Effect Of Dipyridamole Research Articles

Respiratory gating in cardiac PET: Effects of adenosine and dipyridamole

BackgroundRespiratory motion due to breathing during cardiac positron emission tomography (PET) results in spatial blurring and erroneous tracer quantification. Respiratory gating might represent a solution by dividing the PET coincidence dataset into smaller respiratory phase subsets. The aim of our study was to compare the resulting imaging quality by the use of a time-based respiratory gating system in two groups administered either adenosine or dipyridamole as the pharmacological stress agent. Methods and ResultsForty-eight patients were randomized to adenosine or dipyridamole cardiac stress 82RB-PET. Respiratory rates and depths were measured by a respiratory gating system in addition to registering actual respiratory rates. Patients undergoing adenosine stress showed a decrease in measured respiratory rate from initial to later scan phase measurements [12.4 (±5.7) vs 5.6 (±4.7) min−1, P < .001] and tended to have a lower frequency of successful respiratory gating compared to dipyridamole (47% vs 71%, P = .12). As a result, imaging quality was superior in the dipyridamole group compared to adenosine. ConclusionsIf respiratory gating is considered for use in cardiac PET, a dipyridamole stress protocol is recommended as it, compared to adenosine, causes a more uniform respiration and results in a higher frequency of successful respiratory gating and thereby superior imaging quality.

The influence of dipyridamole and its derivatives on the membrane energization state of Rhodobacter sphaeroides bacterial chromatophores

The mechanisms of the specific influence of dipyridamole therapy remain as a subject of research. In the present work the effects of dipyridamole and some its derivatives on the energization state of photosynthetic membranes of purple bacteria chromatophores have been studied. It was shown that under illumination of chromatophores in the presence of dipyridamole the occurrence of its radical form was observed due to the presence of electron-proton donation properties. These properties are vital to trigger the energization of a functionally active photosynthetic membrane when it is illuminated in the presence of dipyridamole and its derivatives. It is obvious that these properties of dipyridamole should be taken into account while studying the effects of this agent as a medical preparation with specific action.

Dipyridamole decreases dialysis risk and improves survival in patients with pre-dialysis advanced chronic kidney disease.

IntroductionDipyridamole decreases proteinuria and improves renal function progression in patients with glomerular disease through its inhibition of platelet activation and enhanced nitric oxide expression. Few studies have evaluated the effects of dipyridamole on renal outcome or survival in CKD stage 5 patients who have not yet received dialysis (CKD 5 ND).Materials and MethodsA prospective cohort study was conducted based on the Taiwan National Health Insurance Research Database. From January 1, 2000 to June 30, 2009, we enrolled 28,497 patients who had a serum creatinine > 6 mg/dL and a hematocrit < 28% and who were treated with erythropoiesis-stimulating agents (ESAs). All patients were further divided into two groups with or without dipyridamole use within 90 days after starting ESA therapy. Patient followed-up took place until dialysis, death before initiation of dialysis or December 31, 2009. The primary outcomes were long-term dialysis and death before initiating dialysis.ResultsThe dipyridamole users and nonusers groups included 7,746 and 20,751 patients, respectively. We found that 20,152 patients (70.7%) required long-term dialysis and 5,697 patients (20.0%) died before a progression to end-stage renal disease required dialysis. After propensity score-matching, dipyridamole users were associated with lower risks for long-term dialysis (adjusted HR, 0.96; 95% CI, 0.93–0.99) and death (adjusted HR, 0.91; 95% CI, 0.85–0.97) compared with nonusers.ConclusionsDipyridamole exhibited a protective effect in reducing the risk for long-term dialysis and death among CKD 5 ND patients. Randomized studies are needed to validate this association.

The neuron-astrocyte-microglia triad in CA3 after chronic cerebral hypoperfusion in the rat: Protective effect of dipyridamole

We investigated the quantitative and morphofunctional alterations of neuron-astrocyte-microglia triads in CA3 hippocampus, in comparison to CA1, after 2 Vessel Occlusion (2VO) and the protective effect of dipyridamole. We evaluated 3 experimental groups: sham-operated rats (sham, n=15), 2VO-operated rats treated with vehicle (2VO-vehicle, n=15), and 2VO-operated rats treated with dipyridamole from day 0 to day 7 (2VO-dipyridamole, n=15), 90days after 2VO. We analyzed Stratum Pyramidalis (SP), Stratum Lucidum (SL) and Stratum Radiatum (SR) of CA3. 1) ectopic neurons increased in SL and SR of 2VO-vehicle, and 2VO-dipyridamole rats; 2) apoptotic neurons increased in SP of 2VO-vehicle rats and dipyridamole reverted this effect; 3) astrocytes increased in SP, SL and SR of 2VO-vehicle and 2VO-dipyridamole rats; 4) TNF-α expression increased in astrocytes, blocked by dipyridamole, and in dendrites in SR of 2VO-vehicle rats; 5) total microglia increased in SL and SR of 2VO-vehicle and 2VO-dipyridamole rats; 6) triads increased in SR of 2VO-vehicle rats and dipyridamole reverted this effect. Microglia cooperated with astrocytes to phagocytosis of apoptotic neurons and debris, and engulfed ectopic non-fragmented neurons in SL of 2VO-vehicle and 2VO-dipyridamole rats, through a new mechanism called phagoptosis. CA3 showed a better adaptive capacity than CA1 to the ischemic insult, possibly due to the different behaviour of astrocytes and microglial cells. Dipyridamole had neuroprotective effects.

Effect of low dose aspirin and dipyridamole on primary patency of arteriovenous grafts in hemodialysis patients: a randomized double-blind placebo-controlled trial

Effect of low dose aspirin and dipyridamole on primary patency of arteriovenous grafts in hemodialysis patients: a randomized double-blind placebo-controlled trial

Effects of pre and post-treatments with dipyridamole in gentamicin-induced acute nephrotoxicity in the rat

This study investigated the pretreatment and post-treatment effects of dipyridamole (20 mg/kg/day, p.o.) in gentamicin-induced acute nephrotoxicity in rats. Rats were administered gentamicin (100 mg/kg/day, i.p.) for 8 days. Gentamicin-administered rats exhibited renal structural and functional changes as assessed in terms of a significant increase in serum creatinine and urea and kidney weight to body weight ratio as compared to normal rats. Renal histopathological studies revealed a marked incidence of acute tubular necrosis in gentamicin-administered rats. These renal structural and functional abnormalities in gentamicin-administered rats were accompanied with elevated serum uric acid level, and renal inflammation as assessed in terms of decrease in interleukin-10 levels. Dipyridamole pretreatment in gentamicin-administered rats afforded a noticeable renoprotection by markedly preventing renal structural and functional abnormalities, renal inflammation and serum uric acid elevation. On the other hand, dipyridamole post-treatment did not significantly prevent uric acid elevation and renal inflammation, and resulted in comparatively less protection on renal function although it markedly reduced the incidence of tubular necrosis. In conclusion, uric acid elevation and renal inflammation could play key roles in gentamicin-nephrotoxicity. Dipyridamole pretreatment markedly prevented gentamicin-induced acute nephrotoxicity, while its post-treatment resulted in comparatively less renal functional protection.

A study of the effect of dipyridamole on erythrocyte deformability using an improved filtration technique

A study of the effect of dipyridamole on erythrocyte deformability using an improved filtration technique

Dipyridamole-induced adverse effects in myocardial perfusion scans: Dynamic evaluation

Aim and BackgroundDipyridamole-induced stress myocardial perfusion scans (MPS) has been widely used for management of coronary artery disease. The adverse effects of dipyridamole and other stress agents have been evaluated. The aim of this research is to confirm the dynamic data on dipyridamole side effects during MPS. MethodsWe collected data of 183 patients who underwent dipyridamole-induced stress MPS by retrospectively reviewing their clinical records, which included the severity of dipyridamole side effects in 3min, 10min, and 20min after infusion. The incidence and severity at all three points, including the effect of age and gender, were obtained. ResultsAdverse effects occurred in 96 patients (69.6%). The most frequent symptoms were dizziness (42.8%), chest tightness (24.6%), abdominal pain (18.1%), and headache (15.2%). Most symptoms were Grade 1 to 2, according to the grading system for common terminology criteria. The median duration of symptom persistence was 36min, not significantly different among age and gender. ConclusionThis study demonstrates that the adverse effects of dipyridamole were generally minimal and its duration was acceptable for clinical usage.

The effect of dipyridamole embedded in a drug delivery system made by electrospun nanofibers on aortic endothelial cells

An important sector of biomedical research is the generation of drug delivery systems (DDSs), which can be used alone or integrated in stents for sustained drug release. In this context, by encapsulating the platelet aggregation inhibitor dipyridamole (DIP) in polycaprolactone (PCL) we tested whether we could generate a DDS with PCL by electrospinning. By characterizing the fibers' structural properties we found that fibers' diameters were affected by the concentration of DIP, which consequently had an impact on the surface area-to-volume ratio and therefore to cumulative drug release. In vitro cell studies on a bovine aortic endothelial cell line showed that PCL itself did not affect the cells according to analysis of the number of viable cells over time and metabolic activity. We found that DIP which was released from the electrospun fibers in the solution was accumulated in the cells and that it had similar effects on the cells as it had directly delivered to them. DIP inhibited the cell growth and enhanced the gap junction coupling of the endothelial cells. The results indicate that the encapsulation and the electrospinning did not affect the biological activity of DIP and show that the method can be used to generate a DDS.

Ticagrelor regulates osteoblast and osteoclast function and promotes bone formation in vivo via an adenosine-dependent mechanism.

As many as 10% of bone fractures heal poorly, and large bone defects resulting from trauma, tumor, or infection may not heal without surgical intervention. Activation of adenosine A2A receptors (A2ARs) stimulates bone formation. Ticagrelor and dipyridamole inhibit platelet function by inhibiting P2Y12 receptors and platelet phosphodiesterase, respectively, but share the capacity to inhibit cellular uptake of adenosine and thereby increase extracellular adenosine levels. Because dipyridamole promotes bone regeneration by an A2AR-mediated mechanism we determined whether ticagrelor could regulate the cells involved in bone homeostasis and regeneration in a murine model and whether inhibition of P2Y12 or indirect A2AR activation via adenosine was involved. Ticagrelor, dipyridamole and the active metabolite of clopidogrel (CAM), an alternative P2Y12 antagonist, inhibited osteoclast differentiation and promoted osteoblast differentiation in vitro. A2AR blockade abrogated the effects of ticagrelor and dipyridamole on osteoclast and osteoblast differentiation whereas A2BR blockade abrogated the effects of CAM. Ticagrelor and CAM, when applied to a 3-dimentional printed resorbable calcium-triphosphate/hydroxyapatite scaffold implanted in a calvarial bone defect, promoted significantly more bone regeneration than the scaffold alone and as much bone regeneration as BMP-2, a growth factor currently used to promote bone regeneration. These results suggest novel approaches to targeting adenosine receptors in the promotion of bone regeneration.-Mediero, A., Wilder, T., Reddy, V. S. R., Cheng, Q., Tovar, N., Coelho, P. G., Witek, L., Whatling, C., Cronstein, B. N. Ticagrelor regulates osteoblast and osteoclast function and promotes bone formation in vivo via an adenosine-dependent mechanism.

Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials

SummaryBackgroundAspirin is recommended for secondary prevention after transient ischaemic attack (TIA) or ischaemic stroke on the basis of trials showing a 13% reduction in long-term risk of recurrent stroke. However, the risk of major stroke is very high for only the first few days after TIA and minor ischaemic stroke, and observational studies show substantially greater benefits of early medical treatment in the acute phase than do longer-term trials. We hypothesised that the short-term benefits of early aspirin have been underestimated.MethodsPooling the individual patient data from all randomised trials of aspirin versus control in secondary prevention after TIA or ischaemic stroke, we studied the effects of aspirin on the risk and severity of recurrent stroke, stratified by the following time periods: less than 6 weeks, 6–12 weeks, and more than 12 weeks after randomisation. We compared the severity of early recurrent strokes between treatment groups with shift analysis of modified Rankin Scale (mRS) score. To understand possible mechanisms of action, we also studied the time course of the interaction between effects of aspirin and dipyridamole in secondary prevention of stroke. In a further analysis we pooled data from trials of aspirin versus control in which patients were randomised less than 48 h after major acute stroke, stratified by severity of baseline neurological deficit, to establish the very early time course of the effect of aspirin on risk of recurrent ischaemic stroke and how this differs by severity at baseline.FindingsWe pooled data for 15 778 participants from 12 trials of aspirin versus control in secondary prevention. Aspirin reduced the 6 week risk of recurrent ischaemic stroke by about 60% (84 of 8452 participants in the aspirin group had an ischaemic stroke vs 175 of 7326; hazard ratio [HR] 0·42, 95% CI 0·32–0·55, p<0·0001) and disabling or fatal ischaemic stroke by about 70% (36 of 8452 vs 110 of 7326; 0·29, 0·20–0·42, p<0·0001), with greatest benefit noted in patients presenting with TIA or minor stroke (at 0–2 weeks, two of 6691 participants in the aspirin group with TIA or minor stroke had a disabling or fatal ischaemic stroke vs 23 of 5726 in the control group, HR 0·07, 95% CI 0·02–0·31, p=0·0004; at 0–6 weeks, 14 vs 60 participants, 0·19, 0·11–0·34, p<0·0001). The effect of aspirin on early recurrent ischaemic stroke was due partly to a substantial reduction in severity (mRS shift analysis odds ratio [OR] 0·42, 0·26–0·70, p=0·0007). These effects were independent of dose, patient characteristics, or aetiology of TIA or stroke. Some further reduction in risk of ischaemic stroke accrued for aspirin only versus control from 6–12 weeks, but there was no benefit after 12 weeks (stroke risk OR 0·97, 0·84–1·12, p=0·67; severity mRS shift OR 1·00, 0·77–1·29, p=0·97). By contrast, dipyridamole plus aspirin versus aspirin alone had no effect on risk or severity of recurrent ischaemic stroke within 12 weeks (OR 0·90, 95% CI 0·65–1·25, p=0·53; mRS shift OR 0·90, 0·37–1·72, p=0·99), but dipyridamole did reduce risk thereafter (0·76, 0·63–0·92, p=0·005), particularly of disabling or fatal ischaemic stroke (0·64, 0·49–0·84, p=0·0010). We pooled data for 40 531 participants from three trials of aspirin versus control in major acute stroke. The reduction in risk of recurrent ischaemic stroke at 14 days was most evident in patients with less severe baseline deficits, and was substantial by the second day after starting treatment (2–3 day HR 0·37, 95% CI 0·25–0·57, p<0·0001).InterpretationOur findings confirm that medical treatment substantially reduces the risk of early recurrent stroke after TIA and minor stroke and identify aspirin as the key intervention. The considerable early benefit from aspirin warrants public education about self-administration after possible TIA. The previously unrecognised effect of aspirin on severity of early recurrent stroke, the diminishing benefit with longer-term use, and the contrasting time course of effects of dipyridamole have implications for understanding mechanisms of action.FundingWellcome Trust, the National Institute of Health Research (NIHR) Biomedical Research Centre, Oxford.

(103) - Measuring the Effect of Dipyridamole and Clopidogrel Using Thromboelastography/Platelet Mapping®: Is There Evidence of a Meaningful Dose-Response Relationship in Children Supported with the Berlin Heart EXCOR Ventricular Assist Device?

(103) - Measuring the Effect of Dipyridamole and Clopidogrel Using Thromboelastography/Platelet Mapping®: Is There Evidence of a Meaningful Dose-Response Relationship in Children Supported with the Berlin Heart EXCOR Ventricular Assist Device?

The effect of dipyridamole on the pharmacokinetics of metformin: a randomized crossover study in healthy volunteers.

PurposeConcomitant treatment with the glucose-lowering drug metformin and the platelet aggregation inhibitor dipyridamole often occurs in patients with type 2 diabetes mellitus who have suffered a cerebrovascular event. The gastrointestinal uptake of metformin is mediated by the human equilibrative nucleoside transporter 4 (ENT4), which is inhibited by dipyridamole in preclinical studies. We hypothesized that dipyridamole lowers the plasma exposure to metformin.MethodsEighteen healthy volunteers (mean age 23 years; 9 male) were randomized in an open-label crossover study. Subjects were allocated to treatment with metformin 500 mg twice daily in combination with dipyridamole slow-release 200 mg twice daily or to metformin alone for 4 days. After a washout period of 10 days, the volunteers were crossed over to the alternative treatment arm. Blood samples were collected during a 10-h period after intake of the last metformin dose. The primary endpoint was the area under the plasma concentration-time curve (AUC0–12h) and the maximum plasma metformin concentration (Cmax).ResultsIn healthy subjects, dipyridamole did not significantly affect Cmax nor AUC0–12h of metformin under steady-state conditions.ConclusionsPrevious in vitro studies report that dipyridamole inhibits the ENT4 transporter that mediates gastrointestinal uptake of metformin. In contrast, co-administration of dipyridamole at therapeutic dosages to healthy volunteers does not have a clinically relevant effect on metformin plasma steady-state exposure. This observation is reassuring for patients who are treated with this combination of drugs.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-016-2039-8) contains supplementary material, which is available to authorized users.

Effect of Dipyridamole Injected for Myocardial Perfusion Imaging on Blood Glucose Concentration; A Preliminary Study.

Dipyridamole inhibits adenosine reuptake and increases cyclic Adenosine Monophosphate (cAMP) levels in platelets, erythrocytes and endothelial cells, all of which influence blood glucose. Acute hyperglycaemia reduces endothelium-dependent vasodilation and suppresses coronary microcirculation; which, in theory, can alter the outcome of a radionuclide scan. The present study was conducted with the aim to investigate the changes in blood glucose level of patients receiving dipyridamole for cardiac scan. A total of 293 patients (85 men and 208 women, age: 60.59±10.43 years) were included in the study. Fasting Blood Glucose (FBG) was measured before and 8 min after dipyridamole (0.568 mg/kg) injection during myocardial perfusion imaging. The data in different groups were analysed by paired t-test. There was not a significant difference between first (106.89 ± 19.21mg/dL) and second (107.98 ± 17.57 mg/dL) FBG measurements (p= 0.293). However, when the patients were grouped based on the quartiles of first measurement, there was an increase in FBG following dipyridamole injection in the first quartile (mean difference: 7.15±21.27 mg/dL, p<0.01); in contrast, FBG levels showed a significant decrease after dipyridamole administration in the 4(th) quartile (mean difference: -9.53±18.20 mg/dL, p<0.001). The differences in 2(nd) and 3(rd) quartiles were negligible. The patients were divided into normal, ischemic and fixed lesions based on the outcome of scans, then the possible correlation of dipyridamole-induced FBG alteration and scan results were investigated. There were no significant difference between the FBG values before and after dipyridamole injection and the final outcome of scan. The effects of dipyridamole on blood glucose highly depend on the initial blood glucose level.

Evaluation of inhibitory effects of dipyridamole against bovine and equine piroplasmosis

Evaluation of inhibitory effects of dipyridamole against bovine and equine piroplasmosis

Nucleoside Transport Inhibition by Dipyridamole Prevents Angiogenesis Impairment by Homocysteine and Adenosine.

Adenosine plays an important role in the pathogenesis of homocysteine-associated vascular complications. This study examined the effects of dipyridamole, an inhibitor for nucleoside transport, on impaired angiogenic processes caused by homocysteine and adenosine in human cardiovascular endothelial cell line (EAhy926). The results showed that dipyridamole restored the extracellular adenosine and intracellular S-adenosylhomocysteine concentrations disrupted by the combination of homocysteine and adenosine. Dipyridamole also ameliorated the impaired proliferation, migration and formation of capillary-like tubes of EAhy926 cells caused by the combination of homocysteine and adenosine. Mechanism analysis revealed that dipyridamole induced the phosphorylation of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinases (ERK) and its effect on cell growth was attenuated by the MEK inhibitor, U0126. Dipyridamole protected against impaired angiogenesis caused by homocysteine and adenosine, at least in part, by activating the MEK/ERK signalling pathway, and this could be associated with its effects in suppressing intracellular S-adenosylhomocysteine accumulation. This is the first paper showing that nucleoside transport inhibition by dipyridamole reduced impaired angiogenic process caused by homocysteine and adenosine.

Nephroprotective role of dipyridamole in diabetic nephropathy: Effect on inflammation and apoptosis.

Inflammation plays significant roles in developing diabetic nephropathy (DN). Adenosine, natural purine nucleoside, acts as potent endogenous anti-inflammatory agent. Extracellular adenosine usually disappears quickly due to rapid uptake into adjacent cells. In this regard; we investigated putative reno-protective effects of dipyridamole, nucleoside transport inhibitor, by exploring its anti-inflammatory mechanisms in-vivo and in-vitro. Daily 6mg/kg/day dipyridamole was given to six-weeks streptozotocin-induced diabetic rats over two-week period in presence/absence of 10mg/kg/day CGS15943, potent non selective adenosine receptors antagonist. Histological changes were assessed in kidney sections. Gene and protein expression of interleukin (IL)-1β, IL-10, IL-18, tumor necrosis factor (TNF)-α and intercellular adhesion molecule (ICAM)-1 was measured. Activation of apoptotic pathway was demonstrated by measuring the activity of caspase-3/8/9 and activation of c-Jun NH2-terminal kinases (JNK)-mitogen-activated-protein kinase (MAPK). In addition, all markers were measured in human mesangial cells cultured in high glucose. Diabetes induced marked changes in the glomerular and tubular structure including focal glomerulosclerosis with marked shrinkage of some glomerular tufts. Diabetes resulted in enhanced production of IL-1β, IL-18, TNF-α and ICAM-1 associated with reduced IL-10 protein level, leading to activation of caspases-3/8/9 and pJNK/JNK in-vivo and in-vitro. Dipyridamole treatment restored diabetes-induced reduction in adenosine levels and resulted in mild glomerular effects and vacuolation of tubular epithelium. Dipyridamole reduced the adhesion molecule, ICAM-1, and restored the normal balance between pro- and anti-inflammatory cytokines in-vivo and in-vitro. Dipyridamole prevented the progression of DN by elevating endogenous levels of protecting adenosine, leading to reduction in inflammation and intrinsic apoptosis.

Effect of dipyridamole on myocardial reperfusion injury: A double-blind randomized controlled trial in patients undergoing elective coronary artery bypass surgery.

Dipyridamole reduces reperfusion-injury in preclinical trials and may be beneficial in patients undergoing coronary angioplasty, but its effect on patients undergoing coronary artery bypass grafting (CABG) is unknown. We hypothesized that dipyridamole limits myocardial reperfusion-injury in patients undergoing CABG. The trial design was a double-blind trial randomizing between pretreatment with dipyridamole or placebo. In all, 94 patients undergoing elective on-pump CABG were recruited between February 2010 and June 2012. The primary endpoint was plasma high-sensitive (hs-) troponin-I at 6, 12, and 24 hours after reperfusion. Secondary endpoints were the occurrence of bleeding, arrhythmias, need for inotropic support, and intensive care unit length of stay. Finally, 79 patients (33 dipyridamole) were included in the per-protocol analysis. Dipyridamole did not significantly affect postoperative hs-troponin-I (change in plasma hs-troponin I -3% [95% confidence interval -23% to 36%]; P > 0.1). Secondary endpoints did not differ between groups. Dipyridamole prior to CABG does not significantly reduce postoperative hs-troponin release.

Medical adjuvant treatment to increase patency of arteriovenous fistulae and grafts.

End-stage renal disease (ESRD) patients often require either the formation of an arteriovenous (AV) fistula or an AV interposition prosthetic shunt for haemodialysis. These access sites should ideally have a long life and a low rate of complications (for example thrombosis, infection, stenosis, aneurysm formation and distal limb ischaemia). Although some of the complications may be unavoidable, any adjuvant technique or medical treatment aimed at decreasing complications would be welcome. This is the second update of the review first published in 2004. To assess the effects of adjuvant drug treatment in ESRD patients on haemodialysis via autologous AV fistulae or prosthetic interposition AV shunts. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched March 2015) and CENTRAL (2015, Issue 2). Randomised controlled trials (RCTs) of active drug versus placebo in people with ESRD undergoing haemodialysis via an AV fistula or prosthetic interposition AV graft. For this update, the two review authors (NCT, ADS) independently assessed trial quality and one review author (NCT) extracted data. Information on adverse events was collected from the trials. The primary outcome was the long-term fistula or graft patency rate. Secondary outcomes included duration of hospital stay, complications and number of related surgical interventions. For this update, an additional six studies were deemed suitable for inclusion, making a total of 15 trials with 2230 participants. Overall the quality of the evidence was low due to short follow-up periods, heterogeneity between trials and moderate methodological quality of the studies due to incomplete reporting. Medical adjuvant treatments used in the trials were aspirin, ticlopidine, dipyridamole, dipyridamole plus aspirin, warfarin, fish oil, clopidogrel, sulphinpyrazone, and human type I pancreatic elastase (PRT-201). Where possible, the included studies were pooled into similar medical adjuvant groups for meta-analyses.All included studies reported on graft patency by measuring graft thrombosis. There was insufficient evidence to determine if there was a difference in graft patency in studies comparing aspirin versus placebo (three RCTs, 175 participants) (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.07 to 2.25; P = 0.30). The meta-analysis for graft patency comparing ticlopidine versus placebo (three RCTs, 339 participants) favoured ticlopidine (OR 0.45, 95% CI 0.25 to 0.82; P = 0.009). There was insufficient evidence to determine if there was a difference in graft patency in studies comparing fish oil versus placebo (two RCTs, 220 participants; OR 0.24, 95% CI 0.03 to 1.95; P = 0.18); and studies comparing clopidogrel and placebo (two RCTs, 959 participants; OR 0.40, 95% CI 0.13 to 1.19; P = 0.10). Similarly, there was insufficient evidence to determine if there was a difference in graft patency in three studies (306 participants) comparing PRT-201 versus placebo (OR 0.75, 95% CI 0.42 to 1.32; P = 0.31); in one trial comparing the effect of dipyridamole versus placebo (42 participants; OR 0.46, 95% CI 0.11 to 1.94, P = 0.29) and dipyridamole plus aspirin versus placebo (41 participants; OR 0.64, CI 0.16 to 2.56, P = 0.52); in one trial comparing low-dose warfarin with placebo (107 participants; OR 1.76, 95% CI 0.78 to 3.99, P = 0.17); and one trial (16 participants) comparing sulphinpyrazone versus placebo (OR 0.43, 95% CI 0.03 to 5.98, P = 0.53). The single trial evaluating warfarin was terminated early because of major bleeding events in the warfarin group. Only two studies published data on the secondary outcome of related interventions (surgical or radiological); there was insufficient evidence to determine if there was a difference in related interventions between placebo and treatment groups. No studies reported on the length of hospital stay and data reporting on complications was limited and varied between studies. The meta-analyses of three studies for ticlopidine (an anti-platelet treatment), which all used the same dose of treatment but with a short follow-up of only one month, suggest ticlopidine may have a beneficial effect as an adjuvant treatment to increase the patency of AV fistulae and grafts in the short term. There was insufficient evidence to determine if there was a difference in graft patency between placebo and other treatments such as aspirin, fish oil, clopidogrel, PRT-201, dipyridamole, dipyridamole plus aspirin, warfarin, and sulphinpyrazone. However, the quality of the evidence was low due to short follow-up periods, the small number of studies for each comparison, heterogeneity between trials and moderate methodological quality of the studies due to incomplete reporting. It, therefore, appears reasonable to suggest further prospective studies be undertaken to assess the use of these anti-platelet drugs in renal patients with an arteriovenous fistula or graft.

Interventions for preventing thrombosis in solid organ transplant recipients

Interventions for preventing thrombosis in solid organ transplant recipients