lower in-hospital mortality (2.8% vs. 10.8%, p = 0.02, adjusted odds ratio 0.23, 95% confidence interval 0.06 to 0.85). During hospitalization, patients treated by angioplasty had a lower frequency of postinfarction angina or positive stress test (11.9% vs. 25.2%, p = 0.01) and less frequently underwent percutaneous or surgical revascularization after the initial treatment (22.0% vs. 47.7%, p < 0.001) than did patients treated by t-PA. At six month follow-up, patients treated by angioplasty had a lower cumulative rate of death (4.6% vs. 11.7%, p = 0.05) and revascularization (31.2% vs. 55.9%, p < 0.001) than those treated by t-PA. CONCLUSIONS In centers with an experienced and readily available interventional team, primary angioplasty is superior to t-PA for the treatment of anterior AMI.