Sirolimus-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the SISR randomized trial

Context  Although vascular brachytherapy is the only approved therapy for restenosis following bare-metal stent implantation, drug-eluting stents are now being used. Data on the relative merits of each are limited. Objective  To determine the safety and efficacy of the sirolimus-eluting stent compared with vascular brachytherapy for the treatment of patients with restenosis within a bare-metal stent. Design, Setting, and Patients  Prospective, multicenter, randomized trial of 384 patients with in-stent restenosis who were enrolled between February 2003 and July 2004 at 26 academic and community medical centers. Data presented represent all follow-up as of June 30, 2005. Interventions  Vascular brachytherapy (n = 125) or the sirolimus-eluting stent (n = 259). Main Outcome Measure  Target vessel failure (cardiac death, myocardial infarction, or target vessel revascularization) at 9 months postprocedure. Results  Baseline patient characteristics were well matched. Lesion length was similar between vascular brachytherapy and sirolimus-eluting stent patients (mean [SD], 16.76 [8.55] mm vs 17.22 [7.97] mm, respectively; P = .61). Procedural success was 99.2% (124/125) in the vascular brachytherapy group and 97.3% (250/257) in the sirolimus-eluting stent group (P = .28). The rate of target vessel failure was 21.6% (27/125) with vascular brachytherapy and 12.4% (32/259) with the sirolimus-eluting stent (relative risk [RR], 1.7; 95% confidence interval [CI], 1.1-2.8; P = .02). Target lesion revascularization was required in 19.2% (24/125) of the vascular brachytherapy group and 8.5% (22/259) of the sirolimus-eluting stent group (RR, 2.3 [95% CI, 1.3-3.9]; P = .004). At follow-up angiography, the rate of binary angiographic restenosis for the analysis segment was 29.5% (31/105) for the vascular brachytherapy group and 19.8% (45/227) for the sirolimus-eluting stent group (RR, 1.5 [95% CI, 1.0-2.2]; P = .07). Compared with the vascular brachytherapy group, minimal lumen diameter was larger in the sirolimus-eluting stent group at 6-month follow-up (mean [SD], 1.52 [0.63] mm vs 1.80 [0.63] mm; P<.001), reflecting greater net lumen gain in the analysis segment (0.68 [0.60] vs 1.0 [0.61] mm; P<.001) due to stenting and no edge restenosis. Conclusion  Sirolimus-eluting stents result in superior clinical and angiographic outcomes compared with vascular brachytherapy for the treatment of restenosis within a bare-metal stent. Trial Registration  ClinicalTrials.gov Identifier: NCT00231257      

Sirolimus-eluting stents vs paclitaxel-eluting stents in patients with coronary artery disease: meta-analysis of randomized trials

Context  Placement of sirolimus-eluting stents or paclitaxel-eluting stents has emerged as the predominant percutaneous treatment strategy in patients with coronary artery disease (CAD). Whether there are any differences in efficacy and safety between these 2 drug-eluting stents is unclear. Objective  To compare outcomes of sirolimus-eluting and paclitaxel-eluting coronary stents on the basis of data generated by randomized head-to-head clinical trials. Data Sources  PubMed and the Cochrane Central Register of Controlled Trials, conference proceedings from major cardiology meetings, and Internet-based sources of information on clinical trials in cardiology from January 2003 to April 2005. Study Selection  Randomized trials comparing the sirolimus-eluting stent with the paclitaxel-eluting stent in patients with CAD reporting the outcomes of interest (target lesion revascularization, angiographic restenosis, stent thrombosis, myocardial infarction [MI], death, and the composite of death or MI) during a follow-up of at least 6 months. Data Extraction  Two reviewers independently identified studies and abstracted data on sample size, baseline characteristics, and outcomes of interest. Data Synthesis  Six trials, including 3669 patients, met the selection criteria. No significant heterogeneity was found across trials. Target lesion revascularization, the primary outcome of interest, was less frequently performed in patients who were treated with the sirolimus-eluting stent (5.1%) vs the paclitaxel-eluting stent (7.8%) (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.49-0.84; P = .001). Similarly, angiographic restenosis was less frequently observed among patients assigned to the sirolimus-eluting stent (9.3%) vs the paclitaxel-eluting stent (13.1%) (OR, 0.68; 95% CI, 0.55-0.86; P = .001). Event rates for sirolimus-eluting vs paclitaxel-eluting stents were 0.9% and 1.1%, respectively, for stent thrombosis (P = .62); 1.4% and 1.6%, respectively, for death (P = .56); and 4.9% and 5.8%, respectively, for the composite of death or MI (P = .23). Conclusions  Patients receiving sirolimus-eluting stents had a significantly lower risk of restenosis and target vessel revascularization compared with those receiving paclitaxel-eluting stents. Rates of death, death or MI, and stent thrombosis were similar.      

Sirolimus-eluting stent or paclitaxel-eluting stent vs balloon angioplasty for prevention of recurrences in patients with coronary in-stent restenosis: a randomized controlled trial

Context  In patients with de novo coronary lesions, drug-eluting stents have drastically reduced restenosis risk compared with bare metal stents and conventional balloon angioplasty. It is less clear whether drug-eluting stents are superior to conventional balloon angioplasty for the treatment of patients with in-stent restenosis. Objectives  To assess if drug-eluting stents are a more effective treatment of in-stent restenosis than conventional balloon angioplasty, and to assess the relative merits of 2 drug-eluting stents, a sirolimus-eluting stent and a paclitaxel-eluting stent. Design, Setting, and Participants  Randomized, open-label, active-controlled trial conducted among 300 patients with angiographically significant in-stent restenosis in 2 tertiary German centers from June 1, 2003, to October 20, 2003. Interventions  After pretreatment with 600 mg of clopidogrel for at least 2 hours before intervention, all patients were randomly assigned to 1 of 3 treatment groups: sirolimus stent, paclitaxel stent, or balloon angioplasty (100 patients in each group). Main Outcome Measures  Primary end point: angiographic restenosis (diameter stenosis 50%) at 6-month follow-up angiography based on "in-segment" analysis. Primary analysis was comparison between stent groups and balloon angioplasty groups; a secondary analysis compared sirolimus and paclitaxel stents. Results  Follow-up angiography was performed in 275 (92%) of 300 patients. The incidence of angiographic restenosis was 44.6% (41/92) in the balloon angioplasty group, 14.3% (13/91) in the sirolimus stent group (P<.001 vs balloon angioplasty), and 21.7% (20/92) in the paclitaxel stent group (P = .001 vs balloon angioplasty). When compared with balloon angioplasty, receiving a sirolimus stent had a relative risk (RR) of angiographic restenosis of 0.32 (95% confidence interval [CI], 0.18-0.56); a paclitaxel stent had an RR of 0.49 (95% CI, 0.31-0.76). The incidence of target vessel revascularization was 33.0% (33/100) in the balloon angioplasty group, 8.0% (8/100) in the sirolimus stent group (P<.001 vs balloon angioplasty), and 19.0% (19/100) in the paclitaxel stent group (P = .02 vs balloon angioplasty). The secondary analysis showed a trend toward a lower rate of angiographic restenosis (P = .19) and a significantly lower rate of target vessel revascularization (P = .02) among sirolimus stent patients compared with paclitaxel stent patients. Conclusions  In patients with in-stent restenosis, a strategy based on sirolimus- or paclitaxel-eluting stents is superior to conventional balloon angioplasty for the prevention of recurrent restenosis. Sirolimus-eluting stents may be superior to paclitaxel-eluting stents for treatment of this disorder.      

Paclitaxel-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the TAXUS V ISR randomized trial

Context  Restenosis within bare-metal stents is often treated with repeat percutaneous coronary intervention, although subsequent recurrence rates are high, with vascular brachytherapy (VBT) affording the best results. The effectiveness of drug-eluting stents in this setting has not been established. Objective  To investigate the safety and efficacy of the polymer-based, slow-release paclitaxel-eluting stent in patients with restenotic lesions after prior stent implantation in native coronary arteries. Design, Setting, and Patients  Prospective, multicenter, randomized trial conducted between June 6, 2003, and July 16, 2004, at 37 North American academic and community-based institutions in 396 patients with in-stent restenosis of a previously implanted bare-metal coronary stent (vessel diameter, 2.5-3.75 mm; lesion length, 46 mm). Interventions  Patients were randomly assigned to undergo angioplasty followed by VBT with a source (n = 201) or paclitaxel-eluting stent implantation (n = 195). Clinical and angiographic follow-up at 9 months was scheduled in all patients. Main Outcome Measure  Ischemia-driven target vessel revascularization at 9 months. Results  Diabetes mellitus was present in 139 patients (35.1%). Median reference vessel diameter was 2.65 mm and median lesion length was 15.3 mm. In the VBT group, new stents were implanted in 22 patients (10.9%) and in the paclitaxel-eluting stent group, multiple stents were required in 57 patients (29.2%), with median stent length of 24 mm. Follow-up at 9 months was complete in 194 patients in the VBT group and 191 patients in the paclitaxel-eluting stent group (96.5% and 97.9%, respectively). For VBT and paclitaxel-eluting stents, respectively, the number of events and 9-month rates for ischemic target lesion revascularization were 27 (13.9%) vs 12 (6.3%) (relative risk [RR], 0.45; 95% confidence interval [CI], 0.24-0.86; P = .01); for ischemic target vessel revascularization, 34 (17.5%) vs 20 (10.5%) (RR, 0.60; 95% CI, 0.36-1.00; P = .046); and for overall major adverse cardiac events, 39 (20.1%) vs 22 (11.5%) (RR, 0.57; 95% CI, 0.35-0.93; P = .02), with similar rates of cardiac death or myocardial infarction (10 [5.2%] vs 7 [3.7%]; RR, 0.71; 95% CI, 0.28-1.83; P = .48) and target vessel thrombosis (5 [2.6%] vs 3 [1.6%]; RR, 0.61; 95% CI, 0.15-2.50; P = .72). Angiographic restenosis at 9 months was 31.2% (53 of 170 patients) with VBT and 14.5% (25 of 172 patients) with paclitaxel-eluting stents (RR, 0.47; 95% CI, 0.30-0.71; P<.001). Conclusion  Treatment of bare-metal in-stent restenotic lesions with paclitaxel-eluting stents rather than angioplasty followed by VBT reduces clinical and angiographic restenosis at 9 months and improves event-free survival. Trial Registration  ClinicalTrials.gov Identifier: NCT00287573      

Sirolimus- vs paclitaxel-eluting stents in de novo coronary artery lesions: the REALITY trial: a randomized controlled trial

Context  Compared with bare metal stents, sirolimus-eluting and paclitaxel-eluting stents have been shown to markedly improve angiographic and clinical outcomes after percutaneous coronary revascularization, but their performance in the treatment of de novo coronary lesions has not been compared in a prospective multicenter study. Objective  To compare the safety and efficacy of sirolimus-eluting vs paclitaxel-eluting coronary stents. Design  Prospective, randomized comparative trial (the REALITY trial) conducted between August 2003 and February 2004, with angiographic follow-up at 8 months and clinical follow-up at 12 months. Setting  Ninety hospitals in Europe, Latin America, and Asia. Patients  A total of 1386 patients (mean age, 62.6 years; 73.1% men; 28.0% with diabetes) with angina pectoris and 1 or 2 de novo lesions (2.25-3.00 mm in diameter) in native coronary arteries. Intervention  Patients were randomly assigned in a 1:1 ratio to receive a sirolimus-eluting stent (n = 701) or a paclitaxel-eluting stent (n = 685). Main Outcome Measures  The primary end point was in-lesion binary restenosis (presence of a more than 50% luminal-diameter stenosis) at 8 months. Secondary end points included 1-year rates of target lesion and vessel revascularization and a composite end point of cardiac death, Q-wave or non–Q-wave myocardial infarction, coronary artery bypass graft surgery, or repeat target lesion revascularization. Results  In-lesion binary restenosis at 8 months occurred in 86 patients (9.6%) with a sirolimus-eluting stent vs 95 (11.1%) with a paclitaxel-eluting stent (relative risk [RR], 0.84; 95% confidence interval [CI], 0.61-1.17; P = .31). For sirolimus- vs paclitaxel-eluting stents, respectively, the mean (SD) in-stent late loss was 0.09 (0.43) mm vs 0.31 (0.44) mm (difference, –0.22 mm; 95% CI, –0.26 to –0.18 mm; P<.001), mean (SD) in-stent diameter stenosis was 23.1% (16.6%) vs 26.7% (15.8%) (difference, –3.60%; 95% CI, –5.12% to –2.08%; P<.001), and the number of major adverse cardiac events at 1 year was 73 (10.7%) vs 76 (11.4%) (RR, 0.94; 95% CI, 0.69-1.27; P = .73). Conclusion  In this trial comparing sirolimus- and paclitaxel-eluting coronary stents, there were no differences in the rates of binary restenosis or major adverse cardiac events. Clinical Trial Registration  ClinicalTrials.gov Identifier: NCT00235092      

Outcomes following coronary stenting in the era of bare-metal vs the era of drug-eluting stents

David J. Malenka, MD; Aaron V. Kaplan, MD; F. Lee Lucas, PhD; Sandra M. Sharp, SM; Jonathan S. Skinner, PhD

JAMA. 2008;299(24):2868-2876.

Context  Although drug-eluting stents reduce restenosis rates relative to bare-metal stents, concerns have been raised that drug-eluting stents may also be associated with an increased risk of stent thrombosis. Our study focused on the effect of stent type on population-based interventional outcomes.

Objective  To compare outcomes of Medicare beneficiaries who underwent nonemergent coronary stenting before and after the availability of drug-eluting stents.

Design, Setting, and Patients  Observational study of 38 917 Medicare patients who underwent nonemergent coronary stenting from October 2002 through March 2003 when only bare-metal stents were available (bare-metal stent era cohort) and 28 086 similar patients who underwent coronary stenting from September through December 2003, when 61.5% of patients received a drug-eluting stent and 38.5% received a bare-metal stent (drug-eluting stent era cohort). Follow-up data were available through December 31, 2005.

Main Outcome Measures  Coronary revascularization (percutaneous coronary intervention, coronary artery bypass surgery), ST-elevation myocardial infarction, survival through 2 years of follow-up.

Results  Relative to the bare-metal stent era, patients treated in the drug-eluting stent era had lower 2-year risks for repeat percutaneous coronary interventions (17.1% vs 20.0%, P < .001) and coronary artery bypass surgery (2.7% vs 4.2%, P < .01). The difference in need for repeat revascularization procedures between these 2 eras remained significant after risk adjustment (hazard ratio, 0.82; 95% confidence interval, 0.79-0.85). There was no difference in unadjusted mortality risks at 2 years (8.4% vs 8.4%, P =.98 ), but a small decrease in ST-elevation myocardial infarction existed (2.4% vs 2.0%, P < .001). The adjusted hazard of death or ST-elevation myocardial infarction at 2 years was similar (hazard ratio, 0.96; 95% confidence interval, 0.92-1.01).

Conclusion  The widespread adoption of drug-eluting stents into routine practice was associated with a decline in the need for repeat revascularization procedures and had similar 2-year risks for death or ST-elevation myocardial infarction to bare-metal stents.

     

Tirofiban and sirolimus-eluting stent vs abciximab and bare-metal stent for acute myocardial infarction: a randomized trial

Context  Bare-metal stenting with abciximab pretreatment is currently considered a reasonable reperfusion strategy for acute ST-segment elevation myocardial infarction (STEMI). Sirolimus-eluting stents significantly reduce the need for target-vessel revascularization (TVR) vs bare-metal stents but substantially increase procedural costs. At current European list prices, the use of tirofiban instead of abciximab would absorb the difference in cost between stenting with sirolimus-eluting vs bare-metal stents. Objective  To evaluate the clinical and angiographic impact of single high-dose bolus tirofiban plus sirolimus-eluting stenting vs abciximab plus bare-metal stenting in patients with STEMI. Design, Setting, and Patients  Prospective, single-blind, randomized controlled study (Single High Dose Bolus Tirofiban and Sirolimus Eluting Stent vs Abciximab and Bare Metal Stent in Myocardial Infarction [STRATEGY]) of 175 patients (median age, 63 [interquartile range, 55-72] years) presenting to a single referral center in Italy with STEMI or presumed new left bundle-branch block and randomized between March 6, 2003, and April 23, 2004. Intervention  Single high-dose bolus tirofiban regimen plus sirolimus-eluting stenting (n = 87) vs standard-dose abciximab plus bare-metal stenting (n = 88). Main Outcome Measures  The primary end point was a composite of death, nonfatal myocardial infarction, stroke, or binary restenosis at 8 months. Secondary outcomes included freedom, at day 30 and month 8, from major cardiac or cerebrovascular adverse events (composite of death, reinfarction, stroke, and repeat TVR). Results  Cumulatively, 14 of 74 patients (19%; 95% confidence interval [CI], 10%-28%) in the tirofiban plus sirolimus-eluting stent group and 37 of 74 patients (50%; 95% CI, 44%-56%) in the abciximab plus bare-metal stent group reached the primary end point (hazard ratio, 0.33; 95% CI, 0.18-0.60; P<.001 [P<.001 by Fischer exact test]). The cumulative incidence of death, reinfarction, stroke, or TVR was significantly lower in the tirofiban plus sirolimus-eluting stent group (18%) vs the abciximab plus bare-metal stent group (32%) (hazard ratio, 0.53; 95% CI, 0.28-0.92; P = .04), predominantly reflecting a reduction in the need for TVR. Binary restenosis was present in 6 of 67 (9%; 95% CI, 2%-16%) and 24 of 66 (36%; 95% CI, 26%-46%) patients in the tirofiban plus sirolimus-eluting stent and abciximab plus bare-metal stent groups, respectively (P = .002). Conclusion  Tirofiban-supported sirolimus-eluting stenting of infarcted arteries holds promise for improving outcomes while limiting health care expenditure in patients with myocardial infarction undergoing primary intervention.      

Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial

Context  Compared with bare metal stents, drug-eluting stents reduce restenosis in noncomplex lesions. The utility of drug-eluting stents has not been evaluated in more difficult stenoses. Objective  To investigate the safety and efficacy of the polymer-based, slow-release paclitaxel-eluting stent in a patient population with more complex lesions than previously studied. Design, Setting, and Patients  Prospective, placebo-controlled, double-blind, multicenter randomized trial conducted from February 2003 to March 2004 at 66 academic and community-based institutions with 1156 patients who underwent stent implantation in a single coronary artery stenosis (vessel diameter, 2.25-4.0 mm; lesion length, 10-46 mm), including 664 patients (57.4%) with complex or previously unstudied lesions (requiring 2.25-mm, 4.0-mm, and/or multiple stents) and 9-month clinical and angiographic follow-up. Interventions  Patients were randomly assigned to receive 1 or more bare metal stents (n = 579) or identical-appearing paclitaxel-eluting stents (n = 577). Main Outcome Measure  Ischemia-driven target vessel revascularization at 9 months. Results  Baseline characteristics were well matched. Diabetes was present in 31% of patients. The mean (SD) reference vessel diameter was 2.69 (0.57) mm, the reference lesion length was 17.2 (9.2) mm, and 78% of lesions were type B₂/C. A mean (SD) of 1.38 (0.58) stents (total mean [SD] length, 28.4 [13.1] mm) were implanted per lesion; 33% of lesions required multiple stents. Stents that were 2.25 mm and 4.0 mm in diameter were used in 18% and 17% of lesions, respectively. Compared with bare metal stents, paclitaxel-eluting stents reduced the 9-month rate of target lesion revascularization from 15.7% to 8.6% (P<.001) and target vessel revascularization from 17.3% to 12.1% (P = .02). Similar rates were observed for cardiac death or myocardial infarction (5.5% for bare metal stent group vs 5.7% for paclitaxel-eluting stent group) and stent thrombosis (0.7% in both groups). Angiographic restenosis was reduced from 33.9% to 18.9% in the entire study cohort (P<.001), including among patients receiving 2.25-mm stents (49.4% vs 31.2%; P = .01), 4.0-mm stents (14.4% vs 3.5%; P = .02), and multiple stents (57.8% vs 27.2%; P<.001). Conclusion  Compared with a bare metal stent, implantation of the paclitaxel-eluting stent in a patient population with complex lesions effectively reduces clinical and angiographic restenosis.      

Comparison of angioplasty with infusion of tirofiban or abciximab and with implantation of sirolimus-eluting or uncoated stents for acute myocardial infarction: the MULTISTRATEGY randomized trial

Context  Abciximab infusion and uncoated-stent implantation is a complementary treatment strategy to reduce major adverse cardiac events in patients undergoing angioplasty for ST-segment elevation myocardial infarction (STEMI). It is uncertain whether there may be similar benefits in replacing abciximab with high-dose bolus tirofiban. Similarly, the use of drug-eluting stents in this patient population is currently discouraged because of conflicting results on efficacy reported in randomized trials and safety concerns reported by registries. Objective  To evaluate the effect of high-dose bolus tirofiban and of sirolimus-eluting stents as compared with abciximab infusion and uncoated-stent implantation in patients with STEMI undergoing percutaneous coronary intervention. Design, Setting, and Patients  An open-label, 2 x 2 factorial trial of 745 patients presenting with STEMI or new left bundle-branch block at 16 referral centers in Italy, Spain, and Argentina between October 2004 and April 2007. Interventions  High-dose bolus tirofiban vs abciximab infusion and sirolimus-eluting stent vs uncoated stent implantation. Main Outcome Measures  For drug comparison, at least 50% ST-segment elevation resolution at 90 minutes postintervention with a prespecified noninferiority margin of 9% difference (relative risk, 0.89); for stent comparison, the rate of major adverse cardiac events, defined as the composite of death from any cause, reinfarction, and clinically driven target-vessel revascularization within 8 months. Results  ST-segment resolution occurred in 302 of 361 patients (83.6%) who had received abciximab infusion and 308 of 361 (85.3%) who had received tirofiban infusion (relative risk, 1.020; 97.5% confidence interval, 0.958-1.086; P < .001 for noninferiority). Ischemic and hemorrhagic outcomes were similar in the tirofiban and abciximab groups. At 8 months, major adverse cardiac events occurred in 54 patients (14.5%) with uncoated stents and 29 (7.8%) with sirolimus stents (P = .004), predominantly reflecting a reduction of revascularization rates (10.2% vs 3.2%). The incidence of stent thrombosis was similar in the 2 stent groups. Conclusions  In patients with STEMI undergoing percutaneous coronary intervention, compared with abciximab, tirofiban therapy was associated with noninferior resolution of ST-segment elevation at 90 minutes following coronary intervention, whereas sirolimus-eluting stent implantation was associated with a significantly lower risk of major adverse cardiac events than uncoated stents within 8 months after intervention. Trial Registration  clinicaltrials.gov Identifier: NCT00229515      

Certificate of need regulations and use of coronary revascularization after acute myocardial infarction

Context  Certificate of need regulations were enacted to control health care costs by limiting unnecessary expansion of services. While many states have repealed certificate of need regulations in recent years, few analyses have examined relationships between certificate of need regulations and outcomes of care. Objective  To compare rates of coronary revascularization and mortality after acute myocardial infarction in states with and without certificate of need regulations. Design, Setting, and Participants  Retrospective cohort study of 1 139 792 Medicare beneficiaries aged 68 years or older with AMI who were admitted to 4587 US hospitals during 2000-2003. Main Outcome Measures  Thirty-day risk-adjusted rates of coronary revascularization with either coronary artery bypass graft surgery or percutaneous coronary intervention and 30-day all-cause mortality. Results  The 624 421 patients in states with certificate of need regulations were less likely to be admitted to hospitals with coronary revascularization services (321 573 [51.5%] vs 323 695 [62.8%]; P<.001) or to undergo revascularization at the admitting hospital (163 120 [26.1%] vs 163 877 [31.8%]; P<.001) than patients in states without certificates of need but were more likely to undergo revascularization at a transfer hospital (73 379 [11.7%] vs 45 907 [8.9%]; P<.001). Adjusting for demographic and clinical risk factors, patients in states with highly and moderately stringent certificate of need regulations, respectively, were less likely to undergo revascularization within the first 2 days (adjusted hazard ratios, 0.68; 95% confidence interval [CI], 0.54-0.87; P = .002 and 0.80; 95% CI, 0.71-0.90; P<.001) relative to patients in states without certificates of need, although no differences in the likelihood of revascularization were observed during days 3 through 30. Unadjusted 30-day mortality was similar in states with and without certificates of need (109 304 [17.5%] vs 90 104 [17.5%]; P = .76), as was adjusted mortality (odds ratio, 1.00; 95% CI, 0.97-1.03; P = .90). Conclusions  Patients with acute myocardial infarction were less likely to be admitted to hospitals offering coronary revascularization and to undergo early revascularization in states with certificate of need regulations. However, differences in the availability and use of revascularization therapies were not associated with mortality.      

Outcomes and complications associated with off-label and untested use of drug-eluting stents

Context  Limited data exist regarding use of drug-eluting stents outside of approved indications in real-world settings. Objectives  To determine the frequency, safety, and effectiveness of drug-eluting stents for off-label (restenosis, bypass graft lesion, long lesions, vessel size outside of information for use recommendation) and untested (left main, ostial, bifurcation, or total occlusion lesions) indications in percutaneous coronary intervention (PCI). Design, Setting, and Patients  Observational, prospective, multicenter registry to evaluate in-hospital, 30-day, and 1-year outcomes among patients undergoing PCI between January and June 2005 in 140 US academic and community medical centers. Of 7752 PCI-treated patients, 6993 (90%) received drug-eluting stents; of these, 5851 (84%) received no other devices. Standard, off-label, and untested use was determined in 5541 (95%) of these 5851 patients, constituting the study cohort. Main Outcome Measures  Frequency of off-label and untested use, 1-year repeat target vessel revascularization, and composite of death, myocardial infarction (MI), or stent thrombosis at in-hospital follow-up and during 1 year of follow-up. Results  Of 5541 patients receiving drug-eluting stents, 2588 (47%) received stents for off-label or untested indications. Adjusted in-hospital risk of death, MI, or stent thrombosis was not statistically different with off-label or untested vs standard use. At 30 days, the risk of this composite end point was significantly higher with off-label use (adjusted hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.24-3.48; P = .005) but not untested use (adjusted HR, 1.45; 95% CI, 0.79-2.67; P = .23). Excluding early events, this end point was not different at 1 year with off-label use (adjusted HR, 1.10; 95% CI, 0.79-1.54; P = .57) or untested use (adjusted HR, 0.91; 95% CI, 0.60-1.38; P = .66). At 1 year, compared with standard use, significantly higher rates of target vessel revascularization were associated with off-label use (adjusted HR, 1.49; 95% CI, 1.13-1.98; P = .005) and untested use (adjusted HR, 1.49; 95% CI, 1.10-2.02; P = .01), although absolute rates were low (standard, 4.4% [n = 113]; off-label, 7.6% [n = 95]; untested, 6.7% [n = 72]). Conclusions  In contemporary US practice, off-label and untested use of drug-eluting stents is common. Compared with standard use, relative early safety is lower with off-label use, and the long-term effectiveness is lower with both off-label and untested use. However, the absolute event rates remain low.      

Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents

Context  Traditionally, stent thrombosis has been regarded as a complication of percutaneous coronary interventions during the first 30 postprocedural days. However, delayed endothelialization associated with the implantation of drug-eluting stents may extend the risk of thrombosis beyond 30 days. Data are limited regarding the risks and the impact of this phenomenon outside clinical trials. Objective  To evaluate the incidence, predictors, and clinical outcome of stent thrombosis after implantation of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice. Design, Setting, and Patients  Prospective observational cohort study conducted at 1 academic hospital and 2 community hospitals in Germany and Italy. A total of 2229 consecutive patients underwent successful implantation of sirolimus-eluting (1062 patients, 1996 lesions, 2272 stents) or paclitaxel-eluting (1167 patients, 1801 lesions, 2223 stents) stents between April 2002 and January 2004. Interventions  Implantation of a drug-eluting stent (sirolimus or paclitaxel). All patients were pretreated with ticlopidine or clopidogrel and aspirin. Aspirin was continued indefinitely and clopidogrel or ticlopidine for at least 3 months after sirolimus-eluting and for at least 6 months after paclitaxel-eluting stent implantation. Main Outcome Measures  Subacute thrombosis (from procedure end through 30 days), late thrombosis (>30 days), and cumulative stent thrombosis. Results  At 9-month follow-up, 29 patients (1.3%) had stent thrombosis (9 [0.8%] with sirolimus and 20 [1.7%] with paclitaxel; P = .09). Fourteen patients had subacute thrombosis (0.6%) and 15 patients had late thrombosis (0.7%). Among these 29 patients, 13 died (case fatality rate, 45%). Independent predictors of stent thrombosis were premature antiplatelet therapy discontinuation (hazard ratio [HR],  89.78; 95% CI, 29.90-269.60; P<.001), renal failure (HR,  6.49; 95% CI, 2.60-16.15; P<.001), bifurcation lesions (HR,  6.42; 95% CI, 2.93-14.07; P<.001), diabetes (HR,  3.71; 95% CI, 1.74-7.89; P = .001), and a lower ejection fraction (HR,  1.09; 95% CI, 1.05-1.36; P<.001 for each 10% decrease). Conclusions  The cumulative incidence of stent thrombosis 9 months after successful drug-eluting stent implantation in consecutive "real-world" patients was substantially higher than the rate reported in clinical trials. Premature antiplatelet therapy discontinuation, renal failure, bifurcation lesions, diabetes, and low ejection fraction were identified as predictors of thrombotic events.      

Effect of homocysteine-lowering therapy with folic acid,vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial

Context  Plasma homocysteine level has been recognized as an important cardiovascular risk factor that predicts adverse cardiac events in patients with established coronary atherosclerosis and influences restenosis rate after percutaneous coronary intervention. Objective  To evaluate the effect of homocysteine-lowering therapy on clinical outcome after percutaneous coronary intervention. Design, Setting, and Participants  Randomized, double-blind placebo-controlled trial involving 553 patients referred to the University Hospital in Bern, Switzerland, from May 1998 to April 1999 and enrolled after successful angioplasty of at least 1 significant coronary stenosis (50%). Intervention  Participants were randomly assigned to receive a combination of folic acid (1 mg/d), vitamin B₁₂ (cyanocobalamin, 400 µg/d), and vitamin B₆ (pyridoxine hydrochloride, 10 mg/d) (n = 272) or placebo (n = 281) for 6 months. Main Outcome Measure  Composite end point of major adverse events defined as death, nonfatal myocardial infarction, and need for repeat revascularization, evaluated at 6 months and 1 year. Results  After a mean (SD) follow-up of 11 (3) months, the composite end point was significantly lower at 1 year in patients treated with homocysteine-lowering therapy (15.4% vs 22.8%; relative risk [RR], 0.68; 95% confidence interval [CI], 0.48-0.96; P = .03), primarily due to a reduced rate of target lesion revascularization (9.9% vs 16.0%; RR, 0.62; 95% CI, 0.40-0.97; P = .03). A nonsignificant trend was seen toward fewer deaths (1.5% vs 2.8%; RR, 0.54; 95% CI, 0.16-1.70; P = .27) and nonfatal myocardial infarctions (2.6% vs 4.3%; RR, 0.60; 95% CI, 0.24-1.51; P = .27) with homocysteine-lowering therapy. These findings remained unchanged after adjustment for potential confounders. Conclusion  Homocysteine-lowering therapy with folic acid, vitamin B₁₂, and vitamin B₆ significantly decreases the incidence of major adverse events after percutaneous coronary intervention.      

Prophylactic Oral Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularization, Valve Replacement, or Repair: PAPABEAR: a randomized controlled trial

Context  Atrial tachyarrhythmias after cardiac surgery are associated with adverse outcomes and increased costs. Previous trials of amiodarone prophylaxis, while promising, were relatively small and yielded conflicting results. Objective  To determine whether a brief perioperative course of oral amiodarone is an effective and safe prophylaxis for atrial tachyarrhythmias after cardiac surgery overall and in important subgroups. Design, Setting, and Patients  Double-blind randomized controlled trial of 601 patients listed for nonemergent coronary artery bypass graft (CABG) surgery and/or valve replacement/repair surgery between February 1, 1999, and September 26, 2003, at a tertiary care hospital. The patients were followed up for 1 year. Intervention  Oral amiodarone (10 mg/kg daily) or placebo administered 6 days prior to surgery through 6 days after surgery (13 days). Randomization was stratified for subgroups defined by age, type of surgery, and use of preoperative -blockers. Main Outcome Measure  Incidence of atrial tachyarrhythmias lasting 5 minutes or longer that prompted therapy by the sixth postoperative day. Results  Atrial tachyarrhythmias occurred in fewer amiodarone patients (48/299; 16.1%) than in placebo patients (89/302; 29.5%) overall (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.34-0.69; P<.001); in patients younger than 65 years (19 [11.2%] vs 36 [21.1%]; HR, 0.51 [95% CI, 0.28-0.94]; P = .02); in patients aged 65 years or older (28 [21.7%] vs 54 [41.2%]; HR, 0.45 [95% CI, 0.27-0.75]; P<.001); in patients who had CABG surgery only (22 [11.3%] vs 46 [23.6%]; HR, 0.45 [95% CI, 0.26-0.79]; P = .002); in patients who had valve replacement/repair surgery with or without CABG surgery (25 [23.8%] vs 44 [44.1%]; HR, 0.51 [95% CI, 0.31-0.84; P = .008); in patients who received preoperative -blocker therapy (27 [15.3%] vs 42 [25.0%]; HR, 0.58 [95% CI, 0.34-0.99]; P = .03); and in patients who did not receive preoperative -blocker therapy (20 [16.3%] vs 48 [35.8%]; HR, 0.40 [95% CI, 0.22-0.71]; P<.001), respectively. Postoperative sustained ventricular tachyarrhythmias occurred less frequently in amiodarone patients (1/299; 0.3%) than in placebo patients (8/302; 2.6%) (P = .04). Dosage reductions of blinded therapy were more common in amiodarone patients (34/299; 11.4%) than in placebo patients (16/302; 5.3%) (P = .008). There were no differences in serious postoperative complications, in-hospital mortality, or readmission to the hospital within 6 months of discharge or in 1-year mortality. Conclusion  Oral amiodarone prophylaxis of atrial tachyarrhythmias after cardiac surgery is effective and may be safe overall and in important patient subgroups. Clinical Trials Registration  ClinicalTrials.gov Identifier: NCT00251706      

Opening of specialty cardiac hospitals and use of coronary revascularization in medicare beneficiaries

Context  Although proponents argue that specialty cardiac hospitals provide high-quality cost-efficient care, strong financial incentives for physicians at these facilities could result in greater procedure utilization. Objective  To determine whether the opening of cardiac hospitals was associated with increasing population-based rates of coronary revascularization. Design, Setting, and Patients  In a study of Medicare beneficiaries from 1995 through 2003, we calculated annual population-based rates for total revascularization (coronary artery bypass graft [CABG] plus percutaneous coronary intervention [PCI]), CABG, and PCI. Hospital referral regions (HRRs) were used to categorize health care markets into those where (1) cardiac hospitals opened (n = 13), (2) new cardiac programs opened at general hospitals (n = 142), and (3) no new programs opened (n = 151). Main Outcome Measures  Rates of change in total revascularization, CABG, and PCI using multivariable linear regression models with generalized estimating equations. Results  Overall, rates of change for total revascularization were higher in HRRs after cardiac hospitals opened when compared with HRRs where new cardiac programs opened at general hospitals and HRRs with no new programs (P<.001 for both comparisons). Four years after their opening, the relative increase in adjusted rates was more than 2-fold higher in HRRs where cardiac hospitals opened (19.2% [95% confidence interval {CI}, 6.1%-32.2%], P<.001) when compared with HRRs where new cardiac programs opened at general hospitals (6.5% [95% CI, 3.2%-9.9%], P<.001) and HRRs with no new programs (7.4% [95% CI, 3.2%-11.5%], P<.001). These findings were consistent when rates for CABG and PCI were considered separately. For PCI, this growth appeared largely driven by increased utilization among patients without acute myocardial infarction (42.1% [95% CI, 21.4%-62.9%], P<.001). Conclusion  The opening of a cardiac hospital within an HRR is associated with increasing population-based rates of coronary revascularization in Medicare beneficiaries.      

Diabetes and coronary revascularization

Context  Patients with diabetes mellitus account for approximately 25% of the nearly 1.5 million coronary revascularization procedures performed each year in the United States and experience worse outcomes compared with nondiabetic patients. Objectives  To summarize the current state of evidence comparing the effectiveness and safety of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) in diabetic patients and to examine developments that may affect future outcomes in this high-risk group. Evidence Acquisition  Using the key terms diabetes mellitus, revascularization, coronary artery bypass, angioplasty, and coronary intervention, we searched MEDLINE from 1985 to 2004 for all randomized controlled trials (RCTs) comparing CABG surgery and PCI that reported outcomes in diabetic patients. Bibliographies and the Web sites of cardiology conferences were also reviewed. Studies comparing drug-eluting stents and bare-metal stents were identified in a similar fashion. The literature was reviewed to identify clinical measures that may impact revascularization outcomes in diabetic patients. Evidence Synthesis  We identified 6 RCTs comparing CABG surgery and PCI in a total of 950 diabetic patients. A mortality benefit for CABG over balloon-only PCI has been demonstrated in diabetic patients with multivessel coronary artery disease but has not been clearly established against stent-assisted PCI or in high-risk CABG patients. Use of glycoprotein IIb/IIIa receptor inhibitors has improved survival in diabetic patients undergoing PCI. Restenosis after PCI in diabetic patients has led to substantially higher repeat revascularization rates than after CABG. The use of drug-eluting stents has led to dramatic reductions in restenosis in diabetic patients. Ongoing RCTs comparing CABG and PCI using drug-eluting stents in diabetic patients will clarify the impact of these advances on outcomes. Conclusions  There is a relative lack of data from RCTs specifically comparing CABG surgery and PCI as currently practiced in diabetic patients. The mortality advantage and decreased rates of revascularization seen with CABG in subgroups from early trials may not be applicable in the era of drug-eluting stents, glycoprotein IIb/IIIa inhibitors, and the latest medical therapies.      

Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study

Context  The benefit of clopidogrel pretreatment before percutaneous coronary intervention (PCI) remains debated and its use has not been universally adopted. Objective  To determine if clopidogrel pretreatment before PCI in patients with recent ST-segment elevation myocardial infarction (STEMI) is superior to clopidogrel treatment initiated at the time of PCI in preventing major adverse cardiovascular events. Design, Setting, and Participants  The PCI-Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY) study was a prospectively planned analysis of the 1863 patients undergoing PCI after mandated angiography in CLARITY–Thrombolysis in Myocardial Infarction (TIMI) 28, a randomized, double-blind, placebo-controlled trial of clopidogrel in patients receiving fibrinolytics for STEMI. Patients were enrolled at 319 sites in 23 countries from February 2003 through October 2004. Interventions  Patients received aspirin and were randomized to receive either clopidogrel (300 mg loading dose, then 75 mg once daily) or placebo initiated with fibrinolysis and given until coronary angiography, which was performed 2 to 8 days after initiation of the study drug. For patients undergoing coronary artery stenting, it was recommended that open-label clopidogrel (including a loading dose) be administered after the diagnostic angiogram. Main Outcome Measures  The primary outcome was the incidence of the composite of cardiovascular death, recurrent MI, or stroke from PCI to 30 days after randomization. Secondary outcomes included MI or stroke before PCI and the aforementioned composite from randomization to 30 days. Results  Pretreatment with clopidogrel significantly reduced the incidence of cardiovascular death, MI, or stroke following PCI (34 [3.6%] vs 58 [6.2%]; adjusted odds ratio [OR], 0.54 [95% CI, 0.35-0.85]; P = .008). Pretreatment with clopidogrel also reduced the incidence of MI or stroke prior to PCI (37 [4.0%] vs 58 [6.2%]; OR, 0.62 [95% CI, 0.40-0.95]; P = .03). Overall, pretreatment with clopidogrel resulted in a highly significant reduction in cardiovascular death, MI, or stroke from randomization through 30 days (70 [7.5%] vs 112 [12.0%]; adjusted OR, 0.59 [95% CI, 0.43-0.81]; P = .001; number needed to treat = 23). There was no significant excess in the rates of TIMI major or minor bleeding (18 [2.0%] vs 17 [1.9%]; P>.99). Conclusions  Clopidogrel pretreatment significantly reduces the incidence of cardiovascular death or ischemic complications both before and after PCI and without a significant increase in major or minor bleeding. These data add further support to the early use of clopidogrel in STEMI and the strategy of routine clopidogrel pretreatment in patients undergoing PCI.