48- Update on Aspirin: A Critical Component of Optimal Medical Therapy
There’s More to It Than Preventing Clots
Aspirin is an important component of optimal medical therapy (OMT). It is included in every optimal medical treatment research study that I have found for cardiovascular disease and diabetes. All the OMT studies to date involve patients at high risk for cardiovascular events. They provide treatments that reduce heart attack and stroke more than they reduce the target risk factor. All the critical components of OMT are antioxidants that inhibit the master metabolic switch mTOR (mechanistic target of rapamycin) and activate AMPK (AMP kinase). Aspirin is no exception. Aspirin inhibits mTOR and activates AMPK. Metformin and aspirin have an additive effect in that regard.
Aspirin’s benefits are not just about preventing a clot. The metabolic effects are important also. Patients with established arterial disease receive dramatic benefit form low-dose daily aspirin treatment (81 mg). This medication lowers the relative risk of a major cardiovascular event by 8% a year. In two years, that is 16%, in three years 24% and so forth. That is a very effective treatment. The downside is stomach ulcer formation and bleeding. Bleeding risk is increased in the presence of cardiovascular risk factors like high blood pressure, diabetes, high cholesterol, and smoking. Said another way, increased cardiovascular risk increases bleeding risk. Optimal medical therapy reduces cardiovascular risk, cardiovascular risk factors, and should reduce the risk of bleeding. It is all tied together.
The impact on mTOR and AMPK is probably the reason aspirin has a powerful effect in preventing cancer of the colon and rectum. The Lynch syndrome is the most common type of hereditary colon cancer and it increases the risk of endometrial and other cancers. Taking aspirin reduced the relative risk of colon cancer in Lynch syndrome patients by 63%. In the broader population, aspirin reduces the risk of colon cancer by 20 percent. The effect on mTOR and AMPK is an important part of the mechanism of cancer prevention in this case. Aspirin benefits were greater with daily use and longer duration of use. Of course, that makes sense. Cancer is a disease due to changes in gene expression (epigenetics) and mutations related to excess oxidant production. Oxidants build, mutations occur, and genes are inappropriately activated over decades in a vicious cycle. mTOR and AMPK are master metabolic switches that are important in that process. Aspirin pushes mTOR and AMPK activity in a protective direction.
So, in chronic disease, we have been thinking about aspirin solely in terms of its effect in preventing clot formation. There is much more to it. As far as I have been able to determine, every medication that reduces the risk of cancer and heart artery disease more than it reduces the target risk factor inhibits mTOR and activates AMPK. Cancer and heart artery disease development occurs over decades. Clinical trials are short. We have proof that combining multiple medicines that inhibit mTOR and activate AMPK over 8 years dramatically lowers heart attack and stroke and prolongs life by 8 years. We also have proof that it reduces all cause mortality. If you look at the diagram at the beginning of the article, patients who received optimal medical treatment after a heart attack, had about twice the reduction of all-cause mortality, compared with the impact on cardiovascular deaths. Aspirin alone is highly effective in vascular disease and cancer. When combined with lisinopril, a statin, metformin, and spironolactone, within 3 months of a heart attack, it reduces mortality by 90% over the next 5 years. Optimal medical treatment should be a universal standard of care. Patients at high risk of heart artery disease or colon cancer should take aspirin.