Revisiting the Evidence for Dipyridamole in Reducing Restenosis: A Systematic Review and Meta-analysis
Trevor SimardPouya MotazedianShan DhaliwalPietro Di SantoRichard G. JungF. Daniel RamirezAlisha LabinazSpencer ShortSimon ParlowJoanne JosephAdil RasheedMark RockleyJeffrey A. MarbachMarie‐Cécile DomecqJuan J. RussoAun‐Yeong ChongRob BeanlandsBenjamin Hibbert
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Atherosclerosis remains a leading cause of morbidity and mortality, with revascularization remaining a cornerstone of management. Conventional revascularization modalities remain challenged by target vessel reocclusion-an event driven by mechanical, thrombotic, and proliferative processes. Despite considerable advancements, restenosis remains the focus of ongoing research. Adjunctive agents, including dipyridamole, offer a multitude of effects that may improve vascular homeostasis. We sought to quantify the potential therapeutic impact of dipyridamole on vascular occlusion. We performed a literature search (EMBASE and MEDLINE) examining studies that encompassed 3 areas: (1) one of the designated medical therapies applied in (2) the setting of a vascular intervention with (3) an outcome including vascular occlusion rates and/or quantification of neointimal proliferation/restenosis. The primary outcome was vascular occlusion rates. The secondary outcome was the degree of restenosis by neointimal quantification. Both human and animal studies were included in this translational analysis. There were 6,839 articles screened, from which 73 studies were included, encompassing 16,146 vessels followed up for a mean of 327.3 days (range 7-3650 days). Preclinical studies demonstrate that dipyridamole results in reduced vascular occlusion rates {24.9% vs. 48.8%, risk ratio 0.53 [95% confidence interval (CI) 0.40-0.70], I2 = 39%, P < 0.00001}, owing to diminished neointimal proliferation [standardized mean differences -1.13 (95% CI -1.74 to -0.53), I2 = 91%, P = 0.0002]. Clinical studies similarly demonstrated reduced occlusion rates with dipyridamole therapy [23.5% vs. 31.0%, risk ratio 0.77 (95% CI 0.67-0.88), I2 = 84%, P < 0.0001]. Dipyridamole may improve post-intervention vascular patency and mitigate restenosis. Dedicated studies are warranted to delineate its role as an adjunctive agent after revascularization.Keywords:
Dipyridamole
Objective To discuss the method and the clinical value of dipyridamole stress test as a substitute for exercise test in ~(99m)Tc-MIBI myocardial perfusion imaging in coronary heart disease(CHD).Methods The resting tomography imaging of myocaidial was performed in 50 patients (30 patients with coronary heart disease,20 cases in control group),then the dipyridamole perfusion imaging was performed after 48 h.Results Tweenty nine of the 30 patients with CHD showed positive in dipyridamole ~(99m)Tc-MIBI myocardial perfusion imaging,and 16 of the 20 patients withont CHD showed normal images.Only one in the studies was discontinued due to dipyridamole side effect.The sensitivity of this test was 96.7%(29/30) and the specificity 80%(16/20).Conclusion Dipyridamole myocardial perfusion imaging is a safe and sensitive method in diagnosis of CHD.
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Dipyridamole is a vasodilator that is used primarily in clinical practice as an antiplatelet agent. It increases coronary blood flow and was originally introduced as an antianginal agent. An ability to prolong a shortened platelet survival has been used to justify its value in preventing thromboembolic complications. Conditions characterized by a reduction in platelet survival and where dipyridamole has been used include heart valve replacement, arterial grafting, cerebrovascular disorders, and disorders of peripheral circulation. The in vivo effect of dipyridamole on platelet aggregation has not been well defined and may depend on additional factors. Prostaglandins appear to have important roles in platelet homeostasis; their relationships to the action of dipyridamole are discussed. Dipyridamole usually is combined with aspirin for synergistic anti-aggregatory purposes. However, the nature of the interaction has not been elucidated and benefit from the addition of dipyridamole has not been demonstrated in clinical studies. A review of clinical studies using dipyridamole indicates that it currently has limited value.
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The laboratory examination of Dipyridamole concerning its antiaggregation effect is presented in the paper. Thirty patients with coronary insufficiency have been taking Dipyridamole for one year. The average dosage was four pills à 75 mg of Dipyridamole a day. The aggregation and adhesion of the platelets with the examined patients was checked before and during the treatment. The inhibition platelet aggregation with Dipyridamole has been confirmed in vitro.
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Dipyridamole stress is the forerunner and prototype of pharmacological stress echo tests in the diagnosis of coronary artery disease. Among the various stress echo tests, it is probably the least technically demanding to perform and the easiest to interpret. Its accuracy is similar to dobutamine stress echocardiography but its feasibility is higher. The prognostic impact of dipyridamole stress echo has also been proven for presentation of hard end-points such as cardiac death. The safety and prognostic value of this test has been conclusively demonstrated as a result of extensive experience in large scale multicentre projects. Dipyridamole stress is many different tests in one: dipyridamole—atropine is best for diagnosis; dipyridamole—dobutamine or dipyridamole—exercise is highly sensitive for the detection of minor forms of coronary artery disease; low and high dose dipyridamole is best suited for prognostic stratification; infra-low dipyridamole with low dose dobutamine administration is probably best suited for selective myocardial viability identification. Each patient should have their own test, tailored on the basis of the clinical picture and the diagnostic issue.
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客观 neutrophils 在 ischemic-reperfusion 损害起一个重要作用,这被知道。在这研究,我们在 neutrophils 上测试了效果和它 dipyridamole 的机制。由 neutrophils 的方法氢过氧化物(H2O2 ) 生产用发光氨被决定放大化合光和活动的百分比被观察不受禁令约束的山峰高度计算。结果 Dipyridamole 本身由刺激的 formyl-MetleuPhe (fMLP ) 生产了 H2O2 的集中依赖者抑制 neutrophils。在低集中的 Dipyridamole (0.3 渭摩尔路 L ? 1 ) 那本身仅仅稍微影响了 neutrophils,显著地在 neutrophils 上提高了腺苷的效果。在另一方面, dipyridamole 没在 neutrophils 上改变 NECA (5 鈥 ? N-ethylcarboxamidoadenosine ) 的禁止的效果。然而, propentofylline,腺苷举起的一个已知的禁止者,也得到一样的结果。结论 Dipyridamole 由刺激 fMLP 的 neutrophils 禁止了 H2O2 的生产。在低集中的 Dipyridamole 在 neutrophils 上提高了腺苷的禁止的效果。包含的机制可能由于腺苷举起上的 dipyridamole 的效果。
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To assess the feasibility, safety and usefulness of dipyridamole stress echocardiography for the detection of coronary artery disease we evaluated 194 patients (124 men, 70 women) with effort chest pain. All patients underwent electrocardiographic submaximal bicycle exercise testing and 2-dimensional echocardiography after dipyridamole injection. Echocardiographic test was considered positive when new wall motion abnormalities were observed after dipyridamole i.v. injection (0.56 mg/kg b.m.). Sensitivity and specificity of electrocardiographic exercise test and dipyridamole stress echocardiography were assessed in 37 persons who underwent selective coronary angiography. The sensitivity and specificity of dipyridamole stress echocardiography, were respectively 85.0% and 91.7% and were higher than those of exercise electrocardiography. 2-dimensional echocardiography after dipyridamole injection is a well tolerated, feasible and effective test in the diagnosis of coronary artery disease.
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Objective To establish a method for mensuration of dipyridamole in Dipyridamole Tablets.Methods Taking advantage of electrode's response to dipyridamole to mensurate the content of dipyridamole in Dipyridamole Tablets.Results The electrode showed Nernst response within the range of 1.0×10-2~4.8×10-5 mol·L-1 with a slope of 40 mV/pC.The detection limit is 3.2×10-5 mol·L-1.Conclusions The method is simple,rapid and accurate,which can be used to mensurate the contents of dipyridamole in tablet.
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高齢者における冠動脈疾患 (CAD) の診断, 評価における dipyridamole 負荷Tl心筋シンチ断層法の有用性と安全性を評価するため, 冠動脈狭窄を有し, かつ運動負荷不能または不十分なCAD42例を対象に検討を加えた. 対象は70歳以上の高齢群 (Group I, 24例) と65歳未満の若年群 (Group II, 18例) に区分した. 両群で性別, 心筋梗塞の既往, 狭心症の頻度, その他の臨床所見, 冠動脈病変の重症度に差をみなかった. Dipyridamole 0.57mg/kgを4分間かけて静注した後201Tl (Tl) 3mCiを静注, 心筋断層像を負荷直後と3時間後の再分布時に撮影し, 視覚判定とともにTl washout rate の異常を潅流異常の診断基準として用いた. Dipyridamole 負荷Tl心筋シンチ断層法のCADの診断率は Group I, Group IIとも83%, 各狭窄冠動脈の診断率は Group Iで73%, Group IIで74%と差をみなかった. また運動負荷Tl心筋シンチで負荷が不十分であったため dipyridamole 負荷Tl心筋シンチを繰り返した3例中2例では dipyridamole 法の診断精度がより優れていた. Dipyridamole による血圧の低下, 心拍数の増加は Group I, IIで差をみず, 異常な血圧の低下も認めなかった. Dipyridamole による心電図虚血変化は Group Iで29%, Group IIで33%, 胸痛の出現は Group Iで21%, Group IIで22%と両群で差をみなかった. また胸痛のため aminophylline の静注を必要としたのは各群1例づつで, 胸痛は aminophylline の静注で容易に消失した. またその他問題となる副作用は存的しなかった. Dipyridamole 負荷Tl心筋シンチは高齢者においても安全に行ない得, かつ有用なCADの診断, 評価法と考えられた.
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There is limited evidence that dipyridamole is generally an effective antithrombotic agent when used alone, nor is there convincing evidence that the combination of aspirin and dipyridamole is more effective than aspirin alone, except perhaps in cerebrovascular disease. There is no consistent evidence to support the routine use of dipyridamole after coronary artery bypass grafting and in patients with occlusive peripheral vascular disease, although these remain common reasons for its use. Dipyridamole is a useful agent in ‘pharmacological stress’ testing in nuclear cardiology imaging and may be valuable when combined with warfarin in certain patient groups, such as those with prosthetic heart valves. When combined with aspirin, dipyridamole may be of value in the secondary prophylaxis of cerebrovascular disease, although further studies are clearly needed. In a significant proportion of cases, evidence‐based medicine cannot support the current widespread continued prescription of dipyridamole in cardiological practice, but the jury is still out on cerebrovascular disease.
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