Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 9  |  Issue : 1  |  Page : 18-21

Beneficial effects of alprostin in patients with critical limb ischemia with peripheral arterial disease: A retrospective study


Department of Vascular Surgery, Shree Krishna Hospital, Karamsad, Gujarat, India

Date of Submission12-May-2021
Date of Decision23-Jun-2021
Date of Acceptance24-Jun-2021
Date of Web Publication23-Mar-2022

Correspondence Address:
Pratiksha Shah
Department of Vascular Surgery, Shree Krishna Hospital, Karamsad, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijves.ijves_51_21

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  Abstract 


Objective: Medical management of nonre-constructible and failed reconstruction in patients with peripheral arterial disease (PAD) has limited options. The objective was to study the safety and efficacy of Alprostin in the management of patients presenting with Stages III and IV PAD. We hypothesized that administration of Alprostin will lead to an increase in the transcutaneous oximetry (TcPO2) and ankle-brachial index (ABI) values. It may also aid in decreasing limb pain, promote ulcer healing, and increase claudication distance. Materials and Methods: A retrospective study comprising 60 patients who had presented to vascular surgery with clinical features of PAD. According to the Fontaine's staging criteria, only those patients who had presented with Stages III and IV were included in the study. Patients with critical limb ischemia and nonre-constructible or failed vascular reconstruction disease, who had not improved with conservative management, and patients presenting with Stages III and IV PAD were given injection Alprostin. A total of 6 cycles (each cycle for 3 days, every month) of Alprostin were given, dose being 166.66 mcg over 5 h/day. A qualitative assessment was performed, assessing change in rest pain, claudication distance, ulcer healing, and development of complications. In addition, a quantitative assessment was performed by measuring the TcPO2 and ABI before and after the administration of Alprostin. Results: The study comprised 60 patients, out of whom 55 were male and 5 were female with a mean age of 48.98. The patients were then classified according to the Fontaine Staging, where 50 patients presented with Stage III and 10 patients presented with Stage IV PAD. After the administration of Alprostin, 100% of patients reported of decrease in pain in lower limb, 70% reported of ulcer healing, 55% reported of increase in claudication distance, and complications were only seen in 5% of the patients. TcPO2 values showed a significant rise after the administration of Alprostin, with P value being 0.001. Finally, ABI values also showed a significant improvement after the administration of Alprostin, with P value being 0.001. Conclusion: PAD is a common circulatory condition in which the narrowed arteries in the limbs reduce blood flow to the extremities, most common being lower limbs. There are several lifestyle modifications that can be made to control PAD. Alprostin is a prostaglandin E1 analog, which acts a vasodilator and inhibits platelet aggregation. It helps to reduce vascular cell adhesion molecule levels in circulation, reduces vascular inflammation, promotes ulcer healing, increases claudication distance, and reduces rate of amputation of the affected limb. Hence, it can be concluded that Alprostin has been shown to be a safe and effective drug in patients with nonre-constructible PAD.

Keywords: Alprostin, peripheral arterial disease, prostaglandins


How to cite this article:
Patel J, Shah P, Gandhi F. Beneficial effects of alprostin in patients with critical limb ischemia with peripheral arterial disease: A retrospective study. Indian J Vasc Endovasc Surg 2022;9:18-21

How to cite this URL:
Patel J, Shah P, Gandhi F. Beneficial effects of alprostin in patients with critical limb ischemia with peripheral arterial disease: A retrospective study. Indian J Vasc Endovasc Surg [serial online] 2022 [cited 2022 May 28];9:18-21. Available from: https://www.indjvascsurg.org/text.asp?2022/9/1/18/340504




  Introduction Top


Peripheral arterial disease (PAD) is an obstructive arterial disease of the lower extremities that reduces arterial flow during exercise or, in advance stages, at rest. It comprises atherosclerosis of the abdominal aorta, iliac, and lower extremity arteries, and is underdiagnosed, undertreated, and poorly understood by the medical community. Patients with PAD may experience numerous problems such as claudication, ischemic rest pain, ischemic ulcerations, repeated hospitalizations, revascularizations, and limb loss.[1] In the United States, more than 8 million people age 40 and older have been reported to have PAD.[2] It is a severe illness with life-threatening complications. Critical limb ischemia (CLI) is the most advanced stage of PAD and it is characterized by the presence of rest pain or ulceration or gangrene on the leg and/or toes. There are numerous treatment options available for patients in early stages of PAD, with the primary treatment goals being to decrease cardiovascular morbidity and mortality, and to improve limb-related symptoms and the quality of life. In advance stages of PAD (i.e., CLI), revascularization is the priority treatment option. However, there are numerous patients in whom management of nonre-constructible and failed reconstruction has limited options. In these patients not amendable to revascularization, prostaglandin E1 (PGE1) is recommended to accelerate ulcer healing, reduce pain, and avoid amputation. Several older studies, among them seven randomized, placebo or reference controlled clinical studies, have shown clinical efficacy of Alprostin (PGE1) in patients with PAD Stage III/IV.[3],[4],[5],[6],[7],[8],[9] Therefore, the objective was to study the safety and efficacy of Alprostin (PGE1) in the management of patients presenting with Stages III and IV PAD. We hypothesized that administration of Alprostin will lead to an increase in the transcutaneous oximetry (TcPO2) and ankle-brachial index (ABI) values. It may also aid in decreasing limb pain, promote ulcer healing, and increase claudication distance.


  Materials and Methods Top


Study design

A retrospective study was conducted in the Vascular Surgery Department of Shree Krishna Hospital from March 21, 2017, to August 31, 2017. A total of 60 patients who had presented to the vascular surgery department with clinical features of PAD were studied. A thorough clinical history and physical examination was performed to determine the Fontaine stage of each patient [Table 1]. TcPO2 (normal ≥55 mmHg) and ABI (normal = 1.0–1.3) were measured before and after the administration of Alprostin for each patient.
Table 1: Fontaine staging

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Inclusion criteria

  1. Patients with CLI and nonre-constructible or failed vascular reconstruction disease
  2. Patients nonresponsive to conservative management
  3. Patients presenting with Fontaine Stage III and IV.


Exclusion criteria

  1. Patients presenting with having a recent history of myocardial infarction (MI) and/or chronic heart failure.


Patients with CLI and nonre-constructible or failed vascular reconstruction disease, who had not improved with conservative management, and patients presenting with Fontaine Stages III and IV PAD were given injection Alprostin. A total of 6 cycles (each cycle for 3 days, every month) of Alprostin were given, dose being 166.66 mcg over 5 h/day. A qualitative assessment was performed, assessing change in rest pain, claudication distance, ulcer healing, and development of complications. In addition, a quantitative assessment was performed by measuring the TcPO2 and ABI before and after the administration of Alprostin.

Ethics

Verbal consent was obtained from each patient to use his/her details for the study. The personal information of all the patients was kept confidential and in no manner manipulated. No harm was done to the patients. The patients' details were solely used for this study only and no other research studies.


  Results Top


The study comprised 60 patients who had presented with clinical features of PAD. There were a total of 55 males and 5 females with a mean age of 48.98. The patients were then classified according to the Fontaine staging, where 50 patients presented with Stage III PAD and 10 patients presented with Stage IV PAD [Table 2]. After the administration of Alprostin, 100% of patients reported of decrease in pain in lower limb, 70% reported of ulcer healing, 55% reported of increase in claudication distance, and complications were only seen in 5% of the patients [Table 3]. TcPO2 values showed a significant rise after the administration of Alprostin, with P value being 0.001. Finally, ABI values also showed a significant improvement after the administration of Alprostin, with P value being 0.001 [Table 4].
Table 2: Patient demographics

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Table 3: Qualitative parameters assessing the effect of Alprostin

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Table 4: Quantitative parameters assessing the effect of Alprostin

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  Discussion Top


This study was designed to examine the safety and efficacy of administering Alprostin (PGE1 analog) patients presenting with CLI and nonre-constructible or failed vascular reconstruction disease, who had not improved with conservative management, and patients presenting with Fontaine stages III and IV PAD. PGE1 analogs have an anti-ischemic and vasodilator effect on patients with PAD. In addition to the known effects on blood flow, viscosity, fibrinolysis and platelet aggregation, it also inhibits monocyte and neutrophil function, suggesting that PGE1 will also have anti-inflammatory effects. Moreover, they also inhibit expression of adhesion molecules (E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecules-1), release of inflammatory cytokines (tumor necrosis factor-alpha, monocyte chemoattractant protein-1), matrix components, and generation and release of growth factors (CYR61, CTGF). These actions may also contribute to the long-term effects of PGE1, particularly in more advanced stages of PAD.[10] In our study, it can be noted that after the administration of Alprostin, 100% of patients reported of decrease in pain in lower limb, 70% reported of ulcer healing, and 55% reported of increase in claudication distance.

TcPO2 is a noninvasive method reflecting local arterial skin blood flow and oxygenation and can be used as a means of determining severity and clinical progression of PAD.[11] In our study, TcPO2 was found to be lower in patients with a mean of 27.68 with standard deviation of ± 11.57, before the administration of Alprostin. Following the administration of Alprostin, it was noted that there was an increase in the TcPO2 values with a mean of 46.78 with standard deviation of ± 13.72. Therefore, it can be concluded that the improvement in TcPO2 values is statistically significant (P ≤ 0.001) after the administration of Alprostin.

The ABI is the ratio of the ankle systolic pressure to the arm systolic pressure; an ABI of < 0.90 indicates that the patient has PAD. A low ABI has been shown to be an independent predictor of increased mortality.[11] Patients with an ABI of <0.90 are twice as likely to have a history of MI, angina, and heart failure than patients with an ABI of 1.0–1.5.[11] In our study, it was found that the ABI was lower before the administration of Alprostin with a mean of 0.65 ± 0.24. It was noted that after the administration of Alprostin, there was an increase in ABI with a mean of 0.98 ± 0.34. Hence, it can be concluded that there was a statistically significant increase (P ≤ 0.001) in blood flow in the lower extremities of the patients following the administration of Alprostin.

Although the above results show a significant benefit in the use of Alprostin in patients with Fontaine Stage III and IV PAD, it must be noted that the study presents some limitations. First, since it is a retrospective study, the long-term management of PAD, increase or decrease in the probability of amputation, and the quality of life cannot be accurately assessed. In addition, to analyze the data correctly, past history of the patients must also be considered. Some comorbidities such as diabetes, hypertension, and cardiovascular conditions are in direct correlation with the development of PAD. Finally, if the study was to be repeated, it would be essential to include a larger study population. This is because a small sample size may not necessarily represent the population correctly. Therefore, it is important to have a bigger sample size, which would be an accurate representation of the population.


  Conclusion Top


PAD is a common circulatory condition in which the narrowed arteries in the limbs reduce blood flow to the extremities, most common being lower limbs. There are several lifestyle modifications that can be made to control PAD. Alprostin is a PGE1 analog, which acts a vasodilator and inhibits platelet aggregation. It helps to reduce vascular cell adhesion molecule levels in circulation, reduces vascular inflammation, promotes ulcer healing, increases claudication distance, and reduces rate of amputation of the affected limb. Hence, it can be concluded that Alprostin has been shown to be a safe and effective drug in patients with nonre-constructible PAD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Olin A, Jeffrey W, Sealove BA. Peripheral Artery Disease: Current Insight into the Disease and Its Diagnosis and Management. Mayo Clinic Proceedings, Mayo Foundation for Medical Education and Research, July 2010. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894725/. [Last accessed on 2020 Mar 12].  Back to cited text no. 1
    
2.
Peripheral Artery Disease. National Heart Lung and Blood Institute, U.S. Department of Health and Human Services. Available from: https://www.nhlbi.nih.gov/health-topics/peripheral-artery-disease. [Last accessed on 2020 Mar 12].  Back to cited text no. 2
    
3.
Altstaedt HO, Berzewski B, Breddin HK, Brockhaus W, Bruhn HD, Cachovan M, et al. Treatment of patients with peripheral arterial occlusive disease Fontaine stage IV with intravenous iloprost and PGE1: A randomized open controlled study. Prostaglandins Leukot Essent Fatty Acids 1993;49:573-8.  Back to cited text no. 3
    
4.
Böhme H, Brülisauer M, Härtel U, Bollinger A. Periphere arterielle Verschlußkrankheit im Stadium III und IV. Kontrollierte Zweizentren Studie zur Wirksamkeit von intraarteriellen Prostaglandin E1 Infusionen. Med Welt 1989;40:1501-3.  Back to cited text no. 4
    
5.
Diehm C, Hübsch Müller C, Stammler F. Intravenöse Prostaglandin E1 Therapie bei Patienten mit peripherer arterieller Verschlußkrankheit (pAVK) im Stadium III – Eine doppelblinde, placebokontrollierte Studie. In: Heidrich H, Böhme H, Rogatti W, editors. Prostaglandin E1 – Wirkungen und Therapeutische Wirksamkeit. Berlin: Springer Verlag; 1988. p. 133-43.  Back to cited text no. 5
    
6.
Menzoian JO. Alprostadil in the treatment of patients with severe peripheral arterial occlusive disease (PAOD) not amenable to surgery: Results of a randomized, placebo controlled multicenter study. Int Angiol 1995;141:104-5.  Back to cited text no. 6
    
7.
Stiegler H, Diehm C, Grom E, Martin M, Morl H, Rudofsky G, et al. Placebokontrollierte, doppelblinde Studie zur Wirksamkeit von I.V. Prostaglandin E1 bei Diabetikern mit pAVK im Stadium IV. Vasa Suppl 1992;35:164-6.  Back to cited text no. 7
    
8.
Trübestein G, Ludwig M, Diehm C, Gruß D, Horsch S. Prostaglandin E1 bei arterieller Verschlußkrankheit im Stadium III und IV – Ergebnisse einer multizentrischen Studie. DMW 1987;112:955-9.  Back to cited text no. 8
    
9.
Trübestein G, Bary SV, Breddin K, Diehm C, Gruss JD, Heinrich H, et al. Intravenous prostaglandin E1 versus pentoxifylline therapy in chronic arterial occlusive disease – A controlled randomized multicenter study. Vasa Suppl 1989;28:44-9.  Back to cited text no. 9
    
10.
Schrör K, Hohlfeld T. Mechanisms of anti-ischemic action of prostaglandin E1 in peripheral arterial occlusive disease. Vasa 2004;33:119-24.  Back to cited text no. 10
    
11.
Benhamou Y, Edet S, Begarin L, Cailleux N, Hanoy M, Bessin C, et al. Transcutaneous oxymetry as predictive test of peripheral vascular revascularization in haemodialysis population. Nephrol Dial Transplant 2012;27:2066-9.  Back to cited text no. 11
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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