Statins Are Associated With Reduced Mortality in Multiple Myeloma

Abstract

The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have activity in one of the pathways influenced by nitrogen-containing bisphosphonates, which are associated with improved survival in multiple myeloma (MM). To understand the benefit of statins in MM, we evaluated the association between statin use and mortality in a large cohort of patients with MM. Patients and MethodsFrom the Veterans Administration Central Cancer Registry, we identified patients diagnosed with MM between 1999 and 2013. We defined statin use as the presence of any prescription for a statin within 3 months before or any time after MM diagnosis. Cox proportional hazards regression assessed the association of statin use with mortality, while controlling for known MM prognostic factors. ResultsWe identified a cohort of 4,957 patients, of whom 2,294 received statin therapy. Statin use was associated with a 21% decrease in all-cause mortality (adjusted hazard ratio, 0.79; 95% CI, 0.73 to 0.86; P , .001) as well as a 24% decrease in MM-specific mortality (adjusted hazard ratio, 0.76; 95% CI, 0.67 to 0.86; P , .001). This association remained significant across all sensitivity analyses. In addition to reductions in mortality, statin use was associated with a 31% decreased risk of developing a skeletal-related event. ConclusionIn this cohort study of US veterans with MM, statin therapy was associated with a reduced risk of both all-cause and MM-specific mortality. Our findings suggest a potential role for statin therapy in patients with MM. The putative benefit of statin therapy in MM should be corroborated in prospective studies.

p53 as a Regulator of Lipid Metabolism in Cancer

“…Thus, the mevalonate pathway promotes tumorigenesis by two mechanisms: (1) by enhancing protein prenylation, which is required for the activation of proteins involved in proliferation and migration, such as Ras and Rho; and (2) by stabilizing conformational mutant p53. It should be noted that the efficacy of statins (cholesterol lowering drugs) that inhibit the mevalonate pathway on tumor suppression is promising, yet they still remain controversial [68,69,70,71,72]. Our study may suggest the importance of knowledge of the p53 status in tumors treated with statins to determine their efficacy.…”

Cholesterol metabolism in cancer: mechanisms and therapeutic opportunities

“…Patients receiving statins for at least 5 years have been found to have a 47% lower risk of colorectal cancer than non-statin users, after adjustment for other known risk factors 97 . In another study, statins decreased patient mortality across various cancer types, regardless of whether they were taken before or after cancer diagnosis [98][99][100][101] . Experiments on leiomyoma have shown that simvastatin treatment not only inhibits cell proliferation and enhances cell apoptosis, but also suppresses levels of extracellular matrix proteins 102 .…”

Cardio-oncology Related to Heart Failure

“…116,117 Recently, a large study of more than 4000 veterans with multiple myeloma demonstrated a 12-month overall survival advantage in individuals with multiple myeloma on a statin. 118 Similarly, in a large study by Nielsen and colleagues 119 of the Danish population with a cancer diagnosis between 1995 and 2007, there was a reduced cancer mortality among statin users compared with those who had never used statins in 13 different types of cancers (adjusted HR for death of any cause 0.82; 95% CI, 0.81–0.85).…”