Cilostazol reduces restenosis after endovascular therapy in patients with femoropopliteal lesions. Batroxobin plus aspirin reduces restenosis after angioplasty for arterial occlusive disease in diabetic patients with lower-limb ischemia. [A clinical trial of using antiplatelet therapy to prevent restenosis following peripheral artery angioplasty and stenting]. Low-molecular-weight heparin for prevention of restenosis after femoropopliteal percutaneous transluminal angioplasty: a randomized controlled trial. Failure of aspirin plus dipyridamole to prevent restenosis after carotid endarterectomy. Potential use of a low-molecular-weight heparin to prevent restenosis in patients with extensive wall damage following peripheral angioplasty. Effect of high dose verapamil on restenosis after peripheral angioplasty. Comparison of effects of high-dose and low-dose aspirin on restenosis after femoropopliteal percutaneous transluminal angioplasty. Frequent reocclusion of patent infarct-related arteries between 4 weeks and 1 year: effects of antiplatelet therapy.
Despite the recent development of endovascular therapy (EVT), a high incidence of restenosis remains as an unsolved issue in patients presenting with femoropopliteal lesions. We investigated whether cilostazol reduces restenosis after successful EVT for de novo femoropopliteal lesions.
                This study was designed as a prospective, randomized, open-label, blinded end point study in a single institution. Between March 2004 and June 2005, we randomized 127 patients who were successfully treated with EVT for de novo femoropopliteal lesions to receive cilostazol (200 mg/d, n = 63) or ticlopidine (200 mg/d, n = 64) in addition to aspirin (100 mg/d). Antiplatelet medications were started at least 1 week before EVT and were continued until the end of follow-up. Patency was defined by duplex ultrasound imaging with peak systolic velocity ratio >2.4.
                There were no significant differences in the patients and lesion characteristics. Sixteen patients dropped out of the study protocol, six of whom were withdrawn due to adverse drug effects (cilostazol, n = 5; ticlopidine, n = 1; P = .09). Ten patients died (cilostazol, n = 4; ticlopidine, n = 6; P = .53) during the follow-up period. Patency rates at 12, 24, and 36 months were 87%, 82%, and 73% in the cilostazol group and 65%, 60%, and 51% in ticlopidine group by intention-to-treat analysis (P = .013) and were 87%, 82%, and 73% in the cilostazol group and 64%, 57%, and 48% in the ticlopidine group (P = .0088) by as-treated analysis. Freedom from target lesion revascularization and all adverse events (restenosis, amputation, and death) was significantly higher in cilostazol group than in ticlopidine group (P = .036, P = .031). No acute, subacute, or chronic thrombotic occlusion was encountered, and bleeding complication rates were similar between the two groups.
                Cilostazol significantly reduces restenosis after EVT in femoropopliteal lesions. Aspirin is routinely given to reduce vascular events after angioplasty. Batroxobin has been shown to effectively prevent thrombosis after angioplasty via inhibition of the fibrinogen concentration. In this randomized clinical trial, the hypothesis that batroxobin plus aspirin is more effective than aspirin alone in reducing the incidence of restenosis/reocclusion in patients with diabetes undergoing angioplasty for lower-limb ischemia.
                Patients with diabetes and symptomatic arterial obstructions (N = 129) were randomized to receive aspirin 100 mg/d plus batroxobin 5 IU every other day for six doses (n = 58) or aspirin alone (n = 71). The primary outcome was restenosis documented by magnetic resonance (MR) angiography or duplex imaging at 12 months. Secondary outcomes included amputation above the ankle, death, and cumulative rate of amputation or death. Kaplan-Meier analysis was used to evaluate limb salvage and survival rates.
                After 12 months, restenosis had occurred in 43.1% and 29.7% of patients in the control and batroxobin groups, respectively (P = .0018). MR angiography and duplex imaging revealed an improved restenosis rate for infrapopliteal lesions and for lesions longer than 10 cm (P = .0016). The primary and cumulative secondary outcomes indicated significant improvements in restenosis rate, symptom relief, and amputation rates in the batroxobin group compared with the aspirin-only group. Kaplan-Meier analysis showed limb salvage and survival rates of 78.3% in the aspirin-only group and 92.2% in the batroxobin group 12 months after angioplasty (log-rank test, P = .0414).
                Batroxobin plus aspirin reduced the rate of restenosis after arterial angioplasty, particularly in lesions located below the knee and in those longer than 10 cm, with better clinical symptom relief and improved rate of limb salvage.
                Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved. To evaluate the clinical effect and restenosis rate of antiplatelet therapy following peripheral artery angioplasty and stenting.
                After successful placement of peripheral artery stents to 103 patients with peripheral arterial occlusive disease (PAOD) in were randomized assigned to 2 groups: antiplatelet therapy group receiving clopidogrel 75 mg plus aspirin 100 mg (n = 56) and control group (n = 47) receiving anticoagulation therapy low molecular weight heparin (LWMH) for 7 d plus long-term warfarin. The patients were followed up 1 day, and 1, 6, 12, and 18 months after the operation to undergo color Doppler ultrasonography, and examinations of blood routine, bleeding time, coagulation time, and ankle-brachial Index. The primary endpoint events included major bleeding rate, and composite rate of restenosis and reocclusion. The secondary endpoint events included cardiovascular events, death, and adverse drug reaction.
                There were no significant differences in the baseline data between these two groups. The thrombotic occlusion rate was 1.8% in the antiplatelet group and 0% in control group, and the restenosis rate was 14.3% in the antiplatelet group and 25.5% in control group (both P > 0.05). The bleeding complication rate of the antiplatelet group was 1.8%, significantly lower than that of the anticoagulation group (19.1%, P < 0.01). There were not significant differences in cardiovascular event rate and mortality 18 months after operation between these two groups.
                Antiplatelet therapy combined with clopidogrel plus aspirin is effective and safe in preventing restenosis following peripheral artery angioplasty and stenting. Restenosis after angioplasty is essentially due to intimal hyperplasia. Low-molecular-weight heparins (LMWHs) have experimentally been shown to have antiproliferative effects in addition to their antithrombotic properties. Their potential in reducing restenosis remains to be established. Therefore, we wanted to test the hypothesis that LMWH plus aspirin is more effective than aspirin alone in reducing the incidence of restenosis/reocclusion in patients undergoing percutaneous transluminal angioplasty (PTA) of femoropopliteal arteries. Further, different effects of LMWH in patients treated for critical limb ischemia (CLI) or claudication only should be investigated.
                After successful PTA, 275 patients with symptomatic peripheral arterial disease (claudication or critical limb ischemia) and femoropopliteal obstructions were randomized to receive either 2500 IU of dalteparin subcutaneously for 3 months plus 100 mg of aspirin daily (n = 137), or 100 mg aspirin daily alone (n = 138). The primary end point was restenosis or reocclusion documented by duplex ultrasonography imaging at 12 months.
                Restenosis/reocclusion occurred in 58 patients (44%) in the dalteparin group and in 62 patients (50%) in the control group (P = .30). In a subgroup analysis according to the severity of peripheral arterial disease, we found that in patients treated for claudication, restenosis/reocclusion developed in 43 (43%) in the dalteparin group, and in 35 (41%) in the control group (P = .70); in patients treated for CLI, restenosis/reocclusion was significantly lower in the dalteparin group (15, 45%) than in the control group (27, 72%; P = .01). No major bleeding events occurred in either group.
                Treatment with 2500 IU dalteparin subcutaneously given for 3 months after femoropopliteal PTA failed to reduce restenosis/reocclusion at 12 months. However, dalteparin may be beneficial in the subgroup of patients with CLI at 12 months follow-up. To evaluate therapy with aspirin plus dipyridamole in reducing restenosis after carotid endarterectomy.
                A total of 163 patients having 175 surgical carotid endarterectomies.
                Eighty-three patients (90 endarterectomies) were randomly assigned to receive oral aspirin, 325 mg, plus dipyridamole, 75 mg, beginning 12 hours preoperatively, followed by a second dose administered within 8 hours after the operation, and given three times daily thereafter for 1 year. Eighty patients (85 endarterectomies) received placebo medication that was identical in appearance to the study drugs.
                After the adequacy of the surgical procedure was confirmed by intraoperative angiography, restenosis at the endarterectomy sites was evaluated using serial duplex ultrasound studies before hospital discharge and at 3-month intervals postoperatively for 1 year.
                Based on the time for developing identifiable restenosis and on efficacy analysis, greater than 50% restenosis developed in 11 operated vessels (16%) in the treated group and in 10 arteries (14%) in the placebo group, yielding an observed risk increase of 14% (95% CI, -52% to 167%; P greater than 0.2). By intention-to-treat analysis, greater than 50% restenosis developed in 16 of 90 operated vessels in treated patients and in 10 of 85 arteries in patients receiving placebo (26% for the treated group and 12% for the placebo group; P = 0.18, Mantel-Haenszel statistic), representing an observed risk increase of 110% (CI, -5% to 365%). Similar differences were observed for greater than 20% restenosis and for the comparison of patients rather than operated vessels by either intention-to-treat or efficacy analyses.
                Because therapy not only failed to reduce carotid restenosis but may have actually increased its frequency, treatment with aspirin plus dipyridamole probably has no clinically important benefit on restenosis in patients having carotid endarterectomy. The long-term outcome of primary successful percutaneous transluminal angioplasty (PTA) for patients with peripheral occlusive arterial disease (POAD) is frequently compromised by the development of restenosis, especially when extensive dissections result from the angioplastic procedure. Unfortunately, prevention of the occlusive process by means of drugs such as antithrombotics, anticoagulants, thrombolytics, corticosteroids, lipid reducers, or cytostatics has not been demonstrated convincingly. The authors sought to clarify whether such patients could benefit from the postsurgical administration of low-molecular-weight heparin. A total of 172 POAD patients with extensive dissections after PTA in the pelvic or upper leg regions were randomized for 7-day post-PTA intravenous treatment with either full heparinization or nadroparin calcium followed by adjunctive oral aspirin for 6 months. The primary outcome measure was the degree of stenosis (normal findings; stenosis < 50%, > 50%, > 80%, occlusion) before and after angioplasty, as well as 3 weeks and 3 and 6 months after dilation; secondary efficacy criteria included changes in the Fontaine stage and in the crurobrachial ratio. No significant treatment-related differences were found at the 3 post-PTA follow-up examinations with regard to the degree of stenosis. This was also the case for the subgroup of patients (n = 62) who had undergone angioplasty in the pelvic region. By contrast, when angioplasty was performed in the superficial femoral artery (n = 110), the degree of restenosis was significantly lower (p<0.01) among patients receiving nadroparin calcium compared to those given heparin at week 3, month 3, and month 6. No intergroup differences emerged for secondary outcome measures in the long term or for safety parameters. These preliminary results indicate that patients with extensive dissections after PTA treatment for POAD in the upper leg region might benefit from a reduction in the rate of restenosis by administration of 7-day weight-adjusted nadroparin calcium. We sought to determine whether treatment with high dose verapamil prevents restenosis in patients at high risk for reoccurrence after successful percutaneous transluminal coronary angioplasty (PTCA).
                Restenosis is the major limitation of PTCA. Calcium antagonists have demonstrated some potential as inhibitors of this process.
                A total of 98 patients with peripheral occlusive arterial disease (POAD), stable angina pectoris, mild hypertension and at least one additional risk factor increasing the likelihood of restenosis after angioplasty were selected for this placebo-controlled, double-blind, randomized trial. Verapamil (240 mg twice daily) or placebo was taken for 6 months. Efficacy variables assessed before and after angioplasty and at 6 weeks and 6 months after PTCA included thickness of the intima/media complex degree of stenosis, interventricular septal thickness, crurobrachial pressure ratios of dorsalis pedis and posterior tibial arteries, distance to claudication and total vessel diameter.
                No significant intergroup differences emerged before or immediately after PTCA. Six weeks after angioplasty, a significant thickening of the intima/media complex in the treated vascular segment of 14.3% occurred in the placebo group versus 0% among verapamil patients (p < 0.01). At 6 months, the intima/media thickness was 35.7% greater in the placebo group but had decreased by 14.3% in the verapamil group (p < 0.001). At 6 months, a marked reduction in septal thickness was observed in the verapamil group versus that in the placebo group (p < 0.001). The rate of restenosis was also significantly lower in the verapamil group (p < 0.001). Few minor side effects were reported.
                In patients with POAD at increased risk for restenosis, the administration of high dose verapamil prevented recurrent stenosis for 6 months after successful peripheral angioplasty and was well tolerated. Long-term treatment with aspirin is recommended in patients with large-vessel peripheral arterial disease since these patients have a high risk of death from cardiovascular causes. Recent studies have demonstrated the prophylactic effect of low-dose aspirin in reducing the risk of cardiovascular events. Since aspirin is also recommended for prevention of late recurrence after peripheral angioplasty, the present study was undertaken to compare the effects of high-dose (1000 mg/d) and low-dose (100 mg/d) aspirin on long-term patency after femoropopliteal angioplasty.
                Two hundred sixteen patients treated successfully by percutaneous transluminal angioplasty for femoropopliteal lesions were randomly allocated to therapy with either 1000 or 100 mg aspirin daily. The follow-up was 24 months. The long-term results were analyzed using the Kaplan-Meier method, and differences between curves of cumulative patency were determined with the Wilcoxon and log-rank statistics. Complete follow-up information (patency after 24 months, restenosis, and death) was obtained in 207 patients. During the 2-year follow-up period, 72 patients--36 in the high-dose and 36 in the low-dose aspirin group, respectively--developed angiographically verified reobstruction within the recanalized segment. By intention-to-treat analysis, the cumulative patency rates at 24 months were 62.5% in the high-dose and 62.6% in the low-dose aspirin group (Wilcoxon, P = .97; log-rank, P = .97). The cumulative survival at 24 months of follow-up was 86.6% in the high-dose and 87.7% in the low-dose aspirin group. The number of patients discontinuing therapy was 30 in the high-dose and 11 in the low-dose aspirin group (P < .01). Fewer patients receiving 100 mg of aspirin discontinued therapy because of gastrointestinal symptoms (4 versus 20).
                The data indicate that 100 mg aspirin is no less effective in the prevention of restenosis after femoropopliteal PTA than a 1000-mg dose and has fewer side effects. This study assessed the effect of the combination of aspirin and dipyridamole on patency of the infarct-related artery between 4 weeks and 1 year after myocardial infarction.
                Patency of the infarct-related artery is an important determinant of prognosis after myocardial infarction. The incidence of late reocclusion and the effects of antiplatelet therapy are unknown.
                To investigate the importance of antiplatelet therapy for the prevention of late reocclusion, 215 patients who had a patent infarct-related artery 4 weeks after myocardial infarction were randomized in a double-blind manner to receive either a combination of 25 mg of aspirin and 200 mg of dipyridamole twice daily or placebo. One hundred fifty-four patients underwent further coronary arteriography 1 year later.
                At 1 year, 38 (25%) of 154 patients had reocclusion of the infarct-related artery; 18 (23%) of 79 patients receiving aspirin and dipyridamole had late reocclusion versus 20 (27%) of 75 who received placebo (p = NS). The rate of reocclusion was related to the severity of the residual coronary artery stenosis at 4 weeks (< 50% stenosis 9.2%; 50% to 69% stenosis 11.6%; 70% to 89% stenosis 30.4%; > or = 90% stenosis 70%, p < 0.01). The majority of reocclusions were silent, and only 17 (45%) of 38 were clinically associated with further infarction. There were no differences for a hierarchic end point of cardiac death, myocardial infarction or revascularization (14.8% aspirin and dipyridamole vs. 17.8% placebo).
                Late reocclusion of the patent infarct-related artery is a frequent event, occurring in 25% of patients. Antiplatelet therapy with the combination of aspirin and dipyridamole does not alter the overall rate of late reocclusion. Other strategies are required to reduce late reocclusion.
There is limited evidence suggesting that restenosis/reocclusion at six months following peripheral endovascular treatment is reduced by use of antiplatelet drugs compared with placebo/control, but associated information on bleeding and gastrointestinal side effects is lacking. There is also some evidence of variation in effect according to different drugs with cilostazol reducing reocclusion/restenosis at 12 months compared with ticlopidine and both LMWH and batroxobin combined with aspirin appearing beneficial compared with aspirin alone. However, available trials are generally small and of variable quality and side effects of drugs are not consistently addressed. Further good quality, large-scale RCTs, stratified by severity of disease, are required.