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Journal of Cardiovascular Magnetic... Sep 2013Regadenoson, dipyridamole and adenosine are commonly used vasodilators in myocardial perfusion imaging for the detection of obstructive coronary artery disease. There... (Comparative Study)
Comparative Study
BACKGROUND
Regadenoson, dipyridamole and adenosine are commonly used vasodilators in myocardial perfusion imaging for the detection of obstructive coronary artery disease. There are few comparative studies of the vasodilator properties of regadenoson, adenosine and dipyridamole in humans. The specific aim of this study was to determine the relative potency of these three vasodilators by quantifying stress and rest myocardial perfusion in humans using cardiovascular magnetic resonance (CMR).
METHODS
Fifteen healthy normal volunteers, with Framingham score less than 1% underwent vasodilator stress testing with regadenoson (400 μg bolus), dipyridamole (0.56 mg/kg) and adenosine (140 μg /kg/min) on separate days. Rest perfusion imaging was performed initially. Twenty minutes later, stress imaging was performed at peak vasodilation, i.e. 70 seconds after regadenoson, 4 minutes after dipyridamole infusion and between 3-4 minutes of the adenosine infusion. Myocardial blood flow (MBF) in ml/min/g and myocardial perfusion reserve (MPR) were quantified using a fully quantitative model constrained deconvolution.
RESULTS
Regadenoson produced higher stress MBF than dipyridamole and adenosine (3.58 ± 0.58 vs. 2.81 ± 0.67 vs. 2.78 ± 0.61 ml/min/g, p = 0.0009 and p = 0.0008 respectively). Regadenoson had a much higher heart rate response than adenosine and dipyridamole respectively (95 ± 11 vs. 76 ± 13 vs. 86 ± 12 beats/ minute) When stress MBF was adjusted for heart rate, there were no differences between regadenoson and adenosine (37.8 ± 6 vs. 36.6 ± 4 μl/sec/g, p = NS), but differences between regadenoson and dipyridamole persisted (37.8 ± 6 vs. 32.6 ± 5 μl/sec/g, p = 0.03). The unadjusted MPR was higher with regadenoson (3.11 ± 0.63) when compared with adenosine (2.7 ± 0.61, p = 0.02) and when compared with dipyridamole (2.61 ± 0.57, p = 0.04). Similar to stress MBF, these differences in MPR between regadenoson and adenosine were abolished when adjusted for heart rate (2.04 ± 0.34 vs. 2.12 ± 0.27, p = NS), but persisted between regadenoson and dipyridamole (2.04 ± 0.34 vs. 1.77 ± 0.33, p = 0.07) and between adenosine and dipyridamole (2.12 ± 0.27 vs. 1.77 ± 0.33, p = 0.01).
CONCLUSIONS
Based on fully quantitative perfusion using CMR, regadenoson and adenosine have similar vasodilator efficacy and are superior to dipyridamole.
Topics: Adenosine; Coronary Circulation; Dipyridamole; Female; Healthy Volunteers; Heart Rate; Humans; Infusions, Parenteral; Magnetic Resonance Imaging; Male; Myocardial Perfusion Imaging; Predictive Value of Tests; Purines; Pyrazoles; Vasodilation; Vasodilator Agents; Young Adult
PubMed: 24063278
DOI: 10.1186/1532-429X-15-85 -
Cleveland Clinic Journal of Medicine Dec 2013Drugs that prevent platelets from sticking together-ie, aspirin, dipyridamole, and clopidogrel-are an important part of therapy to prevent recurrence of ischemic stroke... (Review)
Review
Drugs that prevent platelets from sticking together-ie, aspirin, dipyridamole, and clopidogrel-are an important part of therapy to prevent recurrence of ischemic stroke of atherosclerotic origin. We discuss current indications for these drugs and review the evidence behind our current use of aspirin, dipyridamole, and clopidogrel.
Topics: Aspirin; Carotid Stenosis; Clopidogrel; Dipyridamole; Humans; Platelet Aggregation Inhibitors; Secondary Prevention; Stents; Stroke; Ticlopidine
PubMed: 24307163
DOI: 10.3949/ccjm.80a.12149 -
Cleveland Clinic Journal of Medicine Jul 2014
Topics: Adenosine; Aspirin; Dipyridamole; Female; Heart Arrest; Humans; Platelet Aggregation Inhibitors; Radiopharmaceuticals; Syncope
PubMed: 24987036
DOI: 10.3949/ccjm.81c.07002 -
Lancet (London, England) Mar 2018Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral... (Comparative Study)
Comparative Study Randomized Controlled Trial
Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial.
BACKGROUND
Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy.
METHODS
We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388.
FINDINGS
3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67-1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05-3·16, p<0·0001).
INTERPRETATION
Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice.
FUNDING
National Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation.
Topics: Acute Disease; Aged; Aspirin; Brain Ischemia; Clopidogrel; Denmark; Dipyridamole; Drug Therapy, Combination; Female; Georgia; Hemorrhage; Humans; Ischemia; Ischemic Attack, Transient; Male; Middle Aged; New Zealand; Platelet Aggregation Inhibitors; Prospective Studies; Recurrence; Research Design; Risk Assessment; Stroke; Thrombolytic Therapy; Ticlopidine; Treatment Outcome; United Kingdom
PubMed: 29274727
DOI: 10.1016/S0140-6736(17)32849-0 -
Journal of Affective Disorders Sep 2022Improved treatments for bipolar disorder (BD) are needed. Drug repurposing aims to find novel targets for drugs that have been used for other indications. This study... (Observational Study)
Observational Study
BACKGROUND
Improved treatments for bipolar disorder (BD) are needed. Drug repurposing aims to find novel targets for drugs that have been used for other indications. This study investigated the risk of psychiatric hospitalization associated with use of calcium-channel blockers (CCBs; dihydropyridines, diltiazem, verapamil) and adenosine modulators (allopurinol, dipyridamole) in BD in within-individual design.
METHODS
Individuals diagnosed with BD (ICD-10: F30-F31) were identified from the inpatient, specialized outpatient, sickness absence, and disability pension registers during 1996-2018 in Finland (N = 60,045). The main outcome was hospitalization due to affective symptoms (ICD-10: F30-F39). Within-individual models in stratified Cox regression were used and adjusted hazard ratios (aHR) with 95 % confidence intervals (CIs) reported.
RESULTS
Use of CCBs was associated with a decreased risk of hospitalization due to affective symptoms (aHR 0.83, 95 % CI 0.78-0.88) when all CCBs were analyzed together. Of specific CCBs, use of diltiazem (0.71, 0.55-0.91) and dihydropyridines (0.83, 0.78-0.89) were associated with a decreased risk but verapamil was not (0.93, 0.73-1.19). Use of adenosine modulators in general was associated with a decreased risk of hospitalizations due to affective symptoms (0.87, 0.79-0.96). Both allopurinol (0.85, 0.74-0.97) and dipyridamole (0.89, 0.78-1.00) were associated with a marginally decreased risk. Thiazide diuretic use as a negative control was not associated with the risk of hospitalization due to affective symptoms (0.97, 0.83-1.13).
LIMITATIONS
Due to the observational nature of this study, causation cannot be confirmed.
CONCLUSIONS
Dihydropyridines and diltiazem were associated with a decreased risk of psychiatric hospitalization in bipolar disorder. Results for allopurinol and dipyridamole were inconclusive.
Topics: Adenosine; Allopurinol; Bipolar Disorder; Calcium Channel Blockers; Cohort Studies; Dihydropyridines; Diltiazem; Dipyridamole; Humans
PubMed: 35753501
DOI: 10.1016/j.jad.2022.06.040 -
Molecular Oncology Oct 2020Dipyridamole, an antiplatelet drug, has been shown to synergize with statins to induce cancer cell-specific apoptosis. However, given the polypharmacology of...
Dipyridamole, an antiplatelet drug, has been shown to synergize with statins to induce cancer cell-specific apoptosis. However, given the polypharmacology of dipyridamole, the mechanism by which it potentiates statin-induced apoptosis remains unclear. Here, we applied a pharmacological approach to identify the activity of dipyridamole specific to its synergistic anticancer interaction with statins. We evaluated compounds that phenocopy the individual activities of dipyridamole and assessed whether they could potentiate statin-induced cell death. Notably, we identified that a phosphodiesterase (PDE) inhibitor, cilostazol, and other compounds that increase intracellular cyclic adenosine monophosphate (cAMP) levels potentiate statin-induced apoptosis in acute myeloid leukemia and multiple myeloma cells. Additionally, we demonstrated that both dipyridamole and cilostazol further inhibit statin-induced activation of sterol regulatory element-binding protein 2, a known modulator of statin sensitivity, in a cAMP-independent manner. Taken together, our data support that PDE inhibitors such as dipyridamole and cilostazol can potentiate statin-induced apoptosis via a dual mechanism. Given that several PDE inhibitors are clinically approved for various indications, they are immediately available for testing in combination with statins for the treatment of hematological malignancies.
Topics: Cell Death; Cell Line, Tumor; Cilostazol; Cyclic AMP; Dipyridamole; Drug Synergism; Humans; Hydrolysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Models, Biological; Neoplasms; Phosphodiesterase Inhibitors; Sterols
PubMed: 32749766
DOI: 10.1002/1878-0261.12775 -
International Journal of Cancer Apr 2023Low-dose aspirin has been hypothesized to prevent cancer risk by inhibiting platelet aggregation. However, the anti-cancer effect of low-dose aspirin has recently been...
Low-dose aspirin has been hypothesized to prevent cancer risk by inhibiting platelet aggregation. However, the anti-cancer effect of low-dose aspirin has recently been questioned and its effect on breast cancer development remains unclear. The impact of other antiplatelet drugs on breast cancer risk has rarely been evaluated. Thus, this study aimed to investigate the associations between breast cancer risk and antiplatelet drug use in a nationwide nested case-control study. From the Danish healthcare registries, we identified as cases all women with invasive breast cancer diagnosis between 2001 and 2018 (n = 68 852). The date of diagnosis corresponded to the index date. We matched cases to 10 population controls on age and calendar time, using risk set sampling. Controls were assigned the same index date as their matched case. We used the prescription registry to identify exposure to low-dose aspirin, clopidogrel and dipyridamole. We defined ever use of antiplatelet drugs as at least two prescriptions filled up to 1 year before the index date. We applied conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for breast cancer associated with the use of antiplatelet drugs, overall, by breast cancer subtype and by cumulative dose. Twelve percent of women had ever been exposed to low-dose aspirin, 2% to clopidogrel and 2% to dipyridamole. In multivariable models, breast cancer risk was not associated with ever use of low-dose aspirin (OR = 1.00 [0.97-1.03]), clopidogrel (OR = 0.93 [0.87-1.00]), and dipyridamole (OR = 1.02 [0.94-1.10]), compared with never use, and there was no evidence of a dose-response relation. However, we found an inverse association between dipyridamole use and breast cancer risk among women aged <55 years old, with suggestion of a dose-response relationship (OR per 1000 Defined Daily Doses = 0.72 [0.54-0.95]). Associations did not differ by breast cancer histological type, estrogen receptor status or clinical stage at diagnosis. Overall, the findings from this study do not support the use of antiplatelet drugs for breast cancer prevention.
Topics: Female; Humans; Middle Aged; Aspirin; Breast Neoplasms; Case-Control Studies; Clopidogrel; Denmark; Dipyridamole; Logistic Models; Platelet Aggregation Inhibitors
PubMed: 36346115
DOI: 10.1002/ijc.34343 -
British Journal of Clinical Pharmacology Apr 1998There is limited evidence that dipyridamole is generally an effective antithrombotic agent when used alone, nor is there convincing evidence that the combination of... (Review)
Review
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.
Topics: Cardiovascular Diseases; Cerebrovascular Disorders; Dipyridamole; Humans; Platelet Aggregation Inhibitors
PubMed: 9578178
DOI: 10.1046/j.1365-2125.1998.t01-1-00677.x -
Journal of Comparative Effectiveness... Aug 2015Stroke exacts a huge toll physically, mentally and economically. Antiplatelet therapy is the cornerstone of secondary stroke prevention, and proven drugs available to... (Review)
Review
Stroke exacts a huge toll physically, mentally and economically. Antiplatelet therapy is the cornerstone of secondary stroke prevention, and proven drugs available to successfully realize this therapeutic strategy for the long term include aspirin, dipyridamole plus aspirin and clopidogrel. However, government agencies, corporations, health plans and patients desire more information about the clinical- and cost-effectiveness of these established therapies in real-world settings. This paper provides an update on evidence-based secondary stroke prevention with antiplatelet medications, discusses cost-related issues and offers perspective about the future.
Topics: Aspirin; Clopidogrel; Cost-Benefit Analysis; Dipyridamole; Drug Therapy, Combination; Humans; Platelet Aggregation Inhibitors; Secondary Prevention; Stroke; Ticlopidine
PubMed: 26274799
DOI: 10.2217/cer.15.22 -
Progress in Neuro-psychopharmacology &... Dec 2022Huntington's disease (HD) is a neurodegenerative disorder, characterized by motor dysfunction, psychiatric disturbance, and cognitive decline. In the early stage of HD,...
Huntington's disease (HD) is a neurodegenerative disorder, characterized by motor dysfunction, psychiatric disturbance, and cognitive decline. In the early stage of HD, occurs a decrease in dopamine D receptors and adenosine A receptors (AR), while in the late stage also occurs a decrease in dopamine D receptors and adenosine A receptors (AR). Adenosine exhibits neuromodulatory and neuroprotective effects in the brain and is involved in motor control and memory function. 3-Nitropropionic acid (3-NPA), a toxin derived from plants and fungi, may reproduce HD behavioral phenotypes and biochemical characteristics. This study investigated the effects of acute exposure to CPA (AR agonist), CGS 21680 (AR agonist), caffeine (non-selective of AR and AR antagonist), ZM 241385 (AR antagonist), DPCPX (AR antagonist), dipyridamole (inhibitor of nucleoside transporters) and EHNA (inhibitor of adenosine deaminase) in an HD pharmacological model induced by 3-NPA in adult zebrafish. CPA, CGS 21680, caffeine, ZM 241385, DPCPX, dipyridamole, and EHNA were acutely administered via i.p. in zebrafish after 3-NPA (at dose 60 mg/kg) chronic treatment. Caffeine and ZM 241385 reversed the bradykinesia induced by 3-NPA, while CGS 21680 potentiated the bradykinesia caused by 3-NPA. Moreover, CPA, caffeine, ZM 241385, DPCPX, dipyridamole, and EHNA reversed the 3-NPA-induced memory impairment. Together, these data support the hypothesis that AR antagonists have an essential role in modulating locomotor function, whereas the activation of AR and blockade of AR and AR and modulation of adenosine levels may reduce the memory impairment, which could be a potential pharmacological strategy against late-stage symptoms HD.
Topics: Adenosine; Animals; Caffeine; Dipyridamole; Dopamine; Hypokinesia; Nitro Compounds; Propionates; Receptor, Adenosine A2A; Zebrafish
PubMed: 35843370
DOI: 10.1016/j.pnpbp.2022.110602