Statins compared for non-HDL cholesterol levels in patients with diabetes

Moderate- and high-intensity doses of rosuvastatin and high-intensity doses of simvastatin and atorvastatin were most effective at moderately reducing levels of non-high-density-lipoprotein (HDL) cholesterol in patients with diabetes, a study found.

Researchers conducted a systematic review and network meta-analysis of randomized controlled trials published through December 2021 that compared types and intensities of statins in adults with type 1 or type 2 diabetes. The primary outcome was changes in levels of non-HDL cholesterol, while secondary outcomes were changes in levels of low-density lipoprotein (LDL) cholesterol and total cholesterol, major cardiovascular events (nonfatal stroke, nonfatal myocardial infarction, and death related to cardiovascular disease), and discontinuing statins because of adverse events. In a subgroup analysis, patients at greater risk for major cardiovascular events were compared with those at low or moderate risk. The results of the study were published March 24 by BMJ.

From 42 randomized controlled trials involving 20,193 adults, 11,698 were included in the meta-analysis. Compared with placebo, the greatest reductions in levels of non-HDL cholesterol were seen with high-intensity rosuvastatin (−2.31 mmol/L; 95% credible interval [CrI], −3.39 to −1.21 mmol/L), moderate-intensity rosuvastatin (−2.27 mmol/L; 95% CrI, −3.00 to −1.49 mmol/L), high-intensity simvastatin (−2.26 mmol/L; 95% CrI, −2.99 to −1.51 mmol/L), and high-intensity atorvastatin (−2.20 mmol/L; 95% CrI, −2.69 to −1.70 mmol/L). Any intensity of atorvastatin and simvastatin and low-intensity pravastatin also effectively reduced non-HDL cholesterol levels.

In the 4,670 patients who were at higher risk for major cardiovascular events, high-intensity atorvastatin showed the largest reduction in non-HDL cholesterol levels (−1.98 mmol/L; 95% CrI, −4.16 to 0.26 mmol/L), while high-intensity simvastatin and rosuvastatin were the most effective treatment options for reducing LDL cholesterol levels (−1.93 mmol/L [95% CrI, −2.63 to −1.21 mmol/L] and −1.76 mmol/L [95% CrI, −2.37 to −1.15 mmol/L], respectively). Significant reductions in nonfatal myocardial infarction were found with moderate-intensity atorvastatin versus placebo (relative risk, 0.57 [95% CI, 0.43 to 0.76]; n=4 studies). No significant differences were found for discontinuation of statins, nonfatal stroke, and cardiovascular death.

The researchers noted that only two studies assessed people with type 1 diabetes and that the primary focus of the study was on surrogate outcome (lipid) measures, not cardiovascular disease or major cardiovascular event outcomes. The results should mainly act as guidance for whether individuals will reach target levels of non-HDL cholesterol, LDL cholesterol, and total cholesterol with a specific statin treatment delivered at a certain intensity, they said.

“Given the potential improvement in accuracy in predicting cardiovascular disease when reduction in levels of non-HDL [cholesterol] is used as the primary target, these findings provide guidance on which statin types and intensities are most effective by reducing non-HDL[cholesterol] in patients with diabetes,” the authors wrote.