While statins are the therapy of choice for lowering low-density lipoprotein cholesterol (LDL-C) and reducing cardiovascular disease (CVD) risk, 10-25% of patients can't tolerate them or don't respond effectively enough. Until now, those at greatest risk had only a few alternatives – one being lipoprotein apheresis, an extracorporeal therapy that selectively removes LDL-C (70%), other apoB-containing lipoproteins and inflammatory markers and reduces viscosity from plasma based on electrostatic charge within three hours and requires repeat treatments every two weeks.
Apheresis also reduces lipoprotein (a) (Lp(a)), an independent CVD risk factor that is not reduced by statin therapy. Apheresis is approved by most insurance plans and Medicare for patients with familial hypercholesterolemia (FH), uncontrolled levels and CVD. The University of Kansas Medical Center has the largest lipoprotein-apheresis center in North America.
The University of Kansas Medical Center and The University of Kansas Health System have participated in several studies for using a new class of medications for patients with well-documented statin intolerance and moderate to very high CVD risk. The medication class is proprotein con vertase subtilisin/kexin type 9 monoclonal antibodies, or PCSK9 inhibitors. This is an injectable therapy, performed every 2 weeks, that can lower LDL-C by more than 60%.
Our organization was the major site, among 60 worldwide, for the ODYSSEY ALTERNATIVE randomized trial for the PCSK9 inhibitor alirocumab. I served as the principal investigator (PI). I also was the PI for the 14-site, 2-nation ESCAPE trial, which used alirocumab to wean FH patients off lipoprotein apheresis therapy.
Successful LDL-C reduction
The great news from these studies and others is that PCSK9 inhibitors have been successful in reducing LDL-C by an additional 50-60% while being safe and effective for statin-intolerant patients.
About half of the patients I regularly treat with lipoprotein apheresis at our lipid clinic are statin-intolerant, and the others are at high risk for cardiovascular disease and are unable to reach goal levels of LDL-C with other therapies.
Several of these patients on alirocumab have been able to discontinue apheresis or reduce its frequency, and others have had to continue apheresis but have seen their LDL-C levels – and their associated CVD risk – improve significantly. I have now prescribed PCSK9 inhibitors to more than 200 patients from the atherosclerosis prevention clinic.
The FDA has approved the subcutaneous injectable PCSK9 inhibitors alirocumab (Praluent®) and evolocumab (Repatha®) as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease who require additional lowering of LDL-C. This past March, at the American College of Cardiology meeting in Washington, D.C., a landmark outcome study, Fourier, demonstrated Repatha reduces risk of hard CVD events (heart attack by 27%, stroke by 21% and coronary revascularization by 22%) with their drug compared to a placebo. (Sabatine, M.S. et al. New England Journal of Medicine, March 17, 2017.)
Cost may be issue
These medications cost $10,000-$14,000 per year, and some insurance companies are resisting coverage. We've found that working with the pharmaceutical companies and specialty pharmacies can help overcome this coverage barrier – whether or not the patient's hypocholesterolemia is genetic. In the ESCAPE trial, we actually found cost savings for patients who were able to discontinue lipoprotein-apheresis, which can cost more than $50,000 per year, with alirocumab.
You have options
Statins remain the first, most reliable, affordable and effective way to lower LDL-C and related CVD risk. If you have a patient who is not able to tolerate statins or isn't reaching the goal LDL-C reduction, you may consider adding other therapies, such as ezetimibe (ZETIA®), which works in the gut rather than the liver and can sometimes further lower LDL-C by up to 20%. This past December, ZETIA became generic, and its price should be dropping in the near future. Failing that, a PCSK9 inhibitor may be a good choice.