High-intensity statins help lower cholesterol among diabetics

Treatment with rosuvastatin, given at moderate and high intensity doses, as well as simvastatin and atorvastatin, given at high intensity doses, modestly reduce levels of nonhigh-density lipoprotein cholesterol (non-HDL-C) in diabetic patients over 12 weeks compared with placebo, a study has shown.

“Given the potential improvement in accuracy in predicting cardiovascular disease (CVD) when non-HDL-C is used as the primary target, our findings could inform policy on which statin types and intensities are most effective by reducing non-HDL-C in patients with diabetes and at risk of CVD,” the researchers said.

A systematic review and network meta-analysis was conducted to compare the efficacy of different statins by intensity on levels of non-HDL-C for the prevention of CVD in people with diabetes. The databases of Medline, Cochrane, and Embase were searched from inception to 1 December 2021 for randomized controlled trials comparing statins in adults with type 1 or 2 diabetes mellitus.

The researchers performed a Bayesian network meta-analysis to assess the treatment effect on non-HDL-C by mean differences and 95 percent credible intervals (CIs). They also conducted a subgroup analysis to compare patients at risk of major cardiovascular events with those at low or moderate risk. Evidence certainty was determined through the confidence in network meta-analysis framework.

Forty-two trials including 20,193 adults met the eligibility criteria. Of the participants, 11,698 were included in the meta-analysis. [BMJ 2022;376:e067731]

Levels of non-HDL-C decreased with rosuvastatin at high (−2.31 mmol/L, 95 percent CI, −3.39 to −1.21) and moderate (−2.27, 95 percent CI, −3.00 to −1.49) intensities, and simvastatin (−2.26, 95 percent CI, −2.99 to −1.51) and atorvastatin (−2.20, 95 percent CI, −2.69 to −1.70) at high intensity compared with placebo.

Likewise, atorvastatin and simvastatin at any intensity and pravastatin at low intensity effectively reduced levels of non-HDL-C. In 4,670 patients at higher risk of a major cardiovascular event, high-intensity atorvastatin showed the biggest reduction in non-HDL-C levels (−1.98, 95 percent CI, −4.16 to 0.26; surface under the cumulative ranking curve, 64 percent).

For the reduction in low-density lipoprotein cholesterol (LDL-C) levels, the most effective were high-intensity simvastatin (−1.93, 95 percent CI, −2.63 to −1.21) and rosuvastatin (−1.76, 95 percent CI, −2.37 to −1.15). Additionally, there were significant decreases seen in nonfatal myocardial infarction for atorvastatin at moderate intensity compared with placebo (relative risk, 0.57, 95 percent CI, 0.43−0.76; n=4 studies).

On the other hand, no significant differences were observed for discontinuations, nonfatal stroke, and cardiovascular deaths.

“Our meta-analysis on discontinuations because of adverse events involved fewer studies and patients, and few events were reported,” the researchers said. “Therefore, the results on discontinuations need to be interpreted with caution.” [Stat Methods Med Res 2021;30:1589-1608; J Clin Epidemiol 2021;131:113-122; Res Synth Methods 2020;11:74-90]

Of note, it remains strongly debated whether using lipid or apolipoprotein parameters other than LDL-C as targets for treatment with statins is appropriate.

“The clinical applicability of non-HDL-C and LDL-C are identical, however, with the garnered evidence suggesting that non-HDL-C might be superior to LDL-C as a marker of cardiovascular risk, and therefore, non-HDL-C levels are likely to be a more appropriate target than LDL-C levels for treatment with statins in the future,” the researchers said. [JAMA 2012;307:2499-2506; Circulation 2014;129:553-561; Eur J Prev Cardiol 2014;21:1420-1428; JAMA 2012;307:1302-1309]