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At least 19 recordsLinked to original sources
PubMed1986

Persantine-Aspirin Reinfarction Study. Part II. Secondary coronary prevention with persantine and aspirin.

In the Persantine-Aspirin Reinfarction Study, Part II (PARIS II), 3,128 persons who had recovered from myocardial infarction, suffered from 4 weeks to 4 months previously, were randomized into two groups: dipyridamole (Persantine) plus aspirin (n = 1,563) and placebo (n = 1,565). The average length of follow-up was 23.4 months. Prespecified primary end points were coronary incidence (definite nonfatal myocardial infarction plus death due to recent or acute cardiac event), coronary mortality (death due to recent or acute cardiac event) and total mortality, each at 1 year of patient follow-up and at the end of the study. Coronary incidence in the Persantine plus aspirin group was significantly lower than in the placebo group, both at 1 year (30% reduction) and at the end of the study (24% reduction). The statistically significant differences in coronary incidence, at 1 year and at the end of the study, in favor of the combination treatment remained after adjustment for multiple baseline variables and adjustment for multiple testing (three end points for two time periods). Although there were reductions for other end points, these differences were not statistically significant. Coronary mortality was 20% lower in the Persantine plus aspirin group compared with the placebo group at 1 year, and 6% lower overall. Total mortality in the treated group compared with the placebo group was 11% lower at 1 year and 3% lower overall. The reduced rates of coronary incidence largely reflected lower rates of definite nonfatal myocardial infarction in the Persantine plus aspirin group. Several subgroups were defined a priori and at the end of the study. The beneficial effect of Persantine plus aspirin compared with placebo for coronary incidence tended to be greater for the following groups of patients: those who had a non-Q wave infarct; those who were not taking digitalis; those who were receiving beta-receptor blocking drugs at baseline; those who were in New York Heart Association functional class I; those who had had only one myocardial infarction; or those who were enrolled in the study early, that is within 85 days of the qualifying myocardial infarction.

Actuarial Analysis↗
PubMed1980

Persantine and aspirin in coronary heart disease. The Persantine-Aspirin Reinfarction Study Research Group.

In the Persantine-Aspirin Reinfarction Study (PARIS) trial, 2026 persons who had recovered from myocardial infarction (MI) were randomized into three groups: Persantine plus aspirin (PR/A) (n = 810); aspirin alone (ASA) (n = 810); placebo (PLBO) (n = 406). The average length of follow-up study was 41 months. Results for the three specified primary end points were: total mortality 16% lower in PR/A and 18% lower in ASA compared with PLBO; coronary mortality 24% and 21% lower; incidence of nonfatal MI plus fatal coronary disease 25% and 24% lower. These differences were not satistically significant by the study criterion (Z greater than or equal to 2.6). By life-table analysis, the rates of coronary mortality and coronary incidence were about 50% lower in the PR/A group than in the PLBO group from 8-24 months, and for coronary incidence all Z values were greater than or equal to 2.6; ASA rates were about 30% lower than PLBO rates, and for coronary incidence, Z values were greater than or equal to 2.6 at two points. For these end points, from 8-20 months, PR/A rates were about 30% lower than ASA rates, but all Z values were less than 2.0 PR/A and ASA patients entering within 6 months of last MI showed the largest percentage reductions in mortality; only the difference between PR/A and PLBO groups for 3-year coronary mortality yielded a Z value of 2.6.

Actuarial Analysis↗
PubMed1980

[Persantin and aspirin in coronary heart disease. The persantin-aspirin reinfarction study group (PARIS)].

In the Persantine-Aspirin Reinfarction Study (PARIS) trial 2026 persons who had recovered from myocardial infarction (MI) were randomized into three groups: Persantine plus Aspirin (PR/A) (n = 810); aspirin alone (ASA) (n = 810); placebo (PLBO) (n = 406). The average length of follow-up study was 41 months. Results for the three specified primary end points were: total mortality 16% lower in PR/A and 18% lower in ASA compared with PLBO; coronary mortality 24% and 21% lower; incidence of nonfatal MI plus fatal coronary disease 25% and 24% lower. These differences were not statistically significant by the study criterion (Z greater than or equal to 2.6). By life-table analysis, the rates of coronary mortality and coronary incidence were about 50% lower in the PR/A group than in the PLBO group from 8--24 months, and for coronary incidence all Z values were greater than or equal to 2.6; ASA rates were about 30% lower than PLBO rates, and for coronary incidence, Z values were greater than or equal to 2.6 at two points. For these end points, from 8--20 months, PR/A rates were about 30% lower than ASA rates, but all Z values were < 2.0. PR/A and ASA patients entering within 6 months of last MI showed the largest percentage reductions in mortality; only the difference between PR/A and PLBO groups for 3-year coronary mortality yielded a Z value of 2.6.

Adult↗
PubMed1980

Persantine-aspirin reinfarction study. Design, methods and baseline results. By the persantine-aspirin reinfarction study research group.

The Persantine-Aspirin Reinfarction Study (PARIS) was a randomized, controlled, double-blind study of dipyridamole (Persantine) and aspirin in secondary prevention of coronary heart disease. Two thousand twenty-six men and women with myocardial infarction (MI) documented by electrocardiographic findings, clinical history and cardiac enzymes were followed for a minimum of 3 years and monitored for mortality (total and cause-specific), recurrent MI and other cardiovascular events. The study had a unique structure that provides a model for large-scale industry-sponsored clinical trials. Although financed by a private pharmaceutical firm, the study was completely independent of the funding sponsor. Sixteen American and four British clinics participated in the study, along with a Coordinating Center, and ECG Reading Center, a Central Laboratory, and a Drug Distribution Center. In addition, the study included an independent Data Quality Control Center that monitored the performance of the Coordinating Center. The rationale, organization, design and baseline results are presented in this report.

Adult↗
PubMed1980

The Persantine-aspirin reinfarction study. The Persantine-aspirin Reinfarction Study (PARIS) research group.

The efficacy and safety of a combination of Persantine and aspirin, of aspirin alone and of a placebo as a regimen for preventing reinfarction were compared in 2026 patients who had recovered from a documented acute myocardial infarction (MI) that had occurred 8 weeks to 5 years previously. Baseline variables were comparable, and almost all surviving patients were treated for 3 years. There was a trend toward improved survival rates both for the combination and single drug compared with placebo. Coronary incidence was significantly lower in the combination group compared with placebo at each 4-month interval during the first 24 months of treatment, whereas significant reductions in the aspirin group occurred only at 8 and 24 months. Gastric and renal side effects were more common in the treated groups. To confirm the above results and the findings that the group of patients enrolled within 6 months of last MI had the largest reduction in mortality in the combination group, another study has been designed to compare the combination with a placebo in a large group of patients.

Aspirin↗
PubMedDate not supplied

Persantine improves acute pancreatitis in vitro.

Persantine combined with TNF-a enhances antiproliferative activity in human tumor cells. We hypothesized that the vasodilator persantine would ameliorate acute pancreatitis (AP) in vitro. Rat pancreatic ductal cells were cultured using standard techniques. Acute pancreatitis was induced by adding cerulein (10(-9) M) or TNF-a (200 ng/ml). AP was verified by increased amylase production. Persantine was added at concentrations from 0.1 uM to 100 uM post cerulein or TNF-a treatment. Statistical analysis was achieved by ANOVA. Amylase production was significantly increased (p < 0.05) compared with control upon stimulation with either cerulein or TNF-a. When persantine was added in graded concentrations from 0.1 uM to 100 uM to cerulein treated cells, it decreased amylase production significantly (p < 0.05) at 100 uM. However, when persantine was added to TNF-a treated cells, it decreased amylase production (p < 0.05) at the lower concentrations of 0.1 uM and 1 uM. We have shown for the first time that AP, resulting from either mild (cerulein) or severe (TNF-a) stimulation, is significantly improved by treatment with persantine.

Acute Disease↗
PubMedDate not supplied

Persantine Aspirin Trial in cerebral ischemia. Part II: Endpoint results. The American-Canadian Co-Operative Study group.

The Persantine Aspirin Trial focused on the question of whether the administration of the combination of aspirin and dipyridamole (Persantine) would result in a lower incidence of cerebral or retinal infarction or death than the administration of aspirin alone for persons with a history of recent carotid territory transient ischemic attacks (TIAs). Fifteen centers in the United States and Canada participated and 890 individuals were admitted and randomly allocated to either aspirin (325 mg) plus placebo or aspirin (325 mg) plus Persantine (75 mg) four times daily. Ninety eight percent of the subjects were followed for at least one year; many were followed for four to five years. The results of life table analysis indicate that the overall endpoint rates for the "aspirin only" and "aspirin plus Persantine" groups are identical. Thus, for TIA patients taking aspirin, the addition of Persantine contributes nothing. There was a clustering of stroke endpoints during the first month after randomization. Deaths from all causes were essentially equally divided between the two treatment groups.

Adult↗
PubMed2000

Persantine attenuates hemorrhagic shock-induced P-selectin expression.

Ischemia/reperfusion (I/R), a phenomenon that is associated with conditions such as organ transplantation, trauma, vascular disease, and stroke, involves the recruitment of activated and adherent leukocytes that subsequently mediate tissue injury. Endothelial cell adhesion molecules such as P-selectin mediate I/R-induced leukocyte recruitment and allow the adherent leukocytes to damage the vascular wall and parenchymal cells. This study examines the influence of dypiridamole (persantine) on hemorrhagic shock (H/S)-induced P-selectin expression. H/S was induced in C57BL/6 mice by withdrawing blood to drop the mean arterial blood pressure to 30 to 35 mm Hg for 45 minutes. The mice were resuscitated by infusing the shed blood and Ringer's lactate (50% shed blood volume). In vivo P-selectin expression was determined using a dual monoclonal antibody technique in the heart, lung, liver, kidneys, stomach, small bowel, and colon of a control group, a hemorrhagic shock group, and a hemorrhagic shock group that was pretreated with Persantine (Boehringer, Ingelheim, Ingelheim, Germany). H/S significantly (P < 0.01) increased P-selectin expression in all regional vascular beds of untreated mice. Persantine treatment largely prevented the H/S-induced P-selectin expression in the same vascular beds. Persantine significantly attenuates the upregulation of P-selectin in the hemorrhagic shock model.

Adenosine↗
PubMedDate not supplied

Persantine Aspirin Trial in cerebral ischemia. The American-Canadian Co-operative Study Group.

The Persantine Aspirin Trial is a double-blind multi-centered cooperative study focusing primarily on the question of whether the administration of the combination of aspirin and dipyridamole (Persantine) will result in a greater reduction of cerebral or retinal infarction or death than the administration of aspirin alone. Fifteen centers in the United States and Canada are participating. More than 750 individuals with a history of recent carotid territory transient ischemic attacks (TIAs) have been admitted over the past four years and randomly allocated to either aspirin (325 mg) plus placebo four times daily or aspirin (325 mg) plus Persantine (75 mg) four times daily. It is anticipated that the study will continue through 1983. Analysis and publication of results are planned for 1984.

Animals↗
PubMed1962

The effect of persantin on intercoronary collateral circulation and survival during gradual experimental coronary occlusion. A preliminary report.

Twenty-five dogs were exposed to gradual coronary occlusion by placing Ameroid constrictors around the origins of the left circumflex and anterior descending coronary arteries. Previous experiments have demonstrated that these constrictors absorb water and, over a period of three weeks, narrow the cross-sectional area of the two arteries to 50% or less, and consequently cause the death of 80% of the experimental animals. Twelve of the 25 animals were fed 50 mg. of Persantin three times a day by mouth commencing one day before the operative procedure. Determinations of the concentration of the drug in the blood revealed a level consistent with that obtained in humans after the administration of therapeutic doses. Eleven of the 13 control animals died in the three-month experimental period while only six of the 12 treated animals expired. Injections of Schlesinger mass in all animals dying or killed following the experimental period demonstrated that Persantin significantly accelerated the development of intercoronary anastomoses in the treated group, and in the surviving animals produced a rich anastomotic network much in excess of that seen in the surviving animals in the control series that were exposed to hypoxia alone. On the basis of these experimental findings, it is suggested that Persantin may favourably alter the prognosis of many patients with coronary artery disease.

Animals↗
PubMed1993

Prognostic value of dipyridamole echocardiography early after myocardial infarction in elderly patients. Echo Persantine Italian Cooperative (EPIC) Study Group.

OBJECTIVES: This study was conducted to assess the feasibility, safety and prognostic value of dipyridamole echocardiography in elderly patients recovering from an uncomplicated acute myocardial infarction in a subset analysis performed on the patients entered in the subproject "residual ischemia" of the Echo Persantine Italian Cooperative Study (EPIC). BACKGROUND: Coronary heart disease accounts for two thirds of all deaths in the age group > 65 years, and > 50% of all patients admitted to the hospital with acute myocardial infarction are > 65 years old. The prognostic value of dipyridamole-induced left ventricular dysfunction was clearly established in patients evaluated early after acute infarction. METHODS: In a subgroup analysis of the Echo Persantine Italian Cooperative Study (EPIC), we assessed the value of dipyridamole echocardiography in predicting cardiac events in 190 elderly (> or = 65 years) patients (age 68.4 +/- 3.3 years, range 65 to 78; 147 men and 43 women) evaluated early (mean 10 days) after uncomplicated acute myocardial infarction and followed up for 14 +/- 9.8 months. RESULTS: There was no major side effect during dipyridamole echocardiography. A positive test result occurred in 85 patients (44.7%). During follow-up, there were 62 events (14 cardiac deaths, 7 nonfatal reinfarctions, 21 cases of class III or IV angina and 20 revascularization procedures). Of these 62 events, 44 occurred among 85 patients with positive dipyridamole echocardiography and 18 among 105 patients with negative dipyridamole echocardiography (52% vs. 17%, p < 0.001). Spontaneous events (death, reinfarction, angina) occurred in 31 patients with positive and in 11 with negative dipyridamole echocardiography (36% vs. 10%, p < 0.001). Hard events (myocardial infarction or death) occurred in 14 patients with positive and 7 with negative dipyridamole echocardiography (16% vs. 6%, p < 0.05). Death occurred in 11 patients with positive and in 3 with negative dipyridamole echocardiography (13% vs. 3%, p < 0.01). The positive predictive value of positive dipyridamole echocardiography and negative predictive value of negative dipyridamole echocardiography as related to the occurrence of all events in the follow-up period (death, reinfarction, angina, revascularization procedures) were 52% and 83%, respectively. The relative risk (that is, the relative risk of occurrence of future cardiac events in the group with positive dipyridamole echocardiography compared with that in those with negative dipyridamole echocardiography) was 3 for all events and 4.4 for death. CONCLUSIONS: Dipyridamole echocardiography was well tolerated by elderly patients and proved to be very effective in prognostic stratification early after uncomplicated acute myocardial infarction, even when only survival was considered.

Aged↗
PubMedDate not supplied

Persantine aspirin trial in cerebral ischemia--Part III: Risk factors for stroke. The American-Canadian Co-Operative Study Group.

This third paper from the Persantine Aspirin Trial examines the data to identify risk factors for stroke in persons with a history of carotid territory transient ischemic attacks (TIAs) Fifteen centers in the United States and Canada participated, and 890 subjects were admitted and randomly allocated to either aspirin plus placebo or aspirin plus dipyridamole (Persantine). Persons with the following characteristics were in greater jeopardy for stroke, retinal infarction, or death: older age, history of heart disease, history of peripheral vascular disease, and persisting neurologic deficit from a recent event. Elevated diastolic blood pressure, diabetes, use of estrogen, and smoking were not found to be risk factors. Elevated systolic blood pressure was a risk factor primarily in subjects with a history of heart disease. Estrogen use may actually have had a protective effect for women. This cannot be considered as a report of the natural history of TIA patients; it does identify risk factors in a specific cohort of subjects under treatment.

Aged↗
PubMed1993

[The effects of persantine on pulmonary arterial pressure of rats exposed to hypoxia].

In the chronic hypoxic model of pulmonary hypertension, the increased wall thickness can be attributed in part to proliferation of endothelial cells, medial smooth muscle cell, and adventitial fibroblasts. The cellular mechanisms responsible for this proliferative response to chronic hypoxia may be due to the action of specific growth factors released in areas of vascular injury. Some growth factors such as platelet-derived growth factor and epidermal growth factor, released from activated platelets at sites of tissue injury and thrombus formation, may play a crucial role in this proliferative process. This paper reported the effects of persantine (dipyridamole), an inhibitor of platelet function, on pulmonary arterial pressure of rats exposed to hypoxia for 2 weeks. The results showed that persantine could prevent elevation of pulmonary arterial pressure and increase of right ventricle weight of hypoxic rats.

Animals↗
PubMed1977

Effect of temperature and of cytochalasin B and persantin on the nonmediated permeation of non-electrolytes into cultured Novikoff rat hepatoma cells.

The nonmediated permeation of L-glucose, cytosine, and prednisolone into Novikoff rat hepatoma cells followed first order kinetics with rate constants of 0.00404, 0.173, and 2.4 min-1, respectively. The constants were estimated from a nonlinear least squares fit of the integrated first order rate equation. The rate constants were independent of substrate concentration and correlated with the partition coefficients of the substances in octanol-balanced salt solution (0.00158, 0.0352, and 17.8, respectively) and olive oil-balanced salt solution mixtures which were between 10- and 100-fold lower. Arrhenius plots for the permeation of L-glucose, cytosine, and prednisolone were linear and indicated activation energies of 24.2, 28.0, and 19.6 kcal/mol, respectively. The permeation of L-glucose and cytosine, but not of prednisolone, was impeded in a concentration-dependent manner by the presence of cytochalasin B and Persantin, heretofore thought of as specific inhibitors of facilitated diffusion processes. The relative degree of decrease of the permeation rates of L-glucose and cytosine, however, differed for cytochalasin B and Persantin.

Cell Membrane Permeability↗
PubMed2001

Performance of a polyurethane vascular prosthesis carrying a dipyridamole (Persantin) coating on its lumenal surface.

A porous polyurethane vascular prosthesis with an internal diameter of 5 mm was studied. The graft carries a coating of immobilized dipyridamole (Persantin(R)) on the surface of its lumen. Dipyridamole is a potent nontoxic inhibitor of platelet activation/aggregation, and also a strong inhibitor of vascular smooth muscle cell proliferation. The polyurethane material is also known as Chronoflex(R), and already finds use as a vascular access graft. The coated vascular graft was studied in vitro (hemocompatibility, interaction with blood platelets and cultured endothelial cells), as well as in two established in vivo models. In the first in vivo study, coated grafts were implanted in goats, as a bypass of the carotid artery (four animals, eight grafts, length of the graft was approximately 12 cm). Four uncoated grafts were used as controls in otherwise identical experiments. In the second in vivo experiment, eight sheep were used. Each animal received one coated and one uncoated prosthesis as an interposition graft in the carotid artery (length of the graft was 4 cm). The in vitro experiments revealed that the dipyridamole coating has three beneficial effects: reduced thrombogenicity, reduced adherence of blood platelets, and accommodation of a confluent monolayer of endothelial cells. The goat experiments showed patency of the coated grafts in three of the eight cases. The sheep experiments were not useful for the evaluation of the dipyridamole coating because deterioration of the polyurethane material was observed. The in vivo results indicate that the dipyridamole coating may positively influence the patency rate, probably because the coating promotes the growth of an endothelial cell lining. The sheep data show, however, that the limited stability of the Chronoflex(R) material precludes its issue for the construction of permanent small-bore vascular grafts.

Animals↗
PubMed1995

The multicentre trial philosophy in stress echocardiography: lessons learned from the EPIC study. EPIC-EDIC Study Project. Echo Persantine International Cooperative Study. Echo-Dobutamine International Cooperative Study.

The scientific assessment of diagnostic tests should not be based upon a small series of results published by the best academic institutions, but ought to require large scale, multicentre validation founded on grass roots institutions with real doctors, real patients and real problems. To this purpose, an international network of stress echo laboratories has been organized, and within a few years has collected data from thousands of studies using pharmacological stress echocardiography, performed with either dipyridamole (EPIC: Echo Persantine International Cooperative Study) or dobutamine (EDIC: Echo Dobutamine International Cooperative Study) stresses. In a widely deregulated field, all network laboratories have agreed: to pass a quality control examination on stress echo reading before entering the study; to adopt an identical drug infusion protocol; to code similarly the LV segments; and to adopt a common scoring system for wall motion analysis. A minimum amount of historical, clinical, and-when available-stress electrocardiographic, angiographic and follow-up data have been collected on each patient, and disseminated in the various centres, facilitating the creation of an international stress echo language that will help, not only the production of high quality scientific data, but also the build up of a common stress echo lab, with a standardized way of making the studies, unifying the methods and terminology, and archiving data. To date, we have 50 echo laboratories from 15 nations across four continents (Europe, America, Asia and Africa) actively involved in this project. These data will ultimately fill the gap between the academic theory of journals and the pragmatic experience of daily life in a busy echocardiographic laboratory.

Echocardiography↗