Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Die empfohlene Infusionszeit für die i.v.-Prostaglandin E1 (PGE1)-Therapie beträgt dosisabhängig 2 bzw. 3 h. In der multizentrischen Studie sollte erstmals bei Patienten mit Claudicatio inter- mittens geprüft werden, ob die Dosierung von 60 µg PGE1 auch bei kürzeren Infusionszeiten wirksam und verträglich ist. Randomisiert erhielten 118 Patienten mit Claudicatio intermittens und einer schmerzfreien Gehstrecke zwischen 50 und 200 m (3 km/h, 12%) über 4 Wochen einmal täglich eine i.v.-Infusion von 3 Amp. Prostavasin® (60 µg PGE1) über einen Zeitraum von 1 bzw. 2 h. Als Zielparameter wurde die schmerzfreie Gehstrecke sowie die Verträglichkeit, gemessen an der Häufigkeit von unerwünschten Ereignissen und dem Blutdruckverhalten, bestimmt. Die Wirksamkeit war in beiden Gruppen vergleichbar. Bei der 1-h-Infusion stieg die schmerzfreie Gehstrecke von 87 auf 135 m, bei der 2-h-Infusion von 88 auf 147 m. Die maximale Gehstrecke zeigte einen Zuwachs von 124 auf 200 m bzw. von 147 auf 238 m. Die Unterschiede zwischen beiden Gruppen waren nicht signifikant, allerdings ergab eine Subgruppenanalyse bei Ausgangswerten der schmerzfreien Gehstrecke <80 m einen signifikanten Unterschied zugunsten der 2-stündigen PGE1-Infusion (Gehstreckenzuwachs 58 gegenüber 22 m), Blutdruckverhalten und Häufigkeit von unerwünschten Ereignissen waren in beiden Gruppen vergleichbar. Insgesamt zeigen sowohl die 1- als auch 2-stündige PGE1- Infusion bei Claudicatio intermittens gleich gute Wirksamkeit und Verträglichkeit. Patienten mit initialen schmerzfreien Gehstrecken unter 80 m scheinen jedoch von der 2-stündigen PGE1-Infusion mehr zu profitieren.

Background: Owing to generalized arteriosclerosis, changes in renal excretion are also to be expected in patients with peripheral arterial occlusive disease (PAOD). It is therefore recommended that in the presence of serum creatinine levels >1.5 mg/dl, prostaglandin E-1 therapy should be carefully monitored At the same time, experimental and clinical pilot studies have shown that prostaglandin E-1 has a positive influence on renal function. Against this background tolerability dosage and effect of PGE(1) on the serum creatinine levels were investigated in an analysis of the literature, and also checked in a retrospective survey of 10 angiological centers, Patients and methods: For the analysis of the literature, eight clinical studies on the use of PGE(1) in chronic renal insufficiency, in surgery of the heart and aorta, and following the administration of contrast medium, were analysed with respect to the influence of PGE(1) on renal function. The retrospective survey included 134 patients with PAOD and impaired renal function (serum creatinine levels > 1.5 mg/dl), of whom 103 were in stage Fontaine III/IV and 31 in stage II. The mean age was 71 +/- 10 years, the ankle arterial pressures in non-diabetics in stage III/IV were 40.5 +/- 45.0 mmHg. On average, the patients received either a single daily dose of 10 mu g PGE(1) i.a. (n = 42), or 2 x 40 mu g PGE(1) i.v. (n = 92) for an average period of 20 and 21 days respectively. Results: In all the published studies, the PGE(1) noses applied (up to 40 ng x kg x min) were well tolerated, and elevated serum creatinine levels were lowered creatinine clearance improved, and microalbuminuria reduced. The retrospective survey showed that one-quarter of the patients (25.2%) were returned from stage III/IV to stage II. Progression was recorded in 6.8% of the patients, the stage remained unchanged in 4,9%, while the remaining patients experienced partial healing of ulcers or a reduction in rest pain. Treatment was well tolerated; the serum creatinine levels, which on average were initially 2.02 mg/dl, showed no significant changes during the course of treatment. Conclusions: The PGE(1) dose recommended for PAOD is also well tolerated by patients with impaired renal function. Indeed results obtained in numerous pilot studies even suggest that renal function is likely to be improved by PGE(1) treatment.

Background: Clinical studies oil the efficacy and tolerability of prostaglandin E-1 (PGE(1)) in the treatment of stage III/IV PAOD have so far reported only the effect of a single course of treatment lasting an average of 3-4 weeks. In view of the progressive nature of PAOD, however, worsening of the symptoms may again occur during the further course of the disease. The aim of the present retrospective study was, therefore, to investigate the question whether, under the conditions usually met with in the doctor's office or hospital, patients with stage III/IV PA OD also benefit over the long-term, that is, from repeated treatment with PGE(1) (Prostavasin(R)). Patients and Methods: In 13 angiological centers, the data of 277 patients (mean age 67 +/- 11 years) with the typical profile of instable stage III (n = 93) or stage IV (n = 184) PAOD who underwent more than one course of PGE(1) treatment were analysed. The mean daily dose and duration of the initial Prostavasin(R) treatment in the 169 hospitalized patients were 2 x 40 mu g PGE(1) i.v. for 21 days, and in the 108 ambulatory patients 1 x 60 mu g PGE(1) i.v. for 20 days. Results: Following the first course of treatment, 46% of the patients were returned from stage III/IV to stage II. On the occasion of the second course of treatment, 32% of these patients were still in stage II, while in the remaining patients, after an average treatment-free period of 342 days, the condition had deteriorated. Among this latter group, however, the renewed course of treatment resulted in renewed down-grading to stage II in 67% of the cases. The results seen after a third or fourth course of treatment were similarly positive. However, the success of treatment in patients with US Doppler pressures <50 mmHg was less favorable in comparison with higher Doppler pressures. Here, only 39% as compared with 62% of the cases were down-graded to stage II by the initial treatment. In all 4 courses of treatment, the tolerability of PGE(1) was equally good. Conclusions: In the usual office or hospital setting, intravenous Prostavasin(R) administered to patients with stage III/IV PAOD produces a long-lasting clinical improvement. Even in cases subsequently experiencing clinical deterioration, a renewed course of Prostavasin(R) treatment is successful, and the tolerability of the substance remains good.

For the first time efficacy and safety of a new prostaglandin E1 (PGE1) regimen in the treatment of intermittent claudication were evaluated in a randomized, double-blind, placebo-controlled multicenter clinical trial. The study involved 213 outpatients with a maximum walking distance of 50 to 200 m measured on the treadmill (3 km/hr, 12% grade). After a 2-week run-in phase they received a 2-hour intravenous infusion of 60 μg PGE1 or placebo 5 days a week for 4 weeks. It was followed by a 4-week interval treatment with the same medication administered only twice a week. Patients were monitored for 3 months when they received no study medication. In the PGE1 group the intention-to-treat analysis (n = 208) revealed an increase in walking distance after 4 weeks of 75% (placebo, 43%). At the end of the interval treatment the walking distance had improved to 101% (placebo, 60%). The results remained virtually constant during follow-up (PGE1, 104%, placebo, 63%). Between-group comparisons showed significant differences in favor of PGE1 for all three time points of measurement (p < 0.05, p < 0.01, and p < 0.05). PGE1 was well tolerated; the rate of adverse reactions related to the treatment was 12.8% (placebo, 7.7%). In summary, these results show that the new PGE1 regimen is effective and safe in the treatment of outpatients with intermittent claudication. (J Vasc Surg 1997;25:537-44.)

Objective: We compared the efficacy of a bolus injection (5 min) of LIPO-PGE(1) (Prostaglandin E(1) in lipid emulsion) with conventional PGE(1)-cyclodextrin (PGE(1)-cyclodextrin) infusions (2 h) in patients with intermittent claudication. The quantitative blood-flow in the common femoral artery was measured using a computerized ultrasound Doppler system (MAVIS(R)). We also monitored the transcutaneous oxygen pressure, the skin temperature on the foot, and the reactive change in blood pressure and pulse as well as side effects.Results: Dose finding of LIPO-PGE(1): After bolus injection of 30, 50 and 80 mu g LIPO-PGE(1) a significant dose-dependent increase of the blood flow in the leg (+96.9%, 80 mu g) with a peak 3 h after injection was seen. After LIPO-PGE(1) we observed an enhanced microcirculation (significant rise in the transcutaneous oxygen pressure and the skin temperature of the foot.) We noted longer lasting pharmacodynamic properties with LIPO-PGE(1) (50 mu g) compared to PGE(1)-cyclodextrin (60 mu g). Comparison to PGE(1)-cyclodextrin: In a cross-over, placebo-controlled study, 20 patients with intermittent claudication received 4 weeks therapy with a bolus of 50 mu g LIPO-PGE(1) or a 2 h infusion of 60 mu g PGE(1)-cyclodextrin per day. A significant increase in the blood flow was measured at the end of 4 weeks therapy compared to the initial values before treatment. This rise correlates significantly with the increase in the patient's maximal walking distance (+112%, LIPO-PGE(1)). Compared to conventional PGE(1)-cyclodextrin infusions given over 2 h, a clearly prolonged increase in perfusion of the affected limb after LIPO-PGE(1) was demonstrated. No serious adverse effects were observed.

In 42 patients with POAD in stage IIb the blood-flow in the common femoral artery and in the superficial femoral artery was measured before, 10 days after, 3 and 12 months after femoro-popliteal bypass surgery. Blood-flow was detected noninvasively using a multichannel ultrasound computer system (MAVIS(R)). Simultaneously Doppler pressure, skin temperature and tcPO2-values were measured. Thereafter the patients had to undergo treadmill tests (painfree and maximal walking distance). Compared to healthy volunteers preoperative blood-flow was significantly (p < 0.001) reduced in the common femoral artery and in the superficial femoral artery. Postoperatively the blood-flow increased significantly (p < 0.001) in patients with an open bypass. This increase could still be demonstrated up to one year after bypass surgery. Surprisingly, a significant (p < 0.01) postoperative rise in blood-flow was also observed in the non-operated leg. Doppler pressure, tcPO2-values (calf) in the operated leg and walking distance increased significantly (p < 0.001). The MAVIS(R) as a noninvasive procedure allows to check the further development of the bypass-function independently of subjective influences, because quantitative changes in blood-flow are documented.

In 42 patients with POAD in stage IIb the blood-flow in the common femoral artery and in the superficial femoral artery was measured before, 10 days after, 3 and 12 months after femoro-popliteal bypass surgery. Blood-flow was detected noninvasively using a multichannel ultrasound computer system (MAVISR). Simultaneously Doppler pressure, skin temperature and tcPO2-values were measured. Thereafter the patients had to undergo treadmill tests (painfree and maximal walking distance). Compared to healthy volunteers preoperative blood-flow was significantly (p < 0.001) reduced in the common femoral artery and in the superficial femoral artery. Postoperatively the blood-flow increased significantly (p < 0.001) in patients with an open bypass. This increase could still be demonstrated up to one year after bypass surgery. Surprisingly, a significant (p < 0.01) postoperative rise in blood-flow was also observed in the non-operated leg. Doppler pressure, tcPO2-values (calf) in the operated leg and walking distance increased significantly (p < 0.001). The MAVISR as a noninvasive procedure allows to check the further development of the bypass-function independently of subjective influences, because quantitative changes in blood-flow are documented.

The method of nuclear magnetic resonance (NMR) spectroscopy compared to the parameters absolute-, pain-free walking distance and ankle/arm coefficient in Doppler pressure was used for observation of patients with peripheral arterial occlusive disease stage IIb according to Fontaine. While the classic parameters (walking distances, ankle/arm coefficient) described a homogenous group, NMR-spectroscopy parameters showed marked inter- and intraindividual variations during exercise. Further studies on high magnetic power fields, exercise patterns and muscle recreation analysis have to be carried out to develop a reliable system of non invasive muscle energy monitoring in vascular diseases.

An intensive 4-week vascular training (patients with PAOD IIb) leads to an effective amelioration of painfree walking distance (+120%). Additive i.v. Pentoxifylline was not more effective (+105%) whereas PGE1 showed a remarkable increase (+605%). After one year the results in all groups diminished: training group: +30%, Pentoxifylline group: +30%, PGE1 group: +149%.