Effect of Alirocumab on Lipoprotein(a) Over ≥1.5 Years (from the Phase 3 ODYSSEY Program)

Elevated lipoprotein(a) [Lp(a)] is independently associated with increased cardiovascular risk. However, treatment options for elevated Lp(a) are limited. Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, reduced low-density lipoprotein cholesterol (LDL-C) by up to 62% from baseline in phase 3 studies, with adverse event rates similar between alirocumab and controls. We evaluated the effect of alirocumab on serum Lp(a) using pooled data from the phase 3 ODYSSEY program: 4,915 patients with hypercholesterolemia from 10 phase 3 studies were included. Eight studies evaluated alirocumab 75 mg every 2 weeks (Q2W), with possible increase to 150 mg Q2W at week 12 depending on LDL-C at week 8 (75/150 mg Q2W); the other 2 studies evaluated alirocumab 150-mg Q2W from the outset. Comparators were placebo or ezetimibe. Eight studies were conducted on a background of statins, and 2 studies were carried out with no statins. Alirocumab was associated with significant reductions in Lp(a), regardless of starting dose and use of concomitant statins. At week 24, reductions from baseline were 23% to 27% with alirocumab 75/150-mg Q2W and 29% with alirocumab 150-mg Q2W (all comparisons p <0.0001 vs controls). Reductions were sustained over 78 to 104 weeks. Lp(a) reductions with alirocumab were independent of race, gender, presence of familial hypercholesterolemia, baseline Lp(a), and LDL-C concentrations, or use of statins. In conclusion, in addition to marked reduction in LDL-C, alirocumab leads to a significant and sustained lowering of Lp(a). Elevated lipoprotein(a) [Lp(a)] is independently associated with increased cardiovascular risk. However, treatment options for elevated Lp(a) are limited. Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, reduced low-density lipoprotein cholesterol (LDL-C) by up to 62% from baseline in phase 3 studies, with adverse event rates similar between alirocumab and controls. We evaluated the effect of alirocumab on serum Lp(a) using pooled data from the phase 3 ODYSSEY program: 4,915 patients with hypercholesterolemia from 10 phase 3 studies were included. Eight studies evaluated alirocumab 75 mg every 2 weeks (Q2W), with possible increase to 150 mg Q2W at week 12 depending on LDL-C at week 8 (75/150 mg Q2W); the other 2 studies evaluated alirocumab 150-mg Q2W from the outset. Comparators were placebo or ezetimibe. Eight studies were conducted on a background of statins, and 2 studies were carried out with no statins. Alirocumab was associated with significant reductions in Lp(a), regardless of starting dose and use of concomitant statins. At week 24, reductions from baseline were 23% to 27% with alirocumab 75/150-mg Q2W and 29% with alirocumab 150-mg Q2W (all comparisons p <0.0001 vs controls). Reductions were sustained over 78 to 104 weeks. Lp(a) reductions with alirocumab were independent of race, gender, presence of familial hypercholesterolemia, baseline Lp(a), and LDL-C concentrations, or use of statins. In conclusion, in addition to marked reduction in LDL-C, alirocumab leads to a significant and sustained lowering of Lp(a). Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), reduced low-density lipoprotein cholesterol (LDL-C) levels from baseline to 24 weeks by up to 62% versus controls in 10 phase 3 studies involving mainly patients at high cardiovascular (CV) risk, including those with previous CV events and those with heterozygous familial hypercholesterolemia (HeFH).1Bays H. Gaudet D. Weiss R. Ruiz J.L. Watts G.F. Gouni-Berthold I. Robinson J. Zhao J. Hanotin C. Donahue S. Alirocumab as add-on to atorvastatin versus other lipid treatment strategies: ODYSSEY OPTIONS I randomized trial.J Clin Endocrinol Metab. 2015; 100: 3140-3148Crossref PubMed Scopus (193) Google Scholar, 2Cannon C.P. Cariou B. Blom D. McKenney J.M. Lorenzato C. Pordy R. Chaudhari U. Colhoun H.M. Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial.Eur Heart J. 2015; 36: 1186-1194Crossref PubMed Scopus (314) Google Scholar, 3Farnier M. Jones P. Severance R. Averna M. Steinhagen-Thiessen E. Colhoun H.M. Du Y. Hanotin C. Donahue S. Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: the ODYSSEY OPTIONS II randomized trial.Atherosclerosis. 2016; 244: 138-146Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar, 4Kastelein J.J. Ginsberg H.N. Langslet G. Hovingh G.K. Ceska R. Dufour R. Blom D. Civeira F. Krempf M. Lorenzato C. Zhao J. Pordy R. Baccara-Dinet M.T. Gipe D.A. Geiger M.J. Farnier M. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia.Eur Heart J. 2015; 36: 2996-3003PubMed Google Scholar, 5Ginsberg H.N. Rader D.J. Raal F.J. Guyton J.R. Baccara-Dinet M.T. Lorenzato C. Pordy R. Stroes E. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia and LDL-C of 160 mg/dL or higher.Cardiovasc Drugs Ther. 2016; 30: 473-483Crossref PubMed Scopus (146) Google Scholar, 6Kereiakes D.J. Robinson J.G. Cannon C.P. Lorenzato C. Pordy R. Chaudhari U. Colhoun H.M. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study.Am Heart J. 2015; 169: 906-915.e913Abstract Full Text Full Text PDF PubMed Scopus (279) Google Scholar, 7Moriarty P.M. Thompson P.D. Cannon C.P. Guyton J.R. Bergeron J. Zieve F. Bruckert E. Jacobson T.A. Kopecky S.L. Baccara-Dinet M.T. Du Y. Gipe D. Efficacy and safety of alirocumab versus ezetimibe in statin-intolerant patients, with a statin-re-challenge arm: the ODYSSEY ALTERNATIVE randomized trial.J Clin Lipidol. 2015; 9: 758-769Abstract Full Text Full Text PDF PubMed Scopus (341) Google Scholar, 8Robinson J.G. Farnier M. Krempf M. Bergeron J. Luc G. Averna M. Stroes E.S. Langslet G. Raal F.J. El S.M. Koren M.J. Lepor N.E. Lorenzato C. Pordy R. Chaudhari U. Kastelein J.J. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.N Engl J Med. 2015; 372: 1489-1499Crossref PubMed Scopus (1543) Google Scholar, 9Roth E.M. Taskinen M.R. Ginsberg H.N. Kastelein J.J. Colhoun H.M. Robinson J.G. Merlet L. Pordy R. Baccara-Dinet M.T. Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial.Int J Cardiol. 2014; 176: 55-61Abstract Full Text Full Text PDF PubMed Scopus (234) Google Scholar Previously, a pooled analysis of 3 alirocumab phase 2 studies reported median reductions in lipoprotein (a) [Lp(a)] of 30% after 8 to 12 weeks of treatment.10Gaudet D. Kereiakes D.J. McKenney J.M. Roth E.M. Hanotin C. Gipe D. Du Y. Ferrand A.C. Ginsberg H.N. Stein E.A. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials).Am J Cardiol. 2014; 114: 711-715Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar In individual phase 3 studies, alirocumab reduced Lp(a) by an average of 25% to 30% from baseline to week 24 in patients with HeFH and in non-FH patients.4Kastelein J.J. Ginsberg H.N. Langslet G. Hovingh G.K. Ceska R. Dufour R. Blom D. Civeira F. Krempf M. Lorenzato C. Zhao J. Pordy R. Baccara-Dinet M.T. Gipe D.A. Geiger M.J. Farnier M. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia.Eur Heart J. 2015; 36: 2996-3003PubMed Google Scholar, 8Robinson J.G. Farnier M. Krempf M. Bergeron J. Luc G. Averna M. Stroes E.S. Langslet G. Raal F.J. El S.M. Koren M.J. Lepor N.E. Lorenzato C. Pordy R. Chaudhari U. Kastelein J.J. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.N Engl J Med. 2015; 372: 1489-1499Crossref PubMed Scopus (1543) Google Scholar The aim of the present analysis was to evaluate the maintenance of the Lp(a)-lowering effect with alirocumab over 24 to 104 weeks in a pooled analysis of 10 phase 3 studies (n = 4,915). Potential heterogeneity of treatment effect according to HeFH status and other baseline characteristics were also examined. Data from 10 randomized, double-blind, phase 3, controlled trials were included in this analysis. Efficacy data were pooled into 4 groups according to alirocumab dose, comparator, and concomitant statin use (Figure 1). Two studies used an alirocumab dose of 150 mg every 2 weeks (Q2W). The other 8 studies started with alirocumab 75-mg Q2W that was increased to 150-mg Q2W at week 12 depending on achieved LDL-C at week 8 (indicated in the text as 75/150-mg Q2W). Comparators were placebo or ezetimibe. In 8 studies, patients received concomitant statin (with or without other lipid-lowering therapy). The statin was at maximally tolerated dose in 6 studies (atorvastatin 40 to 80 mg, rosuvastatin 20 to 40 mg, or simvastatin 80 mg daily, unless an investigator-approved reason was given for using a lower dose). All study protocols were approved by the relevant institutional review boards or independent ethics committees, and all patients provided written informed consent. Prespecified end points included percentage change in Lp(a) and LDL-C from baseline at week 12 (before potential dose adjustment) and week 24 (and weeks 52 to 104 for longer trials), analyzed using an intention-to-treat (ITT) approach that included all data regardless of adherence to treatment and also using only on-treatment data. Analytical methods and statistical analysis methods are described in the Supplementary Material. Patient numbers included in the analysis are shown in Figure 1 (further details for individual studies are listed in Supplementary Table 1). Baseline characteristics, including median Lp(a) levels, were generally similar between alirocumab and control groups within each of the 4 study pools (Table 1). There was a higher proportion of men in all groups (∼60%), most patients were white (∼90%; Table 1). Overall, median baseline Lp(a) levels were higher in patients with HeFH (26.0 mg/dl) versus non-FH (22.9 mg/dl; p = 0.0004; Supplementary Table 2). Median baseline Lp(a) levels were lower in studies performed without concomitant statin versus studies performed with statin (p <0.0001; Supplementary Table 3). Furthermore, in an analysis of studies for which baseline PCSK9 levels were available, median baseline levels of free and total PCSK9 were lower in the MONO study (no statin) versus studies performed with statin (p <0.0001; Supplementary Table 3). Correlation analyses suggested that higher baseline PCSK9 levels were associated with higher baseline Lp(a) levels (Supplementary Figure 1). Across the pools, ∼30% of patients displayed Lp(a) >50 mg/dl at baseline (Table 1); baseline characteristics for these patients are listed in Supplementary Table 4. Baseline Lp(a) and LDL-C levels for the individual studies are listed in Supplementary Table 5.Table 1Baseline characteristics of all randomized patients in the 10 studiesTreatment groupsPlacebo-controlled studiesEzetimibe-controlled studiesConcomitant statinConcomitant statinNo concomitant statinAlirocumab150 mg(n=1625)Placebo(n=823)Alirocumab75/150 mg∗75/150 mg indicates that the starting dose of 75-mg Q2W could be increased to 150-mg Q2W at week 12, if LDL-C had not decreased to predetermined levels at week 8.(n=699)Placebo(n=352)Alirocumab75/150 mg∗75/150 mg indicates that the starting dose of 75-mg Q2W could be increased to 150-mg Q2W at week 12, if LDL-C had not decreased to predetermined levels at week 8.(n=686)Ezetimibe(n=444)Alirocumab75/150 mg∗75/150 mg indicates that the starting dose of 75-mg Q2W could be increased to 150-mg Q2W at week 12, if LDL-C had not decreased to predetermined levels at week 8.(n=178)Ezetimibe(n=176)Age (years), mean ± SD60.0 ± 10.860.2 ± 10.655.6 ± 12.955.5 ± 12.561.6 ± 9.762.3 ± 9.763.1 ± 8.161.9 ± 9.1Male1018 (62.6%)496 (60.3%)397 (56.8%)216 (61.4%)483 (70.4%)294 (66.2%)98 (55.1%)94 (53.4%)White1505 (92.6%)760 (92.3%)634 (90.7%)312 (88.6%)582 (84.8%)385 (86.7%)163 (91.6%)163 (92.6%)Black54 (3.3%)25 (3.0%)36 (5.2%)22 (6.3%)39 (5.7%)26 (5.9%)11 (6.2%)11 (6.3%)Asian15 (0.9%)9 (1.1%)10 (1.4%)2 (0.6%)39 (5.7%)25 (5.6%)2 (1.1%)2 (1.1%)American Indian or Alaska Native28 (1.7%)18 (2.2%)4 (0.6%)1 (0.3%)6 (0.9%)1 (0.2%)00Native Hawaiian or Other Pacific Islander0001 (0.3%)001 (0.6%)0Other23 (1.4%)11 (1.3%)15 (2.1%)14 (4.0%)20 (2.9%)7 (1.6%)1 (0.6%)0Body mass index, (kg/m2), mean ± SD30.1 ± 5.730.5 ± 5.430.0 ± 5.530.1 ± 6.030.3 ± 5.930.7 ± 5.629.7 ± 6.428.4 ± 5.5Heterozygous familial hypercholesterolemia348 (21.4%)174 (21.1%)490 (70.1%)245 (69.6%)26 (3.8%)18 (4.1%)14 (7.9%)25 (14.2%)Cardiovascular risk level Very high1451 (89.3%)751 (91.3%)438 (62.7%)224 (63.6%)601 (87.6%)371 (83.6%)73 (41.0%)62 (35.2%) High174 (10.7%)72 (8.7%)261 (37.3%)128 (36.4%)85 (12.4%)73 (16.4%)29 (16.3%)47 (26.7%) Moderate00000071 (39.9%)65 (36.9%)Concomitant medication Maximally tolerated statin1625 (100.0%)823 (100.0%)699 (100.0%)352 (100.0%)479 (69.8%)241 (54.3%)00 High-intensity statin†Atorvastatin 40 to 80 mg daily or rosuvastatin 20 to 40 mg daily.744 (45.8%)367 (44.6%)527 (75.4%)266 (75.6%)421 (61.4%)260 (58.6%)00 Lipid-lowering therapies other than statin450 (27.7%)225 (27.3%)375 (53.6%)205 (58.2%)51 (7.4%)41 (9.2%)43 (24.2%)48 (27.3%) Aspirin1019 (62.7%)529 (64.3%)349 (49.9%)171 (48.6%)481 (70.1%)307 (69.1%)80 (44.9%)82 (46.6%)Lipids, mean ± SD (mg/dL) Low-density lipoprotein cholesterol (Friedewald formula)125.9 ± 45.9125.3 ± 44.5129.0 ± 47.3130.3 ± 45.4109.4 ± 35.6105.0 ± 36.2176.5 ± 66.8177.4 ± 66.0 High-density lipoprotein cholesterol49.8 ± 12.349.8 ± 12.450.5 ± 15.449.7 ± 14.448.0 ± 13.248.3 ± 13.150.5 ± 15.753.3 ± 16.3 Non-high-density lipoprotein cholesterol155.8 ± 49.4155.4 ± 48.6155.5 ± 50.0155.8 ± 48.4139.3 ± 39.7135.4 ± 41.8211.7 ± 75.1210.8 ± 77.4 Fasting triglycerides, median (Q1:Q3)132.0 (93.8 : 182.3)134.5 (94.7 : 188.5)114.0 (85.0 : 161.0)111.0 (86.0 : 156.0)129.0 (96.0 : 185.0)134.0 (97.0 : 187.0)147.5 (105.0 : 218.0)130.0 (89.5 : 201.5) Apolipoprotein ± ± ± ± ± ± ± ± Apolipoprotein ± ± ± ± ± ± ± ± median : : : : : : : : of baseline levels to to to = mg indicates that the starting dose of 75-mg Q2W could be increased to 150-mg Q2W at week 12, if LDL-C had not decreased to predetermined levels at week 40 to 80 mg daily or rosuvastatin 20 to 40 mg in a SD = with placebo or alirocumab reduced Lp(a) and LDL-C from baseline at weeks 12 and 24 in each (Table 2). increase from 75 to 150 mg was associated with an reduction in Lp(a) studies performed with (Supplementary Table no effect was in studies performed without Reductions in Lp(a) were up to end of study in the and studies (Figure 2). patients with baseline Lp(a) to to of patients the study pools achieved Lp(a) mg/dl by week 24 (Supplementary Table in concentrations of Lp(a) and LDL-C from baseline to weeks 12 and 24 150 mg placebo with statin ± ± ± <0.0001 versus ± ± ± <0.0001 versus Low-density lipoprotein ± ± ± <0.0001 versus ± ± ± <0.0001 versus was increased from 75 to 150 mg at week 12 in and of patients in the pools without and with concomitant and in of patients in the placebo with statin ± ± ± <0.0001 versus ± ± ± <0.0001 versus Low-density lipoprotein ± ± ± <0.0001 versus ± ± ± <0.0001 versus was increased from 75 to 150 mg at week 12 in and of patients in the pools without and with concomitant and in of patients in the ezetimibe with statin ± ± ± <0.0001 versus ± ± ± <0.0001 versus Low-density lipoprotein ± ± ± <0.0001 versus ± ± ± <0.0001 versus was increased from 75 to 150 mg at week 12 in and of patients in the pools without and with concomitant and in of patients in the ezetimibe without statin ± ± ± <0.0001 versus ± ± ± <0.0001 versus Low-density lipoprotein ± ± ± <0.0001 versus ± ± ± <0.0001 versus are mean percentage change ± p <0.0001 versus was increased from 75 to 150 mg at week 12 in and of patients in the pools without and with concomitant and in of patients in the in a Data are mean percentage change ± In patients with HeFH from the FH I and FH II studies, Lp(a) was reduced from baseline by at week 24 with alirocumab 75/150-mg Q2W versus with placebo p <0.0001; in patients with HeFH from and Lp(a) decreased by at week 24 in the alirocumab 150-mg Q2W and by in the placebo p <0.0001; Lp(a) reductions with alirocumab were regardless of baseline Lp(a) or LDL-C levels (Figure 3). percentage reductions in Lp(a) a with percentage reductions in LDL-C Supplementary Figure 2). between percentage reduction in Lp(a) versus LDL-C was also in patients with baseline Lp(a) or mg/dl and in patients with and without HeFH (Supplementary 3 and was a significant for Lp(a) percentage reductions and lower achieved LDL-C levels (Supplementary Figure of results by change in Lp(a) levels similar results to the analysis by percentage change in Lp(a) (Supplementary 6 and There was no significant in percentage Lp(a) reductions according to vs other and were patients of other and with white patients of Supplementary Figure There was no in percentage Lp(a) reduction between men and or by baseline use (Supplementary Figure rates of adverse events in the trials included in this analysis were similar between alirocumab and control patients (Supplementary Table adverse events in patients, those in a higher proportion of patients versus placebo were and in trials versus these were and (Supplementary Table studies a between Lp(a) levels and risk of and independent of LDL-C or lipoprotein cholesterol S. S. Thompson S.M. R. Thompson J. and the risk of and PubMed Scopus Google Scholar Elevated Lp(a) levels are also associated with increased risk of Elevated lipoprotein(a) and risk of in the Cardiol. 2014; Full Text Full Text PDF PubMed Scopus Google Scholar of and that Lp(a) be in patients as those with T.A. Jones McKenney J.M. S.M. E.A. lipid for of Clin Lipidol. 2015; 9: Full Text Full Text PDF PubMed Scopus Google Scholar, M.J. J. F. Watts G.F. Ginsberg H. P. E. P. L. Taskinen M.R. L. as a cardiovascular risk Heart J. PubMed Scopus Google Scholar In of treatment effect on Lp(a), and other treatment options are M.J. J. F. Watts G.F. Ginsberg H. P. E. P. L. Taskinen M.R. L. as a cardiovascular risk Heart J. PubMed Scopus Google Scholar, S. R. in the treatment of lipoprotein Lipidol. 2014; PubMed Scopus Google Scholar However, to is no from a controlled that lowering Lp(a) levels CV M.J. J. F. Watts G.F. Ginsberg H. P. E. P. L. Taskinen M.R. L. as a cardiovascular risk Heart J. PubMed Scopus Google Scholar, S. R. in the treatment of lipoprotein Lipidol. 2014; PubMed Scopus Google Scholar, U. Steinhagen-Thiessen E. independent risk for cardiovascular and 2015; Full Text Full Text PDF Scopus Google Scholar The ODYSSEY included a of patients at high risk of CV were not at LDL-C treatment with maximally tolerated statin in most had median Lp(a) levels from to and of displayed baseline levels of a level to at increased CV M.J. J. F. Watts G.F. Ginsberg H. P. E. P. L. Taskinen M.R. L. as a cardiovascular risk Heart J. PubMed Scopus Google Scholar Across all study pools, alirocumab Lp(a) and LDL-C from baseline levels to and to at week with reductions sustained for weeks. was alirocumab and control in effect was including and of the are to higher levels of for to a patients of M.J. J. F. Watts G.F. Ginsberg H. P. E. P. L. Taskinen M.R. L. as a cardiovascular risk Heart J. PubMed Scopus Google Scholar However, analysis was by the proportion of of other and in the Alirocumab Lp(a) levels in patients with with reductions up to 78 weeks. suggested that patients with FH are at high risk of elevated levels of M.J. Ginsberg H.N. L. Raal F.J. Watts G.F. Hovingh G.K. C. Averna M. J. Bruckert E. P. Stroes E. Taskinen M.R. hypercholesterolaemia is and in the for to of the Heart J. PubMed Scopus Google Scholar In this pooled patients with HeFH had higher median baseline levels of Lp(a) with the non-FH patients (26.0 vs In the the percentage reductions in Lp(a) were not on baseline levels of Lp(a) or between percentage reductions in LDL-C and Lp(a) was which was than that reported for the phase 2 D. Kereiakes D.J. McKenney J.M. Roth E.M. Hanotin C. Gipe D. Du Y. Ferrand A.C. Ginsberg H.N. Stein E.A. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials).Am J Cardiol. 2014; 114: 711-715Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar which not for all the The in the lowering of Lp(a) by alirocumab is and Alirocumab is to LDL-C by the of to LDL-C from the The and of the proprotein PubMed Scopus Google Scholar also LDL-C by the of most studies shown effect of these on Lp(a), that Lp(a) is not the that the an for Lp(a) of a PCSK9 antibody, to a increase in the of with the level of R. S.M. is by proprotein convertase subtilisin/kexin type 9 the lipoprotein 2015; PubMed Scopus Google Scholar However, data a of in Lp(a) was reported that 2 FH patients and no significant reductions in Lp(a) no change in LDL-C after treatment with E.A. S.M. F. R. Raal F.J. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, in familial PubMed Scopus Google Scholar for Lp(a) are by in studies, a for (a type 1 in Lp(a) by and M. M. C. M. R. the of PCSK9 and in lipoprotein(a) Clin Lipidol. 2016; Full Text Full Text PDF Google Scholar, B. M. J.R. and 2015; PubMed Scopus Google Scholar treatment is to increase PCSK9 J.J. PCSK9 and lipid lowering 2014; PubMed Scopus Google Scholar, Rader D.J. of and on proprotein convertase subtilisin/kexin type 9 levels in patients with J Cardiol. 2015; Full Text Full Text PDF PubMed Scopus Google Scholar and in the present a between higher baseline Lp(a) and PCSK9 levels, and baseline Lp(a) and PCSK9 levels were lower in studies performed without versus with However, of this is PCSK9 data were only for of the studies performed without statin in which patients were at CV E.M. Taskinen M.R. Ginsberg H.N. Kastelein J.J. Colhoun H.M. Robinson J.G. Merlet L. Pordy R. Baccara-Dinet M.T. Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial.Int J Cardiol. 2014; 176: 55-61Abstract Full Text Full Text PDF PubMed Scopus (234) Google other be for the in baseline Lp(a) levels between The reductions in Lp(a) the ODYSSEY studies the previous data from alirocumab phase 2 studies, in numbers of patients and of maintenance of effect up to 104 D. Kereiakes D.J. McKenney J.M. Roth E.M. Hanotin C. Gipe D. Du Y. Ferrand A.C. Ginsberg H.N. Stein E.A. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials).Am J Cardiol. 2014; 114: 711-715Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar that PCSK9 with alirocumab not only LDL-C also a sustained effect on Lp(a). Reductions in Lp(a) reported for PCSK9 were with those with F.J. Koren M.J. Blom D. P. S. M. M. R. S.M. R. Stein E.A. PCSK9 reduction in Lp(a) with an analysis of 10 trials and the 2016; PubMed Scopus Google Scholar of alirocumab treatment on the of CV events is in the ODYSSEY study and results into the of reductions in LDL-C and Lp(a) on CV risk. Furthermore, studies are or in M. H. H. Y. Baccara-Dinet M.T. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia or at high cardiovascular risk with hypercholesterolemia not controlled with ODYSSEY randomized controlled J. 2016; PubMed Scopus Google were provided by and The from the study this and L. and was provided by of by and for all and data with the Gaudet is a for and received from and in a for and is a for and Robinson received from and for and and are in and of and are of and in received from and and received for and from and with Supplementary

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