Statin Initiation Linked to Decreased Mortality and CVD, But Increased Diabetes Risk in RA Patients


A time-conditional propensity score-matched analysis suggests statin initiation was associated with reductions in risk of cardiovascular disease and all-cause mortality but an increase in the risk of new diabetes in patients with rheumatoid arthritis.

Gulsen Ozen, MD, University of Nebraska

Gulsen Ozen, MD

New research into the effects of statins in specific patient populations has returned results suggesting use of statins was associated with decreased risk of cardiovascular disease and mortality and a “modest” increase in risk of diabetes in people with rheumatoid arthritis.

Presented at the American College of Rheumatology’s annual meeting, results of the study indicate statin initiation was associated with a 32% reduction in risk of cardiovascular disease, 54% reduction in risk of all-cause mortality, and a 33% increase in risk of type 2 diabetes among patients with rheumatoid arthritis within a set of UK-based databases.

“We know that statins have been extensively studied in the general population, but our understanding of statins’ effects in RA patients are limited and mostly based on a few studies. Given that RA patients are already at higher risk for CVD and type 2 diabetes compared to general population, it is important to know the overall benefits and risks of statins,” says Gulsen Ozen, MD, a rheumatologist at University of Nebraska Medical Center in Omaha and a co-author of the study, in a statement.

With an interest in developing a better understanding of the effects of statin initiation in patients with rheumatoid arthritis, Ozen and a team of colleagues from institutions across North America designed their study to examine real-world data related to statin initiation using information from the UK Clinical Practice Research Datalink, the Hospital Episode Statistics, and Office of National Statistics databases. For inclusion in the prevalent new-user cohort study, patients needed to be at least 18 years of age with a diagnosis of rheumatoid arthritis and use of at least 1 disease-modifying antirheumatic drug (DMARD) and no alternative diagnoses from 1998-2018. Individuals were also required to have at least 1 year of baseline data available for analysis during the study period.

Statin initiators identified from the search were matched in a 1:2 ratio to non-users based on time-conditional propensity scores (TCPS) that incorporated data including age, sex, BMI, smoking, alcohol, joint surgeries, prior cardiovascular disease, hypertension, rheumatic diseases comorbidity index, osteoporosis and fracture history, cancer, thyroid, chronic liver, kidney, lung and other heart diseases, healthcare utilization, DMARDs, glucocorticoids, NSAIDs, and cardiovascular disease medications.

The primary outcome of interest for the study were outcomes of cardiovascular disease, all-cause mortality, and type 2 diabetes. Of note, cardiovascular disease outcomes included myocardial infarction, stroke, hospitalizations for heart failure, and cardiovascular mortality. Presence of diabetes was based on diagnostic codes or prescription of antidiabetic therapy. Investigators pointed out the risk of each outcome was assessed using Cox proportional hazards with adjustment for declines of TCPS and imbalanced patient characteristics after matching.

The investigators initial search returned records from 49,701 patients with a diagnosis of RA or DMARD prescription. After application of inclusion criteria, investigators identified a total of 1768 statin users and 3528 non-users for inclusion in their analysis examining cardiovascular disease and mortality and a total of 3608 statin users and 7208 non-users for the analysis examining type 2 diabetes.

When assessing incidence of cardiovascular disease, a cardiovascular disease outcome was observed among 63 statin users and 340 non-users during the study period (3.0 per 100 person-years [PY] vs 2.7 per 100 PY). When assessing incidence of all-cause mortality, results indicated death occurred among 62 statin users and 525 non-users during the study period (2.7 per 100 PY vs 4.1 per 100 PY). When assessing incidence of diabetes, results indicated a new diabetes diagnosis occurred among 128 statin users and 518 non-users (3.0 per 100 PY vs 2.0 per 100 PY).

Upon analysis, results suggested statin initiation was associated with a 32% reduction in risk of cardiovascular disease (HR, 0.68; 95% CI, 0.51-0.90), a 54% reduction in risk of all-cause mortality (HR, 0.46; 95% CI, 0.35-0.60), and 33% increase in risk of type 2 diabetes (HR, 1.33; 95% CI, 1.09-1.63). Additionally, results suggested the NNT to prevent a cardiovascular disease outcome and mortality in 1-year were 102 and 42, respectively, while the NNH for new diabetes was 127. Further analysis demonstrated patients with and without prior cardiovascular disease had similar reductions in risk of cardiovascular disease (36% vs 34%) and all-cause mortality (62% vs 54%) with statin use.

“This may suggest that statins may have other beneficial effects in RA patients beyond lipid reduction. As rheumatologists, besides optimal disease activity control, we need to work on addressing the traditional CVD risk factors in our patients in conjunction with their primary-care providers. We believe that our findings emphasize the benefits of statins in patients with RA,” Ozen added.

This study, “Reduction of Cardiovascular Disease and Mortality versus Risk of New Onset Diabetes with Statin Use in Patients with Rheumatoid Arthritis,” was presented at ACR Convergence 2021.

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