Hidehiko Honda

Antiplatelet Therapy and Stent Thrombosis After Sirolimus-Eluting Stent Implantation

Background— The influences of antiplatelet therapy discontinuation on the risk of stent thrombosis and long-term clinical outcomes after drug-eluting stent implantation have not yet been addressed adequately. Methods and Results— In an observational study in Japan, 2-year outcomes were assessed in 10 778 patients undergoing sirolimus-eluting stent implantation. Data on status of antiplatelet therapy during follow-up were collected prospectively. Incidences of definite stent thrombosis were 0.34% at 30 days, 0.54% at 1 year, and 0.77% at 2 years. Thienopyridine use was maintained in 97%, 62%, and 50% of patients at 30 days, 1 year, and 2 years, respectively. Patients who discontinued both thienopyridine and aspirin had a significantly higher rate of stent thrombosis than those who continued both in the intervals of 31 to 180 days, 181 to 365 days, and 366 to 548 days after stent implantation (1.76% versus 0.1%, P<0.001; 0.72% versus 0.07%, P=0.02; and 2.1% versus 0.14%, P=0.004, respectively). When discontinuation of aspirin was taken into account, patients who discontinued thienopyridine only did not have an excess of stent thrombosis in any of the time intervals studied. Adjusted rates of death or myocardial infarction at 24 months were 4.1% for patients taking thienopyridine and 4.1% for patients not taking thienopyridine (P=0.99) in the 6-month landmark analysis. Conclusions— Discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine therapy only, was associated with an increased risk of stent thrombosis. Landmark analysis did not suggest an apparent clinical benefit of thienopyridine use beyond 6 months after sirolimus-eluting stent implantation.

Chimeric DNA-RNA Hammerhead Ribozyme to Proliferating Cell Nuclear Antigen Reduces Stent-Induced Stenosis in a Porcine Coronary Model

BACKGROUND Stent-induced coronary restenosis is a major clinical and public health problem. Proliferating cell nuclear antigen (PCNA) is an important regulator of cell division, and blocking of its expression after angioplasty may limit intimal proliferation. METHODS AND RESULTS We cloned the porcine PCNA gene and constructed a chimeric hammerhead ribozyme to a segment of the gene with human homology. In vitro studies with both cultured porcine and human vascular smooth muscle cells demonstrated uptake of ribozyme within the nucleus and significant inhibition of cellular proliferation. The ribozyme was then delivered locally into pig coronaries in a stent model. At 30 days, histomorphometric analysis showed neointimal thickness of 0.51+/-0.20 mm in the ribozyme group versus 0.71+/-0.27 and 0.66+/-0.25 mm in stent controls and scrambled ribozyme control, respectively (P=0.002, P=0.03). Quantitative angiographic analysis showed late loss of 1.4+/-0.5 mm for ribozyme versus 1.9+/-0.4 and 2.0+/-0.4 mm for the controls (P=0.05 and P=0. 02). CONCLUSIONS Chimeric hammerhead ribozyme to PCNA inhibits smooth muscle cell proliferation in vitro and reduces both histomorphometric and angiographic restenosis in the porcine coronary stent model when delivered locally.

Effectiveness of right or left radial approach for coronary angiography

The transradial approach for catheterization is becoming increasingly more popular. At present, the choice of the right or left radial artery depends on the operators preference. We examined how the laterality influenced the effectiveness of the approach. Employing Judkins‐type catheters, we performed coronary angiography in 232 patients with the left approach and in 205 patients with the right approach. Although access time did not differ between the two groups of patients, the duration of catheter manipulation was shorter in the left‐ than in the right‐approach group (11.7 ± 5.9 vs. 9.8 ± 4.4 min; P < 0.001). Because of the shorter duration of catheter manipulation, the total procedural duration was shorter in the left‐approach group (13.7 ± 6.4 vs. 11.4 ± 4.8 min; P < 0.001). The fluoroscopy time was shorter in the left‐ than in the right‐approach group (3.7 ± 2.5 vs. 5.0 ± 3.3 min; P < 0.001). The amount of contrast material did not differ between the groups (79 ± 27 vs. 83 ± 25 ml). The rate of guidewire usage to engage the coronary ostium was higher in the right‐ than in the left‐approach group because of the severe tortuosity of the right subclavian artery (20/205 vs. 0/232; P < 0.001). Thus, for operators with significant experience, the left radial approach may provide increased procedural efficacy for coronary angiography compared to the right radial approach. Catheter Cardiovasc Interv 2004;61:333–337.

Elution of everolimus and sirolimus from a biodegradable polymer coated stent inhibits neointimal hyperplasia without inflammation or toxicity

Background: Earfy clinical trials with drug eluting stents have suggested limitations including edge restenosis and malaposition. Persistent bio-stable polymer and/or drug may be causal. Biodegradable polymers hold potential advantage if they are metabolized prior to tissue toxicity and deliver drug during the optimal window. Local delivery of active drug from a slowly biodegradable, high molecular weight polylactic acid (PLA) coated stent could lead to inhibition of intimal hyperplasia without impaired healing. Methods: We compared PLA polymer containing 160 or 220 ug of Everolimus(E), 180 ug Sirolimus(S), and bare metal stent. 40 stents were deployed in coronary artehes of 19 pigs with sacrifice at 28 days. Endpoints were assessed by quantitative coronary angiog raphy @CA), histomorphometry, and histology at 28 and 90 days. Results:There was reduction of intimal hyperplasia as assessed by QCA and histomorphometry by both E and S (Table 1). At both 28 and 90 days, there was complete reendothelialization and ho difference in inflammation or fibrin between the bare stent and druglpolymer groups. Conclusion: Everolimus and Sirolimus delivered via stent and thin layer biodegradable polymer are equally effective at inhibition of intimal hyperplasia. At follow-up evaluation. complete healing without toxic or inflammatory reaction was seen. A clinical trial to determine safety and efficacy of the Everolimus coated stent has commenced.