Purpose: LDL-lowering therapy is beneficial to reduce the risk of cardiovascular disease (CVD). Higher statin doses lower LDL-C levels and prevent CVD; however, they increase adverse events, such as muscle-related adverse events and new-onset diabetes mellitus (DM). Ezetimibe combined with statin therapy improves LDL-C-lowering levels and tolerability in patients with established CVD. We aimed to analyze the efficacy and safety of a fixed-dose rosuvastatin and ezetimibe (R+E) combination therapy in intermediate-risk patients with hypercholesterolemia and no DM after 12 months of visiting a primary physician.
Methods: This multicenter, open-label, single-arm, prospective observational study involved 5717 patients from 258 primary health care centers in Korea enrolled between 2016 and 2018. Patients had no DM or previous CVD but had cardiovascular risk factors and were taking a statin or a fixed-dose combination of E (10 mg) + R (5, 10, or 20 mg). We analyzed 700 patients using propensity score matching.
Findings: A fixed-dose R+E combination therapy significantly reduced LDL-C in 5/10 mg R+E (29.35%), 10/10 mg R+E (36.19%), and 20/10 mg R+E (41.83%) compared with statin monotherapy (19.09%) at 12-month follow-up (P = 0.017). Compared with statin monotherapy, HDL-C levels increased in 5/10 mg R+E (mean change at 12 months; P = 0.004), and triglyceride levels decreased in 10/10 mg R+E (mean change at 12 months; P = 0.033). The fixed-dose R+E combination therapy was associated with fewer adverse events and a neutral effect on glucose deterioration compared with statin monotherapy at 12 months of follow-up.
Implications: In a possible paradigm shift, a fixed-dose R+E combination therapy may be beneficial for primary cardiovascular prevention with potent LDL-lowering efficacy and tolerability; however, further large prospective studies are needed.
Keywords: cardiovascular diseases; dyslipidemia; ezetimibe; glycated hemoglobin A; rosuvastatin.
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