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1.
Expert Opin Drug Saf ; 23(4): 487-495, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38497691

RESUMEN

BACKGROUND: Hemorrhage represents the most common and serious side effect of antithrombotic agents. Many studies have compared the risk of bleeding between different antithrombotic agents, but analysis of time-to-onset for hemorrhage induced by these drugs is yet sparse. METHODS: We conducted a retrospective study based on the adverse drug reaction reports on antithrombotic agents collected by the Henan Adverse Drug Reaction Monitoring Center. We assessed the reporting odds ratio to determine the disproportionate reporting signals for bleeding and the Weibull shape parameter was used to evaluate the time-to-onset data. RESULTS: In the signal detection, crude low molecular weight heparin-hemorrhage was found as a positive signal. The hemorrhage for most antithrombotic agents was random failure profiles. In particular, the hazard of hemorrhage decreased over time for warfarin and clopidogrel and increased for alteplase, nadroparin, and dipyridamole. CONCLUSION: We found that the risk of bleeding in patients taking Crude low molecular weight heparins was significantly higher compared to other antithrombotic agents, but with a small magnificence, which may be attributed to the severely irrational use of this medication under improper management. Statistics in days, results showed that the risk of bleeding decreased over time for warfarin and clopidogrel and increased for alteplase, nadroparin, and dipyridamole.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Fibrinolíticos , Humanos , Fibrinolíticos/efectos adversos , Warfarina/efectos adversos , Nadroparina/efectos adversos , Clopidogrel/efectos adversos , Activador de Tejido Plasminógeno/efectos adversos , Estudios Retrospectivos , Farmacovigilancia , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Anticoagulantes/efectos adversos , Dipiridamol/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos
2.
Purinergic Signal ; 19(3): 551-564, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-36781825

RESUMEN

Some non-adenosinergic drugs are reported to also act through adenosine receptors (ARs). We used mouse hypothermia, which can be induced by agonism at any of the four ARs, as an in vivo screen for adenosinergic effects. An AR contribution was identified when a drug caused hypothermia in wild type mice that was diminished in mice lacking all four ARs (quadruple knockout, QKO). Alternatively, an adenosinergic effect was identified if a drug potentiated adenosine-induced hypothermia. Four drugs (dipyridamole, nimodipine, cilostazol, cyclosporin A) increased the hypothermia caused by adenosine. Dipyridamole and nimodipine probably achieved this by inhibition of adenosine clearance via ENT1. Two drugs (cannabidiol, canrenoate) did not cause hypothermia in wild type mice. Four other drugs (nifedipine, ranolazine, ketamine, ethanol) caused hypothermia, but the hypothermia was unchanged in QKO mice indicating non-adenosinergic mechanisms. Zinc chloride caused hypothermia and hypoactivity; the hypoactivity was blunted in the QKO mice. Interestingly, the antidepressant amitriptyline caused hypothermia in wild type mice that was amplified in the QKO mice. Thus, we have identified adenosine-related effects for some drugs, while other candidates do not affect adenosine signaling by this in vivo assay. The adenosine-modulating drugs could be considered for repurposing based on predicted effects on AR activation.


Asunto(s)
Adenosina , Hipotermia , Ratones , Animales , Adenosina/farmacología , Hipotermia/inducido químicamente , Nimodipina/efectos adversos , Receptores Purinérgicos P1 , Dipiridamol/efectos adversos
3.
Neurochem Res ; 48(6): 1889-1899, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36729312

RESUMEN

Epilepsy is characterized by the manifestation of spontaneous and recurrent seizures. The high prevalence of comorbidities associated with epilepsy, such as cognitive dysfunction, affects the patients quality of life. Adenosine signaling modulation might be an effective alternative to control seizures and epilepsy-associated comorbidities. This study aimed to verify the role of adenosine modulation on the seizure development and cognitive impairment induced by pentylenetetrazole (PTZ) in zebrafish. At first, animals were submitted to a training session in the inhibitory avoidance test and, after 10 min, they received an intraperitoneal injection of valproate, adenosine A1 receptor agonist cyclopentyladenosine (CPA), adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), adenosine A2A receptor antagonist ZM 241385, adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nony1)-adenine hydrochloride (EHNA) or the nucleoside transporter inhibitor dipyridamole. Thirty min after the intraperitoneal injection, the animals were exposed to 7.5 mM PTZ for 10 min, where they were evaluated for latency to reach the seizure stages (I, II, and III). Finally, 24 h after the training session, the animals were submitted to the inhibitory avoidance test to verify their cognitive performance during the test session. Valproate, CPA, and EHNA showed antiseizure effects and prevented the memory impairment induced by PTZ exposure. DPCPX, ZM 241385, and dipyridamole pretreatments caused no changes in seizure development; however, these drugs prevented memory impairment without altering locomotion. Our results reinforce the antiseizure effects of adenosine signaling and support the idea that the involvement of adenosine in memory processes may be a target for preventive strategies against cognitive impairment associated with epilepsy.


Asunto(s)
Epilepsia , Pentilenotetrazol , Animales , Pentilenotetrazol/toxicidad , Adenosina/farmacología , Pez Cebra , Ácido Valproico/efectos adversos , Calidad de Vida , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Convulsiones/prevención & control , Dipiridamol/efectos adversos
4.
Expert Rev Clin Pharmacol ; 15(9): 1027-1038, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36031827

RESUMEN

INTRODUCTION: Antiplatelet therapy is key to prevent recurrences in patients with an acute or prior non-cardioembolic stroke or transient ischemic attack (TIA). The narrow balance between the risks of ischemic recurrence and major bleeding is a relevant clinical dilemma in this population. AREAS COVERED: This review covers the current evidence on antiplatelet therapy for patients with non-cardioembolic stroke or TIA. Randomized controlled trials of antithrombotic strategies for patients with these conditions were searched in Pubmed/Medline from 1970 to 2022. EXPERT OPINION: Numerous randomized controlled trials have defined the current indications to the use of antiplatelet drugs for patients with non-cardioembolic ischemic stroke or TIA. For the management of these subjects, single antiplatelet therapy with aspirin or clopidogrel, or the combination of aspirin and dipyridamole, is usually recommended. After an acute stroke or TIA, a short course of dual antiplatelet therapy with aspirin in combination with clopidogrel or ticagrelor should be considered. The risk of bleeding might be higher with ticagrelor, but a direct comparison with clopidogrel is not available in this setting. The introduction of newer strategies, such as dual-pathway inhibition with aspirin and a direct oral anticoagulant (including emerging factor XI inhibitors under clinical development) may open a new research avenue in this challenging area.


Asunto(s)
Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anticoagulantes , Aspirina/efectos adversos , Clopidogrel/efectos adversos , Dipiridamol/efectos adversos , Quimioterapia Combinada , Factor XI/uso terapéutico , Fibrinolíticos/uso terapéutico , Hemorragia/inducido químicamente , Humanos , Ataque Isquémico Transitorio/tratamiento farmacológico , Ataque Isquémico Transitorio/epidemiología , Ataque Isquémico Transitorio/prevención & control , Inhibidores de Agregación Plaquetaria/efectos adversos , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Ticagrelor/uso terapéutico
5.
J Affect Disord ; 313: 43-48, 2022 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-35753501

RESUMEN

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.


Asunto(s)
Trastorno Bipolar , Dihidropiridinas , Adenosina/uso terapéutico , Alopurinol/efectos adversos , Trastorno Bipolar/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/efectos adversos , Estudios de Cohortes , Dihidropiridinas/uso terapéutico , Diltiazem/uso terapéutico , Dipiridamol/efectos adversos , Humanos
6.
Stroke Vasc Neurol ; 7(5): 406-414, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35393359

RESUMEN

Antiplatelet therapy is one of the mainstays for secondary stroke prevention. This narrative review aimed to highlight the current evidence and recommendations of antiplatelet therapy for stroke prevention.We conducted advanced literature search for antiplatelet therapy. Landmark studies and randomised controlled trials evaluating antiplatelet therapy for secondary stroke prevention are reviewed. Results from Cochrane systematic review, pooled data analysis and meta-analysis are discussed.Single-antiplatelet therapy (SAPT) with aspirin, aspirin/extended-release dipyridamole or clopidogrel reduces the risk of recurrent ischaemic stroke in patients with non-cardioembolic ischaemic stroke or transient ischaemic attack (TIA). Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel or ticagrelor for 21-30 days is more effective than SAPT in patients with minor acute noncardioembolic ischaemic stroke or high-risk TIA. Prolonged use of DAPT is associated with higher risk of haemorrhage without reduction in stroke recurrence than SAPT. Compared with placebo, aspirin reduces the relative risk of recurrent stroke by approximately 22%. Aspirin/dipyridamole and cilostazol are superior to aspirin but associated with significant side effects. Cilostazol or ticagrelor might be more effective than aspirin or clopidogrel in patients with intracranial stenosis.SAPT is indicated for secondary stroke prevention in patients with non-cardioembolic ischaemic stroke or TIA. DAPT with aspirin and clopidogrel or ticagrelor for 21-30 days followed by SAPT is recommended for patients with minor acute noncardioembolic stroke or high-risk TIA. Selection of appropriate antiplatelet therapy should also be based on compliance, drug tolerance or resistance.


Asunto(s)
Isquemia Encefálica , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Aspirina , Isquemia Encefálica/tratamiento farmacológico , Cilostazol/uso terapéutico , Clopidogrel/uso terapéutico , Dipiridamol/efectos adversos , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/tratamiento farmacológico , Ataque Isquémico Transitorio/prevención & control , Inhibidores de Agregación Plaquetaria/efectos adversos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/prevención & control , Ticagrelor/uso terapéutico
7.
Cerebrovasc Dis ; 51(4): 493-498, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35034023

RESUMEN

PURPOSE: The aim of this study is to investigate the effect of gradual dipyridamole titration and the incidence of dipyridamole-induced headache in patients with ischemic stroke or transient ischemic attack (TIA). METHODS: A randomized, double-blind, double-placebo, parallel group, phase 4 clinical trial (KCT0005457) was conducted between July 1, 2019, and February 25, 2020, at 15 medical centers in South Korea. The study included patients aged >19 years diagnosed with a noncardioembolic ischemic stroke or TIA within the previous 3 weeks. The participants were randomized 1:1:1 to receive Adinox® (aspirin 25 mg/dipyridamole 200 mg) and aspirin (100 mg) once daily for the first 2 weeks followed by Adinox® twice daily for 2 weeks (titration group), Adinox® twice daily for 4 weeks (standard group), and aspirin 100 mg once daily for 4 weeks (control group). The primary endpoint was incidence of headache over 4 weeks. The key secondary endpoint was mean cumulative headache. RESULTS: Ninety-six patients were randomized into the titration (n = 31), standard (n = 32), and control (n = 33) groups. The titration and standard groups (74.1% vs. 74.2%, respectively) showed no difference in the primary endpoint. However, the mean cumulated headache was significantly lower in the titration group than in the standard group (0.31 ± 0.46 vs. 0.58 ± 0.51, p = 0.023). Further, adverse drug reactions were more common in the standard group than in the titration group (28.1% vs. 9.7%, respectively, p = 0.054), although not significantly different. CONCLUSION: The titration strategy was effective in lowering the incidence of cumulative dipyridamole-induced headache.


Asunto(s)
Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Aspirina/efectos adversos , Dipiridamol/efectos adversos , Método Doble Ciego , Quimioterapia Combinada , Cefalea/inducido químicamente , Cefalea/diagnóstico , Cefalea/tratamiento farmacológico , Humanos , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/tratamiento farmacológico
8.
Br J Haematol ; 196(3): 690-699, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34553368

RESUMEN

The anti-cancer potential of dipyridamole has been suggested from experiments, but evidence from population-based studies is still lacking. We aimed to explore if dipyridamole use was related to a lower risk of lymphoid neoplasms. We identified individuals with prescription of aspirin after diagnosis of ischaemic cerebrovascular disease since 2006 by linking several Swedish registers. In these aspirin users, those with dipyridamole prescription were further identified as the study group and patients without dipyridamole were randomly selected as reference group with 1:1 ratio using a propensity score-matching approach. After a median of 6·67 years of follow-up, a total of 46 patients with dipyridamole use developed lymphoid neoplasms with an incidence rate of 0·49 per 1 000 person-years, while the rate in the matched group was 0·74 per 1 000 person-years. As compared to non-users, dipyridamole users were associated with a significantly decreased risk of lymphoid neoplasms [hazard ratio (HR) = 0·65; 95% confidence interval (CI) = 0·43-0·98]. Specifically, the reduced risk was observed for non-Hodgkin lymphomas (HR = 0·64; 95% CI = 0·42-0·94), especially B-cell lymphomas (HR = 0·56; 95% CI = 0·35-0·88). Dipyridamole use was related to a lower risk of lymphoid neoplasms, indicating a clinical potential of dipyridamole to be an adjunct anti-tumour agent against lymphoid neoplasms.


Asunto(s)
Dipiridamol/efectos adversos , Leucemia Linfoide/epidemiología , Leucemia Linfoide/etiología , Linfoma/epidemiología , Linfoma/etiología , Inhibidores de Agregación Plaquetaria/efectos adversos , Anciano , Anciano de 80 o más Años , Aspirina/efectos adversos , Aspirina/uso terapéutico , Quimioprevención , Comorbilidad , Dipiridamol/uso terapéutico , Susceptibilidad a Enfermedades , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Leucemia Linfoide/prevención & control , Linfoma/prevención & control , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Vigilancia de la Población , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Suecia/epidemiología
9.
In. Soeiro, Alexandre de Matos; Leal, Tatiana de Carvalho Andreucci Torres; Accorsi, Tarso Augusto Duenhas; Gualandro, Danielle Menosi; Oliveira Junior, Múcio Tavares de; Caramelli, Bruno; Kalil Filho, Roberto. Manual da residência em cardiologia / Manual residence in cardiology. Santana de Parnaíba, Manole, 2 ed; 2022. p.921-927, ilus, tab.
Monografía en Portugués | LILACS | ID: biblio-1353766
10.
Medicine (Baltimore) ; 100(19): e25852, 2021 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-34106629

RESUMEN

BACKGROUND: In recent years, the incidence rate of hypertensive nephropathy has been increasing quickly, which has been a major threat to people's health. Renin-angiotensin-aldosterone system blockers have certain curative effects. However, there are some patients having serious adverse reactions, and the benefit population is limited, so the treatment of hypertensive renal damage is necessary to have beneficial supplement. More and more clinical studies have shown that ginkgo leaf extract and dipyridamole injection (GDI) combined with antihypertensive drugs has achieved good results in the treatment of hypertensive renal damage. It is supposed to be a supplementary treatment in hypertensive nephropathy. OBJECTIVES: To systematically assess the efficacy and safety of GDI combined with antihypertensive drugs on hypertensive renal injury. METHODS: Seven databases including PubMed, Cochrane Library, Embase, Wanfang database, China biomedical literature service system (Sino Med), VIP Chinese Sci-tech journal database (VIP), and China national knowledge internet (CNKI) were retrieved to collect randomized controlled trials (RCTs) in the experimental group containing combined therapy of hypertensive nephropathy with GDI and antihypertensive drugs. The retrieval time was from the establishment of database to July 8, 2020. Two researchers independently selected literature, extracted data, and evaluated the risk of bias in the study. The methodological quality was evaluated with Cochrane handbook and meta-analysis was performed with Stata 14.0 software. RESULTS: Eight studies were included in this study which involved 556 patients. The meta-analyses indicated that, compared with using antihypertensive drugs alone, combined treatment of GDI with antihypertensive drugs can decrease 24-hour urinary total protein (weighted mean difference [WMD] -0.61, 95% confidence interval [CI]: -0.82, -0.39; k = 6, P ≤ .001), blood urea nitrogen (WMD -1.27, 95% CI: -2.45, -0.10; k = 6, P = .033, serum creatinine (WMD -29.50, 95% CI: -56.44, -2.56; number of estimates [k] = 6, P = .032). CONCLUSIONS: Our meta-analyses showed that GDI combined with antihypertensive drugs can improve the renal function of hypertensive patients with renal injury.


Asunto(s)
Antihipertensivos/uso terapéutico , Dipiridamol/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Hipertensión Renal/tratamiento farmacológico , Nefritis/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Vasodilatadores/uso terapéutico , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Dipiridamol/administración & dosificación , Dipiridamol/efectos adversos , Quimioterapia Combinada , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/efectos adversos , Ginkgo biloba , Pruebas Hematológicas , Humanos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Urinálisis , Vasodilatadores/administración & dosificación , Vasodilatadores/efectos adversos
12.
J Cardiovasc Pharmacol ; 77(4): 450-457, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33760800

RESUMEN

ABSTRACT: 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.


Asunto(s)
Enfermedad de la Arteria Coronaria/terapia , Reestenosis Coronaria/prevención & control , Dipiridamol/uso terapéutico , Procedimientos Endovasculares , Arteriosclerosis Intracraneal/terapia , Intervención Coronaria Percutánea , Enfermedad Arterial Periférica/terapia , Inhibidores de Agregación Plaquetaria/uso terapéutico , Animales , Enfermedad de la Arteria Coronaria/fisiopatología , Reestenosis Coronaria/etiología , Reestenosis Coronaria/fisiopatología , Dipiridamol/efectos adversos , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Humanos , Arteriosclerosis Intracraneal/fisiopatología , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Enfermedad Arterial Periférica/fisiopatología , Inhibidores de Agregación Plaquetaria/efectos adversos , Recurrencia , Medición de Riesgo , Factores de Riesgo , Stents , Resultado del Tratamiento , Grado de Desobstrucción Vascular
13.
Circ Cardiovasc Imaging ; 13(9): e010599, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32873071

RESUMEN

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF; heart failure with reduced left ventricular ejection fraction <40%) referred for stress cardiovascular magnetic resonance (CMR) may have a less optimal hemodynamic response to intravenous vasodilator. The aim was to assess the prognostic value of vasodilator stress perfusion CMR in patients with HFrEF. METHODS: Between 2008 and 2018, consecutive patients with HFrEF defined by left ventricular ejection fraction <40% prospectively referred for vasodilator stress perfusion CMR were followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or nonfatal myocardial infarction. Univariable and multivariable Cox regressions were performed to determine the prognostic value of inducible ischemia or late gadolinium enhancement by CMR. RESULTS: Of 1053 patients with HFrEF (65±11 years, median [interquartile range] left ventricular ejection fraction 38.7% [37.2-39.0]), 1018 (97%) completed the CMR protocol and 950 (93%) completed the follow-up (median [interquartile range], 5.6 [3.6-7.3] years); 117 experienced a MACE (12.3%). Stress CMR was well tolerated without any adverse events. Patients without ischemia or late gadolinium enhancement experienced a lower annual event rate of MACE (1.8%) than those with both ischemia and late gadolinium enhancement (12.0%; P<0.001). Using Kaplan-Meier analysis, inducible ischemia and late gadolinium enhancement were significantly associated with the occurrence of MACE (hazard ratio, 2.46 [95% CI, 1.69-3.60]; and hazard ratio, 2.92 [95% CI, 1.77-4.83], respectively, both P<0.001). In multivariable Cox regression, inducible ischemia was an independent predictor of a higher incidence of MACE (hazard ratio, 2.26 [95% CI, 1.52-3.35]; P<0.001). CONCLUSIONS: Stress CMR is safe and has a good discriminative prognostic value to predict the occurrence of MACE in patients with HFrEF.


Asunto(s)
Dipiridamol/administración & dosificación , Insuficiencia Cardíaca/diagnóstico por imagen , Imagen por Resonancia Cinemagnética , Imagen de Perfusión Miocárdica , Volumen Sistólico , Vasodilatadores/administración & dosificación , Función Ventricular Izquierda , Anciano , Medios de Contraste , Dipiridamol/efectos adversos , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Infusiones Intravenosas , Estudios Longitudinales , Imagen por Resonancia Cinemagnética/efectos adversos , Masculino , Meglumina , Persona de Mediana Edad , Infarto del Miocardio/etiología , Imagen de Perfusión Miocárdica/efectos adversos , Compuestos Organometálicos , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Vasodilatadores/efectos adversos
14.
Sci Rep ; 10(1): 12135, 2020 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-32699337

RESUMEN

While the patency of vascular access is essential for hemodialysis patients, optimal pharmaceutical treatment to maintain arteriovenous fistula (AVF) patency remains lacking. As cardiovascular diseases are highly prevalent in patients with end-stage renal disease, various cardiovascular medications have also been used to maintain AVF patency. However, previous studies revealed inconsistent therapeutic effects and a comprehensive evaluation of this issue is needed. The present retrospective, longitudinal cohort study included patients receiving successful AVF creation. The evaluated cardiovascular medications included antiplatelet agents, antihypertensive agents, nitrates and nitrites, statins, dipyridamole, and pentoxifylline. The outcome was AVF primary patency. All laboratory data and medication profiles were recorded at baseline and followed at 3-month interval, until the end of the 2-year study period. Cox proportional regression model with time-dependent covariates was used to evaluate the risk for AVF patency loss. A total of 349 patients were included in the present study, in which 57% were men and the mean age was 65 ± 14 years. Among the included patients, 40% used antiplatelet agents, 27% used dipyridamole and 36% used statins at baseline. Of all the evaluated cardiovascular medications, only dipyridamole showed significant association with a higher risk for loss of AVF patency. To evaluate the effect of combination of antiplatelet agents and dipyridamole, the patients were classified into four groups, I: combine use of antiplatelet agents and dipyridamole, II: antiplatelet only, III: dipyridamole only; IV: none of both were used. Of the four groups, group IV exhibited highest AVF patency (52.4%), which was followed by group III (42.7%), group II (40%), and group I (28.6%), respectively. Compared with group IV, only group I showed a significantly higher risk for AVF patency loss. None of the cardiovascular medications evaluated in the present study showed a beneficial effect on AVF patency. Furthermore, dipyridamole showed an association with a higher risk of AVF patency loss. We do not suggest a beneficial effect of dipyridamole on maintaining AVF patency, particularly in combination with antiplatelet agents.


Asunto(s)
Fístula Arteriovenosa/etiología , Dipiridamol/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Anciano , Fístula Arteriovenosa/diagnóstico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Dipiridamol/farmacología , Dipiridamol/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Fallo Renal Crónico/patología , Fallo Renal Crónico/terapia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Modelos de Riesgos Proporcionales , Diálisis Renal , Estudios Retrospectivos , Factores de Riesgo , Grado de Desobstrucción Vascular/efectos de los fármacos
15.
J Stroke Cerebrovasc Dis ; 29(4): 104632, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32037269

RESUMEN

AIMS: The REDUCE study demonstrated a reduction in the risk of recurrent stroke with patent foramen ovale closure and antiplatelet therapy compared to antiplatelet therapy alone. The clinicians were allowed to choose among aspirin, clopidogrel, or aspirin/dipyridamole with the expectation that all antiplatelet therapies would have similar efficacy in this population. We tested that presumption by comparing recurrent stroke rates among antiplatelet agents within the control arm of the trial. METHODS: We evaluated patients in REDUCE study who were randomized to the medical arm. The primary endpoint for this analysis was freedom from clinical ischemic stroke through at least 2 years of follow-up, to a maximum of 5 years. In the primary analysis, antiplatelet treatment was defined as the agent during the week prior to a recurrent stroke or last known contact. RESULTS: Of 223 patients in the medical treatment arm, the initial agent was aspirin 52%, clopidogrel 30%, and aspirin/dipyridamole 12%. Patients treated with aspirin were similar to those treated with alternatives, but were more likely to be enrolled in the United States. The last reported agent was aspirin alone in 55%, clopidogrel alone in 31%, aspirin/dipyridamole in 7%, and other/nothing/missing in 7%. Recurrent stroke rates were similar for all 3 antiplatelet regimens in unadjusted and adjusted analyses, with no overall difference among agents (P= .17). CONCLUSIONS: Among patients with patent foramen ovale-associated stroke who were managed medically, there were no differences among antiplatelet agents in the risk of recurrent stroke, though confidence intervals were wide.


Asunto(s)
Aspirina/uso terapéutico , Clopidogrel/administración & dosificación , Dipiridamol/administración & dosificación , Foramen Oval Permeable/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prevención Secundaria , Accidente Cerebrovascular/prevención & control , Adolescente , Adulto , Aspirina/efectos adversos , Clopidogrel/efectos adversos , Dipiridamol/efectos adversos , Quimioterapia Combinada , Femenino , Foramen Oval Permeable/complicaciones , Foramen Oval Permeable/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos , Supervivencia sin Progresión , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/etiología , Factores de Tiempo , Adulto Joven
16.
J Forensic Sci ; 65(3): 987-990, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31658383

RESUMEN

We report a fatal case of airway obstruction caused by spontaneous retropharyngeal hematoma (RH) in the setting of treatment with dipyridamole. A 90-year-old woman presented with cervical swelling, neck and chest ecchymoses, and complaints of dyspnea. She suffered cardiopulmonary arrest in the ambulance, and her death was confirmed after transportation to the hospital. The major finding of postmortem computed tomography (PMCT) prior to autopsy was widening of the prevertebral soft tissue. The results of the autopsy indicated that the cause of death was mechanical asphyxia, secondary to pharyngeal and laryngeal compression caused by the RH. There were no evident injuries, medical interventions, or particular diseases, suggesting the spontaneous cause of the RH. To the best of our knowledge, this is the first report of a fatal case secondary to spontaneous RH that was revealed through PMCT imaging.


Asunto(s)
Obstrucción de las Vías Aéreas/etiología , Dipiridamol/efectos adversos , Hematoma/patología , Inhibidores de Agregación Plaquetaria/efectos adversos , Espacio Retroperitoneal/patología , Anciano de 80 o más Años , Obstrucción de las Vías Aéreas/patología , Disnea/etiología , Equimosis/patología , Femenino , Paro Cardíaco/etiología , Humanos , Tomografía Computarizada por Rayos X
18.
Sci Rep ; 9(1): 18439, 2019 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-31804544

RESUMEN

This study investigates a comprehensive model of bone regeneration capacity of dypiridamole-loaded 3D-printed bioceramic (DIPY-3DPBC) scaffolds composed of 100% beta-tricalcium phosphate (ß -TCP) in an immature rabbit model through the time of facial maturity. The efficacy of this construct was compared to autologous bone graft, the clinical standard of care in pediatric craniofacial reconstruction, with attention paid to volume of regenerated bone by 3D reconstruction, histologic and mechanical properties of regenerated bone, and long-term safety regarding potential craniofacial growth restriction. Additionally, long-term degradation of scaffold constructs was evaluated. At 24 weeks in vivo, DIPY-3DPBC scaffolds demonstrated volumetrically significant osteogenic regeneration of calvarial and alveolar defects comparable to autogenous bone graft with favorable biodegradation of the bioactive ceramic component in vivo. Characterization of regenerated bone reveals osteogenesis of organized, vascularized bone with histologic and mechanical characteristics comparable to native bone. Radiographic and histologic analyses were consistent with patent craniofacial sutures. Lastly, through application of 3D morphometric facial surface analysis, our results support that DIPY-3DPBC scaffolds do not cause premature closure of sutures and preserve normal craniofacial growth. Based on this novel evaluation model, this DIPY-3DPBC scaffold strategy is a promising candidate as a safe, efficacious pediatric bone tissue engineering strategy.


Asunto(s)
Regeneración Ósea/efectos de los fármacos , Dipiridamol/administración & dosificación , Regeneración Tisular Dirigida/métodos , Cráneo/lesiones , Andamios del Tejido/química , Animales , Bioimpresión/métodos , Fosfatos de Calcio/efectos adversos , Fosfatos de Calcio/química , Cerámica/efectos adversos , Cerámica/química , Niño , Desarrollo Infantil/efectos de los fármacos , Dipiridamol/efectos adversos , Modelos Animales de Enfermedad , Humanos , Desarrollo Maxilofacial/efectos de los fármacos , Modelos Animales , Impresión Tridimensional , Conejos , Cráneo/efectos de los fármacos , Cráneo/crecimiento & desarrollo , Ingeniería de Tejidos/métodos , Andamios del Tejido/efectos adversos
19.
G Ital Cardiol (Rome) ; 20(9): 529-532, 2019 Sep.
Artículo en Italiano | MEDLINE | ID: mdl-31530954

RESUMEN

Takotsubo syndrome is a transient form of left ventricular dysfunction, more common in postmenopausal women, which involves left ventricular mid-apical akinesis and mimics acute coronary syndrome. It is characterized by left ventricular apical ballooning without significant coronary artery stenosis on coronary angiography. The basic mechanisms of Takotsubo cardiomyopathy are still unclear. There is some evidence that emotional, physical or pharmacological stress associated with increased catecholamine levels, coronary spasm, dynamic left ventricular obstruction, or coronary microvascular dysfunction might be involved. We describe the case of an 81-year-old woman who developed a Takotsubo syndrome only 3 h after pharmacological stress echocardiography with dipyridamole. To our knowledge, this is the first case reported in the literature in such context.


Asunto(s)
Dipiridamol/efectos adversos , Ecocardiografía de Estrés , Cardiomiopatía de Takotsubo/inducido químicamente , Vasodilatadores/efectos adversos , Anciano de 80 o más Años , Femenino , Humanos
20.
Sci Rep ; 9(1): 12443, 2019 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-31455862

RESUMEN

The role of vasodilator myocardial perfusion imaging (MPI) for aortic stenosis (AS) is controversial due to safety and accuracy concerns. In addition, its utility after aortic valve (AV) interventions remains unclear. Patients with AS who underwent thallium-201-gated dipyridamole MPI using a cadmium-zinc-telluride camera were retrospectively reviewed and divided into three groups: mild AS, moderate-to-severe AS, and prior AV interventions. Patients with coronary artery disease with ≥50% stenosis, severe arrhythmia, left ventricular ejection fraction (LVEF) <40%, left bundle branch block or no follow-up were excluded. Relationships between the severity of AS, clinical characteristics, hemodynamic response, serious adverse events (SAE) and MPI parameters were analyzed. None of the 47 patients had SAE, including significant hypotension or LVEF reduction. The moderate-to-severe AS group had higher summed stress scores (SSSs) and depressed LVEF than the mild AS group, however there were no differences after AV interventions. SSS was positively correlated with AV mean pressure gradient, post-stress lung-heart ratio (LHRs), and post-stress end-diastolic volume (EDVs) (P < 0.05). In multivariate analysis, LHRs and EDVs were independent contributors to SSS. Dipyridamole-induced ischemia and LV dysfunction is common, and dipyridamole stress could be a safe diagnostic tool in evaluation and follow-up in patients with AS.


Asunto(s)
Estenosis de la Válvula Aórtica , Dipiridamol/administración & dosificación , Electrocardiografía , Imagen de Perfusión Miocárdica , Función Ventricular Izquierda , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/tratamiento farmacológico , Estenosis de la Válvula Aórtica/fisiopatología , Dipiridamol/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
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