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A controlled clinical trial included 64 pregnant females suffering from chronic glomerulonephritis (CGN) and hypertension: 31 patients received acetylsalicylic acid (ASA) in a dose 125 mg/day and curantyl (150-225 mg/day) from gestation week 12-19 till delivery, 33 control females were not given the drugs. Prenatal care and labour management were similar. Total number of the complications (fetal and natal deaths, preterm labour, intrauterine fetal retardation, late toxicosis, premature detachment of normally located placenta) as well as the number of pregnancies with complications were less in the test group. The same was true for the second pregnancies versus the first ones when ASA and curantyl were not given. It is suggested that low-dose ASA plus curantyl improve placental circulation eventually resulting in less frequent occurrence of pregnancy complications and in better pregnancy outcomes in CGN and hypertensive women.
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Because of the difficulty of permanent anticoagulation in our young population, Smeloff-Cutter ball valves have been used since 1986 at our institution for aortic valve replacement in selected patients without permanent anticoagulation therapy.
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Aspirin (acetylsalicylic acid) is the most widely studied and prescribed antiplatelet drug for patients at high risk of vascular disease. It affects a single pathway in the platelet activation process and provides incomplete protection against cardiovascular events. Adenosine diphosphate receptor antagonists, by blocking an alternate pathway of platelet activation, are slightly more effective than aspirin in reducing serious vascular events in patients at high risk, with similar results for the subset of transient ischaemic attack/ischaemic stroke patients. Clopidogrel is an effective and safe alternative in patients who do not tolerate aspirin, in diabetics, in hypercholesterolaemic patients, or in those with a previous history of cardiac surgery. Moreover, antiplatelet combination therapy using agents with different mechanisms of action is an attractive preventive approach. In this way, dipyridamole combined with aspirin is being tested in the European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) in cerebrovascular disease patients. Clinical and preclinical studies have demonstrated that therapy with clopidogrel and aspirin provides synergistic antiplatelet effects. The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) and PCI-CURE trials demonstrate the benefit of this combination therapy in patients who suffer from unstable angina or non-Q-wave myocardial infarction treated or not by percutaneous coronary intervention. The relative risk reduction in ischaemic events in long-term use was 20%. This antiplatelet regimen was safe and well tolerated. Currently, this therapeutic option is tested in individuals with ischaemic stroke in the Management of Atherothrombosis with Clopidogrel in High-Risk Patients with Recent Transient Ischaemic Attacks or Ischaemic Stroke (MATCH) Trial.
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To investigate whether anticoagulation or platelet inhibition treatment provides better prevention of reobstruction after percutaneous transluminal angioplasty (PTA).
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Terminal circulation can be studied in vivo using capillaroscopy. This paper presents the results of systematic investigations of capillary permeability (KPU) in the nailfold. In addition to the morphology of capillary loops, we investigated the transcapillary passage and interstitial distribution of sodium fluorescein (Na-flu) in healthy persons (42) and in patients suffering from functional microangiopathies (17) or organic vascular disease (58). The effects of various therapeutic measures on the microcirculation were also studied. First, dynamic processes at the capillary loops were recorded on a video system. The second step consisted of quantification of the pericapillary light intensities (FLI) at predetermined times using a computerized video-densitometer. The measured variables, i.e. maximal interstitial FLI, diameter of the juxtacapillary halo (IK-H) and distance between the intracapillary column of red cells and the interstitial peak of FLI, provided information about the permeability of the capillaries and the interstitial diffusion of Na-flu. In healthy subjects, the interstitial FLI reached its highest values 10 sec after the appearance of Na-flu in the capillary loop, the distance between the peak of FLI and the intracapillary column of erythrocytes increased continuously over a period of 2 min, whereas the diameter of the IK-H reached a constant value after 20 sec. In patients suffering from functional microangiopathy, an increased pericapillary FLI as well as an enlarged juxtacapillary zone with elevated Na-flu concentrations could be established as objective criteria in addition to the already known alterations of the morphology of the capillary loops. Similar observations, but of much greater extent, were made in patients suffering from microvessels disease associated with collagen disease. The regional variation in the pericapillary FLI supports the assumption that morphological changes are present in these patients. KPU in patients suffering from organic macroangiopathy revealed no changes in comparison to healthy persons. The effects of conventional therapy in patients with reduced peripheral arterial perfusion on the parameters measured by KPU were of variable magnitude. The increase in trans-capillary leakage and interstitial dispersion of Na-flu was significant during systemic fibrinolysis and during the intra-arterial application of PGE1. The changes in the measured parameters were considerably smaller during therapy with phenprocoumarol and heparin, whereas treatment with inhibitors of platelet aggregation left the results of KPU unchanged.(ABSTRACT TRUNCATED AT 400 WORDS)
The CardioWest temporary total artificial heart serves as a viable bridge to orthotopic heart transplantation in patients who are experiencing end-stage refractory biventricular heart failure. This device is associated with a low, albeit still substantial, risk of thrombosis. Platelet interactions with artificial surfaces are complex and result in continuous activation of contact proteins despite therapeutic anticoagulation. We searched the medical literature (publication dates, January 1962-October 2009) in order to evaluate means of mitigating adverse events that have occurred after implantation of the CardioWest temporary total artificial heart.We conclude that the use of a multitargeted antithrombotic approach, involving anticoagulation (bivalirudin and warfarin) and antiplatelet therapy (dipyridamole and aspirin), can mitigate the procoagulative effects of mechanical circulatory assist devices, particularly those that are associated with the CardioWest temporary total artificial heart. Careful monitoring with use of a variant multisystem approach, involving efficacy tests (thrombelastography and light transmittance aggregometry), safety tests (laboratory analyses), and warfarin genomics, may maximize the therapeutic actions and minimize the bleeding risks that are associated with the multitargeted antithrombotic approach. The development and monitoring of individualized antithrombotic regimens require that informed health professionals appreciate the complexities and grasp the hazards that are associated with these therapies.
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Effects of low-dose acetylsalicylic acid (ASA, 50 mg/day), dipyridamole (sustained-release preparation 400 mg/day), and their combination were investigated in a model of human platelet-vessel wall interaction. In a randomized, double-blind clinical pharmacology trial in 96 healthy subjects, the inhibition of mural platelet thrombus was measured ex vivo using blood samples collected both before and 2 hours after a 3.5-day treatment with ASA, dipyridamole, ASA combined with dipyridamole, or placebo. Both the size and the number of platelet thrombi adherent to a thrombogenic matrix after a 15-minute flow experiment were identified by automated fluorescence microscopy. ASA treatment alone reduced the mean size of all thrombi by about 45%, and dipyridamole alone achieved an approximate 17% reduction in the mean size of all thrombi. The combination of both agents had an additive effect. Formation of the subpopulation of very large thrombi was reduced by ASA and dipyridamole to a similar extent, with their combination producing an effect at least twice as strong as that witnessed in a single treatment. These results suggest that ASA and dipyridamole affect platelet thrombus growth by different mechanisms of action. These findings provide the pharmacologic rationale for the combination of ASA (suppressing the synthesis of prothrombotic thromboxane A2) and dipyridamole (by feedback inhibition of platelet activation via local accumulation of adenosine) as a highly effective and safe combination for secondary prevention of stroke. They are consistent with the clinical findings of the Second European Stroke Prevention Study (ESPS-2). In this large trial, the addition of dipyridamole (400 mg/day in a sustained-release preparation) to aspirin (50 mg/day) doubled the efficacy of aspirin in the secondary prevention of stroke without increasing the risk for bleeding.
Anticoagulants and prescription antiplatelet (ACAP) agents widely used by older adults have the potential to adversely affect traumatic brain injury (TBI) outcomes. We hypothesized that TBI patients on preinjury ACAP agents would have worse outcomes than non-ACAP patients.
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In this study, 591 patients with recent cerebral ischemia of arterial origin were randomly allocated to treatment with aspirin 30 to 325 mg/d or with the combination of aspirin and dipyridamole 400 mg/d in the European/Australian Stroke Prevention in Reversible Ischemia Trial. In an on-treatment analysis, the change in blood pressure measurements from baseline to values after at least 6 months of follow up was assessed with linear regression analysis.
The burden of atherosclerosis is particularly high in western countries in terms of mortality and disability. The cerebral arteries (stroke or transient ischemic attack [TIA]), coronary arteries (myocardial infarction [MI]) and peripheral arteries (intermittent claudication [IC], ischemic limb) can be affected. Atherosclerosis may involve different mechanisms such as inflammation, platelet activation, endothelial damage, balance between proliferation and apoptosis of smooth muscle cells and oxidative stress. Research is focused to counteract each of these aspects. Many antithrombotic drugs are currently available and most of them act as inhibitors of platelet function. Aspirin, ticlopidine, clopidogrel and the combination of aspirin plus dipyridamole are widely used for primary (in high-risk patients) and secondary prevention of atherosclerotic diseases. Research of new pharmacological strategies is driven by the need to reduce the risk of bleeding associated with the use of antiplatelet drugs. In this context cilostazol, a type III phosphodiesterase inhibitor, has demonstrated antiplatelet and vasodilator effects with low rate of bleeding complications. This review will focus on the pharmacological properties of cilostazol and its use in the management of atherothrombotic vascular diseases.
ASA reduces the RR after TIA/stroke by approximately 13 % and has the same efficacy with less side effects in lower dosages (50 - 325 mg/Tag). Ticlopidine is a reserve drug due to its unfavorable side effect profile (neutropenia, TTP). Clopidogrel is better than ASA (RRR 8.7 %) for vascular patients in preventing another vascular event (stroke, MI, vascular death). This effect is pronounced in patients at high risk for atherothrombotic events such as previous MI, cardiac surgery, or diabetes. Dipyridamole+ASA is better than ASA in patients with TIA/stroke (in indirect comparison also than Clopidogrel) for the secondary prevention of recurrent stroke (RRR 23 %), but not for the prevention of other vascular events. Therefore, Clopidogrel should be primarily given to patients with a high vascular risk (one or more cardiovascular risk factors) or to patients with ASA intolerance. Dipyridamole/ASA should be primarily given to TIA/stroke patients with a lower cardiovascular comorbidity. Studies for the combination of Clopidogrel/ASA (MATCH, CHARISMA) and for the comparison of both combinations (PRoFESS) are underway. At present, the combination of clopidogrel and ASA for cerebrovascular prevention should only be given within controlled studies or as an individual treatment with an accordingly acquired informed consent.
Drugs used for improvement or stabilization of peripheral circulation include antiaggregants or anticoagulants for secondary prevention of arteriosclerosis, vasoactive substances and fibrinolytic agents. -Two prospective trials document that aspirin or the combination of aspirin and dipyridamole reduce progression of arterial occlusive disease significantly in comparison to placebo. Aspirin is best suited for secondary prevention of recurrent stenoses or occlusions after carotid or femoral endarterectomy, whereas anticoagulants are preferred in patients with embolism and after peripheral implantation of venous bypasses. -Significant improvement of walking distance is achieved by several compounds influencing blood rheology. The effect does not exceed that obtained by physical training. If reconstructive arterial surgery or percutaneous transluminal angioplasty are not possible, some patients with rest pain or gangrene may be successfully treated by intraarterial administration of prostaglandin E1.
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A sensitive, rapid and simple high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) method for simultaneous determination of dipyridamole and salicylic acid in human plasma has been developed and validated. After the addition of diazepam and rosiglitazone as internal standard (IS), plasma samples were prepared by liquid-liquid extraction followed by an isocratic elution with methanol:2 mM ammonium acetate buffer (pH 4.25; 70/30, v/v) on a Shimadzu VP-ODS C(18) column (5 microm, 150 x 2.0 mm I.D.). Detection was performed on a quadrupole mass spectrometer with ESI interface operating in the positive-ion mode for dipyridamole and negative-ion mode for salicylic acid. Calibration curves were linear (r(2) > 0.99) over the concentration range 10-2500 ng/mL for dipyridamole and 30-4000 ng/mL for salicylic acid with acceptable accuracy and precision, respectively. The intra- and inter-batch precisions were less than 15% of the relative standard deviation. The limits of detection of dipyridamole and salicylic acid were 1 and 15 ng/mL, respectively. The validated HPLC-ESI-MS method was successfully applied to a preliminary pharmacokinetic study of fixed-dose combination of sustained-release dipyridamole/aspirin in Chinese healthy male volunteers.
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After adjustment, use of warfarin (odds ratio [OR], 1.26; 95% CI, 1.11 to 1.43) and combination therapy (OR, 1.34; 95% CI, 0.99 to 1.82) were associated with an increased risk of hospitalization for a bleed compared with nonusers. The odds of aspirin use was greater among cases than controls (OR, 1.07; 95% CI, 0.96 to 1.18) after adjustment.
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There is a theoretical possibility that the negative interaction between ACE inhibitors and aspirin may reduce the beneficial effects of ACE inhibitors in patients with heart failure, but the information obtained from the existing databases is limited by the retrospective nature of the analyses and does not establish the association definitively. Double-blind randomized controlled trials should be conducted to determine whether such a negative interaction indeed exists.
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to assess whether the risk of recurrent ischaemic stroke in patients with symptomatic internal carotid artery (ICA) occlusion has changed over the past decades, to determine risk factors for the occurrence of ischaemic stroke and to assess the risk of endarterectomy (CEA) of a severe contralateral ICA stenosis.
Historically, studies of antithrombotic therapy in ischemic cerebrovascular disease have included both stroke and transient ischemic attack (TIA). Thus, therapy regimes are very similar. Aspirin (75-325 mg within 48 h after onset of symptoms) is still the standard antithrombotic treatment because other agents have performed similarly (or worse). Combinations of agents have shown mixed results. Aspirin combined with clopidogrel has failed to show a significant reduction of stroke/TIA recurrences but increased the bleeding risk if taken for more than several months. The combination of aspirin and dipyridamole is slightly better than aspirin alone and in particular reduced nonfatal stroke/TIA - hence it is recommended as an alternative and may be used in patients with recurrent events while on regular aspirin. In contrast, combined treatment is regularly recommended after endovascular interventions and if both cardio- and cerebrovascular diseases are present. Warfarin and similar compounds have long been the standard treatment for most patients with permanent, paroxysmal or intermittent non-valvular atrial fibrillation, for which there is excellent evidence in most patients (CHADS-VASc score >1). New compounds have been approved in recent years and shown to reduce either ischemic events, intracranial bleeding complications or both when compared with warfarin. None of them requires regular therapy monitoring. Because there are no head-to-head comparisons of these newer agents, definite recommendations as to which to choose, and when, are hard to make. However, there are some notable differences as well as new approved entities.
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A repeated cross-sectional analysis was conducted on pharmaceutical dispensing data for all individuals' ≥ 65 years. Variable medication possession ratio (VMPR) was used to measure adherence. Prescribing of low-dose aspirin, clopidogrel, dipyridamole, warfarin, dabigatran, statins and bisphosphonates with a VMPR≥0.8 were examined.
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Network meta-analysis can provide estimates of treatment efficacy of multiple treatment regimens, even when direct comparisons are unavailable. We used network meta-analysis to compare commonly used antiplatelet regimens in the prevention of serious vascular events after transient ischaemic attack (TIA) or stroke. We performed direct meta-analyses of randomized, controlled trials evaluating antiplatelet agents after TIA or stroke. We chose the endpoint stroke, myocardial infarction, and vascular death. Network meta-analysis was then used to estimate the relative efficacy of the various antiplatelet regimens. Twenty-four trials involving 42688 TIA or stroke patients who suffered 6830 serious vascular events were included. In the network meta-analysis, all antiplatelet regimens (aspirin, aspirin plus dipyridamole, thienopyridines, and combination of aspirin and thienopyridines) were significantly more effective than placebo. The combination of aspirin and dipyridamole was more effective than thienopyridines (OR, 0.84; 95% CI, 0.73-0.97) and more effective than aspirin (OR, 0.78; 95% CI, 0.70-0.87). Our analysis suggests that the most powerful antiplatelet regimen in the prevention of serious vascular events after TIA or stroke is the combination of aspirin and dipyridamole. Network meta-analysis could be used to synthesize accumulating evidence from clinical trials in a broad range of vascular disorders.
Pretreatment of blood with dipyridamole resulted in 22-26% diminished expression of intact PAR-1 receptor (p=0.021 and p=0.024) and 28-31% decrease of annexin V binding (p=0.031 and p=0.02) after incubation with 2 microg/ml and 4 microg/ml of dipyridamole, respectively. Platelet aggregation and thrombin generation markers were not affected in vitro by dipyridamole.
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To explore the effect of Dan Shao Tang (DST) in treating simple hematuria of masked nephritis of deficiency of Yin with damp-heat symptom.
Combination therapy with dipyridamole and aspirin reduces not only the risk of cerebrovascular ischemic events but also the risk of myocardial infarction.
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On the VerifyNow, HTPR on aspirin was identified in 4 of 51 patients (8%) on aspirin-dipyridamole combination therapy (≥ 550 aspirin reaction units on the aspirin cartridge). Eleven of 25 (44%) patients had HTPR on clopidogrel (≥ 194 P2Y12 reaction units on the P2Y12 cartridge). On the PFA-100, 21 of 51 patients (41%) on aspirin-dipyridamole combination therapy had HTPR on the collagen-epinephrine (C-EPI) cartridge. Twenty-three of 25 patients (92%) on clopidogrel had HTPR on the collagen-adenosine diphosphate (C-ADP) cartridge. The proportion of patients with antiplatelet HTPR was lower on the VerifyNow than PFA-100 in patients on both regimens (P < .001).
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To evaluate whether dipyridamole concentrations achieved in the plasma of patients taking an extended-release formulation of the medication through a gastrostomy tube (G-tube) are therapeutic and similar to those achieved in the plasma of patients who receive the drug orally.
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The search identified 7 randomized, controlled trials that involved a total of 39,574 participants and reported recurrent stroke and ICH as outcome measures.
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The rapid decrease in the incidence of headaches over time implies that most patients quickly develop tolerance to dipyridamole-associated headaches. Appropriate information given to the patient when prescribing and dispensing dipyridamole/ASA may reduce early withdrawals from treatment and increase compliance.
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In acute ischemic stroke and transient ischemic attack (TIA), aspirin is recommended to all patients (except immediately following thrombolysis). Heparin and anticoagulant therapy using vitamin K antagonists should be avoided in the acute phase. Secondary preventive antithrombotic treatment includes anticoagulation in patients with cardioembolic stroke and antiplatelet agents aspirin possibly combined with dipyridamole or clopidogrel alone in patients with non-cardioembolic stroke. Other individual risks may modify this treatment regimen.
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Among 2,585 patients (mean age 40.3 +/- 13.5 years) living in a rural environment, 865 underwent aortic valve replacement (AVR), 1,231 mitral valve replacement (MVR) and 489 double valve replacement (DVR). All patients received 2.5 mg/day warfarin and a combination of antiaggregation therapy (dypridamole 3 x 75 mg/day plus aspirin 100 mg/day), irrespective of their prothrombin time and cardiac rhythm.