Prospective studies are needed to investigate the incremental value of reclassifying total CV risk and defining eligibility for lipid-lowering therapy based on CAC scores in individuals at moderate or high-risk.

Outcome-based comparisons of CAC scores vs. assessment of arterial (carotid or femoral) plaque burden by ultrasonography for CV risk reclassification in people at moderate or high-risk are needed.

Although calibrated country-specific versions of the SCORE system are available for many European countries, risk charts based on country-specific cohort data are missing for most countries. Regional total event charts (vs. mortality-only charts) are needed.

Total CV risk estimation by means of the SCORE system and, accordingly, recommendations on eligibility for statins as well as treatment goals are based on TC, whereas LDL-C is the primary lipid analysis method for screening, diagnosis, and management.

There are no outcome-based comparisons of LDL-C vs. ApoB as primary measurement methods for screening, diagnosis, and management.

Against a background of genetic and randomized clinical trial evidence showing no significant effect of increasing HDL levels on the risk of CVD events, the clinical impact of therapies altering the function of HDL particles is unknown. More evidence is needed regarding the apparently adverse association of extremely high levels of HDL-C with clinical outcomes.

Dedicated studies assessing outcomes with specific Lp(a)-lowering therapies are warranted.

More evidence is needed for PCSK9 inhibitors in specific populations, including patients with severe CKD and on dialysis, patients with HIV infection, in children and adolescents with FH, after heart transplantation, and during pregnancy.

The effects of PCSK9 inhibition on specific body compartments (as with siRNA or antisense) or only within plasma (as with monoclonal antibodies) remain to be established.

How early should a PCSK9 inhibitor be initiated in patients with ACS or stroke? In view of evidence of sustained clinical benefit associated with the early initiation of statin treatment in the acute phase of ACS or stroke, the optimal timing of PCSK9 inhibitor treatment in ACS and stroke patients remains to be addressed in outcome studies.

Whether very low LDL-C levels achieved with the combination of statin, ezetimibe, and PCSK9 inhibitor reduce the need for further PCI remains to be addressed in outcome studies.

In patients with chronic HF, a small benefit of n-3 PUFAs has been shown in one RCT and merits further investigation.

What is the optimal screening programme for detecting FH?

In view of limited access to genetic testing in several environments, more evidence is needed regarding outcomes with only clinical vs. genetic screening and diagnosis of FH.

More RCT evidence is required to support the use of statin-based treatment in older people (aged ≥75 years, but particularly in those aged ≥80 years).

More RCT evidence is needed for statin treatment in kidney transplant recipients.

There are no data on the effects of statins, ezetimibe, or fibrates on CV events in dyslipidaemic HIV-infected patients.

More evidence is needed regarding attainment of recommended LDL goals among very high-risk patients in real-world practice in the era of increasingly prescribed combination therapies for LDL lowering.