Cardiovascular disease: risk assessment and reduction, including lipid modification

Identifying and assessing cardiovascular disease risk

NICE guideline CG181 recommends (1.1.8) using the QRISK2 risk assessment tool to assess CVD risk for the primary prevention of CVD in people up to and including age 84 years. The collective new evidence and topic expert feedback indicates that the inclusion of additional clinical variables in QRISK3 has a greater potential value to identify those at most risk of heart disease and stroke.

The new evidence suggests that QRISK3 performs well for people with type 1 diabetes and chronic kidney disease, and may help some people with these conditions to make an informed choice on whether to take statins. There is therefore a potential impact on recommendations 1.1.9 and 1.1.11, which advise against using risk tools for people with type 1 diabetes and chronic kidney disease, respectively. This may also have a consequential impact on recommendations 1.3.23, 1.3.24, and 1.3.27 for the treatment of people with these conditions.

There is also a potential need to amend recommendations 1.1.8 and 1.1.10 to advise the use of QRISK3 in place of QRISK2 because QRISK2 is due to be superseded by QRISK3 in 2018.

New evidence supporting the use of lifetime risk calculation to more accurately assess patients for lifestyle changes and eventually lipid lowering drugs was not specific to the UK population. However, the surveillance literature search strategy did not extend to all observational studies. Additional stakeholder feedback indicating the need to review this area raises a potential impact on recommendation 1.1.4 to consider lifetime risk as an alternative to 10-year risk. This may also have consequential impacts on recommendation 1.1.26 for communicating risk and on recommendations 1.3.18 and 1.3.26 for primary prevention of CVD.

Decision: This area of the guideline should be updated.

Lifestyle modifications for the primary and secondary prevention of CVD

Topic expert advice highlighted that NHS Choices is not considered to be an authoritative source, and references to it in recommendations 1.2.1–1.2.4, 1.2.11 and 1.2.13 should be removed. There is a potential impact to review the wording of these recommendations, which was originally derived from NHS Choices.

Decision: This area of the guideline should be updated.

Lipid modification therapy for the primary and secondary prevention of CVD

NICE guideline CG181 advises that when a decision is made to prescribe a statin, a statin of high intensity and low acquisition cost should be used. In developing the guideline, the committee were unable to judge if rosuvastatin 10 mg, 20 mg or 40 mg would be more effective than atorvastatin 80 mg in reducing CVD events. Given the considerably higher cost of using rosuvastatin at that time, it would have needed to be considerably more effective than atorvastatin for there to be a possibility that its use could be cost effective. In the absence of trial evidence of greater effectiveness the guideline committee were therefore unable to recommend the use of rosuvastatin.

However, the new evidence from an individual patient data (IPD) meta-analysis and a large RCT supporting rosuvastatin at doses of 10–40 mg, which constitute high intensity doses, has a potential impact on recommendation 1.3.18 due to the imminent expiry of the rosuvastatin patent and the drug's future availability in a generic form. There is a potential need to update the health economic model to review cost effectiveness in the light of changing acquisition costs.

Topic expert feedback indicating the need to review recommendation 1.3.28, for using high-intensity statins to achieve a percentage reduction rather than an absolute lipid target level, is supported by new IPD meta-analysis evidence. This indicates large inter-individual variation in lipid level reductions achieved from statins, and that the lower the LDL-C level attained by statins, the greater the clinical benefit accrued. There is a potential impact on this recommendation.

New evidence and topic expert feedback also indicates that statins, particularly rosuvastatin, are effective in reducing the risk of myocardial infarction and hospitalisation due to heart failure, but not death due to heart failure, in people with existing heart failure. There is a potential impact to consider specific recommendations in this context.

New evidence and expert feedback also indicates that patients with statin intolerance are now recognised as a group at increased CVD risk, and that there is a need to set out a clearer definition of statin intolerance. In developing the guideline, the committee decided that statin intolerance should be defined clinically as the inability to tolerate 3 different statins. The evidence reviews for NICE guideline CG181 did not find clear benefit for other drugs so the guideline committee were not able to recommend alternatives to statins. Instead the recommended approach was to seek specialist advice about other possible treatment options.

However, with the emergence of new alternative treatments, there is a potential need for NICE guideline CG181 to cross refer to the following technology appraisals, in the event of statin intolerance:

A large ongoing trial, ODYSSEY Outcomes, was also highlighted by topic experts and is likely to publish in 2018. The trial is evaluating efficacy and safety of alirocumab, in patients with well-documented statin intolerance and moderate to very high CVD risk. This will be monitored for publication by NICE.

Topic experts also noted that the NICE technology appraisals on alirocumab and evolocumab are applicable to patients with inadequate control of non-HDL-cholesterol or LDL-cholesterol, who are on maximum tolerated statin therapy. Baseline pre-treatment LDL-Cholesterol and CVD risk determine eligibility. These interventions and risk assessments are within the scope of NICE guideline CG181 and it was advised by topic experts that these should be linked to the guideline recommendations as part of an update.

Decision: This area of the guideline should be updated.

All other evidence was deemed consistent with current recommendations.