HHE Cardiovascular supplement 2018 - Page 6

PCSK9 inhibitors and LDL-C levels The monoclonal antibodies evolocumab and alirocumab directed at PCSK9 were the first class to be approved. Both can be administered by subcutaneous injection every two to four weeks. They have shown impressive reduction in LDL-C levels when compared with placebo, whether used alone or added to standard therapy in two large randomised controlled trials (RCTs). 12,13 The average LDL-C levels fell by approximately 60% from around 120mg/l (3.15mmol/l) to around 50mg/l (1.3mmol/l). Of note, most trial participants were already taking statins or ezetimibe. adequately powered for hard clinical endpoints. However, when combined in meta-analyses, there was evidence that PCSK9 inhibitors reduced the incidence of all-cause mortality. 14,15 The FOURIER trial 16 was powered to assess the impact of evolocumab on hard clinical outcomes. This study recruited more than 27,000 patients with atherosclerotic CVD and LDL-C >70mg/ dl despite being on a statin (with or without ezetimibe) therapy. They were randomised to evolocumab (either 140mg every two weeks or 420mg monthly) or matching placebo. LDL-C was significantly reduced from a median of 92mg/dl to 30mg/dl within a month. After a median follow-up of 2.2 years, the primary composite endpoint of cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina or coronary revascularisation was significantly lower with evolocumab when compared with placebo (9.8% versus 11.3%; hazard ratio 0.85; 95% CI [0.79–0 %ҒF2v2ǒG&fV'&VGV7Fז6&Ff&7F7G&R@6&'&Wf67V&6FbFRFR6FV6PbWW&6vFfRWfVG2BWr6WBF&WFW0vW&R6֖"&WGvVVFRGvG&VFVB&2ǒV7F6FR&V7F2vW&R&Rg&WVV@vFWf7V""RfW'7W2bRWFFVBWFǗ62rb3R$5G2CRS3FVG26VFrFRdU$U"G&6f&V@FBG&VFVBvF54憖&F"2vVЧFW&FVBB&fVB6&Ff67V"WF6W2FVvFW&Rv2fW&&VVfB6W6P"6&Ff67V"'FƗGWF&Vw&W76Ǘ626vVB6vf6B766F&WGvVVvW"&6VƖRD2B&VVfB6W6R'FƗG3F2ƖW2F@F6RvFvW"&6VƖRD2fP'FƗG&VVfBbG&VFVBvF54憖&F"rF2fFr2FW62vVW&FpBv'&G2gW'FW"fW7FvFFRE54UUD4U25Ccc3C"7GVG0fW7FvFrFR&VVfBbƗ&7V"6Ɩ6WF6W2FVG2vF&V6VB7WFR6&'7G&RF27GVG26WFVBFR&V7'VFV@bcFVG2BG2fFw2&RVvW&ǐvFVBB&VGV7F2D2'54憖&F'2fRG&6FVBF&fVVB6Ɩ6WF6R&66V"2V6V@6F&Gv7B54Bv0&V6VFǒV6VBFRB5$R@5$R"G&2&VB#rFVG2vFf&&R&6VƖRƗBvW&rFW&@FW&66W&F25dB7FGW2vW&RV&VBgFW"BvVV2D2v2SRvW"FP&66V"&vWfW"gFW"VFfrWb6WfVF2FW&Rv26vf6BFffW&V6RFR66FRVG@bז6&Ff&7F7G&R7FƗ6Ff"V7F&Rv&WV&rW&vV@&Wf67V&6F"6&Ff67V"FVFF07GVGv2FW&֖FVBV&ǒGVRF&66V 6vr&V6GFFWfVFG'VpF&FW2BF2W2FR6'BfrWGW&Ff"F2&V6&66V"2@Ɩ6V6VBf"6Ɩ6W6R54憖&F'2B6Ɩ6WF6W0VW&W26R$5G2BRfRfW7FvFV@FR6fWGBVff67bWf7V"@Ɨ&7V"&VGV6rD2'WBRvW&R6VvW2f6r54憖&F'0FW7FRFV"F&֗6RFW&R&RVW&W06VvW2f6rFRvFW7&VBFFb54憖&F'2FR6Ɩ66WGFr6'&W'2b6W'F54ǖ'62@6vf6FǒvW"&FW2bFW&66W&F25dBFW6R&֗6rfFw2VBFFRFWfVV@b6WfW&676W2b54憖&F'2FF&vWBFP54Fv&FW"F&VGV6RD2`R#7FƆVF6&R6