Longterm effects of endothelin receptor antagonism on microvascular damage evaluated by nailfold capillaroscopic analysis in systemic sclerosis.

Abstract

OBJECTIVE:

Systemic sclerosis (SSc) is characterized by microvascular injury, fibrosis, and hypoxia of involved tissues. The vasoactive peptide endothelin-1 (ET-1) seems to be implicated in these events. Using nailfold videocapillaroscopy (NVC), we evaluated longterm effects of ET-1 antagonist treatment on nailfold microvascular damage in patients with SSc, over a 3-year followup period.

METHODS:

Thirty patients with SSc (mean age 64 ± 5 yrs, mean disease duration 8 ± 1 yrs) were recruited during their programmed standard treatment protocols. At baseline (T0), 15 patients with SSc (mean age 63 ± 15 yrs, mean disease duration 7 ± 3 yrs), already receiving cyclic intravenous infusion of iloprost (5 continuous days, average 80 μg/day, every 3 mo), continued the treatment for a further 3 years (ILO group). The remaining 15 patients with SSc (mean age 68 ± 13 yrs, mean disease duration 8 ± 4 yrs), although they continued the same cyclic intravenous iloprost treatment as the previous group, also received bosentan 125 mg twice a day for 3 years (ILO+BOS group). Qualitative analysis (scleroderma patterns) and semiquantitative scoring of the microvascular damage were performed by validated routine NVC methods.

RESULTS:

During followup, a statistically significant increase of capillary number was observed in the ILO+BOS group (p < 0.02), with a significant and progressive increase of angiogenesis (p < 0.01). In contrast, the ILO group showed a statistically significant decrease of capillary number (p < 0.05). After 3 years the number of capillaries was significantly higher in the ILO+BOS group than in the ILO group (p < 0.05). The score for giant capillaries decreased significantly in both groups of patients with SSc (p < 0.05).

CONCLUSION:

In this open study, longterm treatment with ET-1 receptor antagonist in combination with iloprost was found to interfere with progression of nailfold microvascular damage in patients with SSc, as assessed by NVC over a 3-year followup period.

• Authors: Maurizio Cutolo, Giuseppe Zampogna, Laura Vremis, Vanessa Smith, Carmen Pizzorni, Alberto Sulli
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 40 Issue 1 Pg. 40-5 (Jan 2013) ISSN: 0315-162X [Print] Canada
• PMID: 23118114 (Publication Type: Journal Article)

Chemical References

• Antihypertensive Agents
• Endothelin Receptor Antagonists
• Sulfonamides
• Iloprost
• Bosentan

Topics

• Aged
• Aged, 80 and over
• Antihypertensive Agents (pharmacology, therapeutic use)
• Bosentan
• Capillaries (drug effects)
• Drug Therapy, Combination
• Endothelin Receptor Antagonists
• Female
• Follow-Up Studies
• Humans
• Iloprost (pharmacology, therapeutic use)
• Male
• Microscopic Angioscopy
• Microvessels (drug effects, physiopathology)
• Middle Aged
• Nails (blood supply, drug effects)
• Scleroderma, Systemic (drug therapy, physiopathology)
• Sulfonamides (pharmacology, therapeutic use)
• Treatment Outcome