Blinded outcomes and angina assessment of coronary bioresorbable scaffolds: 30-day and 1-year results from the ABSORB IV randomised trial.

BACKGROUND: Previous studies showed more adverse events with coronary bioresorbable vascular scaffolds (BVS) than with metallic drug-eluting stents (DES), although in one randomised trial angina was reduced with BVS. However, these early studies were unmasked, lesions smaller than intended for the scaffold were frequently enrolled, implantation technique was suboptimal, and patients with myocardial infarction, in whom BVS might be well suited, were excluded. METHODS: In the active-controlled, blinded, multicentre, randomised ABSORB IV trial, patients with stable coronary artery disease or acute coronary syndromes aged 18 years or older were recruited from 147 hospitals in five countries (the USA, Germany, Australia, Singapore, and Canada). Enrolled patients were randomly assigned (1:1) to receive polymeric everolimus-eluting BVS (Absorb; Abbott Vascular, Santa Clara, CA, USA) with optimised implantation technique or cobalt-chromium everolimus-eluting stents (EES; Xience; Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetic status, whether patients would have been eligible for enrolment in the previous ABSORB III trial, and site. Patients and clinical assessors were masked to randomisation. The primary endpoint was target lesion failure (cardiac death, target vessel myocardial infarction, or ischaemia-driven target lesion revascularisation) at 30 days, tested for non-inferiority with a 2·9% margin for the risk difference. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02173379, and is closed to accrual. FINDINGS: Between Aug 15, 2014, and March 31, 2017, we screened 18 722 patients for eligibility, 2604 of whom were enrolled. 1296 patients were assigned to BVS, and 1308 patients were assigned to EES. Follow-up data at 30 days and 1 year, respectively, were available for 1288 and 1254 patients with BVS and for 1303 and 1272 patients with EES. Biomarker-positive acute coronary syndromes were present in 622 (24%) of 2602 patients, and, by angiographic core laboratory analysis, 78 (3%) of 2893 of lesions were in very small vessels. Target lesion failure at 30 days occurred in 64 (5·0%) patients assigned to BVS and 48 (3·7%) patients assigned to EES (difference 1·3%, upper 97·5% confidence limit 2·89; one-sided pnon-inferiority=0·0244). Target lesion failure at 1 year occurred in 98 (7·8%) patients assigned to BVS and 82 (6·4%) patients assigned to EES (difference 1·4%, upper 97·5% confidence limit 3·4; one-sided pnon-inferiority=0·0006). Angina, adjudicated by a central events committee at 1 year, occurred in 270 (20·3%) patients assigned to BVS and 274 (20·5%) patients assigned to EES (difference -0·3%, 95% CI -3·4% to 2·9%; one-sided pnon-inferiority=0·0008; two-sided psuperiority=0·8603). Device thrombosis within 1 year occurred in nine (0·7%) patients assigned to BVS and four (0·3%) patients assigned to EES (p=0·1586). INTERPRETATION: Polymeric BVS implanted with optimised technique in an expanded patient population resulted in non-inferior 30-day and 1-year rates of target lesion failure and angina compared with metallic DES. FUNDING: Abbott Vascular.

Quantification of abciximab-induced platelet inhibition is assay dependent: a comparative study in patients undergoing percutaneous coronary intervention.

BACKGROUND: The best method for measuring the degree of platelet inhibition with glycoprotein (GP) IIb-IIIa antagonists during percutaneous coronary intervention (PCI) and the optimal degree of periprocedural inhibition is uncertain. Low molecular weight heparins have been reported to cause less platelet activation than unfractionated heparin. Therefore, compared with unfractionated heparin (UHF), a low molecular weight heparin could enhance measured platelet inhibition. In this study, we compared 3 methods of measuring platelet inhibition and investigated the effects of half doses of abciximab in combination with either UFH or the low molecular weight heparin dalteparin in patients undergoing PCI with planned abciximab administration. METHODS: Abciximab-induced platelet inhibition was measured serially by means of 3 assays: 1) GP IIb-IIIa receptor occupancy, 2) binding of the activated GP IIb-IIIa-specific monoclonal antibody PAC1, and 3) agglutination of platelets with fibrinogen-coated beads (RPFA). Forty patients were randomly allocated to receive either UFH (70 U/kg) or dalteparin (60 IU/kg), followed by a half dose of abciximab (0.125 mg/kg) administered twice at 10-minute intervals. Assays were obtained 10 minutes after each half dose of abciximab and 8 to 10 and 24 hours after abciximab administration. RESULTS: No differences between UFH and dalteparin were observed. At each time-point measured, the mean percent platelet inhibition as determined by means of the receptor occupancy assay and PAC1 binding assay was less than the degree of inhibition determined by means of the RPFA. CONCLUSIONS: The results of targeted levels of platelet inhibition cannot be extrapolated between different clinical trials of GP IIb-IIIa antagonists unless the same assay is used. Dalteparin, compared with UFH, does not enhance platelet inhibition or receptor occupancy by abciximab, as demonstrated by means of 3 separate assays.

Thrombosis and drug-eluting stents: a critical appraisal.

The clinical consequences of stent thrombosis are frequently catastrophic. This article reviews the factors previously implicated in the occurrence of stent thrombosis and analyzes recent reports of thrombosis involving a new sirolimus-eluting stent (Cypher). Factors associated with stent thrombosis include intrinsic stent thrombogenicity and patient-, target lesion-, and procedure-related issues. Stent design may influence the degree of platelet activation after coronary stent deployment. In drug-eluting stents, the mechanical properties of the bare metal stent platform might be altered by the polymer coating, and the propensity for thrombosis might be influenced by both the polymer coating and the medication with which it is impregnated. Cumulative data for the Cypher stent do not suggest a propensity for thrombosis, but several caveats should be observed to enhance the safety of the device.

Durable clinical benefit following Sr90 Beta irradiation therapy for in-stent restenosis in high-volume community practice.

Although randomized clinical trials have demonstrated efficacy of coronary irradiation versus placebo for the treatment of in-stent restenosis (ISR), durable long-term benefit in community practice is less well defined. From January 1, 2001, through June 30, 2002, consecutive percutaneous coronary intervention (n = 3,869) were analyzed at our center with a total of 330 patients undergoing coronary irradiation for ISR (53, Ir192; 12, P32; 265 Novoste Sr90). Novoste Sr90 was successfully performed in 265 of 270 (98%) of patients attempted by 10 operators. The mean patient age was 63 years (range 35 90) with 55% male (145/265) and 45% female (120/265). ISR anatomic subsets included multi-lesion (45/265; 17%), multi-vessel (27/265; 10.0%) and saphenous vein graft (16/265; 6.0%) interventions. At a mean follow-up of 10.5 2.8 (SD) months, fifty-three (20%) of the Novoste Sr90 treated patients had returned for symptoms requiring repeat angiography. Of these, 23 patients had repeat percutaneous coronary intervention (PCI) including 2 target site revascularizations (TSR), twelve non-TSR (distinct from the radiated segment of the target vessel), and 9 non-target vessel revascularizations (TVR). Coronary artery bypass surgery was performed in 11 total patients, 4 due to TSR, and 7 due to non-TVR. Clinical TSR was 2.3% (6/265) and TVR was 6.8% (18/265). In conclusion, the Novoste SR90 Beta-Cath System for the treatment of ISR is associated with a high procedural success rate and low TSR and TVR. Revascularization in follow-up is predominantly due to progressive disease outside the radiated segment and aggressive secondary prevention, especially prolonged anti-platelet therapy, appear critical to long-term procedural success.

Successful long-term therapy following saphenous vein-covered stent deployment for atherosclerotic coronary aneurysm.

We describe a case of atherosclerotic aneurysm involving the left main coronary artery in a patient with prior coronary artery bypass surgery. A saphenous vein-covered stent was used to seal the aneurysm in conjunction with conventional stenting of an associated native vessel coronary stenosis. Focal late restenosis involving the stent graft was successfully treated with repeat angioplasty and brachytherapy. Autologous vein-covered stent deployment should be considered in the treatment of symptomatic or progressively enlarging coronary aneurysms.