Initial experience with factor-Xa inhibition in percutaneous coronary intervention: the XaNADU-PCI Pilot.

BACKGROUND: Direct factor (F)Xa inhibition is an attractive method to limit thrombotic complications during percutaneous coronary intervention (PCI). OBJECTIVES: To investigate drug levels achieved, effect on coagulation markers, and preliminary efficacy and safety of several doses of DX-9065a, an intravenous, small molecule, direct, reversible FXa inhibitor during PCI. PATIENTS AND METHODS: Patients undergoing elective, native-vessel PCI (n = 175) were randomized 4 : 1 to open-label DX-9065a or heparin in one of four sequential stages. DX-9065a regimens in stages I-III were designed to achieve concentrations of > 100 ng mL-1, > 75 ng mL-1, and > 150 ng mL-1. Stage IV used the stage III regimen but included patients recently given heparin. RESULTS: At 15 min median (minimum) DX-9065a plasma levels were 192 (176), 122 (117), 334 (221), and 429 (231) ng mL-1 in stages I-IV, respectively. Median whole-blood international normalized ratios (INRs) were 2.6 (interquartile range 2.5, 2.7), 1.9 (1.8, 2.0), 3.2 (3.0, 4.1), and 3.8 (3.4, 4.6), and anti-FXa levels were 0.36 (0.32, 0.38), 0.33 (0.26, 0.39), 0.45 (0.41, 0.51), and 0.62 (0.52, 0.65) U mL-1, respectively. Stage II enrollment was stopped (n = 7) after one serious thrombotic event. Ischemic and bleeding events were rare and, in this small population, showed no clear relation to DX-9065a dose. CONCLUSIONS: Elective PCI is feasible using a direct FXa inhibitor for anticoagulation. Predictable plasma drug levels can be rapidly obtained with double-bolus and infusion DX-9065a dosing. Monitoring of DX-9065a may be possible using whole-blood INR. Direct FXa inhibition is a novel and potentially promising approach to anticoagulation during PCI that deserves further study.

Long-term effects of intracoronary beta-radiation in balloon- and stent-injured porcine coronary arteries.

BACKGROUND: The data on the long-term safety and efficacy of intracoronary beta-radiation in animal models are limited. METHODS AND RESULTS: A total of 30 coronary arteries in 15 swine were subjected to balloon or stent injury followed by beta-radiation from a centered 32P source (2000 cGy to 1 mm beyond lumen surface) or a sham radiation procedure. The animals received aspirin for 6 months and ticlopidine for 30 days. Five of the 10 animals subjected to radiation died (at 5 days, 7 days, 3 months [n = 2], and 4 months) as a result of layered, occlusive thrombus at the intervention site (3 stent and 2 balloon injury sites). No deaths occurred in the control group. In the surviving animals, balloon-injured and irradiated vessels showed a trend toward larger lumens than controls (2.15 +/- 0.17 versus 1.80 +/- 0.08 mm2, P=0.06) and larger external elastic lamina areas (3.32 +/- 0.21 versus 2.62 +/- 0.10 mm2, P=0.003). In the stent-injured vessels from surviving animals, lumen, neointimal, and external elastic lamina areas were 3.58 +/- 0.33, 3.16 +/- 0.35, and 8.12 +/- 0.42 mm2 for irradiated vessel segments; these values were not different from those in controls (3.21 +/- 0.15, 2.84 +/- 0.27, and 7.76 +/- 0.28 mm2, respectively). Histologically, healing was complete in most survivors, although intramural fibrin and hemorrhage were occasionally seen. CONCLUSION: In the long-term (6 month) porcine model of restenosis, the inhibition by intracoronary beta-radiotherapy of the neointimal formation that is known to be present at 1 month is not sustained. This lack of effect on neointimal formation after balloon and stent arterial injury is accompanied by subacute and late thrombosis that leads to cardiac death on a background of continuous aspirin but relatively brief ticlopidine treatment.

Use of nitric-oxide-eluting polymer-coated coronary stents for prevention of restenosis in pigs.

BACKGROUND: Restenosis after angioplasty remains an unresolved problem despite an increase in use of coronary stents. It has been theorized that nitric oxide (NO) exerts several actions that can prevent restenosis. These include inhibition of proliferation of smooth muscle cells, prevention of arterial spasms, and decreasing aggregation of platelets in response to exposure to collagen. OBJECTIVE: To determine whether NO coated stents decrease restenosis in a pig balloon injury model. METHODS: We used coronary stents impregnated with a slow-release precursor of NO in the porcine model of restenosis. Tantalum coil coronary stents (Cordis) were coated with a polymer impregnated with a slow-release precursor of NO. Polymer-coated stents without active precursors were used as controls. Oversized stents were mounted on a delivery balloon and subsequently deployed in the right coronary and left anterior descending arteries of each animal. RESULTS: Repeated recording of angiograms demonstrated that changes in minimum lumen diameter on going from immediately after stenting to 28-day follow-up for the control and NO-eluting-stent groups were similar, namely decreases of 1.89 +/- 0.33 and 2.08 +/- 0.28 mm, respectively. The morphometric results, showing that severe luminal narrowing occurred for both groups, were similar. The percentage area stenoses were 85 +/- 5% for the control group and 84 +/- 6% for the NO-eluting group. Histology demonstrated that profuse formation of neointima and an inflammatory cell infiltrate occurred. CONCLUSIONS: Severe diameter stenosis occurred both for control and for treatment groups. The degree of angiographic stenosis was markedly worse than that previously reported for this model. Sustained release of a precursor of NO did not prevent restenosis in this model. This might have been due to a lack of efficacy of nitric oxide or to a profuse and overwhelming stimulatory effect of the polymer in the coated stents.

Risk of human immunodeficiency virus in surgeons, anesthesiologists, and medical students.

We postulated that three factors determined the occupational risk of infection from the human immunodeficiency virus (HIV) for surgeons, anesthesiologists, and medical students: first, the risk of needlestick exposure per year (range for surgeons 3.8-6.2, weighted average 4.2; range for anesthesiologists 0.86-2.5, weighted average 1.3; range for third-year medical students 0-5, best estimate 5); second, the risk of seroconversion from a needlestick exposure (0.42%-0.50%); and third, prevalence of HIV in the population served (0.32%-23.6%, depending on geographic location). Thus, the calculated range for occupational risk of HIV infection for a surgeon over a 30-yr period (assuming no change in HIV prevalence or benefit from protective measures) was 0.17%-13.9%; for an anesthesiologist, 0.05%-4.50%. The corresponding range of occupational risk for a medical student during the third year was 0.007%-0.59%. The range of risk is large because the variation in prevalence of HIV infection from one area to another is great. The authors validated the methodology first by using an equation, with estimates from the literature for factors in the equation, to calculate the risk of infection for hepatitis B and then by comparing the results with known rates of infection in the prevaccine era. Calculated occupational risk of hepatitis B infection for anesthesiologists was in the lower range of actual prevalence of infection (calculated range 2.32%-20.6%; known range 6%-26%). Calculated risk versus prevalence for surgeons was fairly close (7.31%-53.4% versus 24.4%).(ABSTRACT TRUNCATED AT 250 WORDS)