Lower On‐Treatment Low‐Density Lipoprotein Cholesterol and Major Adverse Cardiovascular Events in Women and Men: Pooled Analysis of 10 ODYSSEY Phase 3 Alirocumab Trials
Background In statin trials, men and women derived similar relative risk reductions in cardiovascular events per 39 mg/dL low‐density lipoprotein cholesterol (LDL‐C) reduction. We explored whether lower LDL‐C levels and greater LDL‐C percentage reductions than those achieved with statins are associa...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-09-01
|
| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.118.009221 |
| _version_ | 1819205634840592384 |
|---|---|
| author | Antonio J. Vallejo‐Vaz Henry N. Ginsberg Michael H. Davidson Robert H. Eckel Christopher P. Cannon L. Veronica Lee Laurence Bessac Robert Pordy Alexia Letierce Kausik K. Ray |
| author_facet | Antonio J. Vallejo‐Vaz Henry N. Ginsberg Michael H. Davidson Robert H. Eckel Christopher P. Cannon L. Veronica Lee Laurence Bessac Robert Pordy Alexia Letierce Kausik K. Ray |
| author_sort | Antonio J. Vallejo‐Vaz |
| collection | DOAJ |
| description | Background In statin trials, men and women derived similar relative risk reductions in cardiovascular events per 39 mg/dL low‐density lipoprotein cholesterol (LDL‐C) reduction. We explored whether lower LDL‐C levels and greater LDL‐C percentage reductions than those achieved with statins are associated with reduced major adverse cardiovascular event (MACE) rates in women as well as men. Methods and Results Data pooled from 10 phase 3 ODYSSEY randomized trials (n=4983) comparing alirocumab with control (placebo/ezetimibe) were assessed for association between 39 mg/dL lower on‐treatment LDL‐C and percentage LDL‐C change from baseline, and MACE risk by sex, using multivariable Cox regression. Mean baseline LDL‐C was 135 mg/dL (women) and 121 mg/dL (men). Average on‐treatment LDL‐C levels with alirocumab, ezetimibe, and placebo were 71, 114, and 134 mg/dL, respectively, in women (n=1882) and 52, 93, and 122 mg/dL, respectively, in men (n=3090). Overall, 36.5% and 58.7% of women and men, respectively, achieved on‐treatment LDL‐C <50 mg/dL. Each 39 mg/dL lower LDL‐C was associated with a 33% and 22% lower risk of MACE in women (P=0.0209) and men (P=0.0307), respectively, with no significant between‐sex difference (P for heterogeneity=0.4597). Results were similar when analyzed per 50% LDL‐C reduction, 24% (P=0.1094) and 29% (P=0.0125) lower MACE risk in women and men, respectively (P for heterogeneity=0.7499). Alirocumab was generally well tolerated in both sexes. Conclusions The present analysis reinforces the notion that both sexes derive a similar cardiovascular benefit from LDL‐C lowering. Although women had slightly higher on‐treatment LDL‐C than men, both sexes showed a similar lower MACE risk with lower LDL‐C. |
| first_indexed | 2024-12-23T04:54:50Z |
| format | Article |
| id | doaj.art-c953aea1cd0c4013b57ad7c8c761f41a |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-23T04:54:50Z |
| publishDate | 2018-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-c953aea1cd0c4013b57ad7c8c761f41a2022-12-21T17:59:23ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802018-09-0171810.1161/JAHA.118.009221Lower On‐Treatment Low‐Density Lipoprotein Cholesterol and Major Adverse Cardiovascular Events in Women and Men: Pooled Analysis of 10 ODYSSEY Phase 3 Alirocumab TrialsAntonio J. Vallejo‐Vaz0Henry N. Ginsberg1Michael H. Davidson2Robert H. Eckel3Christopher P. Cannon4L. Veronica Lee5Laurence Bessac6Robert Pordy7Alexia Letierce8Kausik K. Ray9Imperial Centre for Cardiovascular Disease Prevention Department of Primary Care and Public Health Imperial College London United KingdomColumbia University New York NYDepartment of Medicine University of Chicago Medicine Chicago ILUniversity of Colorado Anschutz Medical Campus Aurora COCardiovascular Medicine Innovation Brigham and Women's Hospital Boston MASanofi Bridgewater NJSanofi Paris FranceRegeneron Pharmaceuticals, Inc. Tarrytown NYSanofi Chilly‐Mazarin FranceImperial Centre for Cardiovascular Disease Prevention Department of Primary Care and Public Health Imperial College London United KingdomBackground In statin trials, men and women derived similar relative risk reductions in cardiovascular events per 39 mg/dL low‐density lipoprotein cholesterol (LDL‐C) reduction. We explored whether lower LDL‐C levels and greater LDL‐C percentage reductions than those achieved with statins are associated with reduced major adverse cardiovascular event (MACE) rates in women as well as men. Methods and Results Data pooled from 10 phase 3 ODYSSEY randomized trials (n=4983) comparing alirocumab with control (placebo/ezetimibe) were assessed for association between 39 mg/dL lower on‐treatment LDL‐C and percentage LDL‐C change from baseline, and MACE risk by sex, using multivariable Cox regression. Mean baseline LDL‐C was 135 mg/dL (women) and 121 mg/dL (men). Average on‐treatment LDL‐C levels with alirocumab, ezetimibe, and placebo were 71, 114, and 134 mg/dL, respectively, in women (n=1882) and 52, 93, and 122 mg/dL, respectively, in men (n=3090). Overall, 36.5% and 58.7% of women and men, respectively, achieved on‐treatment LDL‐C <50 mg/dL. Each 39 mg/dL lower LDL‐C was associated with a 33% and 22% lower risk of MACE in women (P=0.0209) and men (P=0.0307), respectively, with no significant between‐sex difference (P for heterogeneity=0.4597). Results were similar when analyzed per 50% LDL‐C reduction, 24% (P=0.1094) and 29% (P=0.0125) lower MACE risk in women and men, respectively (P for heterogeneity=0.7499). Alirocumab was generally well tolerated in both sexes. Conclusions The present analysis reinforces the notion that both sexes derive a similar cardiovascular benefit from LDL‐C lowering. Although women had slightly higher on‐treatment LDL‐C than men, both sexes showed a similar lower MACE risk with lower LDL‐C.https://www.ahajournals.org/doi/10.1161/JAHA.118.009221cardiovascular disease risk factorscardiovascular eventslow‐density lipoprotein cholesterolproprotein convertase subtilisin/kexin type 9women |
| spellingShingle | Antonio J. Vallejo‐Vaz Henry N. Ginsberg Michael H. Davidson Robert H. Eckel Christopher P. Cannon L. Veronica Lee Laurence Bessac Robert Pordy Alexia Letierce Kausik K. Ray Lower On‐Treatment Low‐Density Lipoprotein Cholesterol and Major Adverse Cardiovascular Events in Women and Men: Pooled Analysis of 10 ODYSSEY Phase 3 Alirocumab Trials Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease cardiovascular disease risk factors cardiovascular events low‐density lipoprotein cholesterol proprotein convertase subtilisin/kexin type 9 women |
| title | Lower On‐Treatment Low‐Density Lipoprotein Cholesterol and Major Adverse Cardiovascular Events in Women and Men: Pooled Analysis of 10 ODYSSEY Phase 3 Alirocumab Trials |
| title_full | Lower On‐Treatment Low‐Density Lipoprotein Cholesterol and Major Adverse Cardiovascular Events in Women and Men: Pooled Analysis of 10 ODYSSEY Phase 3 Alirocumab Trials |
| title_fullStr | Lower On‐Treatment Low‐Density Lipoprotein Cholesterol and Major Adverse Cardiovascular Events in Women and Men: Pooled Analysis of 10 ODYSSEY Phase 3 Alirocumab Trials |
| title_full_unstemmed | Lower On‐Treatment Low‐Density Lipoprotein Cholesterol and Major Adverse Cardiovascular Events in Women and Men: Pooled Analysis of 10 ODYSSEY Phase 3 Alirocumab Trials |
| title_short | Lower On‐Treatment Low‐Density Lipoprotein Cholesterol and Major Adverse Cardiovascular Events in Women and Men: Pooled Analysis of 10 ODYSSEY Phase 3 Alirocumab Trials |
| title_sort | lower on treatment low density lipoprotein cholesterol and major adverse cardiovascular events in women and men pooled analysis of 10 odyssey phase 3 alirocumab trials |
| topic | cardiovascular disease risk factors cardiovascular events low‐density lipoprotein cholesterol proprotein convertase subtilisin/kexin type 9 women |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.118.009221 |
| work_keys_str_mv | AT antoniojvallejovaz lowerontreatmentlowdensitylipoproteincholesterolandmajoradversecardiovasculareventsinwomenandmenpooledanalysisof10odysseyphase3alirocumabtrials AT henrynginsberg lowerontreatmentlowdensitylipoproteincholesterolandmajoradversecardiovasculareventsinwomenandmenpooledanalysisof10odysseyphase3alirocumabtrials AT michaelhdavidson lowerontreatmentlowdensitylipoproteincholesterolandmajoradversecardiovasculareventsinwomenandmenpooledanalysisof10odysseyphase3alirocumabtrials AT robertheckel lowerontreatmentlowdensitylipoproteincholesterolandmajoradversecardiovasculareventsinwomenandmenpooledanalysisof10odysseyphase3alirocumabtrials AT christopherpcannon lowerontreatmentlowdensitylipoproteincholesterolandmajoradversecardiovasculareventsinwomenandmenpooledanalysisof10odysseyphase3alirocumabtrials AT lveronicalee lowerontreatmentlowdensitylipoproteincholesterolandmajoradversecardiovasculareventsinwomenandmenpooledanalysisof10odysseyphase3alirocumabtrials AT laurencebessac lowerontreatmentlowdensitylipoproteincholesterolandmajoradversecardiovasculareventsinwomenandmenpooledanalysisof10odysseyphase3alirocumabtrials AT robertpordy lowerontreatmentlowdensitylipoproteincholesterolandmajoradversecardiovasculareventsinwomenandmenpooledanalysisof10odysseyphase3alirocumabtrials AT alexialetierce lowerontreatmentlowdensitylipoproteincholesterolandmajoradversecardiovasculareventsinwomenandmenpooledanalysisof10odysseyphase3alirocumabtrials AT kausikkray lowerontreatmentlowdensitylipoproteincholesterolandmajoradversecardiovasculareventsinwomenandmenpooledanalysisof10odysseyphase3alirocumabtrials |