Rationale and design of the MASS COMM trial: A randomized trial to compare percutaneous coronary intervention between MASSachusetts hospitals with cardiac surgery on-site and COMMunity hospitals without cardiac surgery on-site.

BACKGROUND: Emergency surgery has become an increasingly rare event after percutaneous coronary intervention (PCI). There have been no randomized trials evaluating whether cardiac surgery services on-site are essential for patient safety and optimal outcomes during and after PCI. STUDY DESIGN: The MASS COMM trial (ClinicalTrials.gov no. NCT01116882) is a randomized trial comparing the safety and effectiveness of nonemergency PCI at hospitals without surgery on-site (SOS) (non-SOS hospitals) and hospitals with SOS (SOS hospitals). A total of 3,690 subjects will be randomized in a 3:1 fashion to undergo PCI at non-SOS and SOS hospitals, with follow-up at hospital discharge, 30 days, and 12 months after PCI. The rate of major adverse cardiac events (all-cause mortality, myocardial infarction, repeat revascularization, and stroke) will serve as the primary safety end point at 30 days and the primary effectiveness end point at 12 months. The design is a 1-way randomized trial with a statistical hypothesis of noninferiority of nonemergency PCI at non-SOS hospitals for both safety and effectiveness end points. CONCLUSIONS: This multicenter, randomized trial will compare the relative safety and effectiveness of nonemergency PCI at sites with and without cardiac SOS.

Final 5-year results of the TAXUS II trial: a randomized study to assess the effectiveness of slow- and moderate-release polymer-based paclitaxel-eluting stents for de novo coronary artery lesions.

BACKGROUND: The TAXUS II trial was designed to evaluate the safety and efficacy of the commercialized slow-release (SR) and an investigation-only moderate-release (MR) polymer-based TAXUS paclitaxel-eluting stent compared with a bare-metal stent for the treatment of de novo coronary lesions. METHODS AND RESULTS: This prospective, randomized, double-blind, controlled trial enrolled 536 patients in 2 consecutive cohorts to compare TAXUS SR (n=131) and TAXUS MR (n=135) with an identical but uncoated bare-metal stent control (n=270). The present analysis reports final 5-year clinical outcomes of TAXUS II. At 5 years, both TAXUS SR and MR showed superior outcomes compared with control. The 5-year rates of major adverse cardiac events were 27.6%, 20.4%, and 15.1% (P=0.01); rates of target-vessel revascularization were 22.5%, 16.6%, and 9.0% (P=0.004); and rates of target-lesion revascularization were 18.4%, 10.3%, and 4.5% (P<0.001) for the control, TAXUS SR, and TAXUS MR groups, respectively. The rates of all-cause death and myocardial infarction were low and similar between groups, with 2 stent thromboses with bare-metal stents compared with no event beyond 2 years with either of the TAXUS stents. CONCLUSIONS: TAXUS II is the first large TAXUS trial to have reached 5-year follow-up. Both the SR and MR stents lowered the rates of target-vessel and target-lesion revascularization, which indicates their sustained efficacy. Furthermore, the low overall rates of all death, myocardial infarction, and stent thrombosis support the long-term safety of the TAXUS stent system.

Comparison of inflammatory response after implantation of sirolimus- and paclitaxel-eluting stents in porcine coronary arteries.

BACKGROUND: Although both sirolimus (CYPHER) and paclitaxel (TAXUS) drug-eluting stents have demonstrated efficacy and safety in clinical trials, human autopsy data have raised concerns about long-term healing and the potential for local inflammatory reactions. METHODS AND RESULTS: Overlapping stents (CYPHER drug-eluting stents, Bx SONIC bare metal stents, TAXUS drug-eluting stents, and Liberté bare metal stents) were implanted in noninjured coronary arteries of 58 domestic swine. Histopathological evaluation of proximal, overlapped, and distal stented segments was determined with emphasis on inflammation at 30, 90, and 180 days. Circumferential granulomatous inflammation in all stented segments was defined as inflammation consisting of macrophages, multinucleated giant cells, lymphocytes, and granulocytes, including many eosinophils, adjacent to almost all struts. Circumferential granulomatous inflammation was more prevalent in CYPHER (9 of 23, 39%) compared with TAXUS (1 of 21, 5%; P=0.01) and control bare metal stents (0 of 44) in the combined 90- and 180-day cohorts. Only CYPHER specimens showed marked adventitial inflammation (P=0.0025) and fibrosis (P=0.0055) accompanied by extensive remodeling. Fibrin deposition within neointima and medial smooth muscle cell death were greater (both P<0.001) in TAXUS than CYPHER at 30 days, with more fibrin in TAXUS than CYPHER through 90 days (P<0.05). CONCLUSIONS: Although these data cannot be directly extrapolated to humans, the high prevalence in this porcine model of diffuse granulomatous inflammation seen with CYPHER stents, persisting at 180 days and associated with extensive remodeling of the artery, and persistent para-strut fibrin deposition with TAXUS stents emphasize the need for further investigation of biocompatibility with these and other novel combination drug/polymer drug-eluting stents.

Saphenous vein graft stenting and major adverse cardiac events: a predictive model derived from a pooled analysis of 3958 patients.

BACKGROUND: Treatment of saphenous vein graft (SVG) stenosis with percutaneous coronary intervention has a 15% to 20% incidence of major adverse cardiac events (MACE) within 30 days. Although MACE rates are reduced significantly by the use of embolic protection devices (EPDs), neither the level of baseline risk nor the benefit provided by EPDs has been well characterized. METHODS AND RESULTS: Data from 5 randomized controlled trials and 1 registry evaluating EPDs in SVG percutaneous coronary intervention (n=3958 patients) were pooled for analysis. MACE was defined as a composite of death, myocardial infarction, and target vessel revascularization. Baseline variables and 2 summary angiographic variables (an SVG degeneration score and an estimate of lesion plaque volume) were included in a multivariable logistic regression model to predict 30-day MACE, with adjustment for the type of device used and inter-study variation. The angiographic variables were potent predictors of MACE (increasing SVG degeneration score, P<0.0001; larger estimated plaque volume, P<0.0001), with significant contributions from the presence of thrombus (P<0.01), increasing patient age (P<0.01), glycoprotein IIb/IIIa inhibitor use (P=0.02), and current tobacco abuse (P=0.03). The treatment benefit of EPDs was preserved across all categories of risk as categorized by SVG degeneration or plaque volume. CONCLUSIONS: The strongest predictors of 30-day MACE in SVG percutaneous coronary intervention are angiographic estimates of plaque volume and SVG degeneration. Identification of these predictors of 30-day MACE allows reliable prediction of patient outcomes and confirms consistent treatment benefit with the use of EPDs across the range of patients tested in randomized trials.

Offsetting impact of thrombosis and restenosis on the occurrence of death and myocardial infarction after paclitaxel-eluting and bare metal stent implantation.

BACKGROUND: Drug-eluting stents compared with bare metal stents (BMS) may increase late stent thrombosis (ST), although an accompanying increase in the rates of death and myocardial infarction (MI) has not been observed. We hypothesized that the prevention of restenosis-related adverse events by drug-eluting stents might offset some or all of the excess risk from ST. METHODS AND RESULTS: We analyzed a pooled patient-level database from 4 prospective, double-blind trials in which 3445 patients were randomized to paclitaxel-eluting stents or BMS. The occurrence of death or MI within 7 days of ST or target lesion revascularization was assessed. With a median follow-up of 3.2 years, ST occurred in 34 patients (1.0%), 31 (91.1%) of whom sustained death or MI within 7 days. Target lesion revascularization was performed in 425 patients (12.3%), 15 (3.5%) of whom died or had MI within 7 days. ST occurred in 14 BMS and 20 paclitaxel-eluting stent patients, resulting in 12 and 19 deaths or MIs within 7 days, respectively. Target lesion revascularization was performed in 290 BMS and 135 paclitaxel-eluting stent patients, resulting in 11 and 4 deaths or MI events within 7 days, respectively. In total, 23 patients in both the BMS and paclitaxel-eluting stents groups died or had an MI event within 7 days of either ST or target lesion revascularization. CONCLUSIONS: ST, although infrequent, results in a high incident rate of death and MI, whereas the more frequent occurrence of target lesion revascularization is associated with a finite but lower rate of death and MI. The marked reduction in restenosis with drug-eluting stents compared with BMS may counterbalance the potential excess risk from late ST with drug-eluting stents.

Usage patterns and 2-year outcomes with the TAXUS express stent: results of the US ARRIVE 1 registry.

BACKGROUND: It is unclear how well the long-term safety and effectiveness of drug-eluting stents observed in tightly defined randomized controlled trials (RCT) translates to expanded use in routine practice. METHODS: The FDA-mandated TAXUS Express(2) ARRIVE 1 postmarket registry was designed to consecutively enroll patients receiving > or = 1 TAXUS stent in low-, medium-, and high-volume US sites (n = 50). All cardiac events plus an additional 20% sample of records were monitored and all endpoints were independently adjudicated. RESULTS: Detailed follow-up data through 2 years were compiled for 2,487 patients (95%). Simple-use (on-label) ARRIVE 1 patients (35%) had outcomes similar to 4 pooled TAXUS RCTs for death (3.5% vs. 3.4%, respectively, P = 0.78), Q-wave myocardial infarction (QWMI, 0.7% vs. 0.9%, P = 0.72), and stent thrombosis (ST, 2.2% vs. 1.2%, P = 0.12), but lower target vessel revascularization (7.8% vs. 13.4%, P < 0.0001). Compared with simple-use, cases representing expanded use to treat broader patient/lesion characteristics showed higher 2-year rates for death (7.4% vs. 3.5%, respectively, P = 0.0003), target lesion revascularization (9.4% vs. 5.8%, P = 0.0031), and ST (3.4% vs. 2.2%, P = 0.061, concentrated early in the first year). CONCLUSIONS: By including methods usually found in RCT, ARRIVE 1 captured a broad spectrum of disease treated in standard practice with high levels of ascertainment of clinical outcomes. In the more complicated cases, expectedly higher adverse event rates were seen compared to that found in the simple-use cases or pivotal RCT. These results have now been included in the Directions for Use, to aid in physician and patient decision-making.

Carotid artery revascularization in high surgical risk patients with the NexStent and the Filterwire EX/EZ: 1-year results in the CABERNET trial.

OBJECTIVE: The multicenter, single-arm CABERNET trial evaluated outcomes in high-surgical-risk patients with carotid artery stenosis treated with the NexStent plus FilterWire EX/EZ Emboli Protection System. BACKGROUND: For patients at high surgical risk, carotid artery stenting (CAS) offers a less invasive alternative to carotid endarterectomy (CEA). METHODS: The trial enrolled 454 high-surgical-risk patients with carotid stenosis by angiography > or = 50% for symptomatic patients and > or = 60% for asymptomatic patients. The comparator primary endpoint was the 1-year major adverse event (MAE, defined as any death, stroke, or myocardial infarction [MI]) rate. It was compared with a proportionally weighted objective performance criterion (OPC) of 12.1% representative of published CEA results in similar patients plus a prespecified noninferiority margin (delta) of 4%. A second primary endpoint was the composite rate of 30-day MAE plus late (31-365 days) ipsilateral stroke. RESULTS: Symptoms of carotid stenosis were present in 24.2% of patients; 36.6% of patients were considered high-surgical-risk due to comorbid risk factors and 63.4% due to anatomic risk factors. The rate of 30-day MAE plus late ipsilateral stroke was 4.7% (20/438). The comparator primary endpoint of 1-year MAE was 11.6% (51/438) and was noninferior to the OPC of 12.1% (95% upper confidence interval of 14.5% versus OPC plus delta of 16.1%, P = 0.005). Late ipsilateral stroke was 0.7% and target vessel revascularization at 1 year was 2.4%. CONCLUSIONS: The CABERNET trial demonstrates that CAS with NexStent and FilterWire is noninferior to (equivalent or better than) traditional CEA at 1 year in high-surgical-risk patients based on historical controls.

Differential effects between intravenous and targeted renal delivery of fenoldopam on renal function and blood pressure in patients undergoing cardiac catheterization.

A randomized, controlled clinical trial demonstrated that intravenous (IV) fenoldopam did not prevent further deterioration in renal function after contrast administration in patients with chronic renal insufficiency. This lack of effect may have been a consequence of the inability to administer an effective renal dose of IV fenoldopam. This study sought to determine whether compared with IV administration, selective intrarenal (IR) fenoldopam would increase local concentration, leading to a higher glomerular filtration rate (GFR), and, because of first-pass renal elimination, result in lower systemic drug levels and less decrease in systemic blood pressure (BP). A randomized, controlled, open-label, partial crossover design trial was conducted in which 33 patients who underwent coronary angiography were randomized in a 1:2 ratio to control or fenoldopam (initially IV, then crossed over to IR through a bifurcated renal infusion catheter). Compared with IV fenoldopam, IR administration was associated with a significantly higher GFR (73.7 +/- 3.1 vs 62.6 +/- 2.5 ml/min, p = 0.0007) and renal plasma flow (537.2 +/- 34.0 vs 494.0 +/- 35.5 ml/min, p <0.01), lower fenoldopam plasma levels (3.3 +/- 0.3 vs 4.8 +/- 0.3 ng/ml, p <0.0001), and greater nadir systolic BP (125.5 +/- 3.6 vs 117.4 +/- 2.8 mm Hg, p <0.0001). Two hours after drug discontinuation after contrast administration, GFRs in the patients who received IR fenoldopam remained higher than in controls (+15.0 ml/min [+25%] vs -8.0 ml/min [-14.0%], p <0.05). In conclusion, this pilot trial demonstrates that the IR infusion of fenoldopam is safe and practical, producing greater renal effect and less reduction of BP than IV infusion. It would be appropriate to restudy this renal vasodilator for the prevention of contrast nephropathy, using selective IR delivery.

Effectiveness of same day percutaneous coronary intervention followed by minimally invasive aortic valve replacement for aortic stenosis and moderate coronary disease ("hybrid approach").

In 2005, the investigators described a "hybrid" cardiovascular interventional strategy combining percutaneous coronary intervention (PCI) for coronary artery disease (CAD) followed by valve surgery for patients with urgent complex CAD and valve disease to reduce morbidity and mortality. This hybrid approach has been extended prospectively in elderly, high-risk patients with aortic stenosis scheduled for elective minimally invasive aortic valve replacement (MI-AVR) who, on preoperative coronary angiography, were found to have moderate CAD amenable to PCI. In this prospective, observational series, 18 patients (mean age 76 years) underwent elective hybrid MI-AVR with PCI from May 2003 to February 2006. Five patients had undergone previous coronary artery bypass grafting. Patients underwent coronary angiography the day of (n = 12) or evening before (n = 6) MI-AVR, and after identifying moderately severe CAD, all 18 underwent the implantation of drug-eluting stents to the affected coronary arteries, followed by MI-AVR. Although all patients received standard doses of antiplatelet medications, including acetylsalicylic acid (325 mg before PCI and 325 mg/day thereafter) and clopidogrel (300 mg after PCI, 75 mg/day thereafter for 90 days for the Cypher stent), there were no reoperations for bleeding; only 8 of 18 patients required postoperative blood transfusions. One patient died postoperatively from a colonic perforation, and there were no late mortalities after a mean follow-up of 19 months. In conclusion, this hybrid strategy has low morbidity and mortality and may be a new therapeutic option for older, high-risk patients with combined CAD and aortic valve disease.

Effect of diabetes mellitus on five-year clinical outcomes after single-vessel coronary stenting (a pooled analysis of coronary stent clinical trials).

Diabetes mellitus (DM) increases the risk of clinically driven, repeat revascularization of the stented lesion in the first year after coronary stenting. The effect of DM on the risk of repeat revascularization of the stented lesion beyond 1 year, revascularization at other coronary sites, and clinical outcomes of cardiac death and myocardial infarction (MI) has not been reported. We pooled primary data from 4 multicenter trials of second-generation coronary stents that included 1,228 patients, 263 of whom (21%) had DM. Patients were followed annually to assess for prespecified end points, including repeat revascularization procedures, death, or MI. Repeat revascularization of the stented lesion was performed more frequently during the first year in patients with DM (16.0% vs 10.9%, p = 0.01) but decreased to a low frequency (1.8% vs 1.3% per year) thereafter in patients with and without DM. Repeat revascularization of other coronary segments was more frequent in patients with DM during the first and subsequent years (5-year rates, 32.2% vs 24.1%, p = 0.005). Cardiac death or MI was also more frequent among patients with DM (5-year rates, 25.4% vs 17.9%, p = 0.008) and remained significant after adjustment for all differences in baseline characteristics (hazard ratio 1.5, 95% confidence interval 1.1 to 2.0, p = 0.01). In conclusion, diabetic patients are at increased risk for revascularization of the stented lesion only in the first year after single-lesion stenting but are at increased risk for other clinical events, including cardiac death and MI, over the next 4 years.

Percutaneous therapies for valvular heart disease.

Balloon valvuloplasty has been in clinical use for over 20 years, but the prospect of repairing and replacing cardiac valves via catheter-based techniques represents a truly recent development. This review introduces evolving technologies and their relevance to cardiovascular pathologists.

Randomized trial of a distal embolic protection device during percutaneous intervention of saphenous vein aorto-coronary bypass grafts.

BACKGROUND: Stents provide effective treatment for stenotic saphenous venous aorto-coronary bypass grafts, but their placement carries a 20% incidence of procedure-related complications, which potentially are related to the distal embolization of atherosclerotic debris. We report the first multicenter randomized trial to evaluate use of a distal embolic protection device during stenting of such lesions. METHODS AND RESULTS: Of 801 eligible patients, 406 were randomly assigned to stent placement over the shaft of the distal protection device, and 395 were assigned to stent placement over a conventional 0.014-inch angioplasty guidewire (control group). The primary end point-a composite of death, myocardial infarction, emergency bypass, or target lesion revascularization by 30 days-was observed in 65 patients (16.5%) assigned to the control group and 39 patients (9.6%) assigned to the embolic protection device (P=0.004). This 42% relative reduction in major adverse cardiac events was driven by myocardial infarction (8.6% versus 14.7%, P=0.008) and "no-reflow" phenomenon (3% versus 9%, P=0.02). Clinical benefit was seen even when platelet glycoprotein IIb/IIIa receptor blockers were administered (61% of patients), with composite end points occurring in 10.7% of protection device patients versus 19.4% of control patients (P=0.008). CONCLUSIONS: Use of this distal protection device during stenting of stenotic venous grafts was associated with a highly significant reduction in major adverse events compared with stenting over a conventional angioplasty guidewire. This demonstrates the importance of distal embolization in causing major adverse cardiac events and the value of embolic protection devices in preventing such complications.

Impact of sirolimus-eluting stents on outcome in diabetic patients: a SIRIUS (SIRolImUS-coated Bx Velocity balloon-expandable stent in the treatment of patients with de novo coronary artery lesions) substudy.

BACKGROUND: Randomized clinical trials have shown that a sirolimus-eluting stent significantly reduces restenosis after percutaneous coronary revascularization. Diabetic patients are known to have a higher risk of restenosis compared with nondiabetic patients. The purpose of this analysis was to determine the impact of sirolimus-eluting stents on outcomes of diabetic compared with nondiabetic patients. METHODS AND RESULTS: The SIRIUS (SIRolImUS-coated Bx Velocity balloon-expandable stent in the treatment of patients with de novo coronary artery lesions) trial is a randomized, double-blind study that compared sirolimus-eluting and bare metal stent implantation in 1058 patients with de novo native coronary artery lesions. Diabetes mellitus was present in 279 (26%) patients (diabetes mellitus group, 131 patients received sirolimus-eluting stents and 148 patients received bare metal stents) and was absent in 778 patients (no-diabetes mellitus group, 402 patients received sirolimus-eluting stents and 376 patients received bare metal stents). At 270 days, target lesion revascularization was reduced in diabetic patients from 22.3% with bare metal stents to 6.9% with sirolimus-eluting stents (P<0.001) and in nondiabetic patients from 14.1% to 2.99% (P<0.001), respectively. Major adverse cardiac events were reduced in diabetic patients from 25% with bare metal stents to 9.2% with sirolimus-eluting stents (P<0.001) and from 16.5% to 6.5% (P<0.001) in nondiabetic patients, respectively. CONCLUSIONS: Implantation of sirolimus-eluting stents compared with bare metal stents in de novo coronary lesions reduces major adverse cardiac events in patients with and without diabetes mellitus. However, among patients receiving sirolimus-eluting stents, there remains a trend toward a higher frequency of repeat intervention in diabetic patients compared with nondiabetic patients, particularly in the insulin-requiring patients.

Beyond restenosis: five-year clinical outcomes from second-generation coronary stent trials.

BACKGROUND: In the first year after coronary stent implantation, clinical failures are driven mainly by procedural complications and restenosis, but the subsequent relative contributions of restenosis and disease progression to late failures are less clear. METHODS AND RESULTS: We observed 1228 patients for 5 years after the implantation of stents as part of pivotal second-generation coronary stent trials. Clinical events of death, myocardial infarction, repeat revascularization, and repeat hospitalization for acute coronary syndrome or congestive heart failure were attributed to the index stented (target) lesion or other distinct sites (either in the target or other coronary vessels) and further classified as procedural, restenosis, or nonrestenosis. During the first year the hazard rate was 18.3% for target-lesion events and 12.4% for events unrelated to the target lesion. After the first year the average annual hazard rate was 1.7% for target-lesion events and 6.3% for nontarget-lesion events. By the fifth year, restenosis events occurred in 20.3% of patients, whereas 30-day procedural complications or later nonrestenosis events occurred in 37.9%, including 11.4% who also experienced a restenosis event, for a combined cumulative event rate of 46.4%. Diabetes mellitus and multivessel disease were independently associated with increased risk for both restenosis and nonrestenosis events. CONCLUSIONS: In a low-risk clinical trial population, the clinical outcome beyond 1 year after stenting is determined by a high rate of events related to disease progression in segments other than the stented lesion, which itself remains relatively stable.

Magnetic resonance imaging demonstrates improved regional systolic wall motion and thickening and myocardial perfusion of myocardial territories treated by laser myocardial revascularization.

OBJECTIVES: This study was designed to investigate the use of magnetic resonance (MR) functional and perfusion imaging to evaluate laser myocardial revascularization (LMR). BACKGROUND: Most clinical studies of LMR have shown improvements in angina class and exercise capacity, with minimal or absent improvements in myocardial perfusion and function. METHODS: Fifteen patients who underwent percutaneous Biosense-guided holmium:yttrium aluminum garnet LMR to areas of viable but ischemic myocardium were followed clinically and underwent functional and perfusion MRI at baseline, 30 days and 6 months. RESULTS: The mean age was 64 +/- 11 years; four patients were women. The ejection fraction was 47.4 +/- 14.0%. Angina class at baseline was 3.4 +/- 0.6 and improved to 2.5 +/- 1.4 at six months (p = 0.054). Exercise time at baseline was 298 +/- 97 s and increased to 350 +/- 95 s at 30 days and 365 +/- 79 s at six months, p = 0.04. There were no significant changes in nuclear perfusion scans. Although MR determined that resting radial motion and thickening of the target wall were significantly less than normal at baseline (p < 0.001), they improved significantly during follow-up (wall thickening: baseline, 30.6 +/- 11.7%; day 30, 41.2 +/- 13.3% and day 180, 44.2 +/- 11.9%, p = 0.01). The size of the underperfused myocardial area was 14.5 +/- 5.4% at baseline and was reduced to 6.3 +/- 2.8% at 30 days and 7.7 +/- 3.7% at 6 months (p < 0.001). CONCLUSIONS: This small phase I, open-label, uncontrolled study of MR functional and perfusion imaging in patients undergoing Biosense-guided LMR suggests a beneficial effect of this treatment strategy on myocardial function and perfusion. The efficacy of Biosense-guided LMR is being evaluated in a large phase II, randomized, blinded placebo-controlled trial with an MRI substudy (DIRECT).

Cost-effectiveness of distal embolic protection for patients undergoing percutaneous intervention of saphenous vein bypass grafts: results from the SAFER trial.

OBJECTIVES: The goal of this research was to determine the incremental cost and cost-effectiveness of embolic protection in patients undergoing percutaneous revascularization (PCI) of diseased saphenous vein bypass grafts (SVGs). BACKGROUND: Distal protection using the GuardWire balloon occlusion device has been shown to reduce major ischemic complications in patients undergoing SVG PCI, but the cost-effectiveness of this approach is unknown. METHODS: We prospectively measured medical resource utilization and cost for 801 patients undergoing SVG intervention who were randomized to distal protection using the GuardWire (n = 406) or conventional treatment (n = 395) in the Saphenous Vein Graft Angioplasty Free of Emboli Randomized (SAFER) trial. Long-term survival and cost-effectiveness were projected based on observed 30-day outcomes and a validated survival model for postcoronary artery bypass graft patients. RESULTS: Compared with conventional treatment, distal protection increased initial procedural costs by approximately $1,600 ($6,326 vs. $4,779, p < 0.001). However, by reducing ischemic complications, distal protection reduced mean length of stay by 0.4 days and other hospital costs by nearly $1,000 ($6,846 vs. $7,811, p = 0.018). As a result, overall initial hospital costs were only $582 per patient higher with distal protection. Based on the observed 30-day cost and outcome differences in the trial, the incremental cost-effectiveness ratio for distal protection was $3,718 per year of life saved and remained <$40,000 per year of life saved in 97.3% of bootstrap simulations (95% confidence interval, $0 to $43,079). CONCLUSIONS: For patients undergoing PCI of diseased SVGs, distal protection using the GuardWire system is an attractive use of limited health care resources.

Differential mortality risk of postprocedural creatine kinase-MB elevation following successful versus unsuccessful stent procedures.

OBJECTIVES: This study was designed to evaluate the effect of periprocedural myocardial infarction (MI) on mortality according to success of the stent procedure. BACKGROUND: The mortality effect of periprocedural MI relative to successful versus unsuccessful procedures has not been examined. METHODS: All-cause mortality during the first year was evaluated prospectively among 5,850 patients from coronary stent clinical trials. Myocardial infarction was classified according to creatine kinase-MB level as type 1 (>1 but <3 times normal), type 2 (>or=3 but 8 times normal or Q-wave MI). Procedures were classified as successful unless there was a final diameter stenosis >50%; final Thrombolysis In Myocardial Infarction flow grade <3; final National Heart, Lung, and Blood Institute dissection grade >or=D; repeat revascularization within 24 h; or stent thrombosis within 24 h. RESULTS: Myocardial infarction was more frequent after unsuccessful procedures (69.6% vs. 20.4%, p < 0.001). Mortality during the first year was higher in patients with MI (2.8% vs. 1.7%, p = 0.01), but the effect was significant only for type 3 MI (4.7% vs. 1.7%, p = 0.008). Moreover, the mortality difference for any MI was confined to patients with unsuccessful procedures (13.1% vs. 0%, p = 0.03), with no significant effect among patients with otherwise successful procedures (2.1% vs. 1.7%, p > 0.20). The independent predictors of mortality were unsuccessful procedure (p < 0.001), diabetes mellitus (p = 0.001), history of prior MI (p = 0.003), multivessel disease (p = 0.006), and advancing age (p < 0.001), but not periprocedural MI. CONCLUSIONS: The association of periprocedural MI with increased mortality during the first year following stent placement was confined to patients with unsuccessful procedures.

Clinical restenosis after coronary stenting: perspectives from multicenter clinical trials.

OBJECTIVES: We sought to evaluate clinical restenosis in a large population of patients who had undergone coronary stent placement. BACKGROUND: One-year success after coronary stenting is limited mainly by restenosis of and requirement for repeat revascularization of the treated lesion. We studied 6,186 patients (6,219 lesions) pooled from several recently completed coronary stent trials. Clinical restenosis was defined using three different definitions: target lesion revascularization (TLR) beyond 30 days, target vessel revascularization (TVR) beyond 30 days, and target vessel failure (TVF), defined as TVR, any death, or myocardial infarction (MI) of the target vessel territory after hospital discharge. RESULTS: By one year, 638 (12.2%) patients had TLR, 748 (14.3%) had TVR, and 848 (16.0%) had TVF, more than two-thirds higher than the rate of these end points at six months. The severity of angiographic restenosis (> or =50% follow-up diameter stenosis [DS]) in 419 of 1,437 (29%) patients undergoing routine angiographic follow-up correlated directly with the likelihood of TLR (73% vs. 26% for >70% DS compared with <60% DS). Smaller pretreatment minimum lumen diameter (MLD), smaller final MLD, longer stent length, diabetes mellitus, unstable angina, and hypertension were independent predictors of TLR. Prior MI and current smoking were negative predictors. CONCLUSIONS: At one year after stenting, most clinical restenosis reflected TLR, which was predicted by the same variables previously associated with an increased risk of angiographic restenosis. The lower absolute rate of clinical restenosis relative to angiographic restenosis was due to infrequent TLR in lesions with less severe (<60% DS) angiographic renarrowing.

Induction of mild systemic hypothermia with endovascular cooling during primary percutaneous coronary intervention for acute myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate the safety and feasibility of endovascular cooling during primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). BACKGROUND: In experimental models of AMI, mild systemic hypothermia has been shown to reduce metabolic demand and limit infarct size. METHODS: In a multi-center study, 42 patients with AMI (<6 h from symptom onset) were randomized to primary PCI with or without endovascular cooling (target core temperature 33 degrees C). Cooling was maintained for 3 h after reperfusion. Skin warming, oral buspirone, and intravenous meperidine were used to reduce the shivering threshold. The primary end point was major adverse cardiac events at 30 days. Infarct size at 30 days was measured using (99m)Tc-sestamibi SPECT imaging. RESULTS: Endovascular cooling was performed successfully in 20 patients (95%). All achieved a core temperature below 34 degrees C (mean target temperature 33.2 +/- 0.9 degrees C). The mean temperature at reperfusion was 34.7 +/- 0.9 degrees C. Cooling was well tolerated, with no hemodynamic instability or increase in arrhythmia. Nine patients experienced mild episodic shivering. Major adverse cardiac events occurred in 0% vs. 10% (p = NS) of treated versus control patients. The median infarct size was non-significantly smaller in patients who received cooling compared with the control group (2% vs. 8% of the left ventricle, p = 0.80). CONCLUSIONS: Endovascular cooling can be performed safely as an adjunct to primary PCI for AMI. Further clinical trials are required to determine whether induction of mild systemic hypothermia with endovascular cooling will limit infarct size in patients undergoing reperfusion therapy.

Effect of gender on in-hospital and one-year outcomes after contemporary coronary artery stenting.

Despite the similar extent of epicardial coronary artery disease and procedural success, women have been noted to have a twofold higher incidence of in-hospital mortality and vascular complications than men undergoing coronary artery stenting. This analysis of 1,908 women from a pooled data set of 6,186 patients is the largest reported series of prospectively collected data from the contemporary stent era. This study demonstrates that stenting can be performed in women with excellent acute results with no age-independent increase in short- or long-term mortality compared with men, although with a significantly higher risk of vascular complications.