Issue link: https://viewer.e-digitaledition.com/i/674833
IN T HE FIR S T m ajor t r ia l of it s k i nd , Clevela nd Cl i n ic resea rchers used a blinded recha l lenge w ith ator va statin or placebo to objectively conf irm the presence of muscle- related symptoms in patients with a histor y of intolera nce to multiple statins a nd found that evolocumab, a proprotein conver tase subtilisin/kexin ty pe 9 (PCSK9) inhibitor, was a more effective option to lower cholesterol tha n ezetimibe in these patients. The resea rch was presented at the A merica n Col lege of Ca rd iolog y 's 65t h A n nua l Scient i f ic Session a nd simulta neously published online in The Journal of the American Medical Association. " S t a t i n i nt oler a nc e h a s b e en a ver y cha lleng ing clinica l problem," s a y s S t e v e n N i s s e n , M D , C h a i r o f C a r d i o v a s c u l a r M e d i c i n e a t Clevela nd Clinic. " The study showed that PCSK9 in hibitors ca n sig nif i- ca ntly lower cholesterol in patients with documented statin intolera nce, providing a n effective treatment for these diff icult to ma nage patients." T h e G A U S S - 3 t r i a l e n r o l l e d 511 patients with ver y high levels of LDL cholesterol — avera g ing more tha n 210 mg /dL — a nd w ith a histor y of muscle-related statin intolera nce. More t ha n 80 percent of pa r ticipa nts had prev iously repor ted i ntolera nce to t h ree or more st at i ns. T he st udy showed that 42.6 percent of these patients repor ted muscle pa in or wea kness on ator vastatin, but not placebo, a nd 26.5 percent on the placebo, but not ator vastatin. Those who demonstrated statin intolerance only on ator- vastatin were randomized to two a lternative treatments to lower LDL cholesterol — evolocumab or ezetimibe. On average, patients showed a 52.8 percent reduction on evolocumab compared with 16.7 percent reduction with ezetimibe. The PCSK9 inhibitor evolocumab was more e–ective, but had a similar incidence of muscle-related adverse e–ects compared with ezetimibe. Lef t untreated, patients with high levels of LDL cholesterol a re at a n increa sed risk of hea r t disea se. Statins a re the most ef fective dr ug cur rent ly ava i lable to lower LDL , but 5 –105 of patients repor t t hey a re unable to tolerate statins, due to muscle pa in or wea kness. Statin intolera nce wa s prev iously dia g nosed prima ri ly by patient compla ints since there exist no blood tests to document muscle-related sta in intolera nce. E volocu m ab, a PCSK 9 i n h ibit or, i s a n i njec t able non- statin cholesterol-lower ing dr ug self-adm inistered by t he pat ient s once per mont h . Ezet i m ibe, used a s t he cont rol i n t he t r ia l , lowers L DL by decrea si n g t he absor pt ion of cholesterol in t he sma l l intestine. In t he tr ia l, bot h dr ugs ra rely induced muscle sy mptoms, leading to discontinuation, which occur red in one patient g iven evolocumab a nd f ive patients g iven ezetim ibe. The study wa s f unded by A mgen. Dr. Nissen ha s ser ved a s a consu lta nt for ma ny pha r maceutica l compa nies a nd ha s overseen clinica l tr ia ls for A mgen, A stra Zeneca , Cerenis, Eli Li l ly, Nova r tis, Novo Nordisk, The Medicines Compa ny, Orex igen, Ta keda a nd P f izer. However, he does not accept honora r i a , con su lt i n g fees or ot her compen sat ion f rom com mercia l entities. ■ Objectively Identified in Patients STATIN INTOLERANCE 2 4R E C E N T R E S E A R C H