Adverse reactions occur less frequently with the statins than with most other classes of lipid lowering agents. Hepatic dysfunction has been a source of concern; however, the actual risk appears to be very small. Myopathy remains an important side effect. Statin Discontinuation Might Increase Quality of Life in Patients with Advanced Life-Limiting Illness without Affecting Median Survival.
Patients with advanced life-limiting illness commonly take a number of disease-specific medications as well as medications for symptoms and comorbidities (J Am Geriatr Soc 2007 Apr;55(4):590). Polypharmacy can be associated with increased risk of adverse events, decreased quality of life, and increased financial burden (Arch Intern Med 2006 Mar 27;166(6):605). Discontinuing unnecessary medications may improve the patient’s overall well-being, but determining which medications may be safely discontinued can be difficult (J Am Geriatr Soc 2008 Oct;56(10):1946, Drugs Aging 2013 Sep;30(9):655). Since the clinical benefits of statins in the primary and secondary prevention of cardiovascular disease take time to accrue and statins may be associated with an increased risk of adverse events such as gastrointestinal symptoms, myopathy, and musculoskeletal pain (JAMA 1999 Dec 22-29;282(24):2340), statins have been identified as a reasonable candidate for discontinuation in patients with limited life expectancy. A recent randomized trial compared statin discontinuation vs. continuation in 381 patients (mean age 74 years) with advanced life-limiting illness on statin therapy for ≥ 3 months. All patients included in this trial had an estimated life expectancy of 1 month to 1 year and recent functional status deterioration (unrelated to cardiovascular health/status). Most patients (69%) had been taking statins for > 5 years and nearly half of patients (48.8%) had a primary diagnosis of cancer.
Although this trial was originally designed to determine the effect of statin discontinuation on survival, this primary outcome was modified to death within 60 days after a prespecified interim analysis observed a longer median survival than initially projected. Median duration of follow-up was 18 weeks and overall mean survival was 213 days. Comparing statin discontinuation vs. continuation, death within 60 days occurred in 23.8% vs. 20.3% (not significant) and median time to death was 229 days vs. 190 days (not significant). There were also no significant differences in cardiovascular-related events, physical symptoms, statin-specific symptoms, or performance status. Statin discontinuation was associated with an increased total McGill Quality of Life score compared to statin continuation (7.11 vs. 6.85, p = 0.04). Discontinuation of statins was also associated with a per patient cost savings of $3.37 per day, totaling on average $716.46 for the remainder of the patient’s life.
This trial suggests that statin discontinuation may not influence survival or increase the rate of cardiovascular events in patients with advanced life-limiting illness, but may be associated with a small improvement in patient quality of life and significant monetary savings. While these results suggest the benefits of discontinuation may outweigh the risk of cardiovascular events in patients with limited life expectancy, these results do not definitively prove that statin discontinuation does not impact patient survival (likely underpowered for this outcome). The optimal timing for end of life statin discontinuation, however, requires further investigation.
For more information, see the Statins for prevention of cardiovascular disease topic in DynaMed.