Antirestenotic effects of a novel polymer-coated d-24851 eluting stent. Experimental data in a rabbit iliac artery model.

Experimental and clinical data suggest that stents eluting antiproliferative agents can be used for the prevention of in-stent restenosis. Here we investigate in vitro the antiproliferative and apoptotic effect of D-24851 and evaluate the safety and efficacy of D-24851-eluting polymer-coated stents in a rabbit restenosis model (n = 53). Uncoated stents (n = 6), poly (DL: -lactide-co-glycolide) (PLGA)-coated stents (n = 7), and PLGA-coated stents loaded with 0.08 +/- 0.0025 microM (31 +/- 1 mug; low dose; n = 7), 0.55 +/- 0.02 microM (216 +/- 8 mug; high dose; n = 6), and 4.55 +/- 0.1 microM (1774 +/- 39 mug; extreme dose; n = 5) of D-24851 were randomly implanted in New Zealand rabbit right iliac arteries and the animals were sacrificed after 28 days for histomorphometric analysis. For the assessment of endothelial regrowth in 90 days, 12 rabbits were subjected to PLGA-coated (n = 3), low-dose (n = 3), high-dose (n = 3), and extreme-dose (n = 3) stent implantation. In vitro studies revealed that D-24851 exerts its growth inhibitory effects via inhibition of proliferation and induction of apoptosis without increasing the expression of heat shock protein-70, a cytoprotective and antiapoptotic protein. Treatment with low-dose D-24851 stents was associated with a significant reduction in neointimal area and percentage stenosis only compared with bare metal stents (38% [P = 0.029] and 35% [P = 0.003] reduction, respectively). Suboptimal healing, however, was observed in all groups of D-24851-loaded stents in 90 days in comparison with PLGA-coated stents. We conclude that low-dose D-24851-eluting polymer-coated stents significantly inhibit neointimal hyperplasia at 28 days through inhibition of proliferation and enhancement of apoptosis. In view of the suboptimal re-endothelialization, longer-term studies are needed in order to establish whether the inhibition of intimal growth is maintained.

Enoxaparin versus tinzaparin in non-ST-segment elevation acute coronary syndromes: results of the enoxaparin versus tinzaparin (EVET) trial at 6 months.

BACKGROUND: We have previously reported significant benefits of using enoxaparin, compared to tinzaparin, in the 7- and 30-day incidence of the composite triple end point of death, myocardial infarction (MI), or recurrent angina in patients with non-ST-segment elevation acute coronary syndromes (NSTACS). In the present study, we aimed to determine whether the observed benefits of enoxaparin were maintained beyond the early phase and report the results of the 6-m follow-up of patients in the EVET study. METHODS: We recruited 438 patients with NSTACS. All patients received oral aspirin and were randomized to also receive enoxaparin, 100 IU/kg subcutaneously twice daily (equivalent to 1 mg/kg twice daily; n = 220), or tinzaparin, 175 IU/kg subcutaneously once daily (n = 218), for up to 7 days. RESULTS: At 6 m, the incidence of the composite triple end point of death, MI, or recurrent angina was lower among patients receiving enoxaparin compared to those receiving tinzaparin (25.5% vs 44.0%, P < .001). A lower incidence of the secondary composite end point of death or MI was also found in the enoxaparin group compared to tinzaparin group (2.7% vs 6.9%, P = .046). The need for revascularization procedures was also lower in the enoxaparin group compared to tinzaparin group (23.2% vs 37.2%, P = .002). CONCLUSIONS: In patients with NSTACS, enoxaparin significantly reduced the rates of recurrent ischemic events and therapeutic procedures in the short term, with sustained benefit at 6 m compared to tinzaparin.

Localization of accessory pathways by the electrocardiogram: which is the degree of accordance of three algorithms in use?

We evaluated the extent of agreement among three algorithms used for the localization of accessory pathways in patients with overt preexcitation. By the use of one algorithm, three independent couples of observers localized the accessory pathway in 95 consecutive patients showing overt preexcitation in the 12-lead surface electrocardiogram. We defined the following regions: Left atrioventricular ring (LAVR), Right atrioventricular ring (RAVR), Left lateral/left anterolateral (LL/LAL), Left posterior/left posterolateral (LP/LPL), Left posteroseptal (LPS), Right midseptal (RMS), Right posteroseptal (RPS), Right posterior/right posterolateral (RP/RPL), Right lateral/right anterolateral (RL/RAL), and Right anterior/right anteroseptal (RA/RAS). The extent of agreement in each region was evaluated and compared with the expected one, as calculated from the reported. The extent of agreement was as expected: (1) high in the regions LAVR, RAVR, LL/LPS and (2) limited in the regions LPS, RPS, and (3) clearly lower than expected in the regions LP/LPL, RA/RAS, RMS, RL/RAL. In cases with total or partial disagreement, the number of electrocardiograms with duration of QRS complex smaller than 120 ms was greater than in cases with total agreement (30/46 vs 22/50, P < 0.05). The observed agreement among algorithms is clearly lower than the expected one. Minimal preexcitation, limited number of patients, and arbitrarily defined regions were possibly the reasons for some unexpected results.

Enoxaparin versus tinzaparin in non-ST-segment elevation acute coronary syndromes: the EVET trial.

BACKGROUND: Low-molecular weight heparins have different pharmacokinetic and pharmacodynamic characteristics and may vary in efficacy. We compared the efficacy of enoxaparin with that of tinzaparin in the management of non-ST-segment elevation acute coronary syndromes (NSTACS). METHODS: A total of 438 patients with NSTACS were randomized to receive subcutaneous treatment with enoxaparin, 100 IU/kg twice daily (equivalent to 1 mg/kg twice daily; n = 220), or tinzaparin, 175 IU/kg once daily, (n = 218) for as long as 7 days. The primary composite end point was recurrent angina, myocardial infarction (or reinfarction), or death at day 7. Secondary end points were the primary end point at day 30 and the occurrence of individual events at days 7 and 30. RESULTS: The incidence of the primary end point was 12.3% in the enoxaparin group and 21.1% in the tinzaparin group (P =.015). At day 7, the rate of recurrent angina was lower with enoxaparin than with tinzaparin (11.8% vs 19.3%). At day 30, the incidences of the composite end point, recurrent angina, and myocardial infarction were also lower with enoxaparin, 17.7% vs 28.0% (P =.012), 17.3% vs 26.1% and 0.5% vs 2.8%, respectively. The rate of revascularization was lower in the enoxaparin group, 8.6% vs 17.9% (P =.010) at day 7 and 16.4% vs 26.1% (P =.019) at day 30. Rates of bleeding complications were similar in the 2 treatment groups. CONCLUSIONS: This study indicates a benefit of enoxaparin (100 IU/kg twice daily) as compared with tinzaparin (175 IU/kg once daily) in the treatment of patients with NSTACS, which is sustained for at least 30 days.

Histologic comparison of vibrating guidewire with conventional guidewire technique in an experimental coronary in vivo model.

PURPOSE: To compare the damage caused by vibrating guidewire manipulation and conventional guidewire manipulation of soft coronary wires in normal sheep coronary arteries. METHODS: Using an intact sheep model the two methods of passing a coronary guidewire down a normal coronary artery under fluoroscopic screening control were studied. The resulting arterial damage caused by the two techniques was studied histologically. The severity of damage was scored from 1 (no damage) to 4 (severe damage) and expressed as: (a) percentage of damaged sections, (b) mean damage score per section and (c) percentage of sections suffering the most severe degree of damage (scores 3 and 4). RESULTS: One hundred and sixty-eight sections were studied. The percentage of damaged sections was lower in the vibrating guidewire group (p = 0.004). The mean damage score and the percentage of sections with a damage score of 3 or 4 were smaller in the vibrating guidewire group than in the conventional guidewire manipulation group (p = 0.001 and p = 0.009, respectively). CONCLUSIONS: Both methods of guidewire manipulation cause identifiable vascular damage. The extent and severity of damage appear greater when the guidewire is manipulated manually.

A prospective randomized trial comparing the safety and efficacy of three commercially available closure devices (Angioseal, Vasoseal and Duett).

PURPOSE: We compared the safety and efficacy of three closure devices (Angioseal, Vasoseal and Duett) used to close arterial puncture sites in patients who underwent coronary percutaneous procedures. METHODS: A prospective randomized, single-center trial was carried out of consecutive patients who underwent coronary angiography [705 patients: Angioseal (243),Vasoseal (228) and Duett (234)] or angioplasty [146 patients:Angioseal (47), Vasoseal (52) and Duett (47)]. RESULTS: In the angiography patients the device deployment rates were similar, with the Angioseal been significantly slower in achieving hemostasis (p = 0.0001) but resulting in earlier ambulation (p = 0.0001). In the coronary angioplasty patients the deployment rates were similar to those for angiography: time to hemostasis was longer for the Angioseal (p = 0.003), while ambulation times were not different, although prolonged compared with angiography (p = 0.0001). The three devices had similar major complication rates. The Vasoseal had a higher major complication rate after angioplasty than after angiography (p = 0.004). The incidence rate of peripheral embolization was lower when the Angioseal was utilized. Severe complications were mainly seen in patients who received abciximab. CONCLUSIONS: The three closure devices had high rates of successful deployment and were relatively safe. The Angioseal resulted in earlier ambulation after angiography. Utilization of closure devices after abciximab administration possibly increased the complications.