A Multicenter, Randomized, Placebo-Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis: A multicenter, randomized, placebo controlled trial

, George D. Kitas (Lead / Corresponding author), Peter Nightingale, Jane Armitage, Naveed Sattar, Jill J. F. Belch, Deborah P. M. Symmons

Research output: Contribution to journalArticle

3 Citations (Scopus)
11 Downloads (Pure)

Abstract

Objective: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. Methods: A randomized, double-blind, placebo-controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P < 0.05. RA patients age >50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. Results: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient-years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low-density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C-reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI −14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. Conclusion: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta-analysis of statin effects in other populations.

Original languageEnglish
Pages (from-to)1437-1449
Number of pages13
JournalArthritis and Rheumatology
Volume71
Issue number9
Early online date15 Apr 2019
DOIs
Publication statusPublished - Sep 2019

Fingerprint

Primary Prevention
Rheumatoid Arthritis
Randomized Controlled Trials
Placebos
Risk Reduction Behavior
LDL Cholesterol
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Confidence Intervals
Atorvastatin Calcium
Transient Ischemic Attack
Muscular Diseases
C-Reactive Protein
Meta-Analysis
Atherosclerosis
Stroke
Myocardial Infarction
Cholesterol
Lipids
Safety
Population

Cite this

@article{81c8b326a385449687b38dca7d4197a4,
title = "A Multicenter, Randomized, Placebo-Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis: A multicenter, randomized, placebo controlled trial",
abstract = "Objective: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. Methods: A randomized, double-blind, placebo-controlled trial was designed to detect a 32{\%} CVE risk reduction based on an estimated 1.6{\%} per annum event rate with 80{\%} power at P < 0.05. RA patients age >50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. Results: A total of 3,002 patients (mean age 61 years; 74{\%} female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient-years). The study was terminated early due to a lower than expected event rate (0.70{\%} per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6{\%}) experienced a primary end point, compared with 36 (2.4{\%}) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95{\%} confidence interval (95{\%} CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95{\%} CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low-density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C-reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42{\%} (95{\%} CI −14{\%}, 70{\%}). The rates of adverse events in the atorvastatin group (n = 298 [19.8{\%}]) and placebo group (n = 292 [19.5{\%}]) were similar. Conclusion: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34{\%} CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta-analysis of statin effects in other populations.",
author = "Kitas, {George D.} and Peter Nightingale and Jane Armitage and Naveed Sattar and Belch, {Jill J. F.} and Symmons, {Deborah P. M.}",
note = "{\circledC} 2019 The Authors Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.",
year = "2019",
month = "9",
doi = "10.1002/art.40892",
language = "English",
volume = "71",
pages = "1437--1449",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "Wiley",
number = "9",

}

A Multicenter, Randomized, Placebo-Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis : A multicenter, randomized, placebo controlled trial. /; Kitas, George D. (Lead / Corresponding author); Nightingale, Peter; Armitage, Jane; Sattar, Naveed; Belch, Jill J. F.; Symmons, Deborah P. M.

In: Arthritis and Rheumatology, Vol. 71, No. 9, 09.2019, p. 1437-1449.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A Multicenter, Randomized, Placebo-Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis

T2 - A multicenter, randomized, placebo controlled trial

AU - Kitas, George D.

AU - Nightingale, Peter

AU - Armitage, Jane

AU - Sattar, Naveed

AU - Belch, Jill J. F.

AU - Symmons, Deborah P. M.

N1 - © 2019 The Authors Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

PY - 2019/9

Y1 - 2019/9

N2 - Objective: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. Methods: A randomized, double-blind, placebo-controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P < 0.05. RA patients age >50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. Results: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient-years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low-density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C-reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI −14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. Conclusion: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta-analysis of statin effects in other populations.

AB - Objective: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. Methods: A randomized, double-blind, placebo-controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P < 0.05. RA patients age >50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. Results: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient-years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low-density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C-reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI −14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. Conclusion: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta-analysis of statin effects in other populations.

UR - http://www.scopus.com/inward/record.url?scp=85065313611&partnerID=8YFLogxK

U2 - 10.1002/art.40892

DO - 10.1002/art.40892

M3 - Article

C2 - 30983166

VL - 71

SP - 1437

EP - 1449

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 9

ER -