Nomograms Used to Define the Short-Term Treatment with PGE1 in Patients with Intermittent Claudication and Critical Ischemia. The ORACL.E (Occlusion Revascularization in the Atherosclerotic Critical Limb) Study Group. The European Study

Abstract

Infusional, cyclic PGE1 treatment is effective in patients with intermittent claudication and critical limb ischemia (CLI). One of the problems related to chronic PGE1 treatment in vascular diseases due to atherosclerosis is to evaluate the variations of clinical conditions due to treatment in order to establish the number of cycles per year or per period (in severe vascular disease reevaluation of patients should be more frequent) needed to achieve clinical improvement. In a preliminary pilot study a group of 150 patients (mean age 67+/-12 years) with intermittent claudication (walking range from 0 to 500 m) and a group of 100 patients with CLI (45% with rest pain, and 55% gangrene; mean age 68 +/-11 years) the number of PGE1 cycles according to the short-term protocol (STP) needed to produce significant clinical improvement was preliminarily evaluated. Considering these preliminary observations, the investigators established a research plan useful to produce nomograms indicating the number of cycles of PGE1-STP per year needed to improve the clinical condition (both in intermittent claudication and CLI). A significant clinical improvement was arbitrarily defined as the increase of at least 35% in walking distance (on treadmill) and/or the disappearance of signs and symptoms of critical ischemia in 6 months of treatment in at least 75% of the treated patients. With consideration of the results obtained with the preliminary nomograms a larger validation of the nomograms is now advisable. A cost-effectiveness analysis is also useful to define the efficacy of treatment on the basis of its costs. The publication of this report in two angiological journals (Angeiologie and Angiology) will open the research on nomograms to all centers willing to collaborate to the study. The data are being collected in the ORACL.E database and will be analyzed within 12 months after the publication of this report.

Critical Limb Ischemia: Definition and Natural History

“…Good results were achieved with Alprostadil in the ICAI study [15] , and with Iloprost, as demonstrated in a meta-analysis by Loosemore and Dormandy [49]. Recently, interesting results were obtained with intermittent infusion of Iloprost [50], as well as of Alprostadil in the ORACLE Study [51], with a good cost/efficacy ratio.…”

“…In patients for whom revascularization is not possible, or else it fails, an alternative is to try to modify the consequences of the low perfusion pressure on the distal microcirculation by some form of pharmacotherapy to reverse the rest pain and avoid amputation [2,14]. Prostanoids have been shown to have beneficial effects on most of the microcirculatory components by preventing the reciprocal potentiation of platelet activation, leukocyte activation and the damaged vascular endothelium; this is the reason why prostanoids have, in the last few years, been the most widely tested group of drugs in this condition [2,15,49,50,51]. Good results were achieved with Alprostadil in the ICAI study [15] , and with Iloprost, as demonstrated in a meta-analysis by Loosemore and Dormandy [49].…”

Effects of Shock Waves on Microcirculation, Perfusion, and Pain Management in Critical Limb Ischemia

“…At the moment there is important attention to, and new interest in, noninvasive treatment of peripheral vascular disease and its most disruptive complications due to ischemia and pain often leading to amputation. [4][5][6][7][8] In conclusion, local SWs treatment in severe CLI produced, in this preliminary study protocol, positive changes both in perfusion in the microcirculation (objectively detectable) and in pain.…”

“…The higher pressure was considered for the ORACLE score. [4][5][6][7][8] Microcirculatory measurements were performed and recorded at the dorsal part of the foot, at least 3 cm from skin lesions or ulcerations, necrosis, and toes. The measurements were made after 20 minutes of acclimatization and resting supine at 20°.…”

“…Also the effective, continuous control of pain with treatment is considered an important therapeutic target. [4][5][6][7] At present, cyclic prostaglandin E 1 (PGE 1 ) treatment is effective in controlling the level of ischemia, and, indirectly, pain in CLI, by an improvement of perfusion and by reduction in the levels of pain due to local inflammation and ischemia. [2][3][4][5] It is theoretically possible that treatment with SWs may also induce a local, pure reduction in pain, in patients with CLI both in association with PGE 1 treatment and when used as the only treatment.…”