In diabetes, some statins reduce non–HDL-C better than others vs. placebo
A review reaffirmed well-known information about the potency of commonly prescribed statins and suggested that non–high-density lipoprotein cholesterol (HDL-C) may be a better measure of cardiovascular risk than low-density lipoprotein cholesterol in patients on statins, an ACP Journal Club commentary said.
Moderate- and high-intensity doses of rosuvastatin and high-intensity doses of simvastatin and atorvastatin were most effective at reducing levels of non–high-density lipoprotein cholesterol (HDL-C) in patients with diabetes, according to a systematic review and network meta-analysis. Researchers found 42 randomized controlled trials (RCTs) involving 20,193 adults with type 1 or type 2 diabetes, of whom 11,698 were included in the meta-analysis. In a subgroup of 4,670 patients who were at higher risk for major cardiovascular events, high-intensity atorvastatin showed the largest reduction in non–HDL-C levels.
The study was published by The BMJ on March 24 and summarized in the April ACP Diabetes Monthly. The following commentary by Michael Tanner, MD, FACP, was published in the ACP Journal Club section of Annals of Internal Medicine on Aug. 2.
The systematic review by Hodkinson and colleagues found that moderate- or high-dose rosuvastatin and high-dose atorvastatin and simvastatin were most effective for lowering non–HDL-C levels over 12 weeks vs. placebo in patients with diabetes. However, the high-intensity simvastatin dose (80 mg/d) has been restricted in the USA since 2011 because of concerns about muscle damage. This review only reaffirms what is well-known: Rosuvastatin (2.31-mmol/L [89.2-mg/dL] reduction in non–HDL-C) and atorvastatin (2.2-mmol/L [84.9-mg/dL] reduction) are the most potent of the commonly prescribed statins, and fluvastatin and pravastatin are the weakest.
The review suggests that non–HDL-C may be a better measure of cardiovascular risk than low-density lipoprotein cholesterol (LDL-C) in patients receiving statins. Because HDL-C is the only type of cardioprotective cholesterol, non–HDL-C (total cholesterol minus HDL-C) expresses the sum of all atherogenic cholesterol [LDL-C, intermediate-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol and lipoprotein(a)] in one convenient number. In most laboratories, LDL-C is not measured directly but is calculated according to the Friedewald equation: LDL-C = total cholesterol minus HDL-C minus (triglycerides/5). Because recent food intake increases triglyceride levels, and therefore spuriously lowers calculated LDL-C levels, calculated LDL-C using the Friedewald equation is ideally measured in the fasting state. In contrast, the simpler formula for calculating non–HDL-C levels does not include triglyceride levels; therefore, a patient's fasting status is immaterial. This is a major advantage of using non–HDL-C as a measure of cardiovascular risk—it takes fasting out of the equation.
Since 2014, the UK National Institute for Health and Care Excellence has recommended using non–HDL-C instead of LDL-C as the primary target for cardiovascular risk reduction and does not require fasting samples. Perhaps it is time for the American College of Cardiology and American Heart Association to follow suit, and for reporting this value directly, which is not the current standard of clinical laboratory reporting in the USA.
The few RCTs that reported cardiovascular event outcomes found an impressive reduction in nonfatal myocardial infarction for moderate-intensity atorvastatin compared with placebo (relative risk, 0.57 [95% CI, 0.43 to 0.76]; 4 RCTs). Until more outcome data are available for rosuvastatin, atorvastatin may be the most evidence-based choice for lowering non–HDL-C levels in patients with diabetes.