Relevance of hemostasis on restenosis in clinically stable patients undergoing elective PTCA (original) (raw)
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The role of platelets, thrombin and hyperplasia in restenosis after coronary angioplasty
Journal of the American College of Cardiology, 1991
Coronary angioplasty has gained wide aeceptancc as the proecdttre oi choice in many patients aith coronary artery disease Gtce its first introduction in I977 (1). Inttially restricted to patients with single vessel disease and stable angina. its use has been expanded to unstable angina. acute myocardisl infarction and multivessel coron~y artciy Jlrease Despite impmvementr in cquipmcnt nn~! ircnmque. acute reocclusion alter succcssf~l Lgiopla5ty occur\ m approximately 5% of palientr and Me re\tenoG\ Igcilerall) in.53 month& the most important problem after coronar) angioplasty. occurs in 25% to :iR of patients. We reccmly reviewed (1) the mechimiaas of acute wxluion and rc~tcnusis after angioplarty, and the currenity available pharmucologic approaches for their prevention. In thir report. me summarize our current understanding of the process of poangioplasty occlusion and resteno\i\. with \p+cial attention to the contributory role of olateletr. thrombtn and thrombosis. orgaoizUion and incor&xaion of the thrombw and subsequent intimill hyperptwia. proliferation: and Jl the rote of currem pharmacologic rhcrapy and powble future approachcr. Mechanisms of Dilalion of Stenotie Lesions htwhanisms. Experimenta! and clinical observations 131 wgge\t that four mechanisms may be involved in succesrful angiopbw First. balloon inflation results in tears. fractures ad crack\ in the Qmotic plaqile. entargmg the channel ihmugh which blood is able to Row and improving ve-.set patmcy. Secunu. because plaque tears at the point of least re\~.mce. dissection rhrough the intima into the media cawes enliwgrment of the vessel lumen. With further balluon expansion. the media and adventitia of the artery may stretch to conform with the outer diameter of the inflated balloon. A thtrd mechanism by which bslloa angioplasty may \rorh i) through redibtributmn and compression of the pkique. nprcially plaque composed mainly of tbrombotic dcpuril>. fm&. depending on the degree ofeccentricity of the plequc and its composition. balloon i&lion may rewlt in di*tenGon or stretching of only the disease-free arc of the normid vc\w4 wll and produce little or no damage to the plaque itvlf. Although an initial increment in luminal diameter occurs. 11 may he to>1 within hours. days or seeks after the ddatlon as a result of gradual rclaxadon of the over-\Irexhed segment tre,titution of tone or elastic recoil). Recent observation\ IJI derived from microscopic euminalion of athcrcctomy specimens suggest that this mechanism m;by occur in up to !S% ofangioplasty procedures claartfied a> succc4ui bawd on the milial ang!ognm. Restenobis
1998
Background-Arterial injury after percutaneous transluminal coronary angioplasty (PTCA) triggers acute thrombus formation and thrombin generation. Hirudin, a potent and direct thrombin inhibitor, prevents thrombus formation after arterial injury. Two large clinical trials showed marked reduction in acute clinical events but no long-term benefits in reducing restenosis during short-term administration of thrombin inhibitors. Our hypothesis is that adequate, maintained thrombin inhibition, by inhibiting all the thrombin-dependent mechanisms, will reduce neointima formation after PTCA. Methods and Results-Thirty-six pigs received three different regimens of hirudin: bolus (1 mg/kg), short-term (bolusϩ0.7 mg/kg per day for 2 days), and long-term (bolusϩ0.7 mg/kg per day for 14 days). The results on neointima formation at 4 weeks after coronary angioplasty were compared with the control group (100 IU heparin/kg bolus). Hirudin was continuously administered for 2 weeks through an infusion pump. In vivo thrombin generation was persistently increased up to 2 weeks after angioplasty. Inhibition of thrombin activity for 14 days reduced luminal narrowing by 40% (58Ϯ3% versus 35Ϯ3%; PϽ.001). No differences were observed among the bolus and short-term hirudin groups and the control group. Conclusions-Our results indicate that there is a continued, marked thrombin generation that lasts for at least 2 weeks after PTCA. Administration of r-hirudin for 2 weeks significantly reduces neointima formation after PTCA. This observation, if extrapolated to humans, could explain the lack of effect on restenosis observed in the clinical trials with antithrombin agents despite the clear benefits on reducing acute thrombotic complications after PTCA. Therefore an adequate and prolonged administration of thrombin inhibitors is needed to "passivate" the thrombogenic substrate (disrupted arterial wall) and achieve full benefit of this therapeutic approach.
The American Journal of Cardiology, 1984
Restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) occurs 4 to 6 months after the procedure in 25 to 30% of the patients. Although PTCA has become far more effective with improved primary angiographic success rates and decreased complication rates, restenosis rates have not changed since the initial experience. Recurrent arterial stenoses appear to be due to fibrocellular proliferation at the site of the initial PTCA. This proliferative response is probably due to platelet adhesion and subsequent activation of the usual tissue injury responses. Fortunately, restenosis seems to be confined to the period soon after the initial PTCA since the long-term, 3- to 8-year studies demonstrate that restenosis occurs infrequently after that. There are certain predisposing characteristics of patients for restenosis: men with a short duration of symptoms with disease of the proximal left anterior descending arteries who are diabetic and continue to smoke cigarettes after PTCA. Inadequate dilatation of the arteries by PTCA and procedures that result in smooth dilatations without any evidence of dissection are associated with increased risk of restenosis. However, most of these patient and procedural characteristics are not controllable. Studies in which procedural and postprocedural variables have been manipulated have been disappointing. Currently, no alterations in techniques or pharmacologic management have proved effective in decreasing the incidence of restenosis.
Circulation, 2003
Background— Experimental data suggest that tissue factor (TF) may induce neointimal hyperplasia after arterial injury. In this study, we investigated the hypothesis that elevated levels of TF in the circulation contribute to the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA) or stent implantation. Methods and Results— Whole-blood TF procoagulant activity (TF-PCA) was measured using a previously described assay before, at 3 hours after, and at 24 hours after the intervention in 61 patients with stable angina undergoing PTCA (n=20) or stent implantation (n=41). Coronary angiography was performed 4 to 6 months after the intervention, and luminal narrowing ≥50% was defined as restenosis. Whole-blood TF-PCA levels did not correlate with intracellular monocyte tumor necrosis factor-α expression, a marker of activation of these cells. Baseline levels and time course of whole-blood TF-PCA after the intervention were compared in patients who did or did ...
Journal of the American College of Cardiology, 1997
Objectives. The Probucol Angioplasty Restenosis Trial was a prospective, randomized, controlled study that investigated the effectiveness of probucol therapy in reducing the rate of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Background. Antioxidants have an inhibitory effect on smooth muscle cell growth in experiments in vitro and in vivo, which suggests a possible pharmacologic effect on restenosis after PTCA. Methods. One hundred one patients were randomly assigned to receive 1,000 mg/day of probucol or control (no lipid-lowering) therapy 4 weeks before PTCA. After 4 weeks of premedication, both groups underwent PTCA. Probucol was continued until follow-up angiography 24 weeks after PTCA. Angiographic results were analyzed at a core laboratory by quantitative coronary angiography. Results. Dilation was successful in 46 of 50 patients in the probucol group and 45 of 51 in the control group. At follow-up angiography 24 weeks after angioplasty, angiographic restenosis occurred in 9 (23%) of 40 patients in the probucol group and 22 (58%) of 38 in the control group (p ؍ 0.001). Minimal lumen diameter was 1.49 ؎ 0.75 mm (mean ؎ SD) in the probucol group and 1.13 ؎ 0.65 mm in the control group (p ؍ 0.02). Percent diameter stenosis at follow-up angiography in the probucol group was significantly lower than that in the control group (43.9% vs. 56.4%, p ؍ 0.009). The late loss was 0.37 ؎ 0.69 mm in the probucol group and 0.60 ؎ 0.62 mm in the control group (p ؍ 0.13). The loss/gain ratio was 0.32 ؎ 0.74 in the probucol group and 0.56 ؎ 0.81 in the control group (p ؍ 0.059). Net gain was greater in the probucol group than in the control group (0.77 ؎ 0.70 vs. 0.48 ؎ 0.59 mm, p ؍ 0.053). Conclusions. Probucol administered beginning 4 weeks before PTCA appears to reduce restenosis rates.