Which statin is best for reducing non-HDL-C and CVD risk in diabetic patients?

It is estimated that by 2025, type 2 diabetes will affect 380 million people worldwide, with a higher than normal risk of cardiovascular disease (CVD), and about 17.
9 million people will die from CVD each year
.

Lowering blood low-density lipoprotein cholesterol (LDL-C) through lipid-lowering therapy, such as statins, is the cornerstone of primary and secondary prevention of CVD
.

Studies have confirmed that statins are the most effective drugs for reducing the risk of coronary heart disease in diabetic patients
.

The National Cholesterol Education Program recommends that LDL-C values ​​should be used to predict individual lipoprotein-related CVD risk
.

 However, in patients receiving statins, non-high-density lipoprotein cholesterol (HDL-C) may be more closely associated with CVD because non-HDL-C contains all the bad types of cholesterol, such as LDL, lipoproteins, Density lipoprotein and very low density lipoprotein residues, etc.
, but LDL-C does not, so it may be better than LDL-C to assess CVD risk and treatment effect
.

In April 2021, the UK National Institute for Health and Care Excellence (NICE) updated its adult diabetes guidelines, suggesting that non-HDL-C should replace LDL-C as the primary target of lipid-lowering therapy to reduce CVD risk
.

In addition, non-HDL-C calculations are simple and clinicians can calculate by subtracting HDL-C from total cholesterol levels
.

 A recent network meta-analysis, published in BMJ, compared the efficacy of different types and doses of statins for reducing non-HDL-C levels to prevent CVD risk in people with diabetes
.

Methods We included randomised controlled trials comparing different types and doses of statins, including placebo, in adults with type 1 or type 2 diabetes in the Medline, Cochrane Central Register of Controlled Trials and Embase databases
.

The primary endpoint was change in non-HDL-C levels, calculated from measurements of total cholesterol and HDL-C
.

Secondary end points were changes in LDL-C and total cholesterol levels, major cardiovascular events (non-fatal stroke, non-fatal myocardial infarction, and CVD death), and discontinuation due to adverse events
.

 A Bayesian random-effects network meta-analysis was used to evaluate different doses of statins (low, moderate, or high: according to the guideline, statins were divided into three dose strengths by percentage of LDL-C reduction: 20%-30% reduction in Low dose; 31%-39% reduction is intermediate dose; ≥40% reduction is high dose) to reduce the therapeutic effect of non-HDL-C
.

Subgroup analyses compared those at higher risk for major cardiovascular events with those at low/intermediate risk
.

Findings Of 42 randomized controlled trials involving 20,193 people with diabetes, 11,698 were included in the meta-analysis
.

Compared with placebo, high (-2.
31mmol/L, 95%CI: -3.
39 to -1.
21) and moderate (-2.
27mmol/L, -3.
00 to -1.
49) doses of rosuvastatin and high doses of Vastatin (-2.
26mmol/L, -2.
99 to -1.
51) and high-dose atorvastatin (-2.
20mmol/L, -2.
69 to -1.
70) had the greatest reductions in non-HDL-C levels
.

 Atorvastatin and simvastatin at any dose, as well as low-dose pravastatin, were effective in reducing non-HDL-C levels
.

 Among the 4670 patients at high risk of major cardiovascular events, high-dose atorvastatin reduced non-HDL-C levels most significantly (-1.
98mmol/L, -4.
16 to 0.
26)
.

High-dose simvastatin (-1.
93mmol/L, -2.
63 to -1.
21) and rosuvastatin (-1.
76mmol/L, -2.
37 to -1.
15) were the most effective options for lowering LDL-C
.

Compared with placebo, moderate-dose atorvastatin significantly reduced the incidence of non-fatal myocardial infarction (relative risk = 0.
57, 95% CI: 0.
43 to 0.
76, n = 4 studies)
.

No significant differences were found in drug discontinuation, non-fatal stroke, and CVD death
.

Conclusions This network meta-analysis showed that moderate and high doses of rosuvastatin and high doses of simvastatin and atorvastatin were most effective in reducing non-HDL-C levels in diabetic patients, reducing non-HDL-C levels within 12 weeks.
The concentration decreased by 2.
20-2.
31mmol/L
.

 In patients at high risk for major cardiovascular events (secondary prevention), high-dose atorvastatin minimizes non-HDL-C (approximately 2.
0 mmol/L)
.

 The accuracy of predicting CVD may be improved when the primary goal is to reduce non-HDL-C levels
.

These findings are useful to assist clinicians in decision-making and support guidelines for lipid management in diabetic patients with non-HDL-C as the primary goal
.

Source: [1]Fran Lowry.
The Best Statins to Lower Non-HDL Cholesterol in Diabetes?.
Medscape.
April 13, 2022.
[2]HODKINSON A, TSIMPIDA D, KONTOPANTELIS E, et al.
Comparative effectiveness of statins on non -high density lipoprotein cholesterol in people with diabetes and at risk of cardiovascular disease: systematic review and network meta-analysis [J].
BMJ, 2022, 376: e067731.