Trending Clinical Topic: Statins

Ryan Syrek

Disclosures

July 22, 2022

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Statins are lipid-lowering medications that rank among the most commonly prescribed drugs in the world. As such, any news related to their use is typically met with great interest. Concerns about new guidelines, a scientific statement regarding statin intolerance, and recent studies that explore the impact of their use on various noncardiac conditions have once again made statins the top trending clinical topic of the week. The global prevalence of nonalcoholic fatty liver disease (NAFLD) is reportedly increasing at an alarming rate. Now, new findings suggest that statins may be beneficial in addressing NAFLD (see Infographic).

Research presented at the annual International Liver Congress used data from the Rotterdam Elderly Study to look at the possible benefits of statins in people with nonalcoholic steatohepatitis (NASH). Beyond the reduction in NAFLD incidence, looking only at a subset of patients with biopsy-proven NAFLD, statin use was associated with a 45% reduction in NASH (odds ratio [OR], 0.55; P = .031). Researchers determined that statins may be reducing the formation of lipid droplets and influencing the expression of important inflammatory genes. Experts suggest that more research is needed. "As far as I am aware, there is no robust evidence from large, randomized trials to suggest statins lessen chances of NAFLD, or improve its surrogate markers such as ALT or GGT [gamma-glutamyltransferase] levels," Naveed Sattar, PhD, commented in an interview.

Beyond potential benefits of statins, intolerance remains a concern. The US National Lipid Association (NLA) recently issued a new scientific statement on the management of patients with statin intolerance. The statement notes that although statins are generally well tolerated, intolerance is reported in 5%-30% of patients. To identify a tolerable regimen, the NLA recommends using several different strategies (different statin, dose, and/or dosing frequency). To establish intolerance, a minimum of two statins must be attempted, including at least one at the lowest approved daily dosage. In high- and very high-risk patients who are intolerant, the statement suggests initiating nonstatin therapy while additional attempts are made to identify a tolerable statin, in order to limit the time of exposure to elevated levels of atherogenic lipoproteins.

A different set of statin recommendations has recently prompted a strong reaction. A study found that new risk thresholds used to guide statin therapy for primary prevention of atherosclerotic cardiovascular disease in the 2021 European Society of Cardiology (ESC) guidelines dramatically reduce eligibility for statin use in low-risk countries. An editorial that accompanied the results describes them as "alarming," and states that, if confirmed, guidelines should be revisited to "prevent a step backwards in the use of statins in primary prevention." For the study, Mortensen and colleagues compared the clinical performance of the 2021 ESC guidelines with American College of Cardiology (ACC)/American Heart Association (AHA), United Kingdom–National Institute for Health and Care Excellence (NICE), and the 2019 European guidelines in a contemporary European cohort of 66,909 apparently healthy individuals from the Copenhagen General Population Study.

During the 9-year follow-up, a range of 2962-4277 nonfatal and fatal cardiovascular events was observed. Results showed that although the ESC guidelines introduced a new and improved risk model, known as SCORE2, the updated age-specific recommendations dramatically reduced eligibility for a class I recommendation for statin therapy to only 4% of individuals, aged 40-69 years, and less than 1% of women. This is in sharp contrast to the previous 2019 European guidelines as well as current UK-NICE and US-ACC/AHA guidelines that provide class I/strong recommendations to 20%, 26%, and 34% of individuals, respectively, with better clinical performance in both men and women, the authors report.

Even when statins are clearly indicated, getting patients to take them can be difficult. Results from more than 600,000 commercially insured Americans with established atherosclerotic cardiovascular disease (ASCVD) showed:

  • Only 1 in 5 patients (22.5%) were taking a high-intensity statin

  • 27.6% were taking a low- or moderate-intensity statin

  • One-half (49.9%) were not taking any statin.

Women were 30% less likely than men to receive a statin (OR, 0.70). A high Charlson Comorbidity Index score (OR, 0.72) and peripheral artery disease (OR, 0.55) also reduced the odds of a statin prescription. Among statin users, middle-aged (OR, 0.83) and older (OR, 0.44) patients were less likely to be on a high-intensity statin, as were women (OR, 0.68) and patients with peripheral artery disease (OR, 0.43). However, visiting a cardiologist in the previous 12 months increased the odds that a patient was on a high-intensity statin (OR, 1.21), as did the use of other low-density lipoprotein (LDL)-cholesterol–lowering drugs (OR, 1.44).

Those patients who do take statins may experience another benefit: a lower risk for hospitalization from COVID-19. An analysis of data from more than 2 million individuals who use statins revealed a 16% lower risk for hospitalization for COVID-19 compared with matched controls (adjusted hazard ratios, 0.84). Results were similar for in-hospital death associated with COVID-19.

From controversies about guidelines to potential preventive effects in NAFLD and COVID-19, the recent news about statins generated much interest. As was the case last summer, when similar research led to increased attention, the drugs are again the top trending clinical topic of the week.

Learn more about lipid-lowering agents.

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