Table 5.

Gaps to be solved in the future according to the European and the American clinical practice guidelines on dyslipidemia

ACC/AHA 201314	ESC/EAS 201216, 17	NICE 201218
General aspects
Outcomes of RCTs to evaluate alternative treatment strategies for ASCVD risk reduction. These RCTs may compare titration to specific cholesterol or apolipoprotein goals versus fixed-dose statin therapy in high-risk patients. Outcomes of RCTs of new lipid-modifying agents to determine the incremental ASCVD event-reduction benefits when added to evidence-based statin therapy. RCTs to determine whether submaximal statin doses, combined with nonstatin therapies, reduce ASCVD risk in statin-intolerant patients.	There are no recent RCTs of a total risk approach to risk assessment; nor risk management. Current systems of grading evidence give most weight to RCTs, but many lifestyle measures are less amenable to such assessment than are drug treatments, which therefore tend to receive a higher grade. While the GRADE33 system attempts to address this issue, more debate is needed. A systematic comparison of current international guidelines is needed to define areas of agreement and the reasons for discrepancies.	What is the comparative effectiveness of age alone and other routinely available risk factors versus formal structured multifactorial risk assessment for identifying people at high risk of developing CVD disease? When evaluating cost-effectiveness for statin therapy in reducing CVD, is prediction improved by the use of a complete meta-analysis dataset based on individual patient outcomes rather than published outcomes data from individual trials? What is the clinical effectiveness and rate of adverse events of statin therapy using atorvastatin 20 mg per day compared with atorvastatin 40 mg per day and atorvastatin 80 mg per day in people without established CVD?
Specific aspects
Outcomes of RCTs to evaluate statins or the primary prevention of ASCVD in adults >75 years of age. Evaluation of the incidence, pathophysiology, clinical course, and clinical outcomes of new-onset diabetes associated with statin therapy.	The young, women, older people, and ethnic minorities continue to be underrepresented in clinical trials.	What is the effectiveness of statin therapy in older people? What is the effectiveness of statins or other treatments that lower low-density lipoprotein-cholesterol in people with type 1 diabetes?

Abbreviations: ACC, American College of Cardiology; AHA, American Heart Association; ASCVD, atherosclerotic cardiovascular disease; EAS, European Atherosclerosis Society; ESC, European Society of Cardiology; NICE, National Institute for Health and Care Excellence; RCT, randomized clinical trial; CVD, cardio vascular disease; ESC/EAS, European Society of Cardiology.