Cholesterol Management in Difficult-to-Treat Patients

Although some studies have found there to be similar rates of side effects in patients taking statins and those taking placebo, other studies have seen differences in the rates of SAMS between these two groups. Additionally, research has shown that of the patients who reported SAMS, up to 90% were able to tolerate an alternative statin. The European Atherosclerosis Society (EAS) issued a statement regarding the appropriate management of SAMS in 2015, which is summarized in Figure 2

Patients that do not respond adequately to statin therapy can also be challenging to manage.1 Although statin therapy has shown to reduce LDL-C levels by 30–50% in most patients, a significant portion of patients do not achieve this desired reduction due to varied response to therapy. Several factors have been found to be associated with poor response to statin therapy. One common cause of poor response to therapy is medication nonadherence. There are several reasons for which a patient can be nonadherent to their medications, however medication cost is always a significant factor. Fortunately, however, the majority of statin medications are now generic, therefore an increase in adherence rates can hopefully be expected in the future. Poor response to statin therapy can also be related to genetic variations. Several studies have associated polymorphisms of various genes with both variable responses to therapy as well as increased risk of side effects. Drug-drug interactions are another reason that should be considered in patients with an inadequate response to statin therapy. Because many of the statin medications are metabolized through the cytochrome P450 system, various interactions have been identified. Medications with known interactions with statins are listed in Table 1. Pravastatin and rosuvastatin do not rely on the cytochrome P450 system, therefore can be used when drug-drug interactions are a concern.

Treating patients with a poor response to statin therapy is similar to treating patients with FH or statin intolerance.1 It is important to exclude any secondary causes that may contribute to an inadequate response, such as dietary indiscretion or medication nonadherence. When a patient has a clear indication for a statin medication and no known secondary causes for an inadequate response can be identified, titration to the maximum tolerated dose should be attempted. Additionally, a high-intensity statin should be considered in patients using low- or moderate-intensity statin therapy. Addition of ezetimibe, bile acid-binding resins, or niacin to current therapy can also be considered in this patient population as well.

Statin medications have proven to be effective at lowering LDL-C levels and reducing CVD outcomes. Unfortunately, treating patients with FH, statin intolerance, or a poor response to statin therapy can be challenging for clinicians. Various approaches for treating these patient populations have been found to be effective and include determining secondary causes of treatment failure, titrating to maximum tolerated doses, and adding a nonstatin agent to a patient’s therapy.


1.      Miedema MD, Virani S. Harder-to-Treat Patients: Recognizing Them and Adapting Treatment Strategies. Am J Cardiol. 2016 Sept 15;118(6S):13A-18A. DOI: 10.1016/j.amjcard.2016.05.027.