Christopher Metzger

Drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral artery disease: 12-month results from the IN.PACT SFA randomized trial.

Background— Drug-coated balloons (DCBs) have shown promise in improving the outcomes for patients with peripheral artery disease. We compared a paclitaxel-coated balloon with percutaneous transluminal angioplasty (PTA) for the treatment of symptomatic superficial femoral and popliteal artery disease. Methods and Results— The IN.PACT SFA Trial is a prospective, multicenter, single-blinded, randomized trial in which 331 patients with intermittent claudication or ischemic rest pain attributable to superficial femoral and popliteal peripheral artery disease were randomly assigned in a 2:1 ratio to treatment with DCB or PTA. The primary efficacy end point was primary patency, defined as freedom from restenosis or clinically driven target lesion revascularization at 12 months. Baseline characteristics were similar between the 2 groups. Mean lesion length and the percentage of total occlusions for the DCB and PTA arms were 8.94±4.89 and 8.81±5.12 cm (P=0.82) and 25.8% and 19.5% (P=0.22), respectively. DCB resulted in higher primary patency versus PTA (82.2% versus 52.4%; P<0.001). The rate of clinically driven target lesion revascularization was 2.4% in the DCB arm in comparison with 20.6% in the PTA arm (P<0.001). There was a low rate of vessel thrombosis in both arms (1.4% after DCB and 3.7% after PTA [P=0.10]). There were no device- or procedure-related deaths and no major amputations. Conclusions— In this prospective, multicenter, randomized trial, DCB was superior to PTA and had a favorable safety profile for the treatment of patients with symptomatic femoropopliteal peripheral artery disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique Identifiers: NCT01175850 and NCT01566461.

Stenting and angioplasty with protection in patients at high-risk for endarterectomy: SAPPHIRE Worldwide Registry first 2,001 patients.

Previously, the Stenting and Angioplasty with Protection of Patients with High Risk for Endarterectomy (SAPPHIRE) randomized trial showed that carotid artery stenting (CAS) was not inferior to carotid endarterectomy (CEA) in the treatment of high‐surgical risk patients.

Durability of Treatment Effect Using a Drug-Coated Balloon for Femoropopliteal Lesions: 24-Month Results of IN.PACT SFA.

BACKGROUND Evidence from large, randomized, controlled peripheral artery disease trials reporting long-term outcomes using drug-coated balloons (DCBs) is limited. Previously, the DCB showed favorable 1-year outcomes compared with conventional percutaneous transluminal angioplasty (PTA), yet durability of the treatment effect with DCBs remains unknown. OBJECTIVES This study sought to investigate the longer-term outcomes of a paclitaxel-eluting DCB compared to PTA for femoropopliteal lesions. METHODS We enrolled 331 patients with symptomatic (Rutherford 2 to 4) femoropopliteal lesions up to 18 cm in length. Patients were randomly assigned in a 2:1 ratio to treatment with DCB or PTA. The 24-month assessments included primary patency, freedom from clinically driven target lesion revascularization (CD-TLR), major adverse events, and quality of life and functional outcomes as assessed by the EuroQOL-5D quality-of-life questionnaire, walking impairment questionnaire, and 6-min walk test. RESULTS At 24 months, patients treated with DCB showed significantly higher primary patency when compared with PTA (78.9% vs. 50.1%; p < 0.001). The rates of CD-TLR were 9.1% and 28.3% (p < 0.001) for the DCB and PTA groups, respectively. The overall mortality rate in the DCB group was 8.1% versus 0.9% in the PTA group (p = 0.008). There were no device- or procedure-related deaths and no major amputations in either group through 24-month follow-up. The rate of vessel thrombosis was low (1.5% DCB vs. 3.8% PTA; p = 0.243), with no new events reported between 1 and 2 years. Both groups showed similar functional improvement at 2 years, although DCB patients achieved this level of function with 58% fewer reinterventions. CONCLUSIONS The 24-month outcomes from the trial demonstrate a durable and superior treatment effect of DCB versus PTA with significantly higher primary patency, lower CD-TLR, and similar functional status improvement with fewer repeat interventions. (Randomized Trial of IN.PACT Admiral Drug Eluting Balloon vs Standard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease [INPACT SFA I]; NCT01175850; and IN.PACT Admiral Drug-Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Superficial Femoral Artery [SFA] and Proximal Popliteal Artery [PPA] [INPACT SFA II]; NCT01566461).

Wire-Interwoven Nitinol Stent Outcome in the Superficial Femoral and Proximal Popliteal Arteries Twelve-Month Results of the SUPERB Trial

Background—Stent-based therapy in the superficial femoral and popliteal arteries in patients with peripheral artery disease is compromised by restenosis and risk of stent fracture or distortion. A novel self-expanding nitinol stent was developed that incorporates an interwoven-wire design (Supera stent, IDEV Technologies, Inc, Webster, TX) to confer greater radial strength, flexibility, and fracture resistance. Methods and Results—This prospective, multicenter, investigational device exemption, single-arm trial enrolled 264 patients with symptomatic peripheral artery disease undergoing percutaneous treatment of de novo or restenotic lesions of the superficial femoral or proximal popliteal (femoropopliteal) artery. Freedom from death, target lesion revascularization, or any amputation of the index limb at 30 days (+7 days) postprocedure was achieved in 99.2% (258/260) of patients (P<0.001). Primary patency at 12 months (360±30 days) was achieved in 78.9% (180/228) of the population (P<0.001). Primary patency by Kaplan–Meier analysis at 12 months (360 days) was 86.3%. No stent fracture was observed by independent core laboratory analysis in the 243 stents (228 patients) evaluated at 12 months. Clinical assessment at 12 months demonstrated improvement by at least 1 Rutherford–Becker category in 88.7% of patients. Conclusions—The SUPERB Trial, an investigational device exemption study using an interwoven nitinol wire stent in the femoropopliteal artery, achieved the efficacy and safety performance goals predesignated by the Food and Drug Administration. On the basis of the high primary patency rate, absence of stent fracture, and significant improvements in functional and quality-of-life measures, the Supera stent provides safe and effective treatment of femoropopliteal lesions in symptomatic patients with peripheral artery disease. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00933270.

Safety and efficacy of carotid stenting in the very elderly

Background: Carotid artery stenting (CAS) has emerged as an alternative to carotid endarterectomy (CEA) in patients at high risk for complications from surgery. The very elderly (≥80‐year‐old) are one subgroup of patients identified as being at increased risk for carotid surgery. However, there is concern that the very elderly are also at increased risk for complications of CAS. A stroke and death rate of 12% was reported in very elderly patients during the roll‐in phase of Carotid Revascularization Endarterectomy versus Stent Trial (CREST). We are reporting on a large clinical series of CAS with independent neurological assessment in the very elderly. Methods: Between 1994 and 2008, a consecutive series of 418 CAS patients (≥80‐year‐old) were treated at four high‐volume centers with extensive CAS experience. Independent neurologic assessment was performed after CAS procedures. Thirty‐day follow‐up information was available in 389 patients. Results: The average age was 83.2 ± 2.8 years. Most patients were male (63.2%), and the target lesion carotid stenosis was asymptomatic in two‐thirds (68.2%) of patients. The majority of patients treated with CAS had a history of coronary artery disease (74.4%), hypertension (87.8%), and dyslipidemia (71.1%). One third (30.1%) were diabetic and more than half (56.5%) were current or former smokers. Embolic protection devices (EPD) were used in 78.7% of cases with the CAS procedure being performed before EPD availability being the most common reason for not using them. The overall 30‐day incidence of stroke and death was 2.8% (11/389). The cumulative incidence of major cardiovascular events (stroke, death, or myocardial infarction) during that time period was 3.3% (13/389). Conclusions: This large series of CAS with independent neurologic assessment is convincing evidence that the very elderly (≥80 years) can safely undergo CAS with stroke and death rates comparable to younger patients. The key to obtaining these excellent results is that CAS be performed by high volume, experienced operators who exercise restraint regarding patient selection.

Correlates of adverse events during saphenous vein graft intervention with distal embolic protection: a PRIDE substudy.

OBJECTIVES We sought to identify correlates of 30-day adverse events among patients undergoing percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG). BACKGROUND Although the use of distal embolic protection devices during SVG intervention reduces major adverse cardiac events (MACE), many patients still experience MACE despite distal embolic protection, and the major predictors of MACE among these patients are not well-characterized. METHODS Correlates of 30-day MACE and peri-procedural creatine kinase-myocardial band (CK-MB) elevation were assessed among 631 patients undergoing SVG intervention with distal embolic protection enrolled in the PRIDE (PRotection during saphenous vein graft Intervention to prevent Distal Embolization) study, a randomized comparison of the TriActiv System (Kensey-Nash Corp., Exton, Pennsylvania) with an active control group (Guardwire [Medtronic, Santa Clara, California] or Filterwire [Boston Scientific, Minneapolis, Minnesota]). RESULTS Baseline covariates associated with MACE were longer lesion length, greater angiographically assessed estimated plaque volume, and higher SVG degeneration score. Graft age and angina class were not associated with adverse events. Angiographic lesion length was significantly correlated with more complex angiographic metrics such as estimated plaque volume and the SVG degeneration score. In multivariable analyses, angiographic lesion length was the strongest independent correlate of MACE (odds ratio [OR] 2.81 [95% confidence interval (CI) 1.82 to 4.34]/log-increase in lesion length, p < 0.001) with a graded increase in MACE observed with increasing lesion lengths. Similarly, the strongest independent correlate of CK-MB elevation was lesion length (OR 2.54 [95% CI 1.59 to 4.04]/log-increase in lesion length, p < 0.001). The associations between lesion length and both MACE and CK-MB elevation were consistent among the studied embolic protection devices (TriActiv, Guardwire, or Filterwire). CONCLUSIONS Angiographic lesion length was the strongest correlate of short-term adverse events among patients undergoing SVG intervention with distal embolic protection, with incremental effects noted at even relatively short lesion lengths.

Treatment Effect of Drug-Coated Balloons Is Durable to 3 Years in the Femoropopliteal Arteries: Long-Term Results of the IN.PACT SFA Randomized Trial

Background— Randomized controlled trials have reported favorable 1-year outcomes with drug-coated balloons (DCBs) for the treatment of symptomatic peripheral arterial disease when compared with standard percutaneous transluminal angioplasty (PTA). Evidence remains limited on the durability of the treatment effect with DCBs in the longer term. Methods and Results— IN.PACT SFA is a single-blind, randomized trial (Randomized Trial of IN.PACT Admiral Paclitaxel-Coated Percutaneous Transluminal Angioplasty [PTA] Balloon Catheter vs Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery [SFA] and/or Proximal Popliteal Artery [PPA]) that enrolled 331 patients with symptomatic (Rutherford 2–4) femoropopliteal lesions up to 18 cm in length. Patients were randomized 2:1 to receive treatment with DCB or PTA. The 36-month assessments included primary patency, freedom from clinically driven target lesion revascularization, major adverse events, and functional outcomes. At 36 months, primary patency remained significantly higher among patients treated with DCB compared with PTA (69.5% versus 45.1%; log rank P<0.001). The rates of clinically driven target lesion revascularization were 15.2% and 31.1% (P=0.002) for the DCB and PTA groups, respectively. Functional outcomes were similarly improved between treatment groups even though subjects in the DCB group required significantly fewer reinterventions versus those in the PTA group (P<0.001 for target lesion revascularization, P=0.001 for target vessel revascularization). There were no device- or procedure-related deaths as adjudicated by an independent Clinical Events Committee. Conclusions— Three-year results demonstrate a durable and superior treatment effect among patients treated with DCB versus standard PTA, with significantly higher primary patency and lower clinically driven target lesion revascularization, resulting in similar functional improvements with reduced need for repeat interventions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01175850 for IN.PACT SFA phase I in the European Union and NCT01566461 for IN.PACT SFA phase II in the United States.

SUPERB final 3-year outcomes using interwoven nitinol biomimetic supera stent

Long‐term outcomes of an interwoven nitinol stent design represent the best in class for treatment of lower limb arterial obstructive disease

Impact of Anemia on Platelet Reactivity and Ischemic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Study.

Anemic patients remain at increased risk of ischemic and bleeding events. Whether the effects of hemoglobin levels on thrombotic and bleeding risk are independent of platelet reactivity on clopidogrel, however, remains unknown. Patients from the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents study were categorized by the presence of anemia at baseline, defined according the World Health Organization criteria. Platelet reactivity was measured with VerifyNow assay; high platelet reactivity (HPR) on clopidogrel was defined as platelet reactive units value >208. Of 8,413 patients included in the study cohort, 1,816 (21.6%) had anemia. HPR was more prevalent in patients with anemia (58.3% vs 38.4%; p <0.001), an association that persisted after multivariate adjustment (adjusted odds ratio: 2.04; 95% confidence interval [CI]: 1.82 to 2.29; p <0.0001). Patients with anemia had higher 2-year rates of major adverse cardiac events (9.5% vs 5.6%; p <0.0001), major bleeding (11.8% vs 7.7%; p <0.0001), and all-cause mortality (4.0% vs 1.4%; p <0.0001); however, after adjustment for baseline clinical confounders, including HPR, anemia was no longer significantly associated with major adverse cardiac events but was still independently associated with all-cause mortality (adjusted HR 1.61, 95% CI 1.23 to 2.12; p <0.0001) and major bleeding (adjusted HR 1.42, 95% CI 1.20 to 1.68; p <0.0001). The effect of HPR on clinical outcomes was uniform according to anemia status, without evidence of interaction. In conclusion, anemia independently correlated with HPR. After percutaneous coronary intervention with drug-eluting stents, anemia at baseline was significantly associated with higher 2-year hemorrhagic and mortality risk; conversely, its association with ischemic risk was attenuated after multivariate adjustment, including HPR.

An integer based risk score for predicting 30-day major adverse cardiac or cerebrovascular events after percutaneous coronary intervention with drug-eluting stents: results from a large prospective multicentre registry, the STENT Group

AIMS Previous risk models predicting in-hospital major adverse cardiac or cerebrovascular events (MACCE) after percutaneous coronary interventions (PCI) may underestimate actual short-term post-procedure complications due to the trend toward early discharge of patients. METHODS AND RESULTS Using a subset (N=10,679) from the STENT Group registry, a logistic regression model was developed to predict 30-day MACCE which includes death, myocardial infarction, target vessel revascularisation and stroke. An integer-based risk score was created from the model and validated in another subset (N=3,099). In the study subset, there was significant difference between in-hospital and 30-day MACCE N=443 (2.0%) vs. 131 (4.2), p<0.01, respectively. A final risk model included nine variables; absence of pre-procedural statin (odds ratio=1.3, 95% confidence interval=1.0-1.5), haemoglobin level (0.9/1 gm increase, 0.8-0.9), cardiogenic shock (4.4, 3.1-6.3), acute congestive heart failure (1.6, 1.2-2.3), left main disease (2.2, 1.3-3.7), left anterior descending artery lesion (1.3, 1.0-1.5), ostial lesion (1.6, 1.2-2.1), coronary thrombosis (2.0, 1.4-2.9) and ACC/AHA type C lesion (1.3, 1.1-1.6). The c-statistics of the final model were 0.653 and 0.692 in the study and validation subset, respectively. CONCLUSIONS In this large real world registry of DES, in-hospital MACCE did not represent short-term post-procedure prognosis. The risk model consisting of nine variables predicted 30-day MACCE with modest discriminatory value.