Longterm Effects of Endothelin Receptor Antagonism on Microvascular Damage Evaluated by Nailfold Capillaroscopic Analysis in Systemic Sclerosis

2012 ◽  
Vol 40 (1) ◽  
pp. 40-45 ◽  
Author(s):  
MAURIZIO CUTOLO ◽  
GIUSEPPE ZAMPOGNA ◽  
LAURA VREMIS ◽  
VANESSA SMITH ◽  
CARMEN PIZZORNI ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Capillary Number ◽  
Disease Duration ◽  
Progressive Increase ◽  
Endothelin Receptor ◽  
Nailfold Videocapillaroscopy ◽  
Microvascular Damage ◽  
Treatment Protocols ◽  
Longterm Treatment ◽  
Previous Group

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.

Longterm Treatment with Endothelin Receptor Antagonist Bosentan and Iloprost Improves Fingertip Blood Perfusion in Systemic Sclerosis

2014 ◽  
Vol 41 (5) ◽  
pp. 881-886 ◽  
Author(s):  
Maurizio Cutolo ◽  
Barbara Ruaro ◽  
Carmen Pizzorni ◽  
Francesca Ravera ◽  
Vanessa Smith ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Blood Perfusion ◽  
Progressive Increase ◽  
Digital Ulcers ◽  
Endothelin Receptor ◽  
Nailfold Videocapillaroscopy ◽  
Raynaud Phenomenon ◽  
Doppler Flowmetry ◽  
Longterm Treatment ◽  
Capillary Dilation

Objective.To evaluate the longterm effects of endothelin-1 (ET-1) antagonism on peripheral blood perfusion (PBP) in patients with systemic sclerosis (SSc).Methods.Twenty-six patients with SSc already receiving cyclic intravenous iloprost (ILO) for severe Raynaud phenomenon were enrolled. Thirteen patients continued the treatment for a further 3 years (ILO group) and 13 patients, because of the appearance of digital ulcers, received in addition bosentan (BOS; 125 mg twice/day) for 3 years (ILO + BOS group). Both PBP at fingertips and nailfold microangiopathy were evaluated yearly by laser Doppler flowmetry and nailfold videocapillaroscopy, respectively.Results.A progressive significant increase of PBP was observed in the ILO + BOS group during the 3 followup years (p = 0.0007, p = 0.0002, p = 0.01, respectively). In contrast, an insignificant progressive decrease of PBP was observed in the ILO group. Difference of perfusion between the PBP evaluations at basal temperature and at 36°C (to test capillary dilation capacity), was found progressively decreased during the 3-year followup only in the ILO group (p = 0.05, p = 0.26, p = 0.09, respectively). A progressive increase of nailfold capillary number was observed only in the ILO + BOS group after 2 and 3 years of followup (p = 0.05).Conclusion.Longterm treatment of SSc patients with ET-1 antagonism, in combination with ILO, seems to increase fingertip blood perfusion, as well as both capillary dilation capacity and number.

Peripheral Blood Perfusion Correlates with Microvascular Abnormalities in Systemic Sclerosis: A Laser-Doppler and Nailfold Videocapillaroscopy Study

2010 ◽  
Vol 37 (6) ◽  
pp. 1174-1180 ◽  
Author(s):  
MAURIZIO CUTOLO ◽  
CARMELA FERRONE ◽  
CARMEN PIZZORNI ◽  
STEFANO SOLDANO ◽  
BRUNO SERIOLO ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Negative Correlation ◽  
Healthy Subjects ◽  
Blood Perfusion ◽  
Laser Doppler ◽  
Nailfold Videocapillaroscopy ◽  
Microvascular Damage ◽  
Local Skin ◽  
Doppler Flowmetry ◽  
Prostacyclin Analog

Objective.To investigate possible correlations between fingertip blood perfusion (FBP) status, assessed by laser Doppler flowmetry (LDF), and morphological microvascular abnormalities, detected by nailfold videocapillaroscopy (NVC), in patients with systemic sclerosis (SSc). The effects on FBP of intravenous (IV) treatment with the prostacyclin analog iloprost were also investigated.Methods.Thirty-four consecutive patients with SSc and 16 healthy subjects were evaluated. LDF was performed by analyzing blood perfusion at the fingertips in both hands. Patients with SSc were distributed into the appropriate NVC pattern of microangiopathy (early, active, and late). Iloprost was administered to inpatients with SSc by 24-hour IV infusion for 7 consecutive days (4 μg/h).Results.FBP was significantly lower in patients with SSc (p < 0.05) compared to controls. Heating of the LDF probe at 36°C induced a significant increase of FBP in all subjects (p < 0.001), but the slope of variation was significantly lower in patients with SSc compared to controls (p < 0.05). Patients with SSc showing the late NVC pattern of microangiopathy had significantly lower FBP than patients with the active and early NVC patterns (p < 0.05). A negative correlation was observed between FBP and NVC rating of the microvascular damage (p < 0.05). After iloprost treatment, a significant increase of FBP was observed in patients with SSc (p < 0.05).Conclusion.Patients with SSc show a decreased FBP partially reversible by local skin heating. The FBP correlated negatively with the extent of nailfold microvascular damage, and IV iloprost treatment increased the FBP.

Progression of Nailfold Microvascular Damage and Antinuclear Antibody Pattern in Systemic Sclerosis

2013 ◽  
Vol 40 (5) ◽  
pp. 634-639 ◽  
Author(s):  
Alberto Sulli ◽  
Barbara Ruaro ◽  
Vanessa Smith ◽  
Carmen Pizzorni ◽  
Giuseppe Zampogna ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Median Time ◽  
Antinuclear Antibody ◽  
Antinuclear Antibodies ◽  
Rapid Progression ◽  
Slight Reduction ◽  
Nailfold Videocapillaroscopy ◽  
Microvascular Damage ◽  
Antibody Pattern ◽  
Active Disease

Objective.This study evaluates possible correlations between the pattern of antinuclear antibodies (ANA) on indirect immunofluorescence (IIF) testing and nailfold microangiopathy stage (early, active, and late stage) in systemic sclerosis (SSc). Patients with SSc were followed prospectively to monitor progression of microvascular damage.Methods.The ANA pattern on IIF was searched in 42 patients with SSc showing an early pattern of nailfold microangiopathy at baseline, and was followed using nailfold videocapillaroscopy (NVC) for a median time of 91 months.Results.Among patients whose microangiopathy showed a rapid progression from early to late pattern on NVC, the IIF pattern was fine-speckled + nucleolar (Scl-70+) in 44%, centromeric in 33%, nucleolar in 11%, and homogeneous in 11% of patients with SSc. Antitopoisomerase I antibodies were significantly more frequent (57%) in patients with late pattern of microangiopathy on NVC. The median time of progression from early to active disease was significantly lower in patients with both fine-speckled + nucleolar and nucleolar ANA positivity. The severity of microangiopathy was higher in patients with the nucleolar pattern on IIF. Patients already showing a slight reduction of capillary number at baseline were likely to have either the nucleolar or the fine-speckled + nucleolar pattern on IIF. Of note, 37% of patients still showing the early microangiopathy pattern on NVC at the end of the followup were ANA-negative.Conclusion.ANA-negative patients with SSc display a slower progression of nailfold microangiopathy characterized by the early pattern on NVC. Progression to the late NVC pattern (more advanced stage of microvascular damage) seems to be associated with a different autoantibody pattern on IIF (fine-speckled + nucleolar pattern being the most prevalent).

scholarly journals Microvascular damage evaluation in systemic sclerosis: the role of nailfold videocapillaroscopy and laser techniques

Reumatismo ◽  
2017 ◽  
Vol 69 (4) ◽  
pp. 147 ◽  
Author(s):  
B. Ruaro ◽  
A. Sulli ◽  
V. Smith ◽  
C. Pizzorni ◽  
S. Paolino ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Peripheral Blood ◽  
Imaging Technique ◽  
Blood Perfusion ◽  
Clinical Aspects ◽  
Damage Evaluation ◽  
Nailfold Videocapillaroscopy ◽  
Microvascular Damage ◽  
Laser Technologies

Microvascular damage and a decrease in peripheral blood perfusion are typical features of systemic sclerosis (SSc) with serious clinical implications, not only for a very early diagnosis, but also for disease progression. Nailfold videocapillaroscopy is a validated and safe imaging technique able to detect peripheral capillary morphology, as well as to classify and to score any nailfold abnormalities into different microangiopathy patterns. Capillaroscopic analysis is now included in the ACR/EULAR classification criteria for SSc. The decrease in peripheral blood perfusion is usually associated with microvascular damage in SSc, which may be studied by different methods. Several of these make use of safe laser technologies. This paper focuses on these new clinical aspects to assess SSc microvascular impairment.

scholarly journals P169 Analysis of left ventricle dysfunction, pulmonary disease and nailfold videocapillaroscopy patterns in asymptomatic patients with early systemic sclerosis

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Francesco Masini ◽  
Lucio Monaco ◽  
Klodian Gjeloshi ◽  
Emanuele Pinotti ◽  
Roberta Ferrara ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Systemic Sclerosis ◽  
Pulmonary Function ◽  
Diastolic Dysfunction ◽  
Pulmonary Function Tests ◽  
Vascular Damage ◽  
Nailfold Videocapillaroscopy ◽  
Microvascular Damage ◽  
Function Tests ◽  
Asymptomatic Patients

Abstract Background Systemic sclerosis (SSc) is a multi-system connective tissue disease characterized by microvascular damage, inflammation and fibrosis. The aim of our study is to investigate a possible correlation between nailfold videocapillaroscopy patterns and internal organ involvement in patients with early SSc. Methods We enrolled 40 patients with early SSc according to LeRoy criteria and performed echocardiogram, pulmonary function tests (PFTs) and nailfold videocapillaroscopy. Results 20 patients had early pattern and 20 active pattern. A comparative analysis between SSc patients and healthy controls showed an alteration of mitral annular plane systolic excursion (MAPSE) (1.5±0.1 vs 1.7±0.1; p &lt; 0.001), respectively; an increased occurrence of diastolic dysfunction (11/40 vs 0/21; p = 0.01) respectively; a higher values of systolic pulmonary arterial pression (PAPs) (32±6 vs 22±6; p &lt; 0.001) and a higher frequency of patients with pulmonary hypertension (12/40 vs 0/21; p = 0.005) in SSc group. The patients with an active capillaroscopic pattern showed a trend of reduction in MAPSE, diastolic dysfunction, contractility of the right ventricle and pulmonary function tests parameters. We observed a correlation between myocardial and pulmonary vascular damage and between myocardial and pulmonary fibrosis, with lower DLCO value in patients with diastolic dysfunction (64±17 vs 85±9; p &lt; 0.0001). Conclusion A subclinical myocardial damage in these patients may be observed also in the absence of symptoms. In fact, in our study it can be noted that asymptomatic patients present a reduction in the linear myocardial contractility. Furthermore, we observed the presence of grade I diastolic dysfunction in 27.5% of cases, a sign of an initial stiffening of the wall, likely due to a fibrotic damage. In our study linear contractility emerges to be not correlated with the presence of diastolic dysfunction. Such data is very intriguing if we consider that in many studies the resolution of linear contractility with conserved ejection fraction correlated with subendocardial damage induced by microcirculation alterations. The hypothesis is the presence of a double framework at the myocardial level: a vascular damage and the presence of increased inflammation and fibrosis. The presence fibrosis is correlated between the various organs, with the values of DLCO strongly correlating with the presence of diastolic dysfunction; instead DLCO values do not correlate with pulmonary pressure values. The analysis of the capillaroscopic parameters we observed how in the early pattern the presence of vascular damage with MAPSE and PAPs alterations and presence of pulmonary hypertension emerge, while passing from early to active the presence of fibrotic damage becomes evident, the diastolic dysfunction passing from 15% to 40% and DLCO passing from 83% to 75%. The presence of subclinical cardiac and pulmonary damage in patients with systemic sclerosis and that this damage is closely related to the capillaroscopic pattern. Disclosures F. Masini: None. L. Monaco: None. K. Gjeloshi: None. E. Pinotti: None. R. Ferrara: None. T. Salvatore: None. G. Cuomo: None.

Autonomic nervous system dysfunction correlates with microvascular damage in systemic sclerosis patients

2021 ◽  
pp. 239719832110206
Author(s):  
Francesco Masini ◽  
Raffaele Galiero ◽  
Pia Clara Pafundi ◽  
Klodian Gjeloshi ◽  
Emanuele Pinotti ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Confidence Interval ◽  
Autonomic Neuropathy ◽  
Odds Ratio ◽  
Univariate Analysis ◽  
Cardiac Autonomic Neuropathy ◽  
Nailfold Videocapillaroscopy ◽  
Microvascular Damage ◽  
Autonomic Nervous System Dysfunction ◽  
Cardiac Morbidity

Objectives: Cardiac autonomic neuropathy is among the known cardiovascular complications of systemic sclerosis and may affect the whole prognosis of the disease. The aim of our study was to assess cardiac autonomic neuropathy prevalence in our cohort of systemic sclerosis patients and compare its main features with clinical and epidemiological data, particularly with the severity of microvascular damage, as detected by nailfold videocapillaroscopy. Methods: Twenty-six patients with definite systemic sclerosis were consecutively enrolled at our outpatient rheumatology clinic. All patients underwent physical examination, nailfold videocapillaroscopy, and autonomic neuropathy diagnostic tests (orthostatic hypotension test, deep breathing test, lying-to-standing, and Valsalva maneuvers). Results: Cardiac autonomic neuropathy prevalence was 50% (13 cases). On univariate analysis, cardiac autonomic neuropathy was shown to be significantly associated with an active pattern on nailfold videocapillaroscopy (odds ratio 5.86, 95% confidence interval 1.59–9.24; p = 0.032), whereas anti-Scl-70 positivity (odds ratio, 0.24; 95% confidence interval, 0.03–2.12; p = 0.049) and C-reactive protein (odds ratio, 19.32; 95% confidence interval, 1.79–56.71; p = 0.036) reached only a borderline statistical association. The time-dependent Cox multivariate regression model showed cardiac autonomic neuropathy development to be independently associated with an active pattern on nailfold videocapillaroscopy (odds ratio, 7.19; 95% confidence interval, 1.87–8.96; p = 0.042) and anti-Scl-70 positivity (odds ratio, 5.92; 95% confidence interval, 1.06–18.43; p = 0.048). Conclusions: Severe microvascular damage, as detected by nailfold videocapillaroscopy, may suggest the coexistence of autonomic dysfunction and should be considered as a red flag for the identification of patients particularly at risk of cardiac morbidity and mortality.

scholarly journals FRI0257 CAPILLAROSCOPIC VERY EARLY MORPHOLOGICAL AND QUANTITATIVE SPECIFIC ABNORMALITIES ANTICIPATE THE DEVELOPMENT OF THE “SCLERODERMA PATTERN” IN PATIENTS WITH RAYNAUD’S PHENOMENON

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 712.2-713
Author(s):  
M. Pendolino ◽  
C. Pizzorni ◽  
S. Paolino ◽  
F. Goegan ◽  
E. Gotelli ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Raynaud’S Phenomenon ◽  
Raynaud's Phenomenon ◽  
Apical Region ◽  
Nailfold Videocapillaroscopy ◽  
Research Support ◽  
Microvascular Damage ◽  
First Time ◽  
Present Pilot Study ◽  
Scleroderma Pattern

Background:Nailfold videocapillaroscopy (NVC) abnormalities in subjects with isolated Raynaud’s phenomenon (RP) may be present before transition to secondary RP(SRP) and development of a NVC “scleroderma pattern” and are known to predict for evolution to a connective tissue disease (CTD) within few years [1]. In a previous study, we have demonstrated that the very early increase of capillary diameter over 30 μm is an independent predictor for development of Systemic Sclerosis (SSc) associated SRP [2].Objectives:Present pilot retrospective study aimed to investigate in a cohort of patients affected by CTD–related RP the presence of very early capillaroscopic morphological and quantitative abnormalities in the acquired pictures of NVC performed before the development of the NVC scleroderma-pattern. In particular, the study was addressed to identify a “very early”scleroderma pattern, in order to intercept patients with RP at high risk of evolution in a CTD, specifically SSc.Methods:We selected the NVCs of 273 SSc patients presenting one of the validated NVC “scleroderma patterns”. We enrolled 26 SSc patients having a NVC analysis performed before the development ofthe “very early”NVC pattern. As controls, we evaluated 26 patients affected by other CTDs with stable non-scleroderma pattern over time. The 16 images per patient obtained by NVC examination were analyzed for total number of capillaries, number and the limbs diameters of capillaries with a diameter >30 μm, and microhemorrhages. Statistical analysis was performed using non-parametric tests.Results:All 26 SSc patients showed dilated capillaries with a diameter >30 μm in their previous NVC. Patients later developing scleroderma pattern had statically higher number and percentage of capillaries with a diameter >30 μm (p=0.0004 and p=0.0005), as well as a larger apical dilatation >40 μm (p=0.002). A progressive and significant increase in all capillary diameters were only detected in patients later diagnosed for SSc (apical p=0.006, venous p=0.02, arterial p=0.03). A significant homogeneous and progressive dilation was observed from the apical region and then involving both venous and arterial branches, only in SSc patients (p=0.002).Conclusion:Present pilot study demonstrates, for the first time that, before to develop a validated NVC scleroderma-pattern, all potential SSc patients present significant very early morphological and quantitative NVC changes. In particular, the progressive and homogeneous capillary loop dilation over 40 μm in over 40% of total number capillaries significantly could contribute to identify RP patients who will develop a SSc pattern after 4-5 years.References:[1]Cutolo M, Sulli A, Pizzorni C, Accardo S. Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis. J Rheumatol. 2000;27:155-60.[2]Trombetta AC, et al. J Rheumatol 2016;43:599-606.Disclosure of Interests:Monica Pendolino: None declared, Carmen Pizzorni: None declared, Sabrina Paolino: None declared, Federica Goegan: None declared, Emanuele Gotelli: None declared, Carlotta Schenone: None declared, Francesco Cattelan: None declared, Massimo Patanè: None declared, Elisa Alessandri: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

scholarly journals SAT0337 EVALUATION OF BODY COMPOSITION AND BONE STATUS ACCORDING TO MICROVASCULAR INVOLVEMENT IN SYSTEMIC SCLEROSIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1114.3-1114
Author(s):  
S. Paolino ◽  
E. Gotelli ◽  
A. Casabella ◽  
F. Cattelan ◽  
C. Schenone ◽  
...  
Keyword(s):  
Body Composition ◽  
Systemic Sclerosis ◽  
Bone Mass ◽  
The Body ◽  
Whole Body ◽  
Mineral Density ◽  
Nailfold Videocapillaroscopy ◽  
Research Support ◽  
Microvascular Damage ◽  
Bone Status

Background:Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease, characterized by autoimmune inflammatory microvascular damage with progressive loss of capillaries, fibrosis and ischemia of skin and internal organs. (1) Nailfold videocapillaroscopy (NVC) is a safe toll for early diagnosis of SSc, it identify morphological changes of vessel that are predictive for clinical disease progression and organ involvement.(2) About clinical complication the loss of bone mass and body composition abnormalities, particularly muscle mass and strength loss (sarcopenia), are recognized in advanced disease.(3)Objectives:To evaluated in SSc patients, the body composition and the bone status according to the microvascular condition, assessed and scored by nailfold videocapillaroscopy (NVC, “Early”,”Active”,”Late” patterns).Methods:Body composition and bone mineral density (BMD) were assessed by DEXA in 35 female SSc patients classified according to the 2013 EULAR/ACR criteria and 32 sex-matched healthy subjects. Clinical, laboratory, body composition and bone parameters were analysed according to the different NVC patterns. Means were compared by the Student’s t test or one way analysis of variance; medians were compared by the Kruskall Wallis test; and frequencies by the chi square test.Results:Higher prevalence of vertebral (26.4%vs 9.3%) and femoral (32.3% vs 9.3%) osteoporosis (OP) was found in SSc. Particularly SSc patients with “Late” NVC pattern showed a significantly higher prevalence of vertebral (p=0.018) and femoral OP (p=0.016). Regional assessment of bone mass (BM) in 7 different body areas showed a significant lower BMD only at the total spine (P=0.008) and femoral neck (p=0.027) in advanced microvascular damage. Patients with “Late” NVC pattern showed lower whole body lean mass (LM) compared to “Early” and “Active” NVC patterns, particularly at upper limbs. To note, in all body sites, BMD correlate with LM and BMC according to NVC pattern severity.Conclusion:SSc patients with most severe microvascular damage show a significantly altered body composition and bone status suggesting a strong link between microvascular failure and associated muscle/bone sufference.References:[1]Cutolo M et al. Expert Rev Clin Immunol 2019; 15(7):753-64[2]Cutolo M et al. Clin Rheumatol 2019; 38(9):2293-7[3]Corallo C et al. Rheumatol Int 2019;39(10):1767-75.Disclosure of Interests:Sabrina Paolino: None declared, Emanuele Gotelli: None declared, Andrea Casabella: None declared, Francesco Cattelan: None declared, Carlotta Schenone: None declared, Massimo Patanè: None declared, Greta Pacini: None declared, Carmen Pizzorni: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

scholarly journals AB0621 TOLERABILITY AND SAFETY OF ACETYLSALICYLIC ACID IN PATIENTS WITH SYSTEMIC SCLEROSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1606.2-1606
Author(s):  
L. Verardi ◽  
E. De Lorenzis ◽  
G. Natalello ◽  
L. Gigante ◽  
U. La Porta ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Adverse Events ◽  
Low Dose ◽  
Disease Duration ◽  
Rank Test ◽  
Digital Ulcers ◽  
Log Rank Test ◽  
Gastrointestinal Intolerance ◽  
Male Sex ◽  
Observation Period

Background:Systemic Sclerosis (SSc) is characterized by an increased incidence of macro- and microvascular complications. Current evidences on efficacy, safety and tolerability of acetylsalicylic acid (ASA) in SSc patients are limited, and the indication to this treatment is based on the experience of each single centre or physician. Esophagus and stomach are the portions of the digestive tract that are more frequently affected by adverse events due to ASA exposure.Objectives:We evaluated the incidence of adverse events associated with low-dose ASA treatment in a cohort of patients affected by SSc.Methods:Demographic data and disease features of 302 patients affected by SSc treated with low-dose ASA were collected and patients were followed-up for a median period of 6.9 years (range: 0-20 years). The proportion of patients taking ASA for secondary prevention for cardiovascular disease was also noted. The incidence of discontinuation of the drug, gastrointestinal intolerance, bleeding and death in the observation period was recorded.Results:Patients had a median age of 54.0 years (19.6-89.4); 91.9% were female, 13.2% were smokers and 44.0% had a BMI≥30Kg/m2. The prevalence of ischemic heart disease, peripheral vascular disease and stroke was of 8.6%, 5.3% and 3.3%, respectively; 48.7% of the patient took ASA in primary cardiovascular prevention. Therapy started after a median disease duration of 4.8 years (range: 0.0- 30.1 years) since the first non-Raynaud symptom and 56.6% of patients had an early disease (less than three years of disease duration). During the observation period, 30 patients (14.3 per 1000 person-years) discontinued ASA after an average period of assumption of 4.6 years (range: 0.3-18.0 years). The main adverse events were heartburn, dyspepsia and hematochezia, recorded in 18 patients (8.6 per 1000 person-years). Eight of them (3.8 per 1000 person-years) had evidence of digestive tract bleeding. Five patients (2.4 per 1000 person-years) discontinued ASA due to recurrent epistaxis. Twenty-eight patients (13.4 per 1000 person-years) died in the follow-up period, 16 of these (7.6 per 1000 person-years) because of SSc-related causes. None of them had evidence of major bleeding. We used Kaplan-Meier analysis to evaluate the incidence of ASA discontinuation. The history of digital ulcers (Log rank test X24.7, p=0.037) and male sex (Log rank test X24.3, p=0.03) were associated with a higher cumulative ASA discontinuation rate due to gastrointestinal intolerance.Conclusion:In our cohort of SSc patients, ASA resulted safe and well tolerated in most cases, despite the risk of gastroesophageal abnormalities due to disease. Although this comforting results, taking in account the lack of controlled-randomized trials about efficacy and safety, the choice to start antiplatelet therapy with ASA should be mandatorily preceded by a careful evaluation of risks and benefits. Furthermore, an attentive monitoring for possible adverse effects is needed during ASA treatment. Patients with digital ulcers and male sex could present less drug tolerability.References:[1]Valentini G et al. Ann Rheum Dis 2019. Beckett VL et al. Arthritis Rheum 1984. Kavian N et al. Vascul Pharmacol 2015. Lavie CJ et al. Curr Probl Cardiol 2017.Disclosure of Interests:Lucrezia Verardi: None declared, Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Laura Gigante: None declared, Umberto La Porta: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer

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