The use of statins, alone or in combination with metformin, was found to be associated with lower all-cause and prostate cancer mortality among high-risk patients, particularly in post-diagnostic settings.
In a study published in Cancer Medicine, the use of statins, alone or in combination with metformin (Glucophage), was found to be associated with lower all-cause and prostate cancer mortality among high-risk patients, particularly in post-diagnostic settings.1
These data provide critical insight for the design of future randomized clinical trials of statins in high-risk patients with prostate cancer.
“Both metformin and statins have been associated with longer life in prostate cancer patients, yet, because they are commonly prescribed together, no study we know of has looked at these 2 medications separately,” senior author Grace Lu-Yao, PhD, associate director of Population Science at the Sidney Kimmel Cancer Center at Jefferson Health, said in a press release.2
The population-based cohort study assessed patients from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database and verified exposure to metformin and statins using Medicare Prescription Drug Event files. Moreover, the association between all-cause and prostate cancer mortality were evaluated using a Cox proportional hazard model with competing causes of death, and propensity scores were used to adjust imbalances in covariates across groups.
In the 12,700 patients with high-risk prostate cancer studied, metformin plus statin (HR, 0.75%; 95% CI, 0.67-0.83) and statin alone (HR, 0.89; 95% CI, 0.83-0.96) were significantly associated with a lower all-cause mortality, after adjusting for potential confounders. In regard to prostate cancer mortality, metformin plus statin was associated with a 36% risk reduction (95% CI, 0.54-0.85), followed by statin alone (HR, 0.80; 95% Ci, 0.69-0.92). The use of metformin alone was relatively rare though, and there was no significant association with all-cause mortality (HR, 0.89; 95% CI, 0.75-1.05) and prostate cancer mortality (HR, 0.75; 95% CI, 0.53-1.05).
Among post-diagnostic users, the effects were more pronounced. Statin alone was significantly associated with a 27% reduction in all-cause mortality (95% CI, 0.64-0.84) and a 42% reduction in prostate cancer mortality, compared to those who did not use either statins or metformin. Statin in combination with metformin was associated with a 32% reduction in all-cause mortality (95% CI, 0.57-0.80), and a 54% reduction in prostate cancer mortality (95% CI, 0.30-0.69). Metformin alone also did not show any significant effects on all-cause mortality and prostate cancer mortality among either pre-diagnostic or post-diagnostic users.
The study also found that men who took atorvastatin (Lipitor), pravastatin (Pravachol), or rosuvastatin (Crestor), but not lovastatin (Altoprev), demonstrated a reduction in mortality compared with non-users, which is consistent with previous research. Only 1 patient took fluvastatin (Lescol) and no patients took pitavastatin (Livalo) in this study, therefore no statistic survival analysis was available for either. Additionally, of the three statins studied (atorvastatin, pravastatin, and rosuvastatin) men on atorvastatin had a longer median time to progression on androgen deprivation therapy, compared to those who were not treated with any statins.
“Although the exact mechanisms remain unknown, it is worth noting that atorvastatin exhibits one of the most potent lipid-lowering effects per dose of any statin, one of the greatest bioavailability, and one of the longest half-lives,” the authors wrote.
The researchers noted that the findings likely apply to most patients with prostate cancer given the broad representation of various racial and ethnic groups within this study. However, the findings may be limited by the data sources.
1. Tan X, E J, Lin Y, et al. Individual and joint effects of metformin and statins on mortality among patients with high-risk prostate cancer. Cancer Medicine; 2020. doi:10.1002/cam4.2862.
2. Statins May Lower Mortality in High-Risk Prostate Cancer Patients [news release]. Philadelphia, Pennsylvania. Published February 10, 2020. jefferson.edu/about/news-and-events/2020/2/statins-may-lower-mortality-in-high-risk-prostate-cancer-patients.html. Accessed March 4, 2020.