Optimizing Statins First
The current American College of Cardiology algorithm for managing LDL-C in patients with ACS and hypercholesterolemia calls for optimizing statin therapy first, with a goal of reducing LDL cholesterol to less than 70 mg/dL. If the maximum tolerated dose of a statin fails to achieve the target, providers should prescribe ezetimibe, which limits absorption of cholesterol and has been shown to improve outcomes specifically in patients with ACS.
Applying these recommendations to the VA population and assuming a 6% reduction in LDL-C and a 20% reduction with ezetimibe, the researchers determined that 33% of the veterans would likely push LDL-C to or below the target by optimizing statin therapy alone. Two-thirds would have LDL-C below 70 mg/dL if they took a high-intensity statin and added ezetimibe.
That results is comparable to the active arm of ODYSSEY Outcomes trial, the authors noted but may overstate the benefit.
“Estimates vary, but muscle side effects, such as muscle pain and weakness, have occurred in 5% to 10% in some clinical studies,” Nambi told U.S. Medicine. “A percentage of these individuals will not want to continue statins,” although some may be able to tolerate a lower dose.
In addition, adherence to statin therapy is often low. In the VA population, the researchers found that 44.5% of veterans failed to adhere to recommended statin therapy.
Some nonadherent or statin-intolerant patients may do better on PCSK 9 inhibitors. “Tolerance has been better in studies with PCSK9 inhibitor ‘from a side effect standpoint,’” Virani said. “Also, as this is not a daily medication, that may improve adherence.” PCSK9 inhibitors are typically injected once or twice a month.
For high-risk patients who do not reach their goal of LDL-C below 70 mg/dL on high-intensity statins and ezetimibe, adding PCSK9 inhibitors to existing therapy could be considered in keeping with current guidelines, Virani noted.
Limiting the use of alirocumab to patients who have optimized other treatment options rather than prescribing it to all eligible veterans based on the ODYSSEY criteria would lead to a nearly two-thirds reduction in the cost of PCSK9 inhibitor therapy at retail prices, from $150 million to $53 million, according to the Houston team’s analysis. The calculation factors in the increase in costs associated with higher utilization of statins and ezetimibe.
“Although statin undertreatment could be a result of provider clinical inertia, patient intolerance, or refusal to take statin or high-intensity statin therapy,” the authors concluded, “our analyses suggest a modest role for proprotein convertase subtilisin/kexin type 9 inhibitors if current guideline-based lipid-lowering therapy is optimized.”
-
Virani SS, Akeroyd JM, Nambi V, Michos ED, Morris PB, Nasir K, Smith SC Jr, Stone NJ, Petersen LA, Ballantyne CM. Applicability and Cost Implications for Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Based on the ODYSSEY Outcomes Trial. Circulation. 2019 Jan 15;139(3):410-412.
-
Schwartz GG, Steg PG, Szarek M, et al., on behalf of the ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and Cardiovascular Outcomes After Acute Coronary Syndrome. N Engl J Med 2018 Nov 29;379:2097-107.
-
Sabatine MS, Giugliano RP, Keech AC, et al., on behalf of the FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med 2017 May 4;376(18):1713-1722.
