The use of statins — cholesterol-lowering agents to treat cardiovascular disease — alone or in combination with the diabetes treatment metformin, may increase survival in men with high-risk prostate cancer, a study suggests.
The study, “Individual and Joint Effects of Metformin and Statins on Mortality among Patients with High-Risk Prostate Cancer,” was published in the journal Cancer Medicine.
Pre-clinical animal studies have shown an association between the use of metformin and statins, and delayed prostate cancer progression and spread, but research is scarce about the possible connection in humans.
It is also unclear which of these two medications, often prescribed together, contributes most to this effect and whether they might be effective in treating high-risk prostate cancer.
Therefore, an international team of researchers set out to use data from the Surveillance, Epidemiology, and End Results database, linked with Medicare files, to examine the benefits of metformin and statin use among prostate cancer patients.
Their analysis included a pool of 12,700 patients with high-risk prostate cancer, including 5,786 who used statins only, 435 who received only metformin, 1,911 who took both medications, and 4,568 who used no such medications. Most patients receiving metformin (81%) were also taking statins.
After their cancer diagnosis, statin users lived 3.6 years and metformin-plus-statins users lived 3.9 years, compared with patients on neither medication who lived a median of 3.1 years. Metformin alone did not seem to increase survival, with patients surviving also a median of 3.1 years.
Statistical analysis then showed that using statins reduced the risk of death by 11%, while using both treatments reduced that risk by 25%. Both reductions were statistically significant and had been adjusted for factors such as cancer stage and type of treatment.
Prostate cancer-specific mortality was also reduced in both groups — by 20% in users of statins only and by 36% in users of both medications — also after adjusting for cancer stage and treatment.
Interestingly, the survival benefits of statins, either alone or with metformin, were strongest in patients who began using these medications only after their prostate cancer diagnosis.
In this group, compared to those who did not use either medication, the statin and metformin combination was associated with a 32% reduction in overall mortality (compared with a 27% reduction in the statins-only group), and a 54% reduction in prostate cancer mortality (versus a 42% reduction in the statins group). Again, metformin alone did not show a significant effect.
Consistent with the results of a prior Taiwanese study, survival was only extended in men receiving the statins atorvastatin, pravastatin, or rosuvastatin, but not lovastatin. These three medications are known to lower the amount of triglycerides (a type of fat) and “bad” cholesterol, and to raise “good” cholesterol more effectively than other statins.
Atorvastatin, in particular, “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 researchers wrote.
This is the first major epidemiological study to measure the effects of statins and metformin on overall and prostate cancer-specific mortality among high-risk prostate cancer patients. However, future randomized clinical trials are needed to confirm the benefits of statin and metformin use in this patient population.
“Based on the existing evidence, a well-designed clinical trial is warranted to investigate the roles of statins and combination statins/metformin to reduce the mortality of prostate cancer,” the researchers wrote.
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