Pharmacodynamics, pharmacokinetics and safety of ticagrelor in Asian patients with stable coronary artery disease.

This randomized, active-controlled, double-blind study assessed the pharmacodynamics, pharmacokinetics and safety of ticagrelor in Japanese patients and a smaller cohort of non-Japanese Asian patients. The study recruited patients aged 20-80 years who had received aspirin 75-100 mg/day for ≥2 weeks and had percutaneous coronary intervention or acute coronary syndrome >3 months previously. Patients received 4 weeks' treatment with ticagrelor 45 mg bid, ticagrelor 90 mg bid or clopidogrel 75 mg qd (all with aspirin). The inhibition of platelet aggregation (IPA, final-extent) and pharmacokinetics of ticagrelor were assessed on days 1 and 28. Overall, 139 Asian patients were randomized (ticagrelor 45 mg bid, n = 50; ticagrelor 90 mg bid, n = 43; clopidogrel, n = 46) of whom 118 were Japanese. Mean final-extent IPA was greater with ticagrelor 90 mg bid versus ticagrelor 45 mg bid and with both ticagrelor doses versus clopidogrel. At the end of the dosing interval on day 28, mean final-extent IPA was 10.0% higher (95% confidence interval 0.5-19.5%) for ticagrelor 90 mg bid versus ticagrelor 45 mg bid, 15.1% higher (5.8-24.4%) for ticagrelor 45 mg bid versus clopidogrel, and 25.1% higher (15.5-34.7%) for ticagrelor 90 mg bid versus clopidogrel. In Japanese patients, exposure to ticagrelor and its active metabolite AR-C124910XX increased dose-proportionally. The safety profile of ticagrelor was consistent with previous studies. Ticagrelor was associated with enhanced IPA versus clopidogrel in Japanese patients.

Bleeding risk with AZD6140, a reversible P2Y12 receptor antagonist, vs. clopidogrel in patients undergoing coronary artery bypass grafting in the DISPERSE2 trial.

AZD6140, the first reversible oral P2Y(12) receptor antagonist, exhibits greater and more consistent inhibition of platelet aggregation than the irreversible thienopyridine clopidogrel. As a result of its reversible effect, AZD6140 may pose less risk for bleeding when antiplatelet treatment cannot be stopped at least 5 days before coronary artery bypass graft (CABG) surgery or other invasive procedures. The Dose conflrmation Study assessing anti-Platelet Effects of AZD6140 vs. clopidogRel in NSTEMI (DISPERSE2) trial showed overall comparable bleeding rates with antiplatelet treatment with AZD6140 90 mg twice daily or 180 mg twice daily vs. clopidogrel 75 mg once daily in 984 patients with non-ST-elevation acute coronary syndromes. A post hoc exploratory analysis of bleeding outcomes in the subset of 84 patients undergoing CABG in DISPERSE2 suggests reduced risk for total bleeding (41% and 58% vs. 62%), all major bleeding (38% and 50% vs. 62%), and life-threatening bleeding (22% and 38% vs. 54%) with AZD6140 90 mg (n = 32) and 180 mg (n = 26) vs. clopidogrel (n = 26) respectively. Trends suggested that major bleeding rates were reduced with AZD6140 (combined groups) vs. clopidogrel when treatment was stopped < or = 5 days prior to surgery (39% vs. 63%, p = 0.15) but not when treatment was stopped > 5 days before surgery (50% vs. 60%). This observation is consistent with the reversible binding of AZD6140 to the P2Y(12) receptor. Further prospective studies are planned to assess the relationship between this potential clinical benefit of AZD6140 and the reversibility of its antiplatelet effects.

The immediate and long-term effect of optimal balloon angioplasty on the absolute coronary blood flow velocity reserve. A subanalysis of the DEBATE study. Doppler Endpoints Balloon Angioplasty Trial Europe.

BACKGROUND: There are limited data regarding the immediate and long-term effect of balloon angioplasty on the coronary flow reserve evaluated in a multicentre setting. METHODS AND RESULTS: A total of 86 patients with one-vessel disease and normal left ventricular function were analysed before and after optimal balloon angioplasty (diameter stenosis <35%) and at 6-month follow-up. Coronary flow reserve was assessed with a Doppler guide wire. A low coronary flow reserve (2.5 (46% vs 23% and 36% vs 16%, respectively; P<0.05) due to a trend towards restenosis (29% vs 16%; P=0.15) or a low coronary flow reserve at follow-up due to persistent elevated baseline blood flow velocity. Patients without restenosis showed a decrease or increase of coronary flow reserve during follow-up, determined by alterations of hyperaemic blood flow velocity. CONCLUSIONS: Patients with an impaired coronary flow reserve directly after optimal balloon angioplasty showed a higher target lesion revascularization rate compared to patients with a coronary flow reserve >2.5. This patient group consists of patients prone to develop restenosis, while other patients are characterized by a persistently low coronary flow reserve, probably secondary to disturbed autoregulation and/or diffuse mild coronary atherosclerosis. Coronary flow reserve alterations in patients without restenosis were related to changes in hyperaemic blood flow velocity, suggesting that this phenomenon relates to epicardial remodelling.

Coagulation and complement activation.

UNLABELLED: The purpose of this investigation was to assess the effect of heparin coating of a new stent construction (Stent Graft, Jomed Implantate GmbH, Germany) on platelet and coagulation activity. METHODS: Stent grafts with an ePTFE membrane interfoliated between two stents were deployed in tubings to form Chandler loops. Fresh human blood with a low concentration of heparin was rotated for 1 h, then collected and used for measurements of platelet number, thrombin-antithrombin complex (TAT), CD11b, C3a and C5b-9. There were five study groups: Group 1, conventional unmodified stents (n = 8); Group 2, untreated stent grafts (n = 8); Group 3, heparin-coated stents and untreated membrane (n = 7); Group 4, heparin-coated stents and membrane (n = 8); Group 5, heparin-coated PVC tubings with no stents (n = 8). RESULTS: There was a significant drop in platelet count, increase in TAT-values and CD11b expression in Groups 1-3 but not in Group 4 compared to Group 5. Examination by scanning electron microscopy revealed extensive activation on non-modified stents but almost no deposition of thrombotic material on heparin-modified stent grafts. CONCLUSIONS: With unmodified stents and membrane there were signs of significant activation of platelets and coagulation. In contrast, the heparin-coated stent graft induced much less alterations, indicating improved blood compatibility.

Influence of diabetes mellitus on clinical outcomes across the spectrum of acute coronary syndromes. Findings from the GUSTO-IIb study. GUSTO IIb Investigators.

AIMS: We examined the characteristics, outcomes, and effects of hirudin vs heparin treatment of diabetic patients across the spectrum of acute coronary syndromes. METHODS AND RESULTS: We studied the 12,142 patients enrolled in the randomized GUSTO-IIb study. Diabetic patients (n=2175) were older, more often female, more often had prior cardiovascular disease, hypertension, and hyperlipidaemia, and less often were current smokers. Diabetic patients had a higher overall incidence of death or (re)infarction at 30 days (13.1% vs 8.5%, P=0.0001), whether they presented with ST-segment elevation (13.9% vs 9.9%, P=0.0017) or not (12.8% vs 7.8%, P=0.0001), and at 6 months (18.8% vs 11.4%, P=0.0001). Among diabetic patients, hirudin was associated with a tendency toward a lower risk of death or (re)infarction at 30 days (12.2% vs 13.9% with heparin) and 6 months (17.8% vs 20.2%). Diabetic patients had more major bleeding, stroke, heart failure, shock, atrioventricular block, and atrial arrhythmias, but no increased risk for ocular bleeding. CONCLUSIONS: Diabetic patients with acute coronary syndromes had worse 30-day and 6-month outcomes, particularly those without ST-segment elevation. The statistically non-significant trend toward improved outcomes with hirudin was similar among patients with and without diabetes, with a greater point estimate for the absolute difference in patients with diabetes.

Angiographical and Doppler flow-derived parameters for assessment of coronary lesion severity and its relation to the result of exercise electrocardiography. DEBATE study group. Doppler Endpoints Balloon Angioplasty Trial Europe.

AIMS: Evaluation of angiographical and intracoronary Doppler-derived parameters of coronary stenosis severity. METHODS AND RESULTS: A total of 225 patients with one-vessel disease were studied before PTCA and at 6 months follow-up. Exercise electrocardiography was performed to document presence (n = 157) or absence (n = 138) of an ST segment shift (> or =0.1 mV). Intracoronary blood flow velocity analysis was performed to determine the proximal/distal flow velocity ratio, the distal diastolic/systolic flow velocity ratio and coronary flow velocity reserve. Receiver operator characteristic curves were calculated to assess the predictive value of these variables compared with the exercise test. The distal coronary flow velocity reserve demonstrated the best linear correlation for both percentage diameter stenosis and minimum lumen diameter (r = 0.67 and r = 0.66; P<0.01), compared to the diastolic/systolic flow velocity ratio (r = 0.19 and r = 0.14; P<0.01) and the proximal/distal flow velocity ratio (r = 0.03 and r = 0.07; not significant). The areas under the curve were 0. 84+/-0.02; 0.82+/-0.03 and 0.83+/-0.03 for diameter stenosis, minimum lumen diameter and coronary flow velocity reserve, respectively. Logistic regression analysis revealed that the percentage diameter stenosis or minimum lumen diameter and coronary flow velocity reserve were independent predictors for the result of stress testing. CONCLUSIONS: The distal coronary flow velocity reserve is the best intracoronary Doppler parameter for evaluation of coronary narrowings. Angiographical estimates of coronary lesion severity and distal coronary flow velocity reserve are good and independent predictors for the assessment of functional severity of coronary stenosis, emphasizing the complementary role of these parameters for clinical decision making.

Long-term effect of endoscopic transthoracic sympathicotomy on heart rate variability and QT dispersion in severe angina pectoris.

UNLABELLED: We evaluated short and long-term effects on QT dispersion and autonomic balance after endoscopic transthoracic sympathicotomy (ETS). Heart rate variability (HRV) reflects autonomic balance of the heart. QT dispersion is a marker of cardiac electrical instability in patients with ischemic heart disease. Holter recordings for 24 h and a twelve-lead ECG were made prior to, 1 month, 1 year and 2 years after ETS. HRV was analysed in time domain and spectral analysis was performed during controlled respiration in supine position and during head up tilt. Dispersion of QT time and QTc were calculated. Of 88 patients, 62 (60) were eligible for HRV (QT-dispersion) analysis after 1 month, 39 (38) patients after 1 year and 23 (24) patients after 2 years. The HRV analysis showed a significant change of indices reflecting sympatho-vagal balance indicating significantly reduced sympathetic (LF) and increased vagal (HF, rMSSD) tone. These changes still persisted after 2 years. Global HRV increased over time with significant elevation of SDANN after 2 years. QT dispersion was significantly reduced 1 month after surgery and the dispersion was further diminished 2 years later. CONCLUSION: ETS changed HRV and QT dispersion which could imply reduced risk for malignant arrhythmias and death after ETS.

Initial tests with a new cardiac assist device.

Before, during, and after cardiac intervention, there is occasionally a need for circulatory support because of hemodynamic deterioration. For this purpose, a new minimally invasive cardiac assist device has been developed, and an early prototype has been studied in a bench test and in three pigs. The pump is a catheter system with a distal motor driven propeller (0-15,000 rpm) surrounded by a cage. The catheter was first tested in a tube in a water bath, where efficiency with respect to pressure generation and flow properties was measured. In the pig experiments, the pump was placed in the descending part of the aorta via a graft, and hemodynamic effects were recorded with three different propellers. The bench tests showed a velocity dependent pressure generation in the tube to the second power of the rpm, and 30 cm of water (> 22 mm Hg) could easily be achieved with all propellers. A pressure dependent flow in the tube was observed, with maximum flows of 20 L at 12,000 rpm and 27 L at 15,000 rpm. In the animal experiments, there was a velocity dependent mean pressure difference across the propeller, with up to 48 mm of mercury for the biggest propeller. An increase in cardiac output in all of the pigs was observed as well as a drop in pressure in the proximal part of the aorta. This study demonstrates the efficiency of this new device in vitro and in vivo. Hemodynamic changes are pronounced and are related to the speed and size of the propeller.

Antianginal efficacy of the combination of felodipine-metoprolol 10/100 mg compared with each drug alone in patients with stable effort-induced angina pectoris: a multicenter parallel group study. The TRAFFIC Study Group.

OBJECTIVE: The primary objective of this randomized, double-blind, parallel group trial was to compare the antianginal and antiischemic efficacy of a combination tablet of felodipine-metoprolol 10/100 mg once daily with both drugs given separately once daily in patients with stable effort-induced angina pectoris. The secondary objective was to compare the tolerability of the 3 treatments. METHODS: The main criteria for inclusion were stable effort-induced angina pectoris for at least 2 months before the enrollment and a positive bicycle exercise test result. Patients were allocated to once-daily treatment with either felodipine-metoprolol 10/100 mg, felodipine 10 mg, or metoprolol 100 mg. The duration of active double-blind treatment was 4 weeks. There were 3 primary efficacy variables in the study; time until end of exercise, time until onset of chest discomfort, and time until 1-mm ST depression during a standardized exercise test. RESULTS: The number of patients randomized was 397. There was a statistically significant improvement in time until end of exercise with felodipine-metoprolol 10/100 mg compared with metoprolol 100 mg (P =.04) and felodipine 10 mg compared with metoprolol 100 mg ( P =.03). However, for time until onset of pain or time until 1-mm ST-depression there were no significant differences among the treatment groups. At highest comparable workload, ST depression was less pronounced with felodipine-metoprolol than with metoprolol alone (P =.04), and the rate-pressure product was significantly lower in the groups receiving felodipine-metoprolol and metoprolol than in the group receiving felodipine alone. The combination and metoprolol were better tolerated than felodipine alone. CONCLUSIONS: In stable angina pectoris, the combination felodipine-metoprolol 10/100 mg and felodipine 10 mg alone increased exercise time compared with metoprolol 100 mg. The combination tablet and metoprolol 100 mg alone showed a more favorable tolerability profile than felodipine 10 mg alone.

Appropriateness of referral of coronary angiography patients in Sweden. SECOR/SBU Project Group.

OBJECTIVE: To evaluate the appropriateness of referral following coronary angiography in Sweden. DESIGN: Prospective survey and review of medical records. PATIENTS: Consecutive series of 2767 patients who underwent coronary angiography in Sweden between May 1994 and January 1995 and were considered for coronary revascularisation. MAIN OUTCOME MEASURES: Percentage of patients referred for coronary artery bypass graft surgery (CABG) and percutaneous transluminal coronary angioplasty (PTCA) for indications that were judged necessary, appropriate, uncertain, and inappropriate by a multispecialty Swedish national expert panel using the RAND/University of California Los Angeles (UCLA) appropriateness method, and the percentage of patients referred for continued medical management who met necessity criteria for revascularisation. RESULTS: Half the patients were referred for CABG, 25% for PTCA, and 25% for continued medical therapy. CABG was judged appropriate or necessary for 78% of patients, uncertain for 12% and inappropriate for 10%. For PTCA the figures were 32%, 30% and 38%, respectively. Two factors contributed to the high inappropriate rate. Many of these patients did not have "significant" coronary artery disease (although all had at least one stenosis > 50%) or they were treated with less than "optimal" medical therapy. While 96% of patients who met necessity criteria for revascularisation were appropriately referred for revascularisation, 4% were referred for continued medical therapy. CONCLUSIONS: Using the RAND/UCLA appropriateness method and the definitions agreed to by the expert panel, which may be considered conservative today, it was found that 19% of Swedish patients were referred for coronary revascularisation judged inappropriate. Since some cardiovascular procedures evolve rapidly, the proportion of patients referred for inappropriate indications today remains unknown. Nevertheless, physicians should actively identify those patients who will and will not benefit from coronary revascularisation and ensure that they are appropriately treated.

Treatment of a large congenital coronary fistula with coil embolization.

A 77-year-old woman suffering from progressive dyspnea and chest pain for 2 1/2 years was admitted to hospital. There were no ECG changes at exercise test and a dobutamine stress echocardiography was normal. At catheterization, right-sided pressures were within normal limits. Coronary angiography revealed a congenital coronary fistula, 3-4 mm in diameter, from the left anterior descending artery to the proximal pulmonary artery. There was no significant rise in blood oxygen saturation in the pulmonary artery. Transcatheter coil embolization was performed in the distal part of the tortuous fistula. Flow ceased within minutes, demonstrating the feasibility and efficacy of this technique for treating large fistulas.

Randomized evaluation of anticoagulation versus antiplatelet therapy after coronary stent implantation in high-risk patients: the multicenter aspirin and ticlopidine trial after intracoronary stenting (MATTIS).

BACKGROUND: Although the association of ticlopidine and aspirin has been shown to be superior to anti-vitamin K agents and aspirin after coronary stent implantation in low-risk patients, the latter combination has remained an unproven reference regimen for high-risk patients until recently. METHODS AND RESULTS: We randomized 350 high-risk patients within 6 hours after stent implantation to receive during 30 days either aspirin 250 mg and ticlopidine 500 mg/d (A+T group) or aspirin 250 mg/d and oral anticoagulation (A+OAC group) targeted at an international normalized ratio of 2.5 to 3. The primary composite end point was defined as the occurrence of cardiovascular death, myocardial infarction, or repeated revascularization at 30 days. Patients were eligible if (1) the stent(s) were implanted to treat abrupt closure after PTCA; (2) the angiographic result after implantation was suboptimal; (3) a long segment was stented (>45 mm and/or >/=3 stents); or (4) the largest balloon inflated in the stent had a nominal diameter of

Randomised comparison of implantation of heparin-coated stents with balloon angioplasty in selected patients with coronary artery disease (Benestent II)

BACKGROUND: The multicentre, randomised Benestent-II study investigated a strategy of implantation of a heparin-coated Palmar-Schatz stent plus antiplatelet drugs compared with the use of balloon angioplasty in selected patients with stable or stabilised unstable angina, with one or more de-novo lesions, less than 18 mm long, in vessels of diameter 3 mm or more. METHODS: 827 patients were randomly assigned stent implantation (414 patients) or standard balloon angioplasty (413 patients). The primary clinical endpoint was event-free survival at 6 months, including death, myocardial infarction, and the need for revascularisation. The secondary endpoints were the restenosis rate at 6 months and the cost-effectiveness at 12 months. There was also one-to-one subrandomisation to either clinical and angiographic follow-up or clinical follow-up alone. Analyses were by intention to treat. FINDINGS: Four patients (one stent group, three angioplasty group) were excluded from analysis since no lesion was found. At 6 months, a primary clinical endpoint had occurred in 53 (12.8%) of 413 patients in the stent group and 79 (19.3%) of 410 in the angioplasty group (p=0.013). This significant difference in clinical outcome was maintained at 12 months. In the subgroup assigned angiographic follow-up, the mean minimum lumen diameter was greater in the stent group than in the balloon-angioplasty group, (1.89 [SD 0.65] vs 1.66 [0.57] mm, p=0.0002), which corresponds to restenosis rates (diameter stenosis > or =50%) of 16% and 31% (p=0.0008). In the group assigned clinical follow-up alone, event-free survival rate at 12 months was higher in the stent group than the balloon-angioplasty group (0.89 vs 0.79, p=0.004) at a cost of an additional 2085 Dutch guilders (US$1020) per patient. INTERPRETATION: Over 12-month follow-up, a strategy of elective stenting with heparin-coated stents is more effective but also more costly than balloon angioplasty.

Effects of spinal cord stimulation on coronary blood flow velocity.

BACKGROUND: Spinal cord stimulation (SCS) has been used in the treatment of severe angina pectoris since the 1980s. Several studies have shown both an antianginal and an anti-ischaemic effect. There are several theories about the mechanism behind the anti-ischaemic effect of SCS, including the possibility that it is dependent on an increase in coronary flow velocity. OBJECTIVE: To determine if there were effects of SCS on coronary flow velocity during cardiac stress. METHOD: Eight patients with severe anginal pain secondary to coronary artery disease who had been implanted with an SCS device were included in the study. In addition, four patients with syndrome X were examined. If possible, a Doppler guidewire was placed in the vessel corresponding to the ischaemic area revealed on a prior myocardial scintigram. A temporary pacemaker electrode was placed in the right atrium. Atrial pacing started at 80 beats/min and increased by 10 beats/min every 2 min until the patient experienced moderate angina; the pacing frequency was then maintained at the same level. After 2 min of pacing at this frequency, SCS treatment commenced; after a further 5 min, pacing was stopped. Throughout the procedure, coronary flow velocity, assessed as average peak velocity (APV), was monitored continually. RESULTS: APV increased during pacing in all the patients with coronary artery disease (mean increase 53%; P < 0.02). There were no significant changes in APV during maximum pacing frequency when stimulation was introduced. CONCLUSIONS: The results of this study do not support the theory that the anti-ischaemic effect of SCS is dependent on an increase in coronary flow velocity.

Use of abciximab in interventional cardiology.

The advent of platelet membrane glycoprotein (GP) IIb/IIIa inhibitors has changed the landscape of interventional cardiology. Given the commercial availability of abciximab and expected regulatory approvals for other receptor blockers, defining appropriate use of these agents in the interventional setting is mandated. One key issue is selection of patients who may benefit from GP IIb/IIIa receptor blockade. Focusing specifically on abciximab, data from three large-scale, randomized trials demonstrate that abciximab is appropriate for all patients undergoing percutaneous transluminal coronary angioplasty, regardless of risk stratum. Other important issues to consider when prescribing this therapy include benefits in conjunction with stents and new devices, dosing and timing of administration, and the role of prophylactic versus "bailout" administration. This article reflects a distillation of the views and consensus regarding the use of GP IIb/IIIa inhibitors in patients undergoing coronary intervention expressed by a group of international experts convened in Davos, Switzerland, February 16, 1997. This report attempts to review clinical progress to date, formulate recommendations, and map out potentially fruitful lines of inquiry for future investigation.

Electrical stimulation versus coronary artery bypass surgery in severe angina pectoris: the ESBY study.

BACKGROUND: Spinal cord stimulation (SCS) has been shown to have antianginal and anti-ischemic effects in severe angina pectoris. The present study was performed to investigate whether SCS can be used as an alternative to coronary artery bypass grafting (CABG) in selected patient groups, ie, patients with no proven prognostic benefit from CABG and with an increased surgical risk. METHODS AND RESULTS: One hundred four patients were randomized (SCS, 53; CABG, 51). The patients were assessed with respect to symptoms, exercise capacity, ischemic ECG changes during exercise, rate-pressure product, mortality, and cardiovascular morbidity before and 6 months after the operation. Both groups had adequate symptom relief (P<.0001), and there was no difference between SCS and CABG. The CABG group had an increase in exercise capacity (P=.02), less ST-segment depression on maximum (P=.005) and comparable (P=.0009) workloads, and an increase in the rate-pressure product both at maximum (P=.0003) and comparable (P=.03) workloads compared with the SCS group. Eight deaths occurred during the follow-up period, 7 in the CABG group and 1 in the SCS group. On an intention-to-treat basis, the mortality rate was lower in the SCS group (P=.02). Cerebrovascular morbidity was also lower in the SCS group (P=.03). CONCLUSIONS: CABG and SCS appear to be equivalent methods in terms of symptom relief in this group of patients. Effects on ischemia, morbidity, and mortality should be considered in the choice of treatment method. Taking all factors into account, it seems reasonable to conclude that SCS may be a therapeutic alternative for patients with an increased risk of surgical complications.

Use of abciximab in interventional cardiology.

The advent of platelet membrane glycoprotein (GP) IIb/IIIa inhibitors has changed the landscape of interventional cardiology. Given the commercial availability of abciximab and expected regulatory approvals for other receptor blockers, defining appropriate use of these agents in the interventional setting is mandated. One key issue is selection of patients who may benefit from GP IIb/IIIa receptor blockade. Focusing specifically on abciximab, data from three large-scale, randomized trials demonstrate that abciximab is appropriate for all patients undergoing percutaneous transluminal coronary angioplasty, regardless of risk stratum. Other important issues to consider when prescribing this therapy include benefits in conjunction with stents and new devices, dosing and timing of administration, and the role of prophylactic versus "bailout" administration. This article reflects a distillation of the views and consensus regarding the use of GP IIb/IIIa inhibitors in patients undergoing coronary intervention expressed by a group of international experts convened in Davos, Switzerland, February 16, 1997. This report attempts to review clinical progress to date, formulate recommendations, and map out potentially fruitful lines of inquiry for future investigation.

Local delivery of antithrombin inhibits platelet deposition after balloon injury in a porcine coronary model.

BACKGROUND: Thrombin activation and initiation of the coagulation process can lead to thrombotic complications after coronary angioplasty. A therapeutic approach may be effectively to inhibit thrombin activity at the site of the vessel wall injury. OBJECTIVE: The aim of the present study was to investigate the short-term effects of local delivery of antithrombin on coronary vessel wall injury in pigs. METHODS: A coronary balloon angioplasty was performed in the left anterior descending artery. Twenty-four hours before the procedure, platelets were marked with Indium 111 and infused into the pig. Before catheterisation 100 U/kg of heparin was administered. Eight pigs received 250 U (5 ml) of antithrombin and, as a control, eight received 10 mg of albumin (5 ml) delivered using a local drug delivery balloon catheter. Microscopic preparation of the injured part of the vessel was performed, and the amount of radioactivity was measured, giving the number of platelets per cm2. Plasma antithrombin level was measured before and after local delivery. The amount of antithrombin in the vessel wall was measured using a semi-quantitative method involving anti-antithrombin antibodies. RESULTS: The number of platelets per cm2 was significantly lower in the antithrombin group (mean 2.3 x 10(6)) than in the control group (6.3 x 10(6), P= 0.02 ). No macroscopic thrombus was detected in the antithrombin group, whereas three out of eight pigs in the control group had visible thrombus formation (NS). There was an increase in the plasma concentration of antithrombin after local delivery. In the antithrombin group, antithrombin was detected in the intima, the lumen part of the media and in the vasa vasorum. CONCLUSION: Antithrombin can be administered and deposited locally in the coronary vessel wall thereby reducing platelet deposition after balloon injury.