OBJECTIVE:
To describe the pharmacology, pharmacokinetics, efficacy, and safety of a fixed-dose combination of aspirin and extended-release (ER) dipyridamole indicated for the secondary prevention of ...stroke.
DATA SOURCES:
Published articles and abstracts were identified from a MEDLINE search (1966–December 1999) using the search terms dipyridamole, aspirin, antiplatelet, antiaggregation, and stroke prevention. Pertinent articles written in English were considered for review. Additional articles were identified from the references of retrieved literature.
STUDY SELECTION AND DATA EXTRACTION:
Studies including a combination of aspirin/dipyridamole in human subjects were evaluated. Emphasis was placed on randomized, controlled trials.
DATA SYNTHESIS:
Aspirin is a platelet inhibitor that works by inhibiting platelet cyclooxygenase, which reduces the production of thromboxane A2. Dipyridamole is a platelet inhibitor that is thought to work in part by inhibiting platelet cyclic-3',5'-adenosine monophosphate and cyclic-3',5'-guanosine monophosphate phosphodiesterase. The active metabolite of aspirin, salicylic acid, is highly bound to plasma protein and has a plasma half-life of two to three hours. Dipyridamole is also highly bound to plasma proteins, and the ER formulation has a plasma half-life of 13 hours. The first European Stroke Prevention Study (ESPS-1) found the combination of aspirin/dipyridamole to be superior to placebo in the prevention of stroke and transient ischemic attack (TIA). The ESPS-1, however, did not include an aspirin-only treatment arm. Therefore, it was unclear whether the combination of aspirin/dipyridamole was superior to aspirin alone. As a result, a second trial was conducted that included treatment arms of aspirin alone, ER dipyridamole alone, combination therapy, and placebo. The combination of aspirin 25 mg plus ER dipyridamole 200 mg twice daily was shown in the ESPS-2 to be significantly better than either agent given individually in preventing stroke and TIAs (p < 0.001).
CONCLUSIONS:
The American College of Chest Physicians (ACCP) recommends aspirin 50–325 mg/d to be the initial antiplatelet of choice for the prevention of atherothrombotic cerebral ischemic events. However, with the favorable results of the ESPS-2, it may be appropriate to substitute aspirin/ER dipyridamole for aspirin alone as the drug of choice. This combination appears to have a favorable adverse effect profile. The relative effectiveness of aspirin/ER dipyridamole compared with clopidogrel and ticlopidine has yet to be determined. If alternative antiplatelet therapy is needed, the ACCP recommends clopidogrel rather than ticlopidine because of its lower incidence of adverse effects. The ACCP further states that the combination of aspirin plus dipyridamole may be more effective than clopidogrel; these agents have a similarly favorable adverse effect profile.
Severe renal artery stenosis may cause renovascular hypertension; in case of bilateral narrowing or in a stenotic solitary kidney, renal insufficiency (ischemic kidney disease) or rarely pulmonary ...flush edema may occur. Renal artery stenosis may be treated by revascularization, using either percutaneous (balloon angioplasty, stenting) or less common open surgical procedures, both with excellent primary patency rates. However, randomized trials of renal artery angioplasty or stenting have failed to demonstrate a longer-term benefit with regard to blood pressure control and renal function over medical management alone (except for fibromuscular disease). Furthermore, endovascular procedures are associated with substantial risks. It has not yet been demonstrated that renal revascularization leads to a prolongation of event-free survival. Careful patient selection is essential to maximize the potential benefit.
Dofetilide is a new antiarrhythmic agent recently approved for conversion and maintenance of sinus rhythm in patients with atrial fibrillation (AF) and atrial flutter (AFl). It is a class III ...antiarrhythmic that works by selectively blocking the rapid component of the delayed rectifier outward potassium current. Dofetilide prolongs the effective refractory period in accessory pathways, both anterograde and retrograde. This can be seen on the electrocardiogram through a dose‐dependent prolongation of the QT and QTc intervals, with parallel increases in ventricular refractoriness. Approximately 80% of drug is excreted in urine, so dosing must be based on creatinine clearance. The elimination half‐life is approximately 10 hours. In clinical trials dofetilide was superior to flecainide in converting patients with AFl to normal sinus rhythm (NSR; 70% vs 9%, p<0.01). It also was more effective than sotalol in converting patients with both AF and AFl to NSR (29% vs 6%, p<0.05) and maintaining them in NSR for up to 1 year. Most patients converted within 24–36 hours. Dofetilide has a favorable risk:benefit profile. Torsades de pointes is the most serious side effect; it occurs in 0.3–10.5% of patients and is dose related. To minimize the risk of induced arrhythmia, patients who start or restart the drug should be hospitalized a minimum of 3 days for creatinine clearance measurements, continuous electrocardiographic monitoring, and cardiac resuscitation, if necessary.
Purpose: We evaluated the dose‐related impacts of tiagabine (TGB) on cognition and mood in a monotherapy study.
Methods: Patients were 123 adults with uncontrolled partial seizures, each treated with ...a single currently available antiepileptic drug (AED) for management of clinical epilepsy. They completed a battery of neuropsychological tests during an 8 week prospective baseline period and once again at the end of the 12‐week fixed‐dose period (or earlier if they dropped out of the study). Sixty‐six patients were randomized to 6 mg/day TGB and 57 were randomized to 36 mg/day TGB.
Results: Few changes in either abilities or adjustment and mood were noted when all patients were considered as a single group. However, analysis of both dose and attainment of TGB monotherapy showed that patients receiving TGB monotherapy did best, improving particularly in the areas of adjustment and mood with low‐dose TGB and in the area of abilities with high‐dose TGB. Patients who did not attain monotherapy showed no change except that the high‐dose group did not perform as well on measures of mood and adjustment. Baseline AED and changes in seizure control did not affect the results.
Conclusions: Patients attainment of TGB monotherapy was associated with their achievement of positive changes of varying degree on psychological tests. Failure to attain TGB monotherapy was associated with no changes on the tests except in patients receiving high‐dose TGB where it appeared that some alterations in mood might have been avoided if a slower titration schedule had been used.
The effects of tiagabine (TGB) on abilities and on adjustment and mood are as yet incompletely understood. These effects were compared with those of phenytoin (PHT) and carbamazepine (CBZ) in an ...add-on study. Patients included in the analysis were adults with uncontrolled partial seizures who at study entry were on CBZ alone (
n=153) or on PHT alone (
n=124). Of the patients receiving CBZ, 82 were randomized to add-on TGB and 71 were randomized to add-on PHT during the double-blind period. Of the patients receiving PHT, 58 were randomized to add-on TGB and 66 were randomized to add-on CBZ. Eight tests of mental abilities and three of mood and adjustment were given prior to assignment of add-on treatment and after up to 16 weeks of add-on treatment. For the baseline CBZ group, analyses were done to search for differential changes from baseline in the test scores of the add-on TGB and add-on PHT groups, and for the baseline PHT group in the add-on TGB and add-on CBZ groups. In the baseline CBZ group, no differences in test scores were found between PHT and TGB. In the baseline PHT group for the area of abilities, patients treated with TGB had improved verbal fluency, as well as quicker responses on a test of perceptual/motor speed compared with patients treated with CBZ. For the baseline PHT group in the area of adjustment and mood, patients treated with TGB reported less positive mood and more financial concerns compared to patients treated with CBZ. Overall, add-on TGB showed few or no differences in comparison with add-on CBZ and add-on PHT.
We study the process e^{+}e^{-}→Λ_{c}^{+}Λover ¯_{c}^{-} at twelve center-of-mass energies from 4.6119 to 4.9509 GeV using data samples collected by the BESIII detector at the BEPCII collider. The ...Born cross sections and effective form factors (|G_{eff}|) are determined with unprecedented precision after combining the single and double-tag methods based on the decay process Λ_{c}^{+}→pK^{-}π^{+}. Flat cross sections around 4.63 GeV are obtained and no indication of the resonant structure Y(4630), as reported by Belle, is found. In addition, no oscillatory behavior is discerned in the |G_{eff}| energy dependence of Λ_{c}^{+}, in contrast to what is seen for the proton and neutron cases. Analyzing the cross section together with the polar-angle distribution of the Λ_{c}^{+} baryon at each energy point, the moduli of electric and magnetic form factors (|G_{E}| and |G_{M}|) are extracted and separated. For the first time, the energy dependence of the form factor ratio |G_{E}/G_{M}| is observed, which can be well described by an oscillatory function.
Hypertension is a common concomitant condition in renal transplant recipients. There is accumulating evidence that this disorder is an important risk factor for chronic renal graft failure and other ...cardiovascular complications in these patients.
The current retrospective study in 330 patients treated with cyclosporin or azathioprin covered 5 years and aimed to further characterize the interrelation between hypertension and renal graft failure. Furthermore, the association of hypertension with hyperlipidemia and the prevalence of coronary heart disease was evaluated.
Altogether, before transplantation 182 patients were normotensive (no antihypertensive medication except diuretics) and 105 were hypertensive (blood pressure > 160/95 mmHg or patients requiring antihypertensive medication); for the remaining 43 patients no data were available. After transplantation the prevalence of hypertension in the cyclosporin group was 71, 76 and 70% after 1, 3 and 5 years, respectively. The respective numbers for the azathioprin group were 60, 59 and 58%. Hypertension was associated with graft dysfunction both in cyclosporin- and azathioprin-treated patients. Hyperlipidemia (cholesterol, triglycerides) was more severe in hypertensive than in normotensive patients. The prevalence for hypertension was higher in patients with coronary artery disease than in patients without the disease.
The results further support the view that hypertension may be a risk factor for the development of chronic renal graft failure and coronary artery disease in this population. Furthermore, the association of hypertension with hyperlipidemia hints to an unfavorable accumulation of renal and cardiovascular risk factors in a large number of renal allograft recipients.
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