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PubMed2000

The antioxidant drug dipyridamole spares the vitamin E and thiols in red blood cells after oxidative stress.

OBJECTIVE: To test the antioxidant effect of therapeutic doses of dipyridamole on cellular membranes, human erythrocytes were chosen as an appropriate model to study oxidative stress induced by cumene hydroperoxide because of their high content in heme-Fe(2+). METHODS: The oxidative stress was induced by incubation with 160 micromoll(-1) cumene hydroperoxide and expressed by three main factors: lipid peroxidation by means of kinetics of decrease in fluorescence emission of the probe incorporated in the cell membranes, vitamin E oxidation and intracellular thiol content. The concentrations of dipyridamole tested (2-20 micromoll(-1)) did not exceed pharmacological doses. RESULTS: After 7 min of incubation at 25 degrees C with the oxidant and 20 micromoll(-1) dipyridamole thiol content was 50.1%+/-2.6 compared with 31.5%+/-2.4 in the absence of the drug. After 12 min vitamin E content was 88.3%+/-2.3 compared with 64.7%+/-3.4 of untreated cells in the absence of dipyridamole. Dipyridamole added 5 min after the oxidation reaction suppressed the fluorescence decrease for a time proportional to the drug concentration. CONCLUSIONS: Thus, at clinically realistic doses dipyridamole shows a concentration-dependent antioxidant effect. It protects membranes from oxidation and spares the antioxidant power of erythrocytes.

Antioxidants↗

PubMed1995

Effects of dipyridamole in combination with anticoagulant therapy on survival and thromboembolic events in patients with prosthetic heart valves. A meta-analysis of the randomized trials.

The addition of dipyridamole, an antiplatelet agent, to conventional anticoagulant regimens has been shown to reduce the frequency of embolization after valve replacement with a mechanical prosthesis. The purpose of this meta-analysis was to reevaluate the benefit of dipyridamole by analyzing the evidence from all randomized clinical trials. Summary data were extracted from the application to the Food and Drug Administration. Six randomized clinical trials had accrued 1141 patients, of whom 582 received anticoagulant therapy alone and 559 received additional dipyridamole at dosages ranging from 225 to 400 mg per day. The events analyzed were all thromboembolic events, both fatal and nonfatal; hemorrhagic events, both fatal and nonfatal; and the overall mortality. The combination of dipyridamole with anticoagulants reduced the risk of thromboembolic events (fatal or nonfatal) by 56% when compared with the use of anticoagulants alone (p = 0.0001). The risk reduction was seen in fatal and in nonfatal thromboembolic events (risk reduction for fatal events, 64%, p = 0.008; for nonfatal events, 50%, p = 0.005). The overall mortality rate was also significantly reduced by 40% in the group receiving dipyridamole (p = 0.013). There was no difference between treatment groups with respect to hemorrhagic events (risk reduction, -1%, p = 0.94). This meta-analysis supports the use of dipyridamole in this setting and warrants further trials with new antiplatelet agents.

Anticoagulants↗

PubMed2006

Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial.

BACKGROUND: Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of vascular events after ischaemic stroke of presumed arterial origin are inconsistent. Our aim was to resolve this uncertainty. METHODS: We did a randomised controlled trial in which we assigned patients to aspirin (30-325 mg daily) with (n=1363) or without (n=1376) dipyridamole (200 mg twice daily) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin. Our primary outcome event was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever happened first. Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with (NCT00161070). FINDINGS: Mean follow-up was 3.5 years (SD 2.0). Median aspirin dose was 75 mg in both treatment groups (range 30-325); extended-release dipyridamole was used by 83% (n=1131) of patients on the combination regimen. Primary outcome events arose in 173 (13%) patients on aspirin and dipyridamole and in 216 (16%) on aspirin alone (hazard ratio 0.80, 95% CI 0.66-0.98; absolute risk reduction 1.0% per year, 95% CI 0.1-1.8). Addition of the ESPRIT data to the meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or myocardial infarction of 0.82 (95% CI 0.74-0.91). Patients on aspirin and dipyridamole discontinued trial medication more often than those on aspirin alone (470 vs 184), mainly because of headache. INTERPRETATION: The ESPRIT results, combined with the results of previous trials, provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin.

Aged↗

PubMed1994

Low-molecular weight heparin versus aspirin and dipyridamole after femoropopliteal bypass grafting.

Low-molecular weight heparin has theoretical advantages over aspirin and dipyridamole in maintaining vascular-graft patency by virtue of its better antithrombotic effect and antiproliferative activity on vascular, smooth-muscle cells. We tested the hypothesis that low-molecular weight heparin would be more effective than aspirin and dipyridamole in maintaining graft patency in patients undergoing femoropopliteal bypass grafting. Patients were randomised to receive either a daily injection of 2500 IU low-molecular weight heparin, or 300 mg aspirin with 100 mg dipyridamole 8 hourly for 3 months. 94 patients were randomised to low-molecular weight heparin and 106 to aspirin and dipyridamole. Patients were stratified according to indication for surgery and were followed up for 1 year. Kaplan-Meier estimate of graft patency showed 87% graft survival on low-molecular-weight heparin and 72% on aspirin and dipyridamole at 6 months. At 12 months, the respective figures were 78% and 64%. Stratified survival analysis showed that this benefit was confined to those having salvage surgery (log rank test p = 0.0006); for those having surgery for claudication there was no significant benefit. No major bleeding events occurred in either group. We conclude that low-molecular weight heparin is better than aspirin and dipyridamole in maintaining femoropopliteal-graft patency in patients with critical limb ischaemia undergoing salvage surgery. This treatment should have considerable cost benefits.

Adult↗

PubMed1998

Plasma chemotactic activity during dipyridamole induced myocardial ischemia.

BACKGROUND: We have previously reported that transient myocardial ischemia induced during exercise or dipyridamole challenge leads to the release of increased amounts of hydrogen peroxide into circulating blood. It would indicate that the temporary functional changes within myocardial cells may constitute there a sterile inflammatory area. Therefore we decided to evaluate the chemotactic properties of plasma in patients undergoing dipyridamole provocative test, as a sign of released inflammatory mediators. The ischemia occurrence was evaluated with 99mTc-SestaMIBI followed by single photon emission computed tomography (SPECT). METHODS: Blood samples were obtained from the peripheral vein of 42 patients (18 men and 24 women, mean age 61 years). Plasma chemotactic activity was determined by the use of the Boyden chamber method: immediately before dipyridamole challenge (time 0), 7, and 30 min after drug infusion. The migration of control polymorphonuclear neutrophils towards evaluated plasma samples was estimated. RESULTS: Chemotaxis of control PMNs towards plasma isolated from patients without signs of myocardial ischemia 7 min after dipyridamole administration was significantly diminished in comparison with baseline values (p=0.003). Plasma obtained 7 min after dipyridamole infusion from patients manifesting signs of myocardial ischemia by SPECT attracted control PMNs significantly more intensively in comparison to plasma isolated at time 0 (p=0.0005). CONCLUSIONS: The obtained results indicate that transient myocardial ischemia induced by dipyridamole challenge leads to generation of chemotactic factors detectable in peripheral blood plasma.

Angina Pectoris↗

PubMed1988

High dose dipyridamole-echocardiography test in women: correlation with exercise-electrocardiography test and coronary arteriography.

The value of the exercise-electrocardiography test in detecting coronary artery disease in women is limited. Recently, the high dose dipyridamole-echocardiography test (two-dimensional echocardiographic monitoring during intravenous dipyridamole infusion, up to 0.84 mg/kg body weight over 10 min) was proposed as an alternative to exercise testing for the diagnosis of coronary artery disease. To establish the diagnostic usefulness of the exercise-electrocardiography and dipyridamole-echocardiography tests in this disease, the two tests were performed--on different days and in random order--in 83 consecutive women evaluated for a chest pain syndrome. All 83 women had taken no medications for greater than 48 h, and 15 had had a previous myocardial infarction. Positivity of the dipyridamole-echocardiography test was based on detection of a transient asynergy of contraction that was absent or of lesser degree at rest; the exercise-electrocardiography test (by upright cycloergometer) was considered positive when the ST segment was shifted greater than 0.1 mV 0.08 s after the J point. Coronary angiography showed significant coronary artery disease (greater than 70% luminal reduction of at least one major coronary vessel) in 39 women. No significant complications occurred in any patient during either test. Sensitivity and predictive value of a negative test were similar for the dipyridamole-echocardiography and the exercise-electrocardiography test (79 versus 72% and 84 versus 68%, respectively, whereas the dipyridamole-echocardiography test had greater specificity (93 versus 52%, p less than 0.001), accuracy (87 versus 62%, p less than 0.001) and a higher predictive value of a positive test (91 versus 57%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1998

Which variable of stenosis severity best describes the significance of an isolated left anterior descending coronary artery lesion? Correlation between quantitative coronary angiography, intracoronary Doppler measurements and high dose dipyridamole echocardiography.

OBJECTIVES: This study sought to investigate the angiographic or intracoronary Doppler variables of stenosis severity that best correlate with the results of dipyridamole echocardiography. BACKGROUND: Quantitative coronary angiography and intracoronary Doppler flow velocity assessments are the commonly used techniques for the objective identification of significant coronary artery stenosis. METHODS: Thirty patients with an isolated lesion of the left anterior descending coronary artery (LAD) were studied by means of on-line quantitative coronary arteriography, intracoronary Doppler flow velocity measurements and dipyridamole echocardiography 6 months after percutaneous transluminal coronary angioplasty. The quantitative arteriographic analyses were performed on-line; post-stenotic Doppler flow velocities were measured at baseline and after adenosine infusion. Angiographic and Doppler measurements were compared with the corresponding dipyridamole echocardiographic data and analyzed by discriminant analysis. RESULTS: The dipyridamole echocardiographic response was positive in 11 patients (37%). The best cutoff values for predicting an abnormal echocardiographic response were 1) stenotic flow reserve of 2.8 (p = 0.0001); 2) 59% diameter stenosis (p = 0.0001); 3) minimal lumen diameter of 1.35 mm (p = 0.001); 4) coronary flow reserve of 2.0 (p = 0.0002); and 5) maximal peak velocity of 60 cm/s during hyperemia (p = 0.04). Multivariate analysis identified stenotic flow reserve as the only independent predictor of ischemia during dipyridamole echocardiography. CONCLUSIONS: Stenotic flow reserve is the variable that best describes the functional significance of an isolated LAD lesion, and a value of 2.8 is the best predictor of a positive dipyridamole echocardiographic response. Furthermore, angiographic variables of stenosis severity relate to echocardiographic test results better than intracoronary Doppler variables.

Adult↗

PubMed1998

Underestimation of extent and severity of coronary artery disease by dipyridamole stress thallium-201 single-photon emission computed tomographic myocardial perfusion imaging in patients taking antianginal drugs.

OBJECTIVES: This study evaluated the diagnostic value of dipyridamole plus low level treadmill exercise (dipyridamole stress) thallium-201 single-photon emission computed tomography (SPECT) in patients taking antianginal drugs. BACKGROUND: Dipyridamole stress is the major substitute for maximal exercise in patients referred for myocardial perfusion imaging. Although antianginal drugs are commonly suspended before exercise, dipyridamole stress is usually performed without discontinuing these drugs. METHODS: Twenty-six patients underwent two dipyridamole perfusion studies: the first without (SPECT-1) and the second with (SPECT-2) antianginal treatment. Twenty-one patients (81%) received calcium antagonists, 19 (73%) received nitrates, and 8 (31%) received beta-blockers. Eighteen of the patients underwent coronary angiography. Data are presented as the mean value +/- SD. RESULTS: Visual scoring yielded significantly larger and more severe reversible perfusion defects for SPECT-1 than for SPECT-2. Quantitative analysis showed larger perfusion defects on stress images of SPECT-1 in the left anterior descending coronary artery (LAD) (25 +/- 21% vs. 17 +/- 15%, p = 0.003), left circumflex coronary artery (LCx) (56 +/- 35% vs. 48 +/- 36%, p = 0.03) and right coronary artery (RCA) (36 +/- 27% vs. 25 +/- 24%, p = 0.008) territories. Individual vessel sensitivities in the LAD, LCx and RCA territories were 93%, 79% and 100% for SPECT-1 and 64%, 50% and 70% for SPECT-2, respectively. These differences were highly significant for the LAD (p = 0.004) and LCx (p = 0.00004) territories. The overall individual vessel sensitivity of SPECT-1 was significantly higher than that of SPECT-2 (92% vs. 62%, p = 0.000003). Specificity was not significantly different in SPECT-1 compared with SPECT-2 (80% and 93%, p = 0.33). CONCLUSIONS: Continued use of antianginal drugs before dipyridamole plus low level treadmill exercise thallium-201 SPECT may reduce the extent and severity of myocardial perfusion defects, resulting in underestimation of coronary artery disease.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Dipyridamole echocardiography in the detection of vulnerable myocardium in the early postinfarction period.

To evaluate the effect of dipyridamole on regional wall motion after myocardial infarction two-dimensional echocardiograms were obtained on 21 postinfarction patients immediately before and 7 to 10 minutes after the intravenous infusion of ddipyridamole (0.60 mg/kg). All patients underwent coronary angiography, and 20 patients underwent scintigraphy with dipyridamole thallium immediately subsequent to dipyridamole echocardiography. Dipyridamole augmented noninfarct zone regional wall motion in 20 of 31 regions supplied by nonstenotic coronary arteries. In contrast, only one of eight regions of noninfarct zone myocardium supplied by coronary arteries with greater than a 70% luminal diameter narrowing (vulnerable myocardium) was able to augment the regional wall motion subsequent to dipyridamole administration (p = 0.05). Dipyridamole echocardiography appears to be a safe and sensitive technique that may be useful in the detection of vulnerable myocardium in the early postinfarction period.

Adult↗

PubMed1993

Vasodilating effect of dipyridamole on rat endoneurial vessels: morphometric study.

Ischaemia plays an important role in the pathogenetic mechanism of various neuropathies. To study the possible vasodilating effects of dipyridamole on peripheral nerve vessels, morphometric analysis of endoneurial vessels was undertaken in rat sciatic and tibial nerves after chronic dipyridamole treatment. Each rat was injected with 4 mg/kg of dipyridamole intraperitoneally twice daily for 5 days/week and once daily during the weekend for a period of 6 weeks. The mean luminal area and perimeter of endoneurial vessels in the sciatic nerve were significantly greater in dipyridamole-treated animals than in controls. The total fascicular area and densities of endoneurial vessels were not significantly different between experimental and control groups. This study demonstrated that daily administration of dipyridamole over a 6 week period caused endoneurial vessels to dilate resulting in increased luminal area and perimeter. Dipyridamole might be a potent therapeutic agent for peripheral neuropathies attributed to nerve ischaemia.

Animals↗

PubMed2000

Standard versus low-level anticoagulation combined to low-dose dipyridamole after mitral valve replacement.

BACKGROUND: Although the addition of 300 mg dipyridamole to oral anticoagulants has been shown to decrease thromboembolic events after cardiac valve replacement, reports of combined therapy were few and some showed significant dipyridamole-related side effects and intolerance. The aim of this study was to compare the clinical effect of a standard monotherapy (targeting an international normalized ratio - INR - between 2.5 and 3.5) to a less intensive regimen (targeting an INR between 2 and 2.5) combined to a small dose of dipyridamole (225 mg/day). METHODS: Between January 1990 and December 1998, 486 young rheumatic patients with a St Jude mitral valve prosthesis were assigned to follow either standard monotherapy (294 patients) or low-level combined therapy (192 patients). Phenindione has been the anticoagulant of choice. Up to a maximum daily dose of 100mg, patients failing to achieve their target INR range were shifted to warfarin therapy. Prothrombin time was checked monthly and asymptomatic patients with a too low or a too high INR (<1.3 or >5) were briefly hospitalized for INR control. Complete blood picture, renal and hepatic profiles and full echocardiographic study were done biannually. RESULTS: With the exception of a significantly larger left atrium in patients on low-level combined therapy (P=0.001), both groups were comparable as regards to age and sex distribution, number of patients with atrial fibrillation, left atrial thrombus and history of stroke. Patients were monitored for 1712.6 pt yr and follow-up was 96.7% complete. No phenindione-related complications were observed (mean dose 62.3+/-21.4 mg), 20 patients (4.1%) had failed to achieve their target INR range and were switched to warfarin and only three patients (1.6%) had tolerable dipyridamole-related side effects. Compared to standard monotherapy, patients on low-level combined therapy showed significantly lower annualized rates: thromboembolism (1.6 vs 0.43%: risk reduction 71%; P=0.05), thromboembolism and hemorrhage (2.7 vs 0.7%: risk reduction 72%; P=0.005), death due to valve thrombosis or stroke (1.17 vs 0. 14%: risk reduction 81%; P=0.04) as well as both non-fatal (3.3 vs 1. 57%: risk reduction 51%; P=0.04) and total late postoperative complications (5.35 vs 3.14%: risk reduction 40%; P=0.04); respectively. However, total late mortality (32 patients; 1.8% per pt yr) was comparable among both groups. CONCLUSION: Low-level anticoagulation with phenindione combined to low dosage of dipyridamole was clinically more effective than the higher standard monotherapy. With respect to the prescribed doses, both drugs were well tolerated by almost all patients. Use of dipyridamole did not influence overall patients' survival.

Administration, Oral↗

PubMedDate not supplied

Inotropic stress with arbutamine is superior to vasodilator stress with dipyridamole for the detection of reversible ischemia with Tc-99m sestamibi single-photon emission computed tomography.

BACKGROUND: There is a paucity of data comparing the relative merits of inotropic and vasodilator stress Tc-99m sestamibi single-photon emission computed tomography (SPECT) for the detection of coronary artery disease and reversible ischemia. METHODS AND RESULTS: Twenty-seven patients referred for diagnostic coronary arteriography underwent separate day dipyridamole and arbutamine Tc-99m sestamibi SPECT imaging with simultaneous two-dimensional echocardiography. The sensitivity of arbutamine and dipyridamole Tc-99m sestamibi for the detection of coronary artery disease was 100% (21 of 21) and 90% (19 of 21), respectively, with a specificity of 66% (4 of 6) for both. Coronary artery disease was detected in all six patients with single vessel disease by both stress modalities. The sensitivity for prediction of multivessel disease was 66% (10 of 15) for arbutamine and 46% (7 of 15) for dipyridamole stress. Arbutamine stress induced a greater extent and severity of perfusion abnormality at peak stress (peak perfusion score 25 +/- 6.2 and 21 +/- 5.9 for arbutamine and dipyridamole, respectively, p = 0.001) and reversible perfusion defects (difference between peak stress and rest scores 8.8 +/- 5.5 and 5.2 +/- 4.4 for arbutamine and dipyridamole, respectively, p = 0.001). Furthermore a significantly higher percentage of reversible defects induced by arbutamine stress was associated with wall thickening abnormality on simultaneous echocardiography, which is a more specific marker of myocardial ischemia (88% and 24% for arbutamine and dipyridamole, respectively, p = 0.002). CONCLUSION: Inotropic stress may be superior to vasodilators for the determination of the extent and severity of myocardial involvement and reversible ischemia by Tc-99m sestamibi SPECT.

Cardiotonic Agents↗

PubMed1994

pH-related changes in the absorption of dipyridamole in the elderly.

The bioavailability of dipyridamole, a poorly soluble weak base, was evaluated in 11 healthy, older subjects (> or = 65 years), 6 with a low fasting gastric pH (control) and 5 with a fasting gastric pH > 5 (achlorhydric), in a randomized, crossover design. Subjects received 50 mg dipyridamole as a single oral dose both with and without pretreatment with 40 mg famotidine (control subjects) or 1360 mg glutamic acid HCl (achlorhydric subjects). Gastric pH was monitored by Heidelberg radiotelemetric capsule. Gastric emptying of 99mTc-radiolabeled orange juice was measured. Gastric pH appeared to be a primary determinant in dipyridamole absorption in the elderly. Elevated gastric pH resulted in compromised dipyridamole absorption compared to low-gastric pH conditions in all cases. The administration of glutamic acid hydrochloride to achlorhydric subjects prior to the dose of dipyridamole corrected for the decreased Cmax and AUC(0-36) exhibited in achlorhydric subjects without pretreatment. Tmax and ka were slower in achlorhydrics, although pretreatment with glutamic acid HCl tended to normalize these parameters. Based on these results, it would be beneficial for achlorhydrics to take glutamic acid hydrochloride prior to taking dipyridamole and other medications which need a low gastric pH for complete absorption. The administration of 40 mg famotidine was successful in elevating the gastric pH to > 5 in all subjects and maintained it at > 5 for at least 3 hr in all subjects tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Achlorhydria↗

PubMed2002

Efficacy of transdermal nitroglycerin patches evaluated by dipyridamole-induced myocardial ischemia in patients with coronary artery disease. Comparison between continuous and intermittent schedule.

Nitrate tolerance remains a problem despite an enormous number of studies on this phenomenon. The aim of the present study was to compare the efficacy of nitroglycerin transdermal patches intermittently or continuously administered to patients with myocardial ischemia evaluated by the echocardiography dipyridamole stress test. We prospectively studied 34 coronary patients with stable myocardial ischemia. A double-blind, randomized, crossover study technique was used. After a run-in period (1 week) they underwent a dipyridamole stress test to evaluate nitrate responsiveness and then were randomized to 1 week of transdermal nitroglycerine 20 mg/24 h (two patches of 10 mg/24) administered either intermittently or continuously for 1 week. During the following week all patients were given placebo. In the final week, therapy was crossed over the alternate regimen. No significant changes in heart rate, systolic and diastolic blood pressure and rate-pressure product were observed at basal conditions and at peak of dipyridamole infusion among patients after placebo run-in period, after acute, 1 week of intermittent and 1 week of continuous nitroglycerine administration. At peak of dipyridamole infusion after acute administration of nitrate we observed a significant decrease in wall motion score index with respect to placebo. This pattern was similar during intermittent, but not continuous, patch therapy (p < 0.001). Our results suggest that transdermal nitroglycerin patches are an effective anti-ischemic medication, in reducing transient myocardial ischemia induced by dipyridamole. This anti-ischemic effect is lost when an overnight nitrate free dose interval is not used. Moreover the dipyridamole echocardiographic stress test, besides evaluating myocardial ischemia-induced wall motion abnormalities, is adequate to assess both the efficacy and the tolerance of transdermal nitrate therapy.

Administration, Cutaneous↗

PubMed1987

Synergistic inhibitory effects of dipyridamole and vincristine on the growth of human leukaemia and lymphoma cell lines.

The effects of combinations of dipyridamole, an effective blocker of the salvage pathway of DNA synthesis, and 8 types of anti-cancer drugs on the growth of human T, B and myeloid leukaemia/lymphoma cell lines in vitro were examined. In combinations, dipyridamole and vincristine (VCR), and dipyridamole and vindesine had synergistic inhibitory effects. Dipyridamole reduced the efflux of VCR from cells and enhanced their VCR accumulation in a dose-dependent manner at concentrations of up to 10 microM in the lymphoid cell lines, MOLT-3 and BL-TH, and of up to at least 20 microM in the myeloid cell line, ML-1. Dipyridamole also enhanced the accumulation of VCR in PHA-stimulated and un-stimulated lymphocytes of normal donors, but efflux of VCR was more rapid from normal lymphocytes than from cultured cell lines. It is proposed that combination therapy with dipyridamole plus VCR should be effective in the treatment of leukaemia and lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1983

Effects of intravenous epoprostenol on platelets and the cardiovascular system are not potentiated by dipyridamole.

Normal subjects received infusions of epoprostenol (prostacyclin, PGI2) at doses of 2, 4, 6, and 8 ng/kg/min on each of two occasions after pretreatment with dipyridamole (400 mg/day for 3 days) or placebo. Baseline headache and bleeding time were increased and preejection period (PEP) shortened after dipyridamole. The baseline heart rate was increased on dipyridamole by an amount that correlated to the blood dipyridamole level. PGI2 infusion increased heart rate, systolic blood pressure (BP), pulse pressure, left ventricular ejection time index, and degree of flushing and severity of headache, and reduced diastolic BP, PEP, and T wave height. There was no apparent interaction between PGI2 and dipyridamole on these variables. PGI2 inhibited adenosine diphosphate-induced platelet aggregation and increased bleeding time. We conclude that, despite the synergism between dipyridamole and PGI2 that might be predicted and has been demonstrated in some animal experiments, no such interaction is apparent in normal humans after standard doses.

Adult↗

PubMed1998

Do we still need dipyridamole?

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.

Cardiovascular Diseases↗

PubMed1999

Rapid development of tolerance to dipyridamole-associated headaches.

AIMS: In the Second European Stroke Prevention Study headaches associated with dipyridamole frequently (8% of patients taking dipyridamole or dipyridamole plus acetylsalicylic acid (ASA) vs 2% of patients taking ASA or placebo) led to discontinuation of therapy. We have now used data from a recent trial comparing the bioequivalence of two formulations of the fixed combination of 200 mg dipyridamole in an extended release formulation and 25 mg ASA to explore predicting factors for headaches associated with this drug combination. METHODS: The bioequivalence trial employed a two-way crossover, randomised, open design. Trial medication was given for two periods of five days separated by a 72 h washout period. Statistical methods were employed to explore the prevalence, the time course, and the relation to individual pharmacokinetic parameters of treatment associated headaches. RESULTS: Headache episodes, being mostly mild and transient, rapidly declined from 67% of the volunteers on the first day of treatment to 3% on the final days of treatment (days 4-5 of the second period). During the first days the prevalence of the headaches peaked 2-3 h after the morning administration, which coincided with the peak of the plasma concentrations of dipyridamole. The occurrence of headaches was not related to interindividual differences of the pharmacokinetic parameters. CONCLUSIONS: 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.

Adult↗