A large Italian cohort on proprotein convertase subtilisin/kexin type 9 inhibitors

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) represent a breakthrough in the treatment of hypercholesterolaemia as they efficiently and safely reduce low-density lipoprotein cholesterol (LDL-C) and cardiovascular events. Regulatory authorities have provided clinical indications for adding this drug to conventional lipid-lowering therapy. Evolocumab and alirocumab were approved in Italy in 2017 and the Italian Medicines Agency (AIFA) established stringent reimbursement criteria: (a) very high cardiovascular risk in primary (such as familial hypercholesterolaemia) or secondary prevention, (b) 80 years of age, (c) previous treatment with a maximally tolerated statin agent and ezetimibe (ezetimibe monotherapy in case of proven statins intolerance) for at least sixmonths, (d) unacceptable LDL-C levels for their cardiovascular risk as specified in the regulations. The aim of this study is to retrospectively analyse the effects of PCSK9is, added to backbone lipid-lowering treatments, on patients followed in our Center. Between 1 July 2017–30 April 2019, 122 patients (mean age 60 11 years, male 75%) affected by inherited dyslipidaemias added, in accordance with the AIFA reimbursement criteria, a PCSK9i to the maximally tolerated lipid-lowering therapy. Patient’s clinical characteristics, lipid value before and after PCSK9i therapy, adverse cardiovascular events (ACVEs) and adverse events (AEs) reported during the follow-up were analysed. Forty-nine patients (40%) had participated in the Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different POpulations (PROFICIO) study of evolocumab (clinical trials AMG145-20110271, AMG145-20120138, AMG145-20120332 and AMG145-20140316 with consequent switch of patients to the national health system at the end of the clinical trials) while the other 73 patients (60%) started PCSK9i therapy in accordance with Italian prescription rules. Table 1 summarises the patient’s clinical characteristics and Figure 1 reports the flow-chart of patients treated with PCSK9i. All patients had an inherited dyslipidaemia; concomitant lipoprotein(a) (Lp(a))-hyperlipoproteinemia (defined as> 50mg/dl) was present in 40/122 (33%) and 86/122 (70%) had ischaemic heart disease (IHD). Furthermore, only 16/122 (13%) take high-intensity statins due to a high rate of statin intolerance and 34/122 (28%) were on chronically lipoprotein apheresis (LA). The LA treatment was performed at bi-weekly intervals by dextransulphate (Liposorber-LA systems; Kaneka, Osaka, Japan; 26/34 patients), or heparin-induced low-density lipoprotein (LDL) precipitation apheresis (HELP, Plasmat Futura; B. Braun, Melsungen, Germany; 6/34 patients), or immunoadsorption (TheraSorb – LDL pro Adsorber; Miltenyi Biotec, Bergisch Gladbach, Germany; 2/34 patients). At the end of therapy follow-up (13 6 months), a significant decrease in total cholesterol (–38%, p< 0.001), triglycerides (–15%, p< 0.001), LDL-C (–52%, p< 0.001) and Lp(a) levels (–8%, p 0.006) was observed (Table 2). Among patients with IHD, only 27/86 (31%) reached LDL-C below 55mg/dl, as recommended by international guidelines, while 11/86 (13%) showed LDL-C between 56–70mg/dl, 29/86 (34%) had LDLC values between 71–100mg/dl, and 19/86 (22%) still had LDL-C levels above 100mg/dl.