Highly Potent Statin Stands Out for Diabetes and Cataract Risks

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

Whether randomized to rosuvastatin (Crestor) or atorvastatin (Lipitor), people with coronary heart disease (CAD) did not have a statistically significant difference in the incidence of all-cause death over 3 years, from myocardial infarction (MI) and stroke. and coronary revascularization (8.7% versus 8.2%; HR 1.06, 95% CI 0.86-1.30).

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

The investigators noted that it is not clear how a particular statin might be linked to the development of diabetes, while excess cataracts might be linked to rosuvastatin’s more powerful lowering of LDL cholesterol. , namely the prevention of the development of epithelial cells in the lens.

Importantly, a greater reduction in LDL cholesterol with rosuvastatin did not translate into a reduction in clinical events. Recent evidence suggests that in people already on statin therapy, it is inflammation, not cholesterol per se, that contributes most to residual cardiovascular risk.

“Therefore, when using rosuvastatin rather than atorvastatin as statin therapy in people with coronary heart disease, a greater reduction in LDL cholesterol levels can be expected; however, careful monitoring and appropriate lifestyle interventions should be considered to mitigate the risk of developing diabetes mellitus. or cataracts,” Hong and colleagues wrote.

“To determine whether the increased occurrence of diabetes mellitus and cataract surgery is directly related to statin treatment, the mechanism underlying these relationships and the possible mechanism of a drug effect still require investigation. more in-depth,” they warned.

Whether statin-related diabetes onset is a drug or drug class effect has been controversial since the 2009 JUPITER randomized trial reported an increase in diabetes mellitus onset among users. of statins.

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

LODESTAR was a 2 × 2 factorial randomized trial designed to compare two statin dosing strategies with either of the two study statins. The main finding was that the treatment strategy to target LDL cholesterol was not inferior to the high-intensity statin strategy for key clinical outcomes.

The present secondary analysis included 4,400 adults with CAD (mean age 65 years, 28% female) who were randomized to rosuvastatin or atorvastatin. All of them were enrolled in 12 hospitals in South Korea. One in three people suffered from diabetes. More than 55% had undergone percutaneous coronary intervention. About a quarter of the cohort was already taking high-intensity statins before randomization, and more than half were already on moderate-intensity statin therapy.

After patients received their study drugs, the average daily dose of rosuvastatin and atorvastatin was 17.1 mg and 36.0 mg, respectively, over 3 years. The average LDL cholesterol reaches 1.8 mmol/L compared to 1.9 mmol/L (P.<0.001) during this period.

Hong’s group cautioned that investigators did not perform a sample size estimate for LODESTAR with respect to randomization by statin type. Other limitations include the trial’s open-label design, small number of events, inclusion only of Asians, and relatively short follow-up duration.

“Additional studies evaluating the association between statin type, onset of diabetes mellitus, and future cardiovascular events, as well as those evaluating the effects of ezetimibe on onset of diabetes mellitus are needed.” , recommend the authors of the study.