PCSK9阻害薬はスタチン不耐性患者に対する可能性を有している(Abstract 20758)

ODYSSEY ALTERNATIVE：Alirocumabはベースラインレベルが非常に高いスタチン不耐性患者のLDL-Cを低下させる
ODYSSEY ALTERNATIVE: Alirocumab reduced LDL-C in statin intolerant patients with very high baseline levels
PCSK9を標的として阻害するモノクローナル抗体alirocumabは、ベースラインLDL-Cレベルが非常に高いスタチン不耐性患者において、エゼチミブおよびアトルバスタチンと比較し、LDL-C低下作用が有意に大きかった、との研究結果が2014年American Heart Association年次集会で発表された。ODYSSEY ALTERNATIVEスタディでは、ベースラインLDL-Cが非常に高い（～190mg/dL）患者計314人を、2週間毎のalirocumab 75mg自己注射またはエゼチミブ1日10 mg、またはアトルバスタチン1日20mgを24週間内服する群にランダムに割り付けた。Alirocumabの用量は心血管リスクおよび第8週のLDL-C値に応じて12週後に最大150mgまで増加された。50%は第12週の時点で用量増加が不要であった。24週の時点でalirocumabはエゼチミブよりも有意にLDL-Cを低下させた（エゼチミブ群154mg/dL対alirocumab群96mg/dL、p<0.0001）。Alirocumab群患者の42%が第24週の時点でLDL-Cの目標値を達成した。LDL-C目標値を達成したのはalirocumab群患者の方がスタチン群患者よりも有意に多かった（p<0.0001）。さらに、骨関連有害事象は、アトルバスタチンまたはエゼチミブ群よりもalirocumab群の方で少なかった。スタチン不耐性歴を有する患者においてalirocumabは優れた代替療法となり得る、と筆者らは結論付けている。
Full Text

The investigational drug alirocumab produced significantly greater LDL-C reductions in statin-intolerant patients with very high baseline LDL-C levels compared with ezetimibe and atorvastatin according to research presented at the American Heart Association's Scientific Sessions 2014.

Statin intolerance limits many patients from taking cholesterol-lowering statins to lower LDL-C. The drug ezetimibe is often recommended for those who cannot tolerate statins. In this trial, researchers compared the PCSK9 monoclonal antibody alirocumab to ezetimibe in patients with a history of statin intolerance.  Statin intolerant patients were unable to tolerate at least two different statins, including one at the lowest dose, due to muscle related symptoms.

In the ODYSSEY ALTERNATIVE study a total of 314 patients with very high baseline LDL-C levels (~190 mg/dL) were randomized to receive either alirocumab as a 75 mg self-administered injection every 2 weeks, or 10 mg/day of ezetimibe, or 20 mg/day of atorvastatin for 24 weeks. Alirocumab dose was increased to 150 mg at week 12 depending on cardiovascular risk and week 8 LDL-C level.

The primary endpoint was percent change in LDL-C from baseline to week 24.

Researchers found that alirocumab produced significantly greater LDL-C reduction than ezetimibe. At 24 weeks, LDL-C for the ezetimibe arm was 154 mg/dL vs. 96 mg/dL for patients on alirocumab  (p<0.0001).  Fifty percent did not need a dose increase at week 12.  Forty two percent of alirocumab patients achieved their LDL-C goals at week 24.  Significantly more alirocumab patients achieved LDL-C goals (p<0.0001) than patients on statins.  Similar reductions were found in secondary lipid parameters at week 24.

In addition, there were fewer skeletal- related adverse events with alirocumab compared to atorvastatin or ezetimibe.

Patrick Moriarty, M.D., lead author on the study and professor of medicine at the University of Kansas Medical Center in Kansas City, Kansas concluded that alirocumab may be a good alternative therapy in patients with a history of statin intolerance.