Combination therapy with a lower intensity statin may be an effective alternative to higher-intensity monotherapy for some patients with atherosclerotic cardiovascular disease (ASCVD) according to research published online in the Annals of Internal Medicine.

The recent American College of Cardiology and American Heart Association cholesterol guidelines recommend initiating moderate or high-intensity statin monotherapy for patients with low-density lipoprotein (LDL) cholesterol levels of 4.91 mmol/L or greater to reduce their risk for atherosclerotic cardiovascular disease (ASCVD). The challenge in clinical practice is that some patients do not respond to high-intensity statin monotherapy and adverse effects are common.

Researchers reviewed published evidence to compare the clinical benefits, adherence, and harms of a lower-intensity statin combined with another lipid-modifying medication (bile acid sequestrant, ezetimibe, fibrate, niacin, or w-3 fatty acid) with those of higher-intensity statin monotherapy among adults at high risk for ASCVD.  A total of 36 trials were included.

Combination therapy with bile acid sequestrants or ezetimibe decreased LDL cholesterol at least as well as higher-intensity monotherapy but data on adverse events was limited. There was insufficient evidence regarding LDL cholesterol reduction when comparing moderated combination therapy with fibrates, niacin, or w-3 fatty acids. The researchers also found insufficient evidence to compare long-term clinical outcomes, such as mortality or acute coronary events.

The authors conclude that clinicians could consider using lower-intensity statin combined with bile acid sequestrant or ezetimibe among high-risk patients intolerant of or unresponsive to statins; however, this strategy should be used with caution given the lack of evidence on long-term clinical benefits and harms.

Authors of the study are Kimberly A. Gudzune, M.D., M.P.H.; Anne K. Monroe, M.D., MSPH; Ritu Sharma, BSc; Padmini D. Ranasinghe, M.D., M.PH.; Yohalakshmi Chelladurai, MBBS, M.P.H.; and Karen A. Robinson, Ph.D., all of Johns Hopkins University School of Medicine.

This project was funded under contract no. HHSA290201200007I from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.