Prevention of post-thrombotic syndrome with rosuvastatin: A multicenter randomized controlled pilot trial (SAVER)

Aurélien Delluc; Waleed Ghanima; Michael J. Kovacs; Sudeep Shivakumar; Susan R. Kahn; Per Morten Sandset; Clive Kearon; Ranjeeta Mallick; Marc A. Rodger

doi:10.1016/j.thromres.2022.03.014

Prevention of post-thrombotic syndrome with rosuvastatin: A multicenter randomized controlled pilot trial (SAVER)

Aurélien Delluc, Waleed Ghanima, Michael J. Kovacs, Sudeep Shivakumar, Susan R. Kahn, Per Morten Sandset, Clive Kearon, Ranjeeta Mallick, Marc A. Rodger

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

Background: Post-thrombotic syndrome (PTS) is one of the most frequent complications of venous thromboembolism (VTE) leading to considerable morbidity and cost. Apart from appropriate anticoagulation, there is no drug or medical intervention that helps to prevent PTS. We conducted a multicenter randomized controlled trial to determine whether rosuvastatin can prevent PTS. Methods: 312 patients receiving standard anticoagulation for a newly diagnosed VTE were randomly allocated to adjuvant rosuvastatin 20 mg once daily for 180 days (n = 155) or no rosuvastatin (n = 157). At the last study visit (Day 180 ± 21), an independent observer who was blinded to study treatment performed a PTS assessment using the Villalta scale. The primary clinical outcome of the trial was mean Villalta score at Day 180. We also explored the presence of PTS as defined by Villalta score > 4 at Day 180. Patients mean age was 46.7 ± 10.8 years, 55.8% were female. Results: At Day 180, the Villalta score was 3.5 ± 0.3 in the rosuvastatin arm vs. 3.3 ± 0.3 in the control arm (p = 0.59), and presence of PTS (Villalta >4) was 29.7% in the rosuvastatin arm vs. 25.5% in the control arm (p = 0.41). Secondary analyses showed no difference between trial arms for presence of severe PTS at Day 180 (2.0% vs. 2.7%, p = 1) and for changes in Villalta score between baseline and Day 180 (−3.7 ± 4.4 vs. -4.0 ± 5.0, p = 0.59). Conclusion: This randomized controlled pilot trial did not demonstrate efficacy of rosuvastatin to reduce Villalta score. Further studies with longer duration of exposure to rosuvastatin are needed. Trial registration: ClinicalTrials.gov, number NCT02679664.

Original language	English
Pages (from-to)	119-124
Number of pages	6
Journal	Thrombosis Research
Volume	213
DOIs	https://doi.org/10.1016/j.thromres.2022.03.014
Publication status	Published - May 2022
Externally published	Yes

Bibliographical note

Funding Information:
Dr. Waleed Ghanima reports fees for participation in Advisory board from Amgen, Novartis, Pfizer, Principia Biopharma Inc- a Sanofi Company, Sanofi, SOBI, Grifols, UCB, Argenx, Cellphire, Hutchmed. Lecture honoraria from Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Grifols, Sanofi. Research grants from Bayer, and BMS/Pfizer.

Funding Information:
This study was funded by the Canadian Institutes of Health Research ( CIHR # PJT 148716 ) and the Southern and Eastern Norway Regional Health Authority (Grant # 2015112 ).

Funding Information:
Aurélien Delluc, Michael J. Kovacs, Sudeep Shivakumar, Susan R. Kahn, Clive Kearon, Marc A. Rodger are investigators of the CanVECTOR network which received funding from the Canadian Institutes of Health Research (CDT-142654).

Publisher Copyright:
© 2022 Elsevier Ltd

ASJC Scopus Subject Areas

Hematology

PubMed: MeSH publication types

Journal Article
Multicenter Study
Randomized Controlled Trial

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10.1016/j.thromres.2022.03.014

Cite this

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title = "Prevention of post-thrombotic syndrome with rosuvastatin: A multicenter randomized controlled pilot trial (SAVER)",

abstract = "Background: Post-thrombotic syndrome (PTS) is one of the most frequent complications of venous thromboembolism (VTE) leading to considerable morbidity and cost. Apart from appropriate anticoagulation, there is no drug or medical intervention that helps to prevent PTS. We conducted a multicenter randomized controlled trial to determine whether rosuvastatin can prevent PTS. Methods: 312 patients receiving standard anticoagulation for a newly diagnosed VTE were randomly allocated to adjuvant rosuvastatin 20 mg once daily for 180 days (n = 155) or no rosuvastatin (n = 157). At the last study visit (Day 180 ± 21), an independent observer who was blinded to study treatment performed a PTS assessment using the Villalta scale. The primary clinical outcome of the trial was mean Villalta score at Day 180. We also explored the presence of PTS as defined by Villalta score > 4 at Day 180. Patients mean age was 46.7 ± 10.8 years, 55.8% were female. Results: At Day 180, the Villalta score was 3.5 ± 0.3 in the rosuvastatin arm vs. 3.3 ± 0.3 in the control arm (p = 0.59), and presence of PTS (Villalta >4) was 29.7% in the rosuvastatin arm vs. 25.5% in the control arm (p = 0.41). Secondary analyses showed no difference between trial arms for presence of severe PTS at Day 180 (2.0% vs. 2.7%, p = 1) and for changes in Villalta score between baseline and Day 180 (−3.7 ± 4.4 vs. -4.0 ± 5.0, p = 0.59). Conclusion: This randomized controlled pilot trial did not demonstrate efficacy of rosuvastatin to reduce Villalta score. Further studies with longer duration of exposure to rosuvastatin are needed. Trial registration: ClinicalTrials.gov, number NCT02679664.",

author = "Aur{\'e}lien Delluc and Waleed Ghanima and Kovacs, {Michael J.} and Sudeep Shivakumar and Kahn, {Susan R.} and Sandset, {Per Morten} and Clive Kearon and Ranjeeta Mallick and Rodger, {Marc A.}",

note = "Funding Information: Dr. Waleed Ghanima reports fees for participation in Advisory board from Amgen, Novartis, Pfizer, Principia Biopharma Inc- a Sanofi Company, Sanofi, SOBI, Grifols, UCB, Argenx, Cellphire, Hutchmed. Lecture honoraria from Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Grifols, Sanofi. Research grants from Bayer, and BMS/Pfizer. Funding Information: This study was funded by the Canadian Institutes of Health Research ( CIHR # PJT 148716 ) and the Southern and Eastern Norway Regional Health Authority (Grant # 2015112 ). Funding Information: Aur{\'e}lien Delluc, Michael J. Kovacs, Sudeep Shivakumar, Susan R. Kahn, Clive Kearon, Marc A. Rodger are investigators of the CanVECTOR network which received funding from the Canadian Institutes of Health Research (CDT-142654). Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",

year = "2022",

month = may,

doi = "10.1016/j.thromres.2022.03.014",

language = "English",

volume = "213",

pages = "119--124",

journal = "Thrombosis Research",

issn = "0049-3848",

publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Prevention of post-thrombotic syndrome with rosuvastatin

T2 - A multicenter randomized controlled pilot trial (SAVER)

AU - Delluc, Aurélien

AU - Ghanima, Waleed

AU - Kovacs, Michael J.

AU - Shivakumar, Sudeep

AU - Kahn, Susan R.

AU - Sandset, Per Morten

AU - Kearon, Clive

AU - Mallick, Ranjeeta

AU - Rodger, Marc A.

N1 - Funding Information: Dr. Waleed Ghanima reports fees for participation in Advisory board from Amgen, Novartis, Pfizer, Principia Biopharma Inc- a Sanofi Company, Sanofi, SOBI, Grifols, UCB, Argenx, Cellphire, Hutchmed. Lecture honoraria from Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Grifols, Sanofi. Research grants from Bayer, and BMS/Pfizer. Funding Information: This study was funded by the Canadian Institutes of Health Research ( CIHR # PJT 148716 ) and the Southern and Eastern Norway Regional Health Authority (Grant # 2015112 ). Funding Information: Aurélien Delluc, Michael J. Kovacs, Sudeep Shivakumar, Susan R. Kahn, Clive Kearon, Marc A. Rodger are investigators of the CanVECTOR network which received funding from the Canadian Institutes of Health Research (CDT-142654). Publisher Copyright: © 2022 Elsevier Ltd

PY - 2022/5

Y1 - 2022/5

N2 - Background: Post-thrombotic syndrome (PTS) is one of the most frequent complications of venous thromboembolism (VTE) leading to considerable morbidity and cost. Apart from appropriate anticoagulation, there is no drug or medical intervention that helps to prevent PTS. We conducted a multicenter randomized controlled trial to determine whether rosuvastatin can prevent PTS. Methods: 312 patients receiving standard anticoagulation for a newly diagnosed VTE were randomly allocated to adjuvant rosuvastatin 20 mg once daily for 180 days (n = 155) or no rosuvastatin (n = 157). At the last study visit (Day 180 ± 21), an independent observer who was blinded to study treatment performed a PTS assessment using the Villalta scale. The primary clinical outcome of the trial was mean Villalta score at Day 180. We also explored the presence of PTS as defined by Villalta score > 4 at Day 180. Patients mean age was 46.7 ± 10.8 years, 55.8% were female. Results: At Day 180, the Villalta score was 3.5 ± 0.3 in the rosuvastatin arm vs. 3.3 ± 0.3 in the control arm (p = 0.59), and presence of PTS (Villalta >4) was 29.7% in the rosuvastatin arm vs. 25.5% in the control arm (p = 0.41). Secondary analyses showed no difference between trial arms for presence of severe PTS at Day 180 (2.0% vs. 2.7%, p = 1) and for changes in Villalta score between baseline and Day 180 (−3.7 ± 4.4 vs. -4.0 ± 5.0, p = 0.59). Conclusion: This randomized controlled pilot trial did not demonstrate efficacy of rosuvastatin to reduce Villalta score. Further studies with longer duration of exposure to rosuvastatin are needed. Trial registration: ClinicalTrials.gov, number NCT02679664.

AB - Background: Post-thrombotic syndrome (PTS) is one of the most frequent complications of venous thromboembolism (VTE) leading to considerable morbidity and cost. Apart from appropriate anticoagulation, there is no drug or medical intervention that helps to prevent PTS. We conducted a multicenter randomized controlled trial to determine whether rosuvastatin can prevent PTS. Methods: 312 patients receiving standard anticoagulation for a newly diagnosed VTE were randomly allocated to adjuvant rosuvastatin 20 mg once daily for 180 days (n = 155) or no rosuvastatin (n = 157). At the last study visit (Day 180 ± 21), an independent observer who was blinded to study treatment performed a PTS assessment using the Villalta scale. The primary clinical outcome of the trial was mean Villalta score at Day 180. We also explored the presence of PTS as defined by Villalta score > 4 at Day 180. Patients mean age was 46.7 ± 10.8 years, 55.8% were female. Results: At Day 180, the Villalta score was 3.5 ± 0.3 in the rosuvastatin arm vs. 3.3 ± 0.3 in the control arm (p = 0.59), and presence of PTS (Villalta >4) was 29.7% in the rosuvastatin arm vs. 25.5% in the control arm (p = 0.41). Secondary analyses showed no difference between trial arms for presence of severe PTS at Day 180 (2.0% vs. 2.7%, p = 1) and for changes in Villalta score between baseline and Day 180 (−3.7 ± 4.4 vs. -4.0 ± 5.0, p = 0.59). Conclusion: This randomized controlled pilot trial did not demonstrate efficacy of rosuvastatin to reduce Villalta score. Further studies with longer duration of exposure to rosuvastatin are needed. Trial registration: ClinicalTrials.gov, number NCT02679664.

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U2 - 10.1016/j.thromres.2022.03.014

DO - 10.1016/j.thromres.2022.03.014

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SN - 0049-3848

VL - 213

SP - 119

EP - 124

JO - Thrombosis Research

JF - Thrombosis Research

ER -

Prevention of post-thrombotic syndrome with rosuvastatin: A multicenter randomized controlled pilot trial (SAVER)

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

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