New ESC/EAS Consensus Statement on the use of PCSK9 inhibitors
European Society of Cardiology/European Atherosclerosis Society Task Force consensus statement on proprotein convertase subtilisin/kexin type 9 inhibitors: practical guidance for use in patients at very high cardiovascular risk
Landmesser U, Chapman M.J, Farnier M, et al
Eur Heart J 2016 Oct 27 [Epub ahead of print]
The key clinical issue for patients with atherosclerotic cardiovascular disease is attainment of guideline-recommended LDL-C levels (<1.8 mmol/L or 70 mg/dL) for patients at very high cardiovascular risk.
The main objective of this consensus document is to recommend the appropriate clinical use of PCSK9 antibodies in patients at very high CV risk and with poorly controlled LDL-C levels despite maximal statin/ezetimibe therapy. The outlined approach is supported by the Cholesterol Treatment Trialists’ Collaboration, and, consistently with European guidelines, focuses on three priority groups:
- patients at very high risk not at LDL-C goal
- patients with FH
- patients with statin intolerance
Patients at very high CV risk not at LDL-C goalPCSK9 inhibitors may be considered in very high CV risk patients, defined as patients with atherosclerotic CVD (based on clinical or imaging criteria) or diabetes mellitus (with target organ damage or with a major CV risk factor), who despite recommended maximally tolerated statin plus ezetimibe therapy require more than 50% reduction in LDL-C levels (with LDL-C levels >3.6 mmol/L or >140 mg/dL) to reach the recommended goal (<1.8 mmol/L or <70 mg/dL).
FH patientsUntil results from major outcomes trials are reported, PCSK9 inhibitor treatment may be considered for severe FH patients with or without atherosclerotic CVD and LDL-C levels >5.0 mmol/L or >200 mg/dL, despite maximally tolerated statin/ezetimibe therapy. For patients with additional risk factors (diabetes mellitus, lipoprotein(a) >50 mg/dL, marked hypertension, and premature familial atherosclerotic CVD), the LDL-C threshold is lower (>4.5 mmol/L or >175 mg/dL). Evolocumab should be considered for HoFH patients except those with confirmed negative/negative LDL-receptor mutations for whom lomitapide may be a preferred option.
Patients with statin intolerance, including those with a risk of developing type 2 diabetes mellitus and those with statin-associated muscle symptomsPatients who complain of muscle symptoms and have a CK level <10-fold the upper limit of normal (ULN) should be interviewed and receive counselling from their clinician to emphasize the clinical benefits of statin therapy. After a statin washout, patients with CK ≥ 4 x ULN but <10 x ULN at baseline and with recurrent symptoms should undertake two de-challenges/re-challenges with separate statins, started at the lowest recommended daily dose. An additional statin challenge is recommended for patients with CK either normal or <4 x ULN at baseline. Patients with no symptoms after statin washout should continue statin treatment. All patients should be up-titrated to the maximally tolerated statin dose wherever possible, and ezetimibe should be considered in patients not at LDL-C goal. Very high-risk patients intolerant of at least two statins at any dose, with muscle symptoms and/or CK elevation, and with substantially elevated LDL-C levels despite ezetimibe therapy may be considered for treatment with a PCSK9 inhibitor.
In summary, this Joint Task Force recommends treatment with a PCSK9 monoclonal antibody in very high CV risk patients with clinical or imaging evidence of atherosclerotic CVD, including those with progressive atherosclerotic CVD, or diabetes mellitus (with target organ damage or a major CV risk factor) or in patients with severe FH with substantially elevated LDL-C levels despite maximal statin/ezetimibe therapy, as well as for patients with verified statin intolerance. These recommendations identify a patient population who are likely to derive the greatest benefit from PCSK9 inhibition, while respecting the financial restraints within healthcare budgets.
Find this consensus document at Eur Heart J