Background: Intolerance to the daily use of statins can be dealt with by the use of Proprotein Catylase
Subtilisin Kexin Type 9 (PCSK9) inhibitors. Alternative statin dosing has previously been utilized in
patients with statin intolerance.
Methods: Since the introduction of PCSK9 inhibitors for clinical use in 2015, we evaluated the
effectiveness of alternative statin dosing in patients with daily statin intolerance defined as the inability to
tolerate the daily use of any dose of statin. Alternative statin dosing was defined as weekly, twice weekly,
or every other day atorvastatin or rosuvastatin. From our lipid clinic population of 505 patients with primary
hypercholesterolemia (71% with atherosclerotic cardiovascular disease), 338 (67%) had daily statin
intolerance. Alternative statin dosing was agreed to by 122 patients of these 338. At the time of this analysis,
87 patients (59% with atherosclerotic cardiovascular disease) could be assessed concerning the effectiveness
of alternative statin dosing to achieve their LDL-cholesterol goal.
Results: Of the 87 patients undergoing alternative statin dosing with or without ezetimibe, 30 (34%)
achieved their goal. An additional 22 patients had a >30% reduction in LDL-cholesterol with oral therapy
alone. Twenty-nine of the 87 patients later received PCSK9 inhibition with 27 achieving either their goal or
a >30% reduction in LDL cholesterol. The baseline LDL-cholesterol of those achieving their goal LDLcholesterol with alternative statin dosing (154 + 40 mg/dL) could not be distinguished (p=0.79) from those
who later required PCSK9 inhibition to achieve their goal (157 + 41 mg/dL). Intolerance to alternative statin
dosing was seen in 24 of the 87 (28%) patients.
Conclusion: In conclusion, prior to initiating PCSK9 inhibition in patients with daily statin
intolerance, a trial of alternative statin dosing should be attempted. The success of alternative statin
dosing cannot be predicted by the baseline level of LDL-cholesterol.
Effectiveness and Tolerability of Alternative Statin Dosing in Daily Statin Intolerant Patients in the Era of PCSK9 Inhibitors