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June 18/25, 2019 Circulation. 2019;139:e1082–e1143. DOI: 10.1161/CIR.0000000000000625 e1120

CLINICAL STATEMENTS AND GUIDELINES including depletion of ubiquinone or coenzyme Q10. Available evidence, however, does not support the use of coenzyme Q10 supplementation for routine use in patients treated with statins or for the treatment of SAMS.S5-20,S5-21

10.	 The majority of SAMS are subjective myalgia in the absence of other findings,S5-3,S5-13,S5-14,S5-23,S5-30 and an asymptomatic increase in transaminases (>3 times upper limit of normal) is an infrequent statin-associated side effect.S5-1,S5-22,S5-24 Therefore, CK and transaminase levels should not be routinely measured given the unlikely impact on clinical outcomes, and the lack of established cost effectiveness.S5-15

6 IMPLEMENTATION

Recommendations for Implementation Referenced studies that support recommendations are summarized in Online Data Supplements 42 to 46.

COR LOE Recommendations

I A 1.  Interventions focused on improving adherence to prescribed therapy are recommended for management of adults with elevated cholesterol levels, including telephone reminders, calendar reminders, integrated multidisciplinary educational activities, and pharmacist-led interventions, such as simplification of the drug regimen to once-daily dosing.S6-1–S6-4

I B-NR 2.  Clinicians, health systems, and health plans should identify patients who are not receiving guideline-directed medical therapy and should facilitate the initiation of appropriate guideline-directed medical therapy, using multifaceted strategies to improve guideline implementation.S6-5,S6-6

I B-NR 3.  Before therapy is prescribed, a patientclinician discussion should take place to promote shared decision-making and should include the potential for ASCVD riskreduction benefit, adverse effects, drug-drug interactions, and patient preferences.S6-7,S6-8

Synopsis

Guideline publication does not guarantee guideline implementation. Healthcare delivery is complex, and barriers to guideline implementation can occur at the patient, clinician, health system, and health plan levels, leading to gaps in care. A more concerted effort, with multifaceted strategies aimed at the patient, clinician, health system, and health plan, is needed to overcome the barriers and achieve wider guideline implementation (Table S7). The patient is a key player in successful guideline implementation, and the clinician–patient discussion is crucial to the successful initiation and continuation of guideline-directed management and therapy (Table 7). As part of the clinician–patient discussion, the patient should be encouraged to state what was heard, ask questions, express values and preferences, and state ability and willingness to adhere to lifestyle changes and medications. This is where a discussion of out-of-pocket costs can occur. Clinicians should use multiple interventions to promote adherence, including asking more specific questions about adherence, aiming for once-daily dosing, using automated reminders, participating in multidisciplinary educational activities, and using pharmacist-led interventions.

Recommendation-Specific Supportive Text

1.	Interventions focused on improving adherence to prescribed therapy are recommended for management of adults with elevated cholesterol levels. A Cochrane systematic review demonstrated that intensification of patient care interventions improves both short- and long-term adherence to medication, as well as meaningful reduction in LDL-C levels. Interventions include telephone reminders, calendar reminders, integrated multidisciplinary educational activities, simplification of the drug regimen to once-daily dosing, and pharmacist-led interventions.S6-1–S6-4 Clinicians may wish to review Table S7 in the Web Supplement, “Strategies to Improve Guideline Implementation by Setting and Target Audience Measures to Improve Lipid Medication Adherence.” 2.	Clinicians do not follow guidelines for many reasons,S6-9 and cholesterol guideline implementation has not been optimal.S6-10–S6-13 Interventions aimed at the clinician may improve guideline implementation. Educational outreach or academic detailing visits are generally effective for improving processof-care, clinical, cost-reduction, and cost-effectiveness outcomes.S6-5 Audits of individual clinical performance and feedback are generally effective in improving process-of-care and clinical outcomes.S6-5 Reminders and individual pay-for-performance are generally effective for cost reduction.S6-5

Even if guideline-directed management and therapy are prescribed, patients may be nonadherent or not get the prescribed medication for a variety of reasons.S6-14 Patients who are initially adherent to statin therapy may not demonstrate long-term adherence.S6-15,S6-16 Adherent patients, with and without clinical ASCVD, have improved outcomes and reduced costs.S6-15,S6-17–S6-20 Formulary restrictions and prior authorization requirements have been associated with care delays and nonadherence.S6-21 Interventions aimed at the patient may improve adherence and clinical outcomes. Guideline implementation strategies that are aimed at the patient, clinician, health system, and health plan are needed. Barriers to guideline

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