Low-intensity statin plus ezetimibe lowers LDL better than moderate-intensity statin alone

The combination of low-dose rosuvastatin plus ezetimibe represents a favourable alternative to moderate-intensity rosuvastatin alone for cholesterol management, with the combination more effective at lowering low-density lipoprotein cholesterol (LDL-C) and achieving LDL-C goals, as shown in a study.

In a cohort of patients with hypercholesterolemia, the proportion of those who met the target LDL-C levels at week 8 of treatment was significantly higher in the combination therapy arm (rosuvastatin 2.5 mg plus ezetimibe 10 mg; 51.5 percent) than in the rosuvastatin 5-mg (32.9 percent; p=0.0092), rosuvastatin 2.5-mg (22.4 percent; p<0.0001), and ezetimibe 10-mg (5.7 percent; p<0.0001) arms. [Clin Ther 2021;doi:10.1016/j.clinthera.2021.07.016]

“Statins are the basis of lipid management due to their proven benefits… [However], the use of statins is suboptimal in real-world practice, and low-intensity statins are occasionally used, especially for patients with a low risk of cardiovascular disease… These might be due to concerns about the statin-associated adverse effects,” according to a team of South Korea-based investigators.

“It is recommended to use combination therapy with complementary mechanisms of action to maximize the effect with a lower dose and reduce the risk of several adverse reactions… The addition of a cholesterol absorption inhibitor, ezetimibe, can provide a complementary action and increase the LDL-C–reducing efficacy of statins,” they pointed out. [Expert Opin Pharmacother 2020;21:531-539]

In the study, a total of 279 patients (mean age 62.3 years, 60.4 percent male) had been randomly assigned to one of four treatment arms: 68 received 2.5/10 mg of rosuvastatin and ezetimibe, 70 received 10 mg of ezetimibe, 67 received 2.5 mg of rosuvastatin, and 70 received 5 mg of rosuvastatin.

Of the patients, 30.2 percent had diabetes and 60.7 percent had hypertension. In terms of risk category, 110 patients were at very high risk, 76 were at high risk, 43 were at moderate risk, and 28 were at low risk.

In the low- and moderate-risk groups, all patients achieved target LDL-C levels in the combination therapy arm (100 percent) compared with only 65.2 percent in the rosuvastatin 5-mg, 47.6 percent in the rosuvastatin 2.5-mg, and 13 percent in the ezetimibe 10-mg arms.

However, in the high- and very-high-risk groups, only 31.8 percent of the patients in the combination therapy arm achieved the target.

The greater likelihood of attaining the target LDL-C goal with the combination therapy than with moderate-intensity rosuvastatin monotherapy in patients with varied risk profiles could be explained by a greater decrease yielded by the combination therapy in LDL-C, non-high-density lipoprotein cholesterol, and apoB protein, as well as beneficial changes in lipid ratios, the investigators pointed out.

In terms of safety, the combination of ezetimibe plus low-intensity rosuvastatin was well tolerated, with most adverse events being mild and no serious ones reported in any patients. Furthermore, the safety profiles were similar to those in the low-intensity rosuvastatin and the ezetimibe arms. Few patients discontinued treatment due to adverse events.

Despite the presence of several limitations to the study such as the small sample size and the use of surrogate markers, the findings suggest that combination therapy with low-intensity rosuvastatin 2.5 mg with ezetimibe 10 mg is a more effective strategy compared with rosuvastatin 5 mg for cholesterol management in patients with low and moderate risk, according to the investigators.