Paclitaxel-Coated Balloon vs Uncoated Balloon for Coronary In-Stent Restenosis: The AGENT IDE Randomized Clinical Trial.

Importance: Drug-coated balloons offer a potentially beneficial treatment strategy for the management of coronary in-stent restenosis. However, none have been previously evaluated or approved for use in coronary circulation in the United States. Objective: To evaluate whether a paclitaxel-coated balloon is superior to an uncoated balloon in patients with in-stent restenosis undergoing percutaneous coronary intervention. Design, Setting, and Participants: AGENT IDE, a multicenter randomized clinical trial, enrolled 600 patients with in-stent restenosis (lesion length <26 mm and reference vessel diameter >2.0 mm to ≤4.0 mm) at 40 centers across the United States between May 2021 and August 2022. One-year clinical follow-up was completed on October 2, 2023. Interventions: Participants were randomized in a 2:1 allocation to undergo treatment with a paclitaxel-coated (n = 406) or an uncoated (n = 194) balloon. Main Outcomes and Measures: The primary end point of 1-year target lesion failure-defined as the composite of ischemia-driven target lesion revascularization, target vessel-related myocardial infarction, or cardiac death-was tested for superiority. Results: Among 600 randomized patients (mean age, 68 years; 157 females [26.2%]; 42 Black [7%], 35 Hispanic [6%] individuals), 574 (95.7%) completed 1-year follow-up. The primary end point at 1 year occurred in 17.9% in the paclitaxel-coated balloon group vs 28.6% in the uncoated balloon group, meeting the criteria for superiority (hazard ratio [HR], 0.59 [95% CI, 0.42-0.84]; 2-sided P = .003). Target lesion revascularization (13.0% vs 24.7%; HR, 0.50 [95% CI, 0.34-0.74]; P = .001) and target vessel-related myocardial infarction (5.8% vs 11.1%; HR, 0.51 [95% CI, 0.28-0.92]; P = .02) occurred less frequently among patients treated with paclitaxel-coated balloon. The rate of cardiac death was 2.9% vs 1.6% (HR, 1.75 [95% CI, 0.49-6.28]; P = .38) in the coated vs uncoated balloon groups, respectively. Conclusions and Relevance: Among patients undergoing coronary angioplasty for in-stent restenosis, a paclitaxel-coated balloon was superior to an uncoated balloon with respect to the composite end point of target lesion failure. Paclitaxel-coated balloons are an effective treatment option for patients with coronary in-stent restenosis. Trial Registration: ClinicalTrials.gov Identifier: NCT04647253.

Rationale and design of a randomized study comparing the agent drug coated balloon to plain old balloon angioplasty in patients with In-stent restenosis.

BACKGROUND: Drug-coated balloon (DCB) technology was developed as an alternative treatment for obstructive coronary artery disease (CAD) and in-stent restenosis (ISR). Management of coronary ISR is clinically challenging and frequently encountered in practice. The Agent DCB uses an inactive excipient to effectively deliver a targeted, therapeutic dose of paclitaxel to the vessel wall. STUDY DESIGN: AGENT IDE is a prospective, multicenter, randomized controlled trial to evaluate superiority of the Agent DCB to balloon angioplasty in treating patients with ISR. A total of 480 patients with ISR of a previously treated lesion length <26 mm and reference vessel diameter >2.0 mm to ≤4.0 mm will be initially randomized. Subjects presenting with recent myocardial infarction (MI), complex lesions, or thrombus in the target vessel will be excluded. An adaptive group sequential design with one formal interim analysis for sample size re-estimation will be conducted, and the sample size may be increased to a maximum of 600 subjects. The primary endpoint is the rate of 12-month target lesion failure (TLF; composite of any ischemia-driven revascularization of the target lesion (TLR), target vessel related MI, or cardiac death) and will be tested for superiority in the test arm against the control. Functional status and general health-related quality of life will be measured by changes in the EQ-5D scores. Subjects will be followed for 5 years following the index procedure. CONCLUSION: This study will prospectively evaluate the safety and efficacy of Agent DCB in patients treated for coronary ISR.

Intravascular Lithotripsy for Peripheral Artery Calcification: 30-Day Outcomes From the Randomized Disrupt PAD III Trial.

OBJECTIVES: The study sought to compare short-term outcomes in patients with femoropopliteal artery calcification receiving vessel preparation with intravascular lithotripsy (IVL) or percutaneous transluminal angioplasty (PTA) prior to drug-coated balloon (DCB) for symptomatic peripheral artery disease. BACKGROUND: Endovascular treatment of calcified peripheral artery lesions is associated with suboptimal vessel expansion and increased complication risk. Although initial results from single-arm studies with IVL have been reported, comparative evidence from randomized trials is lacking for most devices in the presence of heavy calcification. METHODS: The Disrupt PAD III (Shockwave Medical Peripheral Lithoplasty System Study for PAD) randomized trial enrolled patients with moderate or severe calcification in a femoropopliteal artery who underwent vessel preparation with IVL or PTA prior to DCB or stenting. The primary endpoint was core lab-adjudicated procedural success (residual stenosis ≤30% without flow-limiting dissection) prior to DCB or stenting. RESULTS: In patients receiving IVL (n = 153) or PTA (n = 153), procedural success was greater in the IVL group (65.8% vs. 50.4%; p = 0.01) and the percentage of lesions with residual stenosis ≤30% (66.4% vs. 51.9%; p = 0.02) was greater in the IVL group, while flow-limiting dissections occurred more frequently in the PTA group (1.4% vs. 6.8%; p = 0.03). Post-dilatation (5.2% vs. 17.0%; p = 0.001) and stent placement (4.6% vs. 18.3%; p < 0.001) were also greater in the PTA group. The rates of major adverse events (IVL: 0% vs. PTA: 1.3%; p = 0.16) and clinically driven target lesion revascularization (IVL: 0.7% vs. PTA: 0.7%; p = 1.0) at 30 days were comparable between groups. CONCLUSIONS: IVL is an effective vessel preparation strategy that facilitates definitive endovascular treatment in calcified femoropopliteal arteries in patients with peripheral artery disease. (Shockwave Medical Peripheral Lithoplasty System Study for PAD [Disrupt PAD III]; NCT02923193).

Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Artery Disease.

BACKGROUND: Coronary calcification hinders stent delivery and expansion and is associated with adverse outcomes. Intravascular lithotripsy (IVL) delivers acoustic pressure waves to modify calcium, enhancing vessel compliance and optimizing stent deployment. OBJECTIVES: The purpose of this study was to assess the safety and effectiveness of IVL in severely calcified de novo coronary lesions. METHODS: Disrupt CAD III (NCT03595176) was a prospective, single-arm multicenter study designed for regulatory approval of coronary IVL. The primary safety endpoint was freedom from major adverse cardiovascular events (cardiac death, myocardial infarction, or target vessel revascularization) at 30 days. The primary effectiveness endpoint was procedural success. Both endpoints were compared with a pre-specified performance goal (PG). The mechanism of calcium modification was assessed in an optical coherence tomography (OCT) substudy. RESULTS: Patients (n = 431) were enrolled at 47 sites in 4 countries. The primary safety endpoint of the 30-day freedom from major adverse cardiovascular events was 92.2%; the lower bound of the 95% confidence interval was 89.9%, which exceeded the PG of 84.4% (p < 0.0001). The primary effectiveness endpoint of procedural success was 92.4%; the lower bound of the 95% confidence interval was 90.2%, which exceeded the PG of 83.4% (p < 0.0001). Mean calcified segment length was 47.9 ± 18.8 mm, calcium angle was 292.5 ± 76.5°, and calcium thickness was 0.96 ± 0.25 mm at the site of maximum calcification. OCT demonstrated multiplane and longitudinal calcium fractures after IVL in 67.4% of lesions. Minimum stent area was 6.5 ± 2.1 mm2 and was similar regardless of demonstrable fractures on OCT. CONCLUSIONS: Coronary IVL safely and effectively facilitated stent implantation in severely calcified lesions.

Effectiveness and Safety of a Paclitaxel-Eluting Stent for Superficial Femoral Artery Lesions up to 190 mm: One-Year Outcomes of the Single-Arm IMPERIAL Long Lesion Substudy of the Eluvia Drug-Eluting Stent.

Purpose: To report the clinical effect of a drug-eluting stent on femoropopliteal occlusive disease in patients with long lesions. Materials and Methods: The global IMPERIAL Long Lesion substudy (ClinicalTrials.gov identifier NCT02574481) is a prospective, single-arm, multicenter trial of the Eluvia Drug-Eluting Vascular Stent for treating femoropopliteal lesions >140 mm and ≤190 mm in length. Fifty patients (mean age 68.2 years; 32 men) with long lesions (mean length 162.8±34.7 mm) were enrolled; 20 patients had diabetes. Fourteen of the lesions were severely calcified and 16 were occluded. Primary patency (duplex ultrasound peak systolic velocity ratio ≤2.4 in the absence of clinically-driven target lesion revascularization or bypass of the target lesion) and major adverse events [30-day all-cause death and 1-year target limb major amputation or target lesion revascularization (TLR)] were assessed at 12 months. Results: At 12 months, no deaths, target limb amputations, or stent thrombosis had occurred. The Kaplan-Meier estimate of primary patency was 91.0% (95% CI 82.5% to 99.6%). The MAE-free rate at 12 months was 93.5% due to 3 clinically-driven TLRs. The corresponding Kaplan-Meier estimate of freedom from TLR was 93.9% (95% CI 87.2% to 100%). Conclusion: The IMPERIAL Long Lesion substudy demonstrated excellent patency and safety through 1 year among patients with long femoropopliteal occlusive disease treated with the Eluvia stent.

The CLOSER trial: a multi-center study on the clinical safety and effectiveness of CloserTM VSS, a novel resorbable transfemoral vascular access sealing system.

OBJECTIVES: To evaluate the safety and effectiveness of the Closer Vascular Sealing System (VSS) against prespecified performance goals (PGs) in sealing femoral arterial access following 5-7 Fr procedures. BACKGROUND: Inconsistent safety profiles, costs and learning curves of earlier generation vascular closure devices have limited their widespread use following transfemoral procedures. METHODS: In this prospective single-arm, multi-center trial, we compared the clinical outcomes in patients undergoing 5-7 Fr transfemoral diagnostic or interventional procedures and access sites managed with Closer VSS against pre-specified PGs. The primary endpoints were time to hemostasis (TTH) and 30-day access site closure-related major complications; secondary endpoints included time to ambulation (TTA), time to discharge eligibility (TTDE), time to discharge (TTD), 30-day access site minor complications, procedure and device success. RESULTS: A total of 220 subjects (49.5% interventional) were enrolled. The mean TTH was 1.78 ± 7.81 min in the intention to treat and 0.98 ± 3.71 min in the per protocol cohort. Median TTH was 0 min with immediate hemostasis achieved in 80.5% of subjects, mean TTA was 2.50 ± 1.05 hr, and mean TTDE was 2.83 ± 1.54 hr. Thirty-day follow-up was completed on 219 subjects. There were no access site closure-related major complications, minor complication rate was 0.0% for diagnostic and 2.75% for interventional procedures. CONCLUSIONS: In patients undergoing 5-7 Fr transfemoral diagnostic and interventional procedures, the CLOSER Trial met both its primary effectiveness and safety PGs. Immediate hemostasis was achieved in the majority of patients without major complication.

Stellarex Drug-Coated Balloon for Treatment of Femoropopliteal Disease: Twelve-Month Outcomes From the Randomized ILLUMENATE Pivotal and Pharmacokinetic Studies.

BACKGROUND: Drug-coated balloons (DCBs) are a predominant revascularization therapy for symptomatic femoropopliteal artery disease. Because of the differences in excipients, paclitaxel dose, and coating morphologies, varying clinical outcomes have been observed with different DCBs. We report the results of 2 studies investigating the pharmacokinetic and clinical outcomes of a new DCB to treat femoropopliteal disease. METHODS: In the ILLUMENATE Pivotal Study (Prospective, Randomized, Single-Blind, U.S. Multi-Center Study to Evaluate Treatment of Obstructive Superficial Femoral Artery or Popliteal Lesions With A Novel Paclitaxel-Coated Percutaneous Angioplasty Balloon), 300 symptomatic patients (Rutherford class 2-4) were randomly assigned to DCB (n=200) or standard angioplasty (percutaneous transluminal angioplasty [PTA]) (n=100). The primary safety end point was freedom from device- and procedure-related death through 30 days, and freedom from target limb major amputation and clinically driven target lesion revascularization through 12 months. The primary effectiveness end point was primary patency through 12 months. In the ILLUMENATE PK study (Pharmacokinetic Study of the Stellarex Drug-Coated Angioplasty Balloon), paclitaxel plasma concentrations were measured after last DCB deployment and at prespecified times (at 1, 4, 24 hours and at 7 and 14 days postprocedure) until no longer detectable. RESULTS: In the ILLUMENATE Pivotal Study, baseline characteristics were similar between groups: 50% had diabetes mellitus, 41% were women, mean lesion length was 8.3 cm, and 44% were severely calcified. The primary safety end point was met (92.1% for DCB versus 83.2% for PTA, P=0.025 for superiority) and the primary patency rate was significantly higher with DCB (76.3% for DCB versus 57.6% for PTA, P=0.003). Primary patency per Kaplan-Meier estimates at day 365 was 82.3% for DCB versus 70.9% for PTA (P=0.002). The rate of clinically driven target lesion revascularization was significantly lower in the DCB cohort (7.9% versus 16.8%, P=0.023). Improvements in ankle-brachial index, Rutherford class, and quality of life were comparable, but the PTA cohort required twice as many revascularizations. Pharmacokinetic outcomes showed that all patients had detectable paclitaxel levels after DCB deployment that declined within the first hour (54.4±116.9 ng/mL to 1.4±1.0 ng/mL). CONCLUSIONS: The data demonstrate superior safety and effectiveness of the Stellarex DCB in comparison with PTA, and plasma levels of paclitaxel fall to low levels within 1 hour. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifiers: NCT01858428 and NCT01912937.

High-risk percutaneous coronary intervention in a patient with a single coronary artery presenting as STEMI and cardiogenic shock.

Cardiogenic shock due to ST elevation myocardial infarction in a patient with a single coronary artery involving the sole vessel is a rare presentation. This can be clinically and angiographically challenging. Proper recognition of the topography of diseased vessels and a systematic guarded approach can lead to procedural success. We report a case of an 81-year-old woman who presented with chest pain followed by a near syncope associated with an acute myocardial infarction. Coronary angiography revealed a single proximally occluded right coronary artery and an anomalous left main coronary artery (originating from the proximal right coronary artery) and occluded distal left circumflex artery. The right coronary artery was successfully stented following predilation without compromising the anomalous left main origin. The flow in the chronically occluded left circumflex artery (originating from the anomalous left main) which was depended on the retrograde supply from right coronary artery through collaterals, was also re-established.

S.M.A.R.T. self-expanding nitinol stent for the treatment of atherosclerotic lesions in the superficial femoral artery (STROLL): 1-year outcomes.

PURPOSE: To assess safety and efficacy of the S.M.A.R.T. Vascular Stent System (Cordis Corp, Fremont, California) in obstructive superficial femoral artery (SFA) disease. MATERIALS AND METHODS: The single-arm, multicenter STROLL study (S.M.A.R.T. Nitinol Self-Expanding Stent in the Treatment of Obstructive Superficial Femoral Artery Disease) included 250 patients (250 lesions in SFA or proximal popliteal artery). The efficacy endpoint was primary patency defined by freedom from binary restenosis (peak systolic velocity ratio > 2.5) as derived by duplex ultrasound plus clinically driven target lesion revascularization (TLR) at 12 months. RESULTS: Mean age of patients was 67.7 years ± 10.3; 47.2% of patients had diabetes; distribution of Rutherford/Becker classes 2, 3, and 4 was 45.8%, 51.4%, and 2.8%. Mean lesion length and reference vessel diameter were 77.3 mm ± 35.3 and 4.9 mm ± 0.7, respectively (23.6% cases with total occlusions). The 30-day freedom from major adverse events (death, index limb amputation, clinically driven TLR) was 100%. The 1-year primary patency was 81.7% by Kaplan-Meier estimate. The presence of diabetes or total occlusion had no effect on primary patency. Ankle-brachial index was 0.4-0.8 in 84.6% of patients at baseline and improved to > 0.8 in 81.0% of patients at 12 months. The proportion of patients in Rutherford/Becker class 3-4 was reduced from 54.2% at baseline to 8.0% at 12 months. Four patients (2.0%) experienced single-stent strut fracture (type I) at 1 year, without associated loss of stent patency. CONCLUSIONS: The S.M.A.R.T. Vascular Stent System proved to be safe and effective for endovascular treatment of obstructive SFA and proximal popliteal artery disease, based on 1-year vessel patency and associated hemodynamic and clinical improvements.

Cardiac troponin release following hybrid coronary revascularization versus off-pump coronary artery bypass surgery.

OBJECTIVES: Cardiac ischaemic marker release is associated with adverse clinical outcomes after cardiac surgery. We sought to compare the release of cardiac troponin I (cTnI) after hybrid coronary revascularization (HCR) with off-pump coronary artery bypass surgery (OPCAB). METHODS: Using data from a prospective single-centre registry, we compared cTnI measured at postoperative day 1 following one-stage HCR and OPCAB among patients with normal baseline cTnI. Multivariable linear regression analysis was used to adjust for variables that may have influenced cardiac marker release other than the used revascularization strategy. RESULTS: Sixty-five consecutive patients underwent elective HCR (n = 33) or OPCAB (n = 32). Overall, no differences were seen in comorbidities, CABG risk scores and the lesion-specific SYNTAX score. Procedural complications were lower (15.2 vs 34.4%, P = 0.072), but 30-day and 1-year clinical outcomes (death, myocardial infarction, and repeat revascularization) were similar between the two groups (3.0 vs 3.1% and 9.1 vs 6.2%, respectively). Post-procedural cTnI release measured at 24 h after surgery was significantly lower following HCR compared with OPCAB [ratio of upper reference level URL: median: 3.5, interquartile range (IQR): 0.8-9.1 vs 12.8, IQR: 6.9-21.8, P = 0.001]. After adjusting for potential confounders, HCR was associated, on average, with cTnI less than half (46%) compared with CABG (P <0.0001). CONCLUSIONS: HCR is associated with lower postoperative cTn release, compared with OPCAB. Further research into the clinical implications of this finding is warranted.

Proper patient selection yields significant and sustained reduction in systolic blood pressure following renal artery stenting in patients with uncontrolled hypertension: long-term results from the HERCULES trial.

The Safety and Effectiveness Study of the Herculink Elite Renal Stent to Treat Renal Artery Stenosis (HERCULES) trial is a prospective, multicenter trial evaluating the safety, effectiveness, and durability of the RX Herculink Elite renal stent system (Abbott Vascular, Abbott Park, IL) in select patients with atherosclerotic renal artery stenosis and uncontrolled hypertension. A total of 202 patients were enrolled between August 2007 and October 2009. The primary endpoint, 9-month binary restenosis, was 10.5% determined by core laboratory adjudicated duplex ultrasound and/or angiography. Additional analyses included changes in blood pressure, antihypertensive medications, renal function (RF), major adverse events (MAEs) (death, ipsilateral nephrectomy, and embolic events resulting in kidney damage), and clinically driven target lesion revascularization (CD-TLR) between baseline and 36 months. Freedom from MAE was 98.5% at 30 days. At 36 months, freedom from death, nephrectomy, and CD-TLR were 90.1%, 100%, and 91.8%, respectively. After 30 days there were no site-reported embolic events resulting in kidney damage. The mean baseline systolic blood pressure of 162±18 mm Hg significantly decreased postprocedure and through 36 months (mean systolic blood pressure 141 mm Hg [P<.0001] and 146 mm Hg [P<.0001], respectively). No differences were noted in antihypertensive medications or RF compared with baseline. The HERCULES trial demonstrated sustained clinically and statistically significant reduction in SBP in patients with uncontrolled HTN. Coupled with the low core laboratory-adjudicated in-stent restenosis, acceptable procedural complication rates (1.5%), and <10% CD-TLR, the study suggests that there may be a role for renal artery stenting using contemporary stent technology.

Clinical outcomes after hybrid coronary revascularization versus coronary artery bypass surgery: a meta-analysis of 1,190 patients.

BACKGROUND: Hybrid coronary revascularization (HCR) represents a minimally invasive revascularization strategy in which the durability of the internal mammary artery to left anterior descending artery graft is combined with percutaneous coronary intervention to treat remaining lesions. We performed a systematic review and meta-analysis to compare clinical outcomes after HCR with conventional coronary artery bypass graft (CABG) surgery. METHODS: A comprehensive EMBASE and PUBMED search was performed for comparative studies evaluating in-hospital and 1-year death, myocardial infarction (MI), stroke, and repeat revascularization. RESULTS: Six observational studies (1 case control, 5 propensity adjusted) comprising 1,190 patients were included; 366 (30.8%) patients underwent HCR (185 staged and 181 concurrent), and 824 (69.2%) were treated with CABG (786 off-pump, 38 on-pump). Drug-eluting stents were used in 328 (89.6%) patients undergoing HCR. Hybrid coronary revascularization was associated with lower in-hospital need for blood transfusions, shorter length of stay, and faster return to work. No significant differences were found for the composite of death, MI, stroke, or repeat revascularization during hospitalization (odds ratio 0.63, 95% CI 0.25-1.58, P = .33) and at 1-year follow-up (odds ratio 0.49, 95% CI 0.20-1.24, P = .13). Comparisons of individual components showed no difference in all-cause mortality, MI, or stroke, but higher repeat revascularization among patients treated with HCR. CONCLUSIONS: Hybrid coronary revascularization is associated with lower morbidity and similar in-hospital and 1-year major adverse cerebrovascular or cardiac events rates, but greater requirement for repeat revascularization compared with CABG. Further exploration of this strategy with adequately powered randomized trials is warranted.

Comparative study of same sitting hybrid coronary artery revascularization versus off-pump coronary artery bypass in multivessel coronary artery disease.

OBJECTIVE: We compared the outcomes of same sitting robotic-assisted hybrid coronary artery revascularization (HCR) with off-pump coronary artery bypass grafting (OPCABG) in similar patients with multivessel coronary artery disease. BACKGROUND: HCR is a novel procedure in selected patients with multivessel coronary artery disease (CAD). Although there are some data on staged HCR, the data on same sitting HCR are limited. METHODS: We conducted a prospective study comparing same sitting robotic-assisted HCR patients (n = 25) to a group of consecutive low to moderate risk OPCABG patients (n = 27) during the study period. HCR patients underwent robotic internal mammary artery takedown followed by OPCABG via minithoracotomy. After confirming graft patency, immediate percutaneous coronary intervention on the nonbypass arteries was performed. Comparative analyses were performed on in-hospital and 30 day outcomes. RESULTS: The baseline characteristics were similar for both groups including the severity of CAD (Syntax score 33.5+/-8.2 vs. 34.9+/-8.2, P = 0.556). Overall MACE was similar between both groups; however, the HCR group showed improved hospital outcomes with lower need for postoperative transfusions (12% vs. 67%, P < 0.001), and shorter length of hospital stay (5.1+/-2.8 vs. 8.2+/-5.4 days, P < 0.01). Despite lower postoperative costs, the HCR group had higher overall hospital costs due to higher procedural costs ($33,984 +/-$4,806 vs. $27,816+/-$11,172, P < 0.0001). Propensity model analysis showed similar findings. The HCR group showed improved quality of life measures with shorter time to return to work (5.3+/-3.0 vs. 8.2+/- 4.6 weeks, P = 0.01). CONCLUSIONS: Same sitting HCR appears to be feasible and may offer superior outcomes to standard OPCABG, further studies are warranted.

Drug-eluting stent thrombosis in routine clinical practice: two-year outcomes and predictors from the TAXUS ARRIVE registries.

BACKGROUND: Stent thrombosis (ST) is an uncommon but serious complication of drug-eluting and bare metal stents. To assess drug-eluting stent ST in contemporary practice, we analyzed 2-year data from the 7492-patient ARRIVE registry. METHODS AND RESULTS: Patients were enrolled at the initiation of percutaneous coronary intervention with no inclusion/exclusion criteria beyond use of the paclitaxel-eluting TAXUS stent. Two-year follow-up was 94% with independent adjudication of major cardiac events. A second, autonomous committee adjudicated Academic Research Consortium (ARC) definite/probable ST. Cumulative 2-year ARC-defined ST was 2.6% (1.0% early ST [<30 days], 0.7% late ST [31 to 365 days], and 0.8% very late ST [>1 year]). Simple-use (single-vessel and single-stent) cases had lower rates than expanded use (broader patient/lesion characteristics, 2-year cumulative: 1.4% versus 3.3%, P<0.001; early ST: 0.4% versus 1.4%, P<0.001; late ST: 0.5% versus 0.8%, P=0.14; very late ST: 0.4% versus 1.0%, P=0.008). Within 7 days of ST, 23% of patients died; 28% suffered Q-wave myocardial infarction. Mortality was higher with early ST (39%) than late ST (12%, P<0.001) or very late ST (13%, P<0.001). Multivariate analysis showed anatomic factors increased early ST (lesion >28 mm, lesion calcification) and late ST (vessel <3.0 mm); biological factors increased very late ST (renal disease, prior brachytherapy). Although early ST (71.4%) and very late ST (23.1%) patients had dual antiplatelet therapy at the time of ST, premature thienopyridine discontinuation was a strong independent predictor of both. CONCLUSIONS: The relative risks of early and late ST differ. Knowledge of ST risk for specific subgroups may guide revascularization options until the completion of randomized trials in these broad populations.

A randomized comparison of a novel bioabsorbable vascular closure device versus manual compression in the achievement of hemostasis after percutaneous femoral procedures: the ECLIPSE (Ensure's Vascular Closure Device Speeds Hemostasis Trial).

OBJECTIVES: This trial compared the performance of a novel bioabsorbable vascular closure device (VCD) versus manual compression (MC) for access site hemostasis in patients undergoing percutaneous trans-femoral coronary or peripheral procedures. BACKGROUND: From a patient's perspective, access site management after percutaneous procedures remains challenging. METHODS: Patients enrolled in this multicenter, nonblinded trial underwent 6-F diagnostic or interventional procedures were randomly assigned 2:1 to VCD versus MC. The primary efficacy end points were time to hemostasis (TTH) and time to ambulation (TTA), and the primary safety end points were periprocedural and 30-day incidence of arterial access-related complications. RESULTS: The trial assigned 401 patients (mean age 62.7 +/- 10.9 years, 66.1% men) to VCD (n = 267) versus MC (n = 134) after 87 "roll-in" patients treated at 17 participating institutions. The baseline characteristics of the groups were similar. Procedural success was 91.8% in the VCD versus 91.0% in the MC group (p = NS). Mean TTH was 4.4 +/- 11.6 min in the VCD versus 20.1 +/- 22.5 min in the MC group (95% confidence interval: 19.0 to 12.3; p < 0.0001). Likewise, TTA was significantly shorter in the VCD (2.5 +/- 5.0 h) than in the MC (6.2 +/- 13.3 h) group (95% confidence interval: 5.5 to 1.9; p = 0.0028). No patient died or suffered a major access-site-related adverse event. Minor adverse events were few among all study groups. CONCLUSIONS: After 6-F percutaneous invasive procedures, TTH and TTA were both significantly shorter in patients assigned to VCD than in patients managed with MC. The 30-day rates of access-site-related complications were remarkably low in all groups. (Safety and Effectiveness Study of the Ensure Medical Vascular Closure Device; NCT00345631).

Carotid artery revascularization in high-surgical-risk patients using the Carotid WALLSTENT and FilterWire EX/EZ: 1-year outcomes in the BEACH Pivotal Group.

OBJECTIVES: The multicenter, single-arm BEACH (Boston Scientific EPI: A Carotid Stenting Trial for High-Risk Surgical Patients) evaluated outcomes in high-surgical-risk patients with carotid artery stenosis treated with the Carotid WALLSTENT plus FilterWire EX/EZ Emboli Protection System (Boston Scientific, Natick, Massachusetts). BACKGROUND: Carotid artery stent (CAS) placement offers a less invasive alternative for high-risk surgical carotid endarterectomy (CEA) patients. METHODS: The trial enrolled 480 pivotal patients who were candidates for carotid revascularization but considered high surgical risk due to pre-specified anatomic criteria and/or medical comorbidities. The primary end point (all stroke, death, or Q-wave myocardial infarction [MI] through 30 days; non-Q-wave MI through 24 h; and ipsilateral stroke or neurologic death through 1 year) was compared with a proportionally weighted objective performance criterion (OPC) of 12.6% for published surgical endarterectomy results in similar patients, plus a pre-specified noninferiority margin of 4%. RESULTS: Among pivotal patients, 41.2% were at high surgical risk due to comorbid risk factors, and 58.8% due to anatomic risk factors; 76.7% were asymptomatic with flow-limiting carotid stenosis >80%. At 1 year, the composite primary end point occurred in 8.9% (40 of 447), with a repeat revascularization rate of 4.7%. With an upper 95% confidence limit of 11.5% for the primary composite end point, the BEACH trial results met the pre-specified criteria for noninferiority relative to the calculated OPC plus noninferiority margin (16.6%) for historical surgical CEA outcomes in similar patients (p < 0.0001 for noninferiority). CONCLUSIONS: The BEACH trial results demonstrate that CAS with the WALLSTENT plus FilterWire embolic protection is non-inferior (equivalent or better than) to CEA at 1-year in high-surgical-risk patients.

Effect of torcetrapib on the progression of coronary atherosclerosis.

BACKGROUND: Levels of high-density lipoprotein (HDL) cholesterol are inversely related to cardiovascular risk. Torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, increases HDL cholesterol levels, but the functional effects associated with this mechanism remain uncertain. METHODS: A total of 1188 patients with coronary disease underwent intravascular ultrasonography. After treatment with atorvastatin to reduce levels of low-density lipoprotein (LDL) cholesterol to less than 100 mg per deciliter (2.59 mmol per liter), patients were randomly assigned to receive either atorvastatin monotherapy or atorvastatin plus 60 mg of torcetrapib daily. After 24 months, disease progression was measured by repeated intravascular ultrasonography in 910 patients (77%). RESULTS: After 24 months, as compared with atorvastatin monotherapy, the effect of torcetrapib-atorvastatin therapy was an approximate 61% relative increase in HDL cholesterol and a 20% relative decrease in LDL cholesterol, reaching a ratio of LDL cholesterol to HDL cholesterol of less than 1.0. Torcetrapib was also associated with an increase in systolic blood pressure of 4.6 mm Hg. The percent atheroma volume (the primary efficacy measure) increased by 0.19% in the atorvastatin-only group and by 0.12% in the torcetrapib-atorvastatin group (P=0.72). A secondary measure, the change in normalized atheroma volume, showed a small favorable effect for torcetrapib (P=0.02), but there was no significant difference in the change in atheroma volume for the most diseased vessel segment. CONCLUSIONS: The CETP inhibitor torcetrapib was associated with a substantial increase in HDL cholesterol and decrease in LDL cholesterol. It was also associated with an increase in blood pressure, and there was no significant decrease in the progression of coronary atherosclerosis. The lack of efficacy may be related to the mechanism of action of this drug class or to molecule-specific adverse effects. (ClinicalTrials.gov number, NCT00134173 [ClinicalTrials.gov].).

Safety and efficacy of the 2.25-mm sirolimus-eluting Bx Velocity stent in the treatment of patients with de novo native coronary artery lesions: the SIRIUS 2.25 trial.

Smaller reference vessel diameter is a recognized determinant of in-stent restenosis. The SIRIUS 2.25 trial was a prospective, nonrandomized study including 100 patients (mean age 63.4 years; 64% men, 40% with diabetes mellitus) assessing the safety and efficacy of the 2.25-mm sirolimus-eluting Bx Velocity stent in patients with de novo native coronary lesions. Using propensity score matching for gender, diabetes mellitus, left anterior descending artery target vessel, lesion length, and reference vessel diameter, the outcomes were compared with historical control groups (angioplasty and Palmaz-Schatz stent arms from the STRESS/BENESTENT I/II trials and the Bx Velocity bare metal stent arm from the RAVEL and SIRIUS trials having a reference vessel diameter <3 mm). Use of the 2.25-mm sirolimus-eluting Bx Velocity stent was associated with a high rate of procedural success (97%) and a low rate of in-hospital major adverse cardiac events (2%). The primary end point, 6-month in-lesion binary angiographic restenosis, occurred less frequently in patients treated with the 2.25-mm sirolimus-eluting Bx Velocity stent than in each of 3 historical controls (16.9% vs 30.6%, p = 0.12; 36.5%, p <0.001; 45.9%, p <0.001, respectively). This translated into lower rates of 6-month target lesion revascularization in the 2.25-mm sirolimus-eluting Bx Velocity stent group (4.0% vs 15.0% in each of 3 control groups, p = 0.01 to <0.001). By multivariate analysis, in-lesion binary restenosis was predicted by multiple implanted stents (odds ratio 10.4, p = 0.002). Four of 13 patients who developed restenosis (30.8%) had a diffuse pattern of restenosis. In the long lesion tertile (mean lesion length 19.5 mm), the in-lesion binary restenosis rate was 27.6%. In conclusion, use of the 2.25-mm sirolimus-eluting Bx Velocity stent was safe and provided favorable 6-month clinical outcomes. Use of multiple stents (in longer lesions) was an independent predictor of in-lesion restenosis.