A 52-week placebo-controlled trial of evolocumab in hyperlipidemia

Dirk J Blom, Tomas Hala, Michael Bolognese, Michael J Lillestol, Phillip D Toth, Lesley Burgess, Richard Ceska, Eli Roth, Michael J Koren, Christie M Ballantyne, Maria Laura Monsalvo, Kate Tsirtsonis, Jae B Kim, Rob Scott, Scott M Wasserman, Evan A Stein, DESCARTES Investigators, Ktut Arya, Maureen McKeirnan, David Sullivan, Gerald Watts, Bernhard Paulweber, Koenraad Cornelli, Marc De Meulemeester, Jaak Mortelmans, Didier Vanriet, Jean Bergeron, Peter Dzongowski, Anil Gupta, Sam Henein, Ben Lasko, Calvin Powell, Vera Adamkova, Ondrej Cermak, Richard Ceska, Jiri Charvat, Tomas Hala, Zdenek Hamouz, Jan Macha, Hana Rosolova, Olga Smejkalova, Jindrich Spinar, Jan Vojacek, Annesofie Krogsaa, Bettina Storgaard Nedergaard, Susanne Wermuth, Laszlo Bajnok, Csaba Farsang, Tamas Forster, Zoltan Laszlo, Geza Lupkovics, Andras Papp, Imre Szakal, Marianna Zsom, Dirk Blom, Lesley Burgess, Kathleen Coetzee, Iftikhar Ebrahim, Johannes Lombaard, Shirley Middlemost, Visvakuren Naidoo, Somasundram Pillay, Armen Arslanian, Christie Ballantyne, Harold Bays, Richard Beasley, Michael Bolognese, Ronald Brazg, Lisa Connery, Victor Elinoff, Wayne Harper, John Hoekstra, Kier Huehnergarth, Randall Huling, Alan Kivitz, Michael Koren, Michael Lillestol, Robert Lipetz, Sashi Makam, Phyllis Marx, Samer Nakhle, Jung Oh, Warren Pleskow, Bruce Rankin, Robert Remler, Margaret Rhee, Daniel Ries, Eli Roth, John Rubino, William Saway, Rashmi Schramm, Cynthia Strout, Phillip Toth, Traci Turner, Larry Watkins, Robert Weiss, Matthew Wenker, Hayes Williams, Charles H Hennekens, Felicita Andreotti, Colin Baigent, W Virgil Brown, Barry Davis, Stephen D Wiviott, Traci Turner, William E Tarr Jr, Dirk J Blom, Tomas Hala, Michael Bolognese, Michael J Lillestol, Phillip D Toth, Lesley Burgess, Richard Ceska, Eli Roth, Michael J Koren, Christie M Ballantyne, Maria Laura Monsalvo, Kate Tsirtsonis, Jae B Kim, Rob Scott, Scott M Wasserman, Evan A Stein, DESCARTES Investigators, Ktut Arya, Maureen McKeirnan, David Sullivan, Gerald Watts, Bernhard Paulweber, Koenraad Cornelli, Marc De Meulemeester, Jaak Mortelmans, Didier Vanriet, Jean Bergeron, Peter Dzongowski, Anil Gupta, Sam Henein, Ben Lasko, Calvin Powell, Vera Adamkova, Ondrej Cermak, Richard Ceska, Jiri Charvat, Tomas Hala, Zdenek Hamouz, Jan Macha, Hana Rosolova, Olga Smejkalova, Jindrich Spinar, Jan Vojacek, Annesofie Krogsaa, Bettina Storgaard Nedergaard, Susanne Wermuth, Laszlo Bajnok, Csaba Farsang, Tamas Forster, Zoltan Laszlo, Geza Lupkovics, Andras Papp, Imre Szakal, Marianna Zsom, Dirk Blom, Lesley Burgess, Kathleen Coetzee, Iftikhar Ebrahim, Johannes Lombaard, Shirley Middlemost, Visvakuren Naidoo, Somasundram Pillay, Armen Arslanian, Christie Ballantyne, Harold Bays, Richard Beasley, Michael Bolognese, Ronald Brazg, Lisa Connery, Victor Elinoff, Wayne Harper, John Hoekstra, Kier Huehnergarth, Randall Huling, Alan Kivitz, Michael Koren, Michael Lillestol, Robert Lipetz, Sashi Makam, Phyllis Marx, Samer Nakhle, Jung Oh, Warren Pleskow, Bruce Rankin, Robert Remler, Margaret Rhee, Daniel Ries, Eli Roth, John Rubino, William Saway, Rashmi Schramm, Cynthia Strout, Phillip Toth, Traci Turner, Larry Watkins, Robert Weiss, Matthew Wenker, Hayes Williams, Charles H Hennekens, Felicita Andreotti, Colin Baigent, W Virgil Brown, Barry Davis, Stephen D Wiviott, Traci Turner, William E Tarr Jr

Abstract

Background: Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab.

Methods: We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52.

Results: Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain.

Conclusions: At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks. (Funded by Amgen; DESCARTES ClinicalTrials.gov number, NCT01516879.).

Source: PubMed

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