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Patients with rheumatoid arthritis who stop taking their statins are at greatly increased risk of death, a longitudinal study found.
After adjustment for variables including age, sex, and comorbidities, patients who discontinued statin therapy had a 60% increase in cardiovascular mortality (HR 1.60, 95% CI 1.15 to 2.23, P=0.005), according to Mary A. De Vera, PhD, of the Arthritis Research Centre of Canada in Vancouver, and colleagues.
Discontinuation also was associated with a 79% increase in all-cause mortality (HR 1.79, 95% CI 1.46 to 2.20, P<0.0001), the researchers reported online in Arthritis Care & Research.
Patients with rheumatoid arthritis have twice the risk of cardiovascular mortality compared with the general population, and statins are recommended in these patients for cholesterol lowering and to prevent ischemic heart disease.
Previous studies have suggested that more than half of all individuals who are prescribed statins eventually stop taking them, and De Vera's group reported earlier that more than one-third of patients with rheumatoid arthritis discontinued the drugs over an 8-year period.
To explore the impact of this on mortality, the researchers analyzed data from an established cohort of 37,000 patients with rheumatoid arthritis in British Columbia, and determined that 4,102 had been prescribed a statin.
Mean age of the patients was 66.6 years, and mean disease duration was 19 months. A total of 60% were women.
During 16,144 person-years of follow-up, 45.4% of patients discontinued taking a statin.
And during a mean follow-up of 4 years, there were 467 deaths from any cause and 198 deaths from cardiovascular disease. Among patients who died of cardiovascular disease, the most common causes were acute myocardial infarction in 31.3%, ischemic heart disease in 30.8%, and cerebrovascular accidents in 15.2%.
Aside from statin discontinuation, other factors associated with heightened risk of cardiovascular death were:
- Older age, HR 1.07 (95% CI 1.05 to 1.09, P<0.0001)
- Male sex, HR 1.53 (95% CI 1.15 to 2.04, P=0.004)
- Previous myocardial infarction, HR 1.47 (95% CI 1.03 to 2.09, P=0.03)
- Use of antihypertensive medications, HR 1.87 (95% CI 1.26 to 2.78, P=0.002)
- Use of heart failure medications, HR 1.79 (95% CI 1.31 to 2.45, P=0.0002)
The researchers also calculated the effects of time since discontinuation and found a 0.4% increase in cardiovascular mortality for each month since stopping treatment (HR 1.004, 95% CI 1.001 to 1.016).
For all-cause mortality, factors other than stopping statin treatment that were associated with risk included:
- Older age, HR 1.07 (95% CI 1.05 to 1.08, P<0.0001)
- Male sex, HR 1.40 (95% CI 1.17 to 1.69, P=0.0004)
- Higher comorbidity scores, HR 1.18 (95% CI 1.10 to 1.25, P<0.0001)
- Previous hospitalization for infection, HR 1.36 (95% CI 1.03 to 1.78, P=0.02)
- Use of antihypertensive medications, HR 1.64 (95% CI 1.29 to 2.08, P<0.0001)
- Use of heart failure medications, HR 1.59 (95% CI 1.31 to 1.94, P<0.0001)
Current arthritis treatments also influenced all-cause mortality, according to the researchers.
Use of corticosteroids doubled the risk (HR 2.28, 95% CI 1.87 to 2.79, P<0.0001), while methotrexate use halved the risk (HR 0.54, 95% CI 0.39 to 0.74, P=0.0001).
For all-cause mortality, each month since stopping statins was associated with a 1% increase in risk (HR 1.010, 95% CI 1.002 to 1.015).
"By demonstrating the impact of statin discontinuation for specific [cardiovascular disease] mortality and all-cause mortality outcomes, our study suggests the importance of ensuring compliance with statin treatment among [rheumatoid arthritis] patients prescribed statins," stated De Vera and colleagues.
Mechanisms by which statins could influence mortality in patients with rheumatoid arthritis include effects on cholesterol, as well as immune modulation and anti-inflammatory effects.
Limitations of the study included its reliance on administrative data, the possibility of inaccuracies in diagnosis, and a lack of information on whether medication was actually taken.
Strengths were its population-based design, which can minimize selection bias, and completeness of data on medications prescribed.
The researchers concluded that their findings "provide support for raising awareness among health professionals and people with [rheumatoid arthritis] of the importance of therapy compliance among patients prescribed statins."
The study was supported by a grant from the Canadian Institutes of Health Research.
The authors also have received support from the Canadian Arthritis Network/The Arthritis Society of Canada, and the Michael Smith Foundation for Health Research.
- Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, RN, BC-ADM, Nurse Planner