Treatment of severe intermittent claudication with PGE1--a short-term vs a long-term infusion plan--a 20 week, European randomized trial--analysis of efficacy and costs.

The efficacy, safety, and cost of prostaglandin E1 (PGE1) in the treatment of severe intermittent claudication was studied by comparing a long-term treatment protocol (LTP) with a short-term treatment protocol (STP) in a randomized 20-week study. The study included 109 patients (96 completed the study) with an average total walking distance of 65.5 +/- 8 m (range 20-109). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP, phase 2 was the main treatment phase. In the LTP, treatment was performed with 2-hour infusions (60 microg PGE1, 5 days each week for 4 weeks). In phase 3 (4-week interval period) PGE1 was administered twice a week (same dosage). In phase 4 (monitoring lasting 3 months, from week 9 to 20) no drugs were used. In STP, phase 2 treatment was performed in 2 days by a 2-hour infusion (1st day: morning 20 microg, afternoon 40 microg; 2nd day morning and afternoon 60 microg). The reduced dosage was used only at the first cycle (week 0) to evaluate reduced tolerability or side effects. Full dosage (60 microg b.i.d.) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, and 12. The observation period was between weeks 12 and 20. A treadmill test was performed at inclusion, at the beginning of each phase, and at the end of the 20th week. A similar progressive physical training plan (based on walking) and a reduction in risk factors levels plan was used in both groups. Intention-to-treat analysis indicated an increase in walking distance, which improved at 4 weeks (101.5% in STP vs 78.3% in LTP), at 8 weeks (260.9% STP vs 107.3% LTP), and at 20 weeks (351% STP vs 242% LTP). Comparable increases in pain-free walking distance were observed in the two groups. No serious drug-related side effects were observed. Local, mild adverse reactions were seen in 7% of the treated subjects in the LTP and 5% in the STP. Average cost of LTP was approximately 6,588 ECU; for STP the average cost was approximately 1,881 ECU. The cost to achieve an improvement in walking distance of 1 m was 35.6 ECU with the LTP and 9.45 ECU with the STP (26% of the LTP cost; p<0.02). For an average 100% increase in walking distance the LTP cost was 1,937 ECU vs 550 ECU with STP (p<0.02). The cost of PGE1 (including infusion and operative costs) was 25% of the total cost for LTP (24.9% for STP). In summary, between-group-analysis favors STP, in terms of walking distance and costs. Results indicate good efficacy and tolerability of PGE1 treatment. With STP less time is spent in infusion and more can be spent in the exercise program. STP reduces costs, speeds up rehabilitation, and may be used in a larger number of nonspecialized units available to follow the protocol.

[Analysis of costs and results of prostaglandin (PGE1 alpha-cyclodestrin) therapy of peripheral arterial diseases]. / Analisi di costi e risultati del trattamento con prostaglandine (PGE1 alpha-ciclodestrina) in pazienti con arteriopatie periferiche.

BACKGROUND: In this study patients with peripheral vascular disease were treated with PGE1 alpha-ciclodestrina. In the intermittent claudication group (walking distance at inclusion between 200-600 m) we included 55 patients treated with PGE1 alpha-ciclodestrina (15 diabetics) and 22 controls (not treated with PGE1 alpha-ciclodestrina). In the critical ischemia group 46 patients were treated and 47 patients followed up as controls (rest pain or necrotic lesions had been present for more than 2 weeks). METHODS: Patients with intermittent claudication were evaluated by a treadmill test (walking distance was the endpoint) and in those with critical ischemia the number of minor and major amputations in 12 months were considered as endpoints. A dose of PGE1 alpha-ciclodestrina (60-80 micrograms/day for 2 days) was repeated either every 6 or, in alternative, every 10 weeks. In the control group only antiplatelet agents, support treatment (control of risk factors) and exercise were used. RESULTS: All subgroups of patients treated with PGE1 alpha-ciclodestrina with intermittent claudication increased their walking distance (including the subgroup of diabetics). In critical ischemia there were no major amputations (only 2 minor amputations) in the PGE1 alpha-ciclodestrina group vs 10.6% (of major amputations) in the control group. Also an evaluation of laser Doppler flow, volume flow and transcutaneous PO2 indicated in subgroups of patients an improvement of microcirculation and limb perfusion with PGE1 alpha-ciclodestrina. CONCLUSIONS: The cost analysis and the quality of life evaluation indicated a benefit of preserving limbs from amputation.

["Responders and non-responders" to PGE1 and alpha-cyclodextrin]. / "Responders e non-responders" alla PGE1 alpha-ciclodestrina.

BACKGROUND: In this study we evaluated a group of 76 patients (mean age 66 +/- 12) treated with the short-term PGE1 alpha-ciclodestrina protocol (60 micrograms/die for 2 days). Responders to PGE1 alpha-ciclodestrina treatment were considered patients with an increase in flow/perfusion and an associated improvement in signs/symptoms. Moderate responders were considered patients with only flow/perfusion increase or only sign/symptoms improvement. Non-responders were characterised by no increase in flow/perfusion and no clinical improvement. METHODS: Signs/symptoms variations were measured on an analogue scale line. Perfusion measurements (laser Doppler, transcutaneous PO2, arterial inflow with straingauge plethysmography) were recorded after the two days of the short term treatment. RESULTS: In the group of 38 patient with claudication (200-600 m) 54% were considered responders, 12% non responders and 34% moderate responders. In the more severe claudication group (distance < 200 m) including 18 patients, 66% were responders, 8% non responders and 26% were considered moderate responders. In the rest pain group (13 patients) there were 63% responders, 9% non-responders and 28% moderate responders. In the gangrene group (10 patients) 60% were considered responders, 10% non-responders and 3% moderate responders. The overall percentages were 61.25% of responders, 10% of non-responders and 28.75% moderate responders. CONCLUSIONS: The evaluation of the response to PGE1 alpha-ciclodestrina treatment may indicate which group of patients will benefit from the treatment and which group will have no benefits or only limited benefits. This may induce changes in treatment (i.e. increasing doses, more prolonged treatment) or other solutions (revascularisation if possible, arterial infusion or amputation).

[Cardiovascular morbidity/mortality modified by the use of FGE1 alpha-cyclodextran and calcium heparin in patients with severe vascular diseases]. / Morbidità/mortalità cardiovascolare modificata dall'uso di PGE1 alpha-ciclodestrina ed eparina calcica in pazienti con patologia vascolare severa.

BACKGROUND: Morbidity and mortality were evaluated in three groups of vascular patients: one group was treated with PGE1 alpha-ciclodestrina according to the short term protocol; the second group was treated with PGE1 alpha-ciclodestrina and subcutaneous calcium heparin (SCH; 0.5 ml once daily, in the evening) while a third group was a historical reference group. METHODS: All included patients had a follow up of at least 12 months. The historical reference group had been managed without PGE1 alpha-ciclodestrina or SCH while in the two PGE1 alpha-ciclodestrina groups included patients who had been treated with at least four PGE1 alpha-ciclodestrina short-term treatment cycles per year. The 3 groups were comparable for sex and age distribution. In the PGE1 alpha-ciclodestrina group 142 patients (64 +/- 17; M:F = 84:58) had been treated (47 for intermittent claudication and 95 for critical ischemia). The historical reference group included 157 patients (65 +/- 18: M:F = 91:66); 53 with intermittent claudication and 104 with critical ischemia). The group treated with PGE1 alpha-ciclodestrina and SCH included 74 patients (27 with claudication and 47 with critical ischemia). RESULTS: In claudicants yearly cardiovascular morbidity was reduced from 15.5% in the reference group to 10.2% in patients treated with PGE1 alpha-ciclodestrina and to 7.9% in those treated with PGE1 alpha-ciclodestrina and SCH. Mortality decreased from 11.3% in the reference group to 6% in the PGE1 alpha-ciclodestrina group and to 5.1% in the PGE1 alpha-ciclodestrina + SCH group. In patients with critical limb ischemia morbidity decreased from 28.6% in the reference group to 23.2% in PGE1 alpha-ciclodestrina-group and to 19.4% in the PGE1 alpha-ciclodestrina + SCH group. Mortality also decreased from 16% (reference group) to 13% in the PGE1 alpha-ciclodestrinagroup, to 10.3% in the PGE1 alpha-ciclodestrina + SCH group. CONCLUSION: Cyclic treatment with PGE1 alpha-ciclodestrina produces an important decrease in cardiovascular morbidity and mortality which could be further reduced by the chronic use of subcutaneous calcium heparin.

[Non-invasive diagnosis of acute rejection in heart transplant]. / Diagnosi non invasiva del rigetto acuto nel trapianto cardiaco.

The purpose of this study was to evaluate the sensibility of some clinical and non-invasive parameters in the early diagnosis of cardiac rejection in heart transplant patients. Eighteen patients (15 males and 3 females) aged 13-57 years (mean 44 +/- 14), with orthotopic heart transplant were followed clinically for a mean period of 15 +/- 8.7 months (range 3-27). They were all treated with cyclosporin, associated with azathioprine or prednisone, or both. During the same day of the endomyocardial biopsy, the patients were submitted to a clinical examination, 12 leads ECG and 2-dimensional and Doppler-echocardiography. The following parameters were evaluated: systolic and diastolic blood pressure, heart rate, body weight, summated QRS voltage in the 12 leads ECG, interventricular septum and left ventricular posterior wall end-diastolic thickness, left ventricular myocardial mass and fractional shortening, isovolumic relaxation time. Biopsy specimens were graded according to the Billingham criteria. Totally, 251 biopsies were performed: 130 were negative, 98 positive for mild or moderate rejection, 23 had a resolving rejection pattern; in 61 cases the patients were treated for acute rejection. Compared to negative biopsies, during acute rejection the QRS voltage and the isovolumic relaxation time significantly decreased, while left ventricular wall thickness and body weight increased. To evaluate the effects of the acute immunosuppressive therapy, the same parameters before and after treatment were compared. The QRS voltage, the wall thickness and the isovolumic relaxation time were significantly modified, returning to the pre-rejection values. In conclusion, both clinical and non-invasive information, may be useful to suspect an episode of acute rejection in heart transplant patients and to program myocardial biopsy.

[Cerebral and renal aspergillosis in a patient with orthotopic heart transplant: diagnosis, treatment and follow-up]. / Aspergillosi cerebrale e renale in un paziente con trapianto cardiaco ortotopico: diagnosi, trattamento e follow-up.

A cardiac transplant recipient developed systemic aspergillosis with abscesses from aspergillus fumigatus in the brain and the right kidney. Surgical resections were performed (lobectomy for the brain abscess, partial resection for the renal abscess followed, after extension of the infection, by right nephrectomy) combined with therapy with itraconazole, a new antimycotic agent. Recovery from the infection was obtained and at 18 months of follow-up the patient feels well without signs of recurrences of the infection.