Elevated cholesterol levels have long been known to increase the risk of heart attack and stroke. This has led to major improvements in public awareness and efforts to avoid saturated fats. LDL cholesterol travels in the bloodstream and can be absorbed into the lining of the blood vessels, leading to the development of atherosclerotic plaque. It is these same plaques that can rupture, leading to heart attack and stroke.
The development of HMG-CoA-reductase inhibitors, or statins, was a major advance in the field of cardiology.
Statins are processed in the liver and decrease the amount of LDL cholesterol your body produces. These medications can lower the LDL cholesterol by up to 50% and have been shown in study after study to significantly improve outcomes in patients with cardiovascular disease. Statins result in a 20% to 30% reduction in death, repeat heart attack, or stroke in people who have already had a heart attack. By lowering cholesterol, statins can significantly slow or even prevent the progression of plaque or blockages that form in the arteries.
Unfortunately, many people cannot tolerate statin therapy for a variety of reasons. Amongst the reported side effects, the most common are muscle aches and joint pain, which occur in about 10% to 20% of people. While it is relatively easy to stop one statin and switch to another, many patients become frustrated if they experience side effects from multiple types of statins. While there have been other lipid-lowering options, these other therapies typically do not lower cholesterol by more than 20%. This is simply not going to be adequate in many people, especially those with prior heart attack and stroke.
Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors are a new class of medication that may offer new hope to patients who simply cannot tolerate statins. The liver normally removes LDL cholesterol from the blood stream and utilizes LDL cholesterol to make energy for the body. PCSK9 is an enzyme in our blood that binds to the LDL receptors in the liver, which prevents the receptor from binding and taking in LDL cholesterol. This leads to an increase in the LDL cholesterol in the blood stream and thus allows progression of atherosclerotic plaque in the arteries.
PCSK9 inhibitors are a new class of humanized monoclonal antibodies that bind PCSK9 and prevent PCSK9 from binding the LDL receptor. This allows more LDL receptors in the liver to remove LDL cholesterol from the blood.
In a study published in 2016 in the European Heart Journal, my colleagues and I pooled data from multiple studies. We found that PCSK9 inhibitors decrease LDL cholesterol by 60%, even in patients already taking statins. Thus, if you are a patient with an LDL cholesterol of 180 mg/dL, starting a PCSK9 inhibitor may help get your LDL cholesterol to below 80 mg/dL. Additionally, very large randomized controlled trials in patients with coronary artery disease have demonstrated that PCSK9 inhibitors further reduce the risk of death, heart attack or stroke when added to standard medical therapy, including statins.
PCSK9 inhibitors, unfortunately, require administration by subcutaneous injection. However, these medications have a long duration of action and only require administration every other week or even once monthly. They also seem to be very well tolerated.
In conclusion, PCSK9 inhibitors may help those patients with high cholesterol who are unable to tolerate statins reach their cholesterol goals and reduce their risk of future heart attack or stroke. If you have cardiovascular disease or know someone who does, I encourage you to revisit the issue with an open mind and know there is a new promising alternative treatment that you should consider giving a chance.
Dr. Michael Lipinski is with Cardiovascular Associates of Charlottesville and Sentara Martha Jefferson Hospital.