Review of the risks and benefits of statins in primary prevention of cardiovascular diseases in adults

By Dr. Chinta SidharthanAug 29 2022Reviewed by Aimee Molineux

A recent recommendation statement by the US Preventive Services Task Force (USPSTF), published in the Journal of the American Medical Association, reviewed evidence from trials and studies to assess the risks and benefits of using statins to prevent or reduce morbidities or mortalities related to cardiovascular disease (CVD).

Background

The prevalence of CVD varies across demographic factors such as sex, race, and ethnicity and is one of the major causes of morbidity and death in the United States (US), responsible for more than a fourth of all the deaths in the country. Black adults of both sexes have the highest prevalence of CVD. While statins have long been used in the treatment of CVD, the data on the use of statins in the primary prevention of CVD is still inconclusive. The present review evaluates data from existing trials and studies to provide recommendations on using statins for adults 40 years and above with no history or symptoms of known CVD.

About the study

The review assessed evidence on the benefits and risks of statin use in reducing CVD-associated morbidity and mortality across demographic and socioeconomic characteristics, varying statin intensity, and fixed-dose or titration of statins based on low-density lipoprotein cholesterol (LDL-C) levels.

The review included 22 trials that reported the benefits of statin use in the primary prevention of CVD, with a mean follow-up duration of 3.3 years and the mean age of the participants ranging from 52 to 66 in most trials. Of the 22 trials, 15 reported race and ethnicity. The pooled analyses included 18 trials (n = 85,816) that assessed the statin-associated reduction in all-cause mortality, 15 trials (n = 74,390) that evaluated statin-associated decrease in risk of composite cardiovascular outcomes such as myocardial infarction and stroke, and 12 trials (n = 75,138) that studied cardiovascular mortality. The participants in all trials presented at least one CVD risk factor, the most common being dyslipidemia.

The USPSTF also reviewed 19 trials (n = 75,005) and three observational studies (n = 417,523) that reported the negative impacts of statin therapy in adults without a history of known CVD. Of these, nine trials (n = 46,388) assessed statin-associated risk of myalgia, 12 trials (n = 55,358) studied elevated aminotransferase levels with statin use, 13 trials (n = 71,733) looked at the statin-associated risk of cancer, and six trials (n = 59,083) and the three observational studies examined the risk of new-onset diabetes with statin therapy.

Results

The pooled analyses of the trials reporting the benefits of statin therapy presented decreased risks of all-cause mortality and composite cardiovascular outcomes. Although not statistically significant, the pooled analyses reported a slightly lower risk of cardiovascular mortality risk. Of the two trials with participants 75 years or older, one reported no statin-associated decrease in all-cause mortality or composite cardiovascular outcome. In contrast, the other reported a higher risk of all-cause and CVD-associated morality, albeit with no statistical significance.

The stratified analyses did not report differences in the benefits of statin use across demographic and clinical variables, including age, sex, race, ethnicity, and the occurrence of risk factors. None of the trials reported the variations in statin therapy benefits across socioeconomic groups nor compared fixed-dose and titrated statin treatments to manage LDL-C levels.

The pooled analyses of the trials reporting the harmful effects of statin use presented no elevated risk of myalgia. The analyses also reported no difference between statins and placebos in the elevation of aminotransferase levels or the risk of cancer or diabetes. While the evidence is limited, there appear to be no increased renal or cognitive risks associated with statin use.

Conclusions

To summarize, the USPSTF recommends that clinicians evaluate the presence of CVD risk factors (such as dyslipidemia, hypertension, smoking, or diabetes) and the estimated 10-year risk of CVD while prescribing statins. The 10-year risk of CVD is estimated using the American College of Cardiology/American Heart Association Pooled Cohort Equations.

In this updated recommendation, the USPSTF concludes that for adults 40 to 75 years of age with one or more CVD risk factors, statin therapy will have a moderate net benefit in those at 10% or greater 10-year CVD risk and a small net benefit in those between 7.5 and 10% 10-year CVD risk. The review remains inconclusive due to a lack of evidence on the benefits of statin use in adults above 75 years with no known CVD history.

Among other recommendations, the review emphasizes the need for improved risk prediction across all racial and socioeconomic groups, as well as more studies on the harms and benefits of stain use in populations above 76 and below 40.