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Biomedical subjects

V Fuster

Publications and source records attributed to V Fuster.

At least 217 records · Page 12Linked to original sources
PubMed1994

Aortic dissection: a medical perspective.

Over the past 3 years, a greater understanding of predisposing factors and the pathology of the aortic wall has yielded more insights into the pathogenesis, as well as into more accurate diagnostic and preventive methods. This update will discuss: (1) the incidence, definition, and recent classification of aortic dissection; (2) epidemiology, medical, and recent surgical series; (3) the pathogenesis and risk factors; (4) clinical features and evolving noninvasive imaging approaches to diagnosis; and (5) management from a medical perspective.

Aortic Dissection↗
PubMed1994

13C-NMR spectroscopy of human atherosclerotic lesions. Relation between fatty acid saturation, cholesteryl ester content, and luminal obstruction.

Previous investigations have used 13C-nuclear magnetic resonance (NMR) spectroscopy to demonstrate the similarities between lipoproteins and the mobile lipids of atheroma. In this study, we tested the hypothesis that 13C-NMR changes are related to indices of histological severity. We classified 20 human arteries according to their obstruction ratio (OR), defined as the ratio of the plaque area to the area delimited by the external elastic lamina. In group A, OR was < 40%, and in group B, OR was > 40%. We analyzed at 9.4 T the resonances of unsaturated (UFA) and polyunsaturated (PUFA) carbons, the resonances of the carbons 19 and 21 (C19, C21) of cholesteryl esters (CE), the methine carbon peak of fatty acids (CH2)n, the choline peak from phospholipids (PL), and the glycerol peak from triglyceride (TG). The UFA/PUFA, UFA/(CH2)n, and PUFA/(CH2)n ratios are markers of fatty acid saturation. (C19, C21)/(CH2)n, choline/(CH2)n, and glycerol/(CH2)n are indices of CE, PL, and TG content, respectively. UFA/PUFA in group A is 1.15 +/- 0.34 versus 1.63 +/- 0.32 in group B (P = .005). PUFA/(CH2)n is 0.26 +/- 0.10 in group A versus 0.16 +/- 0.04 in group B (P = .049). C19, C21/(CH2)n in group A is 0.32 +/- 0.15 versus 0.63 +/- 0.23 for group B (P = .003). No significant difference was found in UFA/(CH2)n or in the TG or PL ratios. 13C spectral examination of human atherosclerosis demonstrates decreased resonances for polyunsaturated fatty acyl chains and cholesteryl esters with increasing obstruction.

Adult↗
PubMed1994

A new approach for local intravascular drug delivery. Iontophoretic balloon.

BACKGROUND: Catheter-based systems are being developed to deliver drugs directly into the vessel wall. Pressure-mediated trauma and lack of homogeneous delivery are key limitations of these approaches. METHODS AND RESULTS: We studied a new catheter-based delivery system that uses electrical current to force the drug into the vessel wall. The in vivo feasibility of this approach has been assessed by delivering 125I-hirudin into porcine carotid arteries. Vascular levels of hirudin after active iontophoresis (4 mA/cm2, 5 minutes) were 80-fold greater than those achieved by passive diffusion (without electricity). Tissue hirudin levels declined over time; by 1 hour after delivery, 80% of the drug had left the vessel wall, and by 3 hours later, the levels of hirudin within the wall were similar to those achieved by passive diffusion. Autoradiography revealed distribution of the drug throughout the entire circumference of the arterial wall within the intima, media, and adventitia. Iontophoresis-mediated vessel wall trauma was minimal (less than 10% endothelial denudation and medial smooth muscle cell damage). Balloon injury after local delivery changed neither kinetics nor distribution of the drug into the arterial wall. CONCLUSIONS: (1) High local concentrations of hirudin in the arterial wall may be achieved with the iontophoretic balloon catheter. (2) The drug is distributed throughout the entire vessel wall without significant damage. (3) The retention of hirudin in the arterial wall is time dependent. (4) This technique might be useful to deliver therapeutic agents before or after percutaneous vascular interventions.

Angioplasty, Balloon↗
PubMed1994

Recombinant hirudin for unstable angina pectoris. A multicenter, randomized angiographic trial.

BACKGROUND: Coronary artery thrombosis plays an important pathophysiological role in unstable angina and non-Q-wave myocardial infarction. To date, heparin and thrombolytic therapy has not provided complete or consistent benefit. We hypothesized that recombinant hirudin, a direct thrombin inhibitor, would prevent accumulation of coronary artery thrombus in a manner superior to heparin. METHODS AND RESULTS: Patients with rest ischemic pain, abnormal ECG, and baseline angiogram indicating a > or = 60% stenosis of a culprit coronary artery or saphenous vein graft with visual appearance of thrombus were randomized to one of two different doses of heparin (either a target activated partial thromboplastin time [aPTT] of 65 to 90 or 90 to 110 seconds) or one of four doses of hirudin (0.05, 0.10, 0.20, or 0.30 mg.kg-1.h-1 infusion) in a dose-escalating protocol. After 72 to 120 hours of study drug, a repeat coronary angiogram was obtained, and the paired studies underwent quantitative analysis. The primary end point was change in the average cross-sectional area of the culprit lesion. Other efficacy end points also involved changes in culprit lesion dimensions and TIMI flow grade. Recombinant hirudin led to a dose-dependent elevation of aPTT that appeared to plateau at the 0.2-mg/kg dose. A higher proportion of hirudin-treated patients had their aPTT within a 40-second range (16% heparin versus 71% hirudin, P < .001). Overall, the 116 patients treated with hirudin tended to show more improvement than the 50 patients receiving heparin relative to the primary efficacy variable--the average cross-sectional area (P = .08)--as well as minimal cross-sectional area (P = .028), minimal luminal diameter (P = .029), and percent diameter stenosis (P = .07). CONCLUSIONS: Recombinant hirudin appears to be a promising antithrombotic intervention compared with heparin for inhibition of coronary artery thrombus. Large-scale comparative trials are warranted.

Angina, Unstable↗
PubMed1994

Diagnosing and managing unstable angina. Agency for Health Care Policy and Research.

This Quick Reference Guide for Clinicians contains recommendations on the care of patients with unstable angina based on a combination of evidence obtained through extensive literature reviews and consensus among members of an expert panel. Principal conclusions include the following. (1) Many patients suspected of having unstable angina can be discharged home after adequate initial evaluation. (2) Further outpatient evaluation may be scheduled for up to 72 hours after initial presentation for patients with clinical symptoms of unstable angina judged at initial evaluation to be at low risk for complications. (3) Patients with acute ischemic heart disease judged to be at intermediate or high risk of complications should be hospitalized for careful monitoring of their clinical course. (4) Intravenous thrombolytic therapy should not be administered to patients without evidence of ST segment elevation and acute myocardial infarction. (5) Assessment of prognosis by noninvasive testing often aids selection of appropriate therapy. (6) Coronary angiography is appropriate for patients judged to be at high risk for cardiac complications or death based on their clinical course or results of noninvasive testing. (7) Coronary artery bypass surgery should be recommended for almost all patients with left main disease and many patients with three-vessel disease, especially those with left ventricular dysfunction. (8) The discharge care plan should include continued monitoring of symptoms; appropriate drug therapy, including aspirin; risk-factor modification; and counseling.

Ambulatory Care↗
PubMed1994

Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture.

BACKGROUND: Rupture of atherosclerotic plaques is probably the most important mechanism underlying the sudden onset of acute coronary syndromes. Macrophages may release lytic enzymes that degrade the fibrous cap and therefore produce rupture of the atherosclerotic plaque. This study was designed to quantify macrophage content in coronary plaque tissue from patients with stable and unstable coronary syndromes. METHODS AND RESULTS: Hematoxylin and eosin and immunostaining with anti-human macrophage monoclonal antibody (PG-M1) were performed. Computerized planimetry was used to analyze 26 atherectomy specimens comprising 524 pieces of tissue from 8 patients with chronic stable angina, 8 patients with unstable angina, and 10 patients with non-Q-wave myocardial infarction. Total plaque area was 417 +/- 87 mm2 x 10(-2) in patients with stable angina, 601 +/- 157 mm2 x 10(-2) in patients with unstable angina, and 499 +/- 87 mm2 x 10(-2) in patients with non-Q-wave myocardial infarction (P = NS). The macrophage-rich area was larger in plaques from patients with unstable angina (61 +/- 18 mm2 x 10(-2)) and non-Q-wave myocardial infarction (87 +/- 32 mm2 x 10(-2)) than in plaques from patients with stable angina (14 +/- 5 mm2 x 10(-2)) (P = .024). The percentage of the total plaque area occupied by macrophages was also larger in patients with unstable angina (13.3 +/- 5.6%) and non-Q-wave myocardial infarction (14.6 +/- 4.6%) than in patients with stable angina (3.14 +/- 1%) (P = .018). Macrophage-rich sclerotic tissue was largest in patients with non-Q-wave myocardial infarction (67 +/- 30 mm2 x 10(-2)) and unstable angina (55 +/- 19 mm2 x 10(-2)) than in patients with stable angina (11.5 +/- 4.1 mm2 x 10(-2)) (P = .046). Macrophage-rich atheromatous gruel was also largest in patients with non-Q-wave myocardial infarction (15 +/- 4 mm2 x 10(-2)) than in patients with unstable angina (3.3 +/- 1.7 mm2 x 10(-2)) or stable angina (2.4 +/- 1.2 mm2 x 10(-2)) (P = .026). CONCLUSIONS: Macrophage-rich areas are more frequently found in patients with unstable angina and non-Q-wave myocardial infarction. This suggests that macrophages are a marker of unstable atherosclerotic plaques and may play a significant role in the pathophysiology of acute coronary syndromes.

Aged↗
PubMed1994

Effect of an eccentric severe stenosis on fibrin(ogen) deposition on severely damaged vessel wall in arterial thrombosis. Relative contribution of fibrin(ogen) and platelets.

BACKGROUND: Coronary thrombosis is a dynamic process dependent on the pathological substrate, the local shear forces, and blood factors. METHODS AND RESULTS: We investigated the effect of a severe (80%) eccentric stenosis on fibrin(ogen) interaction with a deeply damaged vessel wall, its relation to platelet deposition in thrombus formation, and the influence of time on thrombus growth. Porcine 125I-fibrinogen and autologous 111In-platelets were injected into pigs instrumented for extracorporeal circulation and treated with low-dose heparin (aPTT ratio < 1.5) that has been previously shown and herein confirmed not to affect platelet and/or fibrin(ogen) attachment. Tunica media, as a model of severely injured vessel wall, was mounted in a tubular perfusion chamber containing an eccentric axisymmetric sinusoidal stenosis obstructing the lumen and exposed for 1, 5, and 10 minutes to perfusing blood. A shear rate of 424 s-1 at the laminar, parallel parabolic local flow perfused segments one to two orders of magnitude greater at the apex of the stenosis. Fibrin(ogen) deposition, its axial distribution with respect to the apex, and its relation to platelet deposition were determined by an ex vivo analysis of the test substrates. Fibrin(ogen) and platelet deposition were both significantly higher at the apex of the stenosis than at either the prestenotic or poststenotic area at all the studied perfusion times (P < .02). However, fibrin(ogen) deposition demonstrated a significantly smaller degree of increase from the prestenotic area to the apex as well as a smaller degree of decrease from the latter to the poststenotic region, compared with platelet deposition (P < .05). Although both fibrin(ogen) and platelet deposition increased over time, the ratio of fibrin(ogen) to platelets showed a progressive decrease that became significant from 5 to 10 minutes (P < .03) at either low or high shear rate. The rate of platelet deposition was relatively constant; however, fibrin(ogen) deposition progressively decreased, especially at the apex. CONCLUSIONS: On severely damaged vessel wall, fibrin(ogen) and platelet deposition is maximal at the apex of the stenosis where shear rate is extremely high and parallel streamlines are deformed. Nevertheless, fibrin(ogen) deposition is significantly less dependent on high shear rate than is platelet deposition, and the pattern is not influenced by time. Finally, fibrin(ogen) deposition appears to be predominant in the thrombus layers adjacent to a severely damaged vessel wall regardless of the local shear stress levels and flow conditions.

Animals↗
PubMed1994

Lewis A. Conner Memorial Lecture. Mechanisms leading to myocardial infarction: insights from studies of vascular biology.

Myocardial infarction is the most frequent cause of mortality in the United States as well as in most western countries. In this review, the processes leading to myocardial infarction are described based on the most recent studies of vascular biology; in addition, evolving strategies for prevention are outlined. The following was specifically discussed. (1) Five phases of the progression of coronary atherosclerosis (phases 1 to 5) and eight morphologically different lesions (types I, II, III, IV, Va, Vb, Vc, and VI) in the various phases are defined. (2) The present understanding of the pathogenesis of each of the phases of progression and of the various lesion types preceding myocardial infarction is described; particular emphasis is placed on the physical, structural, cellular, and chemical characteristics of the "vulnerable or unstable plaques" prone to disruption (types IV and Va lesions). (3) The fate of plaque disruption (type VI lesion) in the genesis of the various coronary syndromes and especially acute myocardial infarction is defined; particular emphasis is placed on the combination of plaque disruption and a high thrombogenic risk profile--local factors (ie, degree of plaque disruption, exposure of lipid-macrophage-rich plaque, etc) and systemic factors (ie, catecholamines, RAS, fibrinogen, etc)--in the genesis of myocardial infarction. (4) Strategies of regression or stabilization of "vulnerable or unstable plaques" for prevention of myocardial infarction are presented within the context of recent favorable experience with risk factor modification and lipid-modifying angiographic trials, beta-blockade and angiotensin-converting enzyme inhibition, antithrombotic strategies, and the possible role of estrogens. The recent past has been very fruitful in yielding a better understanding of the processes leading to myocardial infarction, and the near future appears very promising in terms of preventing the number 1 killer in the western world.

Coronary Artery Disease↗
PubMed1994

Inhibition of growth of thrombus on fresh mural thrombus. Targeting optimal therapy.

BACKGROUND: Residual mural thrombus on severely damaged arterial wall is very thrombogenic. We tested the hypothesis that direct thrombin inhibition will block thrombus growth on fresh thrombus better than indirect thrombin inhibition, cyclooxygenase inhibition, or both. METHODS AND RESULTS: A fresh mural thrombus was formed by directly perfusing fresh porcine blood for 5 minutes over severely damaged arterial wall at a high shear rate in a well-characterized ex vivo perfusion system. The average platelet (P) and fibrinogen (F) deposition (D) achieved in 5 minutes were 382 +/- 32 x 10(6) platelets/cm2 and 296 +/- 36 x 10(12) fibrinogen molecules/cm2, respectively. Thrombus growth on the fresh mural thrombus was quantitated by directly perfusing blood from pigs with 111In-labeled platelets and 125I-labeled fibrinogen for an additional 5 minutes over the preformed mural thrombus. Treatment included recombinant hirudin (1 mg/kg per hour IV) as a probe for thrombin, aspirin (5 mg/kg IV) as a platelet inhibitor of cyclooxygenase, heparin (moderate, 100 IU/kg per hour IV; high-dose, 250 IU/kg per hour IV) as an indirect thrombin inhibitor, and heparin (100 IU/kg per hour) plus aspirin (5 mg/kg IV). Thrombus growth as measured by labeled PD (x 10(6)/cm2) and FD (x 10(12) molecules/cm2) was mildly but not significantly reduced by aspirin (1034 +/- 92 and 436 +/- 78, respectively) compared with baseline (1113 +/- 67 and 545 +/- 52, respectively). Inhibition of thrombus growth with heparin was dose dependent. A regression analysis showed an inverse correlation of PD and FD with mean plasma heparin concentrations (r = -.81, P = .0001 and r = -.49, P = .0007, respectively). Recombinant hirudin led to a profound inhibition of thrombus growth (PD, 30 +/- 12; FD, 109 +/- 21), which was significant compared with all groups, even the highest dosage of heparin (250 IU/kg per hour). CONCLUSIONS: Specific thrombin inhibition markedly inhibits platelet and fibrinogen deposition onto fresh mural thrombus at a high shear rate. Aspirin alone or in combination with heparin has little effect on evolving thrombosis. Heparin dose dependently reduces thrombus growth, but even the highest dosage is less effective than hirudin. Thrombin appears to be the primary activator of platelets by fresh thrombus.

Animals↗
PubMed1994

Local delivery of r-hirudin by a double-balloon perfusion catheter prevents mural thrombosis and minimizes platelet deposition after angioplasty.

BACKGROUND: The major morbidity of percutaneous transluminal coronary angioplasty is acute thrombosis and restenosis of the dilated lesion. Platelet-thrombus deposition occurs within minutes after injury, is primarily mediated by thrombin, causes acute occlusion, and contributes to late restenosis. Experimentally, specific thrombin inhibitors have prevented mural thrombosis. However, local therapy may be more effective than systemic treatment. We tested the hypothesis that high local concentrations of an antithrombin drug at the site of arterial injury following balloon angioplasty inhibit platelet thrombus formation equally or better than conventional systemic treatment and at lower systemic anticoagulant levels. METHODS AND RESULTS: Balloon angioplasty of the carotid arteries of 29 pigs was performed using systemic intravenous treatment with heparin (100 U/kg, groups I and II), suboptimal r-hirudin (0.3 mg/kg, group III), and higher-dose r-hirudin (0.7 mg/kg, group IV), which is the lowest dose that completely inhibited arterial thrombosis in the pig. Immediately after balloon angioplasty of the first carotid, additional local therapy with placebo (group I) or r-hirudin (groups II, III, and IV; 0.3 mg/kg in 1 mL) was administered with distal perfusion through a new percutaneous double-balloon catheter. After 1 hour of local drug delivery, angioplasty of the contralateral carotid was performed. Reflow for 1 hour was permitted to both carotids to compare the short-term effect of local plus systemic treatment with systemic treatment on quantitative 111In-labeled platelet deposition and macroscopic mural thrombus formation on deeply injured carotid segments. Local drug delivery of placebo compared with systemic heparin treatment resulted in no change of platelet deposition (x 10(6)/cm2, mean +/- SEM) in controls (group I, 91.0 +/- 23.5 versus 80.8 +/- 19.4), but local delivery of r-hirudin resulted in a significant reduction in group II (15 +/- 2.5 versus 71.3 +/- 14.5; P < .02) and group III (11.4 +/- 2.5 versus 80.5 +/- 11.4; P < .01) and was borderline in group IV (7.4 +/- 1.8 versus 14.1 +/- 7.4; P = .05), respectively. The incidence of macroscopic mural thrombus formation with local and systemic treatment was 86% and 75% in group I, 16% and 70% in group II, 14% and 71% in group III, and 0% and 16% in group IV, respectively. CONCLUSIONS: Local therapy with the specific thrombin inhibitor r-hirudin significantly reduces short-term quantitative platelet deposition and macroscopic mural thrombus formation following balloon angioplasty compared with systemic treatment of conventional doses of heparin and hirudin and requires a significantly smaller amount of the recombinant drug.

Angioplasty, Balloon, Coronary↗
PubMed1994

Persistent thrombin generation in humans during specific thrombin inhibition with hirudin.

BACKGROUND: The degree to which antithrombotic drugs suppress thrombin generation is unknown. Because hirudin, unlike antithrombin III, binds intravascular thrombin rapidly and selectively to yield a circulating inactive complex of 3- to 4-hour half-life, we used intravenous hirudin in humans to investigate the course of thrombin generation during and early after anticoagulation with this potent, direct antithrombin. METHODS AND RESULTS: Intravascular thrombin was measured with an ELISA for the thrombin-hirudin complex formed during and for 18 hours after stopping a 6-hour infusion of hirudin at 0.1, 0.2, and 0.3 mg.kg-1.h-1 in three groups of six patients each. With free hirudin in 20- to 10,000-fold molar excess of thrombin and peak activated partial thromboplastin times of 2.3 to 3.0 times baseline, mean plasma thrombin-hirudin complex increased from 794 +/- 85 pg/mL (mean +/- SEM) 15 minutes after the start of the infusion to 1617 +/- 151 pg/mL at 6 hours of infusion to 2667 +/- 654 pg/mL at 24 hours. During the 24-hour observation period, plasma concentration of fragment 1.2 (the peptide released during conversion of prothrombin to thrombin) never fell below baseline but rather increased transiently during the hirudin infusion. Plasma concentrations of thrombin-antithrombin III complex (in ng/mL) decreased from 4.34 +/- 0.40 at baseline to 1.64 +/- 0.13 at 6 hours (P < .001) and gradually increased after stopping the infusion to 5.7 +/- 0.87 at 24 hours (nonsignificant compared with baseline). CONCLUSIONS: Measurement of thrombin-hirudin complex may be used as a marker of thrombin generation in humans. Persistent accumulation of thrombin-hirudin complex and generation of fragment 1.2 during and after completion of potent anticoagulation with hirudin suggest thrombin generation is not blocked by high-affinity thrombin inhibition. The persistent formation of thrombin during declining plasma levels of hirudin may contribute to the pathogenesis of rethrombosis early after antithrombin therapy or during inadequate anticoagulation.

Aged↗
PubMed1994

Blood group polymorphisms and geography in the Sierra de Gredos, Spain.

The present research is designed to contribute to our knowledge of the influence of geography on the genetic population structure in the Sierra de Gredos (central Spain). This mountain range separates two distinct areas: the Tormes-Alberche valley in the north and the Tiétar valley in the south. Unrelated blood donors (226), whose 4 grandparents were born in the study area, were tested for blood group markers (A1A2BO, RH, MNSs, Kell, P, and Lewis). R matrix analysis in relation to other Spanish populations agrees reasonably well with the cluster analysis of the Prevosti distance matrix using the UPGMA algorithm. Comparisons suggest a certain degree of genetic variation between the populations of these two valleys. The Sierra de Gredos can thus be considered a biological barrier limiting the gene flow between the valleys.

Algorithms↗
PubMed1994

Platelet deposition induced by severely damaged vessel wall is inhibited by a boroarginine synthetic peptide with antithrombin activity.

Thrombin plays a key role in platelet activation and thrombosis. Specific inhibition of thrombin appears to be one of the best approaches to prevent thrombus formation. We have studied the effects of a synthetic alpha-aminoboronic acid derivative- [Ac, (D) Phe-Pro-Boro-Arg-Hydrochloric acid] - on platelet deposition on severely damaged arterial wall. Platelet deposition was evaluated under well characterized rheological conditions in an original perfusion chamber and detected by autologous 111In-labeled platelets. The study was performed "in vivo" in a porcine model of arterial thrombosis triggered by severely damaged vessel wall at blood flow conditions mimicking mild stenosis (1690 s-1) and patent (212 s-1) vessels. In addition, ex-vivo platelet aggregation activity was evaluated by whole blood impedance aggregometry using collagen, ADP and thrombin as agonists. The synthetic alpha-aminoboronic peptide was intravenously administered as a bolus followed by continuous infusion. Ex vivo thrombin-induced whole blood platelet aggregation was totally abolished, while ADP- and Collagen-induced whole blood platelet aggregation was not modified. The effects of the synthetic antithrombin on platelet deposition were evaluated in native blood (non-anticoagulated) conditions and in combination with heparin. Under both experimental conditions, the synthetic peptide significantly inhibited platelet deposition at local flow conditions of both high (1690 s-1) and low (212s-1) shear rates. Our results suggest that specific inhibition of locally generated thrombin might be a good strategy to prevent platelet dependent arterial thrombus formation independently of the local flow shear rate of the area at risk.

Adenosine Diphosphate↗
PubMed1993

Conjunctive antithrombotic therapy for thrombolysis in myocardial infarction.

Disruption of an atherosclerotic plaque in coronary arteries with a minor stenosis is the usual stimulus for acute coronary thrombosis and myocardial infarction. In this article the pathogenesis of arterial thrombosis and contributions of local arterial wall substrates, the rheology of blood flow, systemic factors, and the critical role of thrombin in the formation of thrombus are discussed. More potent antithrombotic therapy may accelerate exogenous thrombolysis, allows endogenous thrombolysis, and should reduce recurrent infarction and ischemia and death, as well as need for coronary revascularization. Maximal antithrombotic therapy for acute myocardial infarction includes an intravenous bolus of heparin at 100 U/kg followed by an intravenous infusion--at 1,200 U/hr for patients weighing 60-80 kg, 1,300 U/hr for those weighing > 80 kg, and 1,000 U/hr for those weighing < 60 kg (or 17 U/kg/hr)--to maintain the activated partial thromboplastin time at 2-3 times control (60-90 sec) for at least 5-7 days. To convert intravenous to subcutaneous administration, use 14,000-17,000 U every 12 hours and initially overlap the intravenous infusion by 2 hours. The loading dose of aspirin on admission to the hospital is 160 mg followed by 80 mg/day. High-risk patients should be considered for conversion of heparin to warfarin therapy for at least 3 months at an international normalized ratio of 2.5-4.0 for the prevention of recurrent ischemia, reinfarction, death, thromboembolism, reactivation of thrombosis, and reduced necessity for revascularization.

Animals↗