Introduction: Despite statin monotherapy, many high-risk patients are not at recommended low-density lipoprotein cholesterol goals. Moreover, these patients are also likely to exhibit an atherogenic dyslipidemia characterized by decreased high-density lipoprotein cholesterol and elevated triglycerides.

As a consequence, combination lipid-altering drug therapies are frequently required to improve the lipid profile. The long-term safety and tolerability of these combination therapies are key determinants for good compliance and cardiovascular benefits.

Areas covered: This review summarizes the safety data published on combination drugs for the treatment of hyperlipidemia by examining the various combinations with a statin and also the other combination therapies used when statin treatment is not tolerated. The reader will gain insight into the incidence and severity of the major adverse events expected with combination therapies and the recommendations on the use of these combined treatments. A specific focus is made on muscle-related side effects.

Expert opinion: The existing data suggest that ezetimibe, bile acid sequestrants and ω-3 fatty acids appear unlikely to increase the risk of adverse events, particularly myopathy, when used in combination with a statin, even with a high-dose statin. Although the combination of niacin or fenofibrate with moderate-dose statins appears to be safe, prescribing a combination of these drugs with high-dose statins needs caution and requires giving careful information to the patient.