Antiaggregatory effects of picotamide in long-term treatment: a 2-year, double-blind placebo-controlled trial.

The ex vivo antiaggregatory activity of picotamide, a dual antithromboxane agent, was assessed to find whether it was maintained in long-term treatment. In a double-blind, placebo-controlled 2-year study, 50 type 2 diabetic patients (35 men and 15 women; mean age 66 +/- 5 years) were enrolled and randomly given picotamide, 300 mg t.i.d. or the corresponding placebo. Platelet aggregation studies were performed at baseline and after 1, 3, 6, 12, 18 and 24 months. Compliance to the treatment was assessed by pill count at each visit. Forty-nine patients concluded the study. Starting from month 1, compared with placebo, picotamide-treated patients showed a significant inhibition of agonist-induced (ADP, arachidonic acid and collagen) platelet aggregation (-41%). The antiaggregatory effect was maintained throughout the study. At month 24, in the picotamide group, platelet aggregation was significantly lower compared with placebo (-30%). After 24 months of treatment, 20 out of 23 (86%) picotamide-treated patients showed a significant inhibition of platelet aggregation, whereas the remaining three patients had a normal platelet response. During the study, 12 patients suffered from thrombotic events of death: nine in the placebo group and three in the picotamide group, respectively. It was concluded that picotamide maintains its antiaggregatory effect, in long-term treatment, in more than 85% of patients.

Effects of picotamide, an antithromboxane agent, on carotid atherosclerotic evolution. A two-year, double-blind, placebo-controlled study in diabetic patients.

BACKGROUND AND PURPOSE: We assessed the effects of long-term treatment with picotamide, an antiplatelet agent with dual antithromboxane activity, on the evolution of early asymptomatic carotid atherosclerotic lesions in diabetic patients. METHODS: In a double-blind, placebo-controlled, 2-year study, 50 type II normotensive diabetic patients (35 men; mean age, 66 +/- 5 years) with asymptomatic mild or moderate nonstenotic (< 50%) carotid atherosclerotic lesions and negative history of cerebrovascular ischemic events were enrolled and randomly given picotamide (300 mg TID) or the corresponding placebo. A high-resolution, real-time B-scan echographic assessment of carotid arteries was performed at baseline and after 1, 3, 6, 12, 18, and 24 months of double-blind treatment. Prevalence and evolutionary trends of carotid atherosclerotic lesions (number per patient and mean stenosis expressed as percent) were considered as efficacy primary end points. RESULTS: At baseline, mean +/- SD numbers of carotid atherosclerotic lesions per patient were 2.7 +/- 1.8 and 2.2 +/- 1.2 in the picotamide and placebo groups, respectively. Mean +/- SD percent stenosis was 25.3 +/- 7% in the picotamide group and 27.3 +/- 6% in the placebo group. Forty-nine patients completed the study. At month 24, the placebo group (n = 24) showed a significant progression in number of carotid atherosclerotic lesions (3.04 +/- 1.8; P < .02 versus baseline) and in mean percent stenosis (35 +/- 17%; 95% confidence interval, 33% to 37%; P < .01 versus baseline). In the picotamide group (n = 25), mean number of carotid atherosclerotic lesions (2.7 +/- 1.6) and percent stenosis (26 +/- 9%; 95% confidence interval, 24.8% to 27.2%) remained unchanged. At month 24, compared with randomized placebo, lesion numbers (P < .03) and percent stenosis (P < .01) in the picotamide group were significantly lower. During the study, 12 patients experienced major or minor ischemic vascular events (9 in the placebo group and 3 in the picotamide group; P = .07). CONCLUSIONS: In diabetic patients compared with patients receiving placebo, long-term treatment with picotamide can slow the evolution of early carotid atherosclerotic lesions, inhibiting progression of plaque number and growth.

[The regression of left ventricular hypertrophy and improvement in diastolic filling during antihypertensive therapy with cilazapril]. / Regressione dell'ipertrofia e miglioramento del riempimento diastolico ventricolare sinistro in corso di terapia antipertensiva con cilazapril.

In order to evaluate the effects of cilazapril on left structure and function in essential hypertension, we evaluated 10 patients (4 females and 6 males) affected with mild-to-moderate systemic hypertension. All patients were treated with cilazapril 5 mg/day over a 6-months period and underwent a 24 hours ambulatory blood pressure monitoring and a complete Doppler echocardiographic examination at study entry, after 3 and 6-months of therapy. After therapy, mean systolic and diastolic arterial pressure decreased significantly from 153 +/- 16/102 +/- 8 mmHg to 135 +/- 13/83 +/- 6 mmHg respectively (p < 0.005/0.001 respectively). Moreover there was a significant decrease of left ventricular mass from 109 +/- 27 to 87 +/- 23 g/m2 (p < 0.005). Ejection phase indices did not change significantly, whereas left ventricular diastolic filling improved after therapy with a significant increase of M1/M2 ratio from 0.9 +/- 0.2 to 1.1 +/- 0.3 (p < 0.02). In conclusion, these data demonstrate that cilazapril 5 mg/day is effective in reducing blood pressure in mild-to-moderate essential hypertension. This normalization of blood pressure measurements is paralleled by a significant decrease of left ventricular mass index and by an improvement of left ventricular diastolic filling.

[Diabetes and atherosclerosis: a follow-up echographic study of atherosclerotic carotid lesions]. / Diabete ed aterosclerosi: studio ecografico evolutivo delle lesioni aterosclerotiche carotidee.

A two years follow up on 105 diabetic patients and 50 normal subjects was carried out by high resolution real time echotomography, aiming to evaluate the prevalence and the evolutionary trends of carotid atherosclerotic plaques. The prevalence of atherosclerotic lesions was higher in diabetic patients than in normal subjects, and the most part of them showed an "intermediate" echographic pattern, minimal stenosis and regular surface. The results of the two years follow up indicate that the "soft" and the "hard" plaque types were those showing a more significant progression toward to the "mixed" type. "Hard" and "mixed" plaques, particularly those showing irregular surface, resulted most associated with higher degree of vessel stenosis. Four diabetic patients experienced three minor and one major ischemic events during the follow up; however all the patients had shown plaques with "intermediate" pattern, regular surface, and no signs of vessel stenosis progression. Further studies, performed for longer period of time with a higher number of patients are needed to evaluate the evolutionary trends of carotid plaques in diabetic patients and their relationship with clinical ischemic events.

[Restrictive cardiomyopathy in eosinophilic leukemia: echocardiographic and nuclear magnetic resonance aspects]. / Miocardiopatia restrittiva in corso di leucemia eosinofila: aspetti ecocardiografici e di risonanza magnetica nucleare.

This paper reports a case of endomyocardial disease due to hypereosinophilic syndrome. Two-dimensional echocardiography showed prevalent right ventricular involvement, with obliteration of the apex due to an echogenic mass progressively filling the whole ventricular cavity. RMN accurately defined the presence and the characteristics of the infiltrative mass in the right ventricular chamber. A different intensity of spin-echo imaging sequence was used to differentiate between thrombotic and infiltrative leukemic images. It is concluded that prevalent right ventricular involvement during eosinophilic endomyocardiopathy is a relatively rare disease which can be detected and evaluated by the use of echocardiography and RMN studies.

Regression of left ventricular hypertrophy and systolic function in hypertensive patients during long-term treatment with ketanserin.

It is now generally accepted that antihypertensive therapy can induce regression of left ventricular hypertrophy (LVH) in hypertensive subjects. However, the influence of LVH reversal on both the systolic and diastolic functions, and particularly the ability of the heart to meet sudden overloads caused by exercise and/or recurrence of hypertension, remain unanswered questions. The long-term effects of ketanserin, a selective serotonin S2-receptor antagonist with additional alpha 1-adrenergic blocking properties, on LVH and systolic function were studied in 13 untreated subjects (age range 35-55 years) with mild-to-moderate essential hypertension, echocardiographic evidence of LVH, and normal ejection fraction. Blood pressure values and echocardiographic measurements of dimensions, wall thicknesses, and indices of LV mass were determined before and after 3, 6, and 12 months treatment; ejection fractions at rest and during exercise were evaluated by equilibrium multigated radionuclide angiocardiography at baseline and after 12 months of therapy. Mean arterial pressure was significantly reduced from the first month of treatment (p less than 0.001) and remained well controlled up to the end of the trial. Both posterior and septum wall thicknesses decreased after 3 months of therapy and remained stable throughout the whole study period. LV mass index decreased from a mean +/- SD of 187.7 +/- 47.6 g/m2 to a mean of 157.81 +/- 31.63 g/m2 (p less than 0.01) at the third month, reaching greater decreases after 6 months (156.05 +/- 31.00 g/m2) and after 12 months (153.21 +/- 28.80 g/m2) of treatment. A significant correlation was found between LV mass and posterior wall thickness at the different observation times in the study. Finally, the regression of LVH at the end of therapy was not associated with impairment of systolic function, as assessed by measurements of ejection fraction at rest and during exercise.

Clinical efficacy of picotamide in long-term treatment of intermittent claudication.

The clinical efficacy of picotamide was investigated in a randomized, double-blind, placebo-controlled study in patients with peripheral occlusive arterial disease of the lower limbs at functional stage II of the Fontaine classification. Forty patients with a history of claudication for at least six months were admitted to the study and were given either 3 x 300 mg tablets of picotamide (20 subjects) or three identical placebo tablets (20 subjects) for six months. The two groups of patients were similar in regard to clinical features and potential risk factors. At the end of treatment painfree walking distance and systolic ankle-arm pressure ratio improved more in the picotamide than in the placebo group (p = 0.05). Systolic ankle pressure curves, determined before and after the six-month treatment, showed a positive trend to a higher postexercise ankle pressure and a faster return to the preexercise levels in the picotamide group; however, the difference was not statistically significant. Laboratory monitoring revealed a slight prolongation of bleeding time, a significant decrease in arachidonic acid-induced platelet aggregation, and an enhanced fibrinolysis with absence of interference with hemostasis in the picotamide group. One patient in the placebo group developed a major cardiovascular event (angina pectoris) during the study. These results indicate that picotamide is an effective drug that may modify the natural course of intermittent claudication and associated vascular problems.

Clinical investigation of the effect of ketanserin: a new antihypertensive drug.

The antihypertensive effect of a recently introduced antiserotoninic drug, ketanserin, was examined in a single-blind, placebo-controlled parallel group study in 28 patients with mild to moderate hypertension. Supine and standing blood pressure, electrocardiogram, heart rate and laboratory parameters of liver, kidney and bone marrow functions were checked before and after 3 months of treatment. After 12 weeks' treatment with ketanserin (20-40 mg twice a day), there was a highly significant reduction of both systolic and diastolic blood pressure, as compared to placebo in the supine position (p less than 0.0001/p less than 0.001). In the standing position, the reduction of systolic pressure was more significant than the diastolic pressure (p less than 0.0001/p less than 0.01). Eleven out of 28 hypertensive patients showed electrocardiographic evidence of left ventricular hypertrophy (LVH) according to the ECG criteria of Romhilt and Estes. Although a reduction of the mean point score for LVH as compared to placebo was observed in the ketanserin group, that difference was not statistically significant. These preliminary observations suggest a possible role of ketanserin in the regression of LVH due to essential hypertension.