Statins have outstanding high potency for diabetes and cataract risk

Two high-intensity statin regimens showed similar clinical efficacy when directly compared in secondary prevention, but one regimen was associated with a higher risk of diabetes and cataracts in results from the LODESTAR trial.

Whether they were randomized to rosuvastatin (Crestor) or atorvastatin (Lipitor), those with existing coronary artery disease (CAD) had no statistically significant difference in all-cause mortality combined. over 3 years, myocardial infarction (MI), stroke, and coronary revascularization (8.7% vs. 8.2%; HR 1.06, 95% CI 0.86-1.30).

Regarding safety, the rosuvastatin group had a higher rate of new-onset diabetes requiring initiation of antidiabetic medication (7.2% vs. 5.3%; HR 1.39, 95% CI 1.03 -1.87) and cataract surgery (2.5% vs 1.5%; HR 1.66). , 95% CI 1.07-2.58), Myeong-Ki Hong, MD, PhD, of Severance Hospital and Yonsei University of Medicine in Seoul, Korea, and colleagues reported in BMJ.

The investigators noted that it is unclear how a particular statin might be associated with new-onset diabetes, while overt cataracts may be associated with rosuvastatin’s stronger reduction of LDL cholesterol. specifically, preventing the growth of epithelial cells in the crystalline lens.

Importantly, greater LDL cholesterol reduction with rosuvastatin did not result in fewer clinical events. Recent evidence suggests that in people treated with statins, it is inflammation, not cholesterol, that is the greater contributor to residual cardiovascular risk.

“Therefore, when using rosuvastatin instead of atorvastatin as a statin regimen in people with coronary artery disease, a greater reduction in LDL cholesterol levels can be expected; however, meticulous monitoring and appropriate lifestyle interventions to minimize the risk of new-onset diabetes.” or cataracts,” Hong and colleagues wrote.

“To determine whether increases in new-onset diabetes and cataract surgery are directly related to statin treatment, the mechanisms underpinning these relationships may be unclear,” they cautioned. and the mechanism that may cause the drug’s effects still needs to be further studied.”

The question of whether statin-associated new-onset diabetes is due to the drug or an effect of the drug class has been controversial since the 2009 JUPITER randomized trial reported an increase in the incidence of new-onset diabetes in people using statins.

Other safety endpoints did not differ between the two potent statins.

LODESTAR was a 2 × 2 randomized factorial trial designed to compare two statin dosing strategies with one of two study statins. The main finding was that the targeted LDL cholesterol treatment strategy was noninferior to the high-intensity statin strategy on key clinical outcomes.

The current secondary analysis included 4,400 adults with CAD (median age 65 years, 28% women) randomized to rosuvastatin or atorvastatin. All were enrolled from 12 hospitals in Korea. One in three people have diabetes. More than 55% had undergone percutaneous coronary intervention. Approximately one-quarter of the cohort had been using high-intensity statin therapy before randomization, and more than half had been using moderate-intensity statin therapy.

After patients received study drug, the mean daily doses of rosuvastatin and atorvastatin were 17.1 mg and 36.0 mg, respectively, over 3 years. Average LDL cholesterol reached 1.8 mmol/L compared to 1.9 mmol/L (P<0.001) during this period.

Hong’s team cautions that the investigators did not perform sample size estimates for LODESTAR regarding randomization by statin type. Other limitations include the trial’s open-label design, small number of events, inclusion of only Asians, and relatively short follow-up period.

The study authors urge: “Further studies are needed to evaluate the association between statin type, new-onset diabetes and future cardiovascular events, as well as studies evaluating the effects Use of ezetimibe in new-onset diabetes”.