The Effect of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibition on the Risk of Venous Thromboembolism
The relationship between cholesterol levels and risk of venous thromboembolism (VTE) is uncertain. We set out to determine the effect of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition on the risk of VTE, explore potential mechanisms, and examine the efficacy in subgroups with clini...
Uloženo v:
| Vydáno v: | Circulation (New York, N.Y.) Ročník 141; číslo 20; s. 1600 |
|---|---|
| Hlavní autoři: | , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
19.05.2020
|
| Témata: | |
| ISSN: | 1524-4539, 1524-4539 |
| On-line přístup: | Zjistit podrobnosti o přístupu |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | The relationship between cholesterol levels and risk of venous thromboembolism (VTE) is uncertain. We set out to determine the effect of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition on the risk of VTE, explore potential mechanisms, and examine the efficacy in subgroups with clinically and genetically defined risk.
We performed a post hoc analysis of the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) testing whether evolocumab reduces the risk of VTE events (deep venous thrombosis or pulmonary embolism). Data from FOURIER and ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment with Alirocumab) were then combined in a meta-analysis to assess the class effect of PCSK9 inhibition on the risk of VTE. We also analyzed baseline lipids in FOURIER to investigate potential mechanisms explaining the reduction in VTE with evolocumab. Last, an exploratory genetic analysis was performed in FOURIER to determine whether a VTE polygenic risk score could identify high-risk patients who would derive the greatest VTE reduction from evolocumab.
In FOURIER, the hazard ratio (HR) for VTE with evolocumab was 0.71 (95% CI, 0.50-1.00;
=0.05), with no effect in the 1st year (HR, 0.96 [95% CI, 0.57-1.62]) but a 46% reduction (HR, 0.54 [95% CI, 0.33-0.88];
=0.014) beyond 1 year. A meta-analysis of FOURIER and ODYSSEY OUTCOMES demonstrated a 31% relative risk reduction in VTE with PCSK9 inhibition (HR, 0.69 [95% CI, 0.53-0.90];
=0.007). There was no relation between baseline low-density lipoprotein cholesterol levels and magnitude of VTE risk reduction. In contrast, in patients with higher baseline lipoprotein(a) (Lp[a]) levels, evolocumab reduced Lp(a) by 33 nmol/L and risk of VTE by 48% (HR, 0.52 [95% CI, 0.30-0.89];
=0.017), whereas, in patients with lower baseline Lp(a) levels, evolocumab reduced Lp(a) by only 7 nmol/L and had no effect on VTE risk (
0.087 for HR;
0.037 for absolute risk reduction). Modeled as a continuous variable, there was a significant interaction between baseline Lp(a) concentration and magnitude of VTE risk reduction (
=0.04). A polygenic risk score identified patients who were at >2-fold increased risk for VTE and who derived greater relative (
=0.04) and absolute VTE reduction (
=0.009) in comparison with those without high genetic risk.
PCSK9 inhibition significantly reduces the risk of VTE. Lp(a) reduction may be an important mediator of this effect, a finding of particular interest given the ongoing development of potent Lp(a) inhibitors. |
|---|---|
| AbstractList | The relationship between cholesterol levels and risk of venous thromboembolism (VTE) is uncertain. We set out to determine the effect of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition on the risk of VTE, explore potential mechanisms, and examine the efficacy in subgroups with clinically and genetically defined risk.BACKGROUNDThe relationship between cholesterol levels and risk of venous thromboembolism (VTE) is uncertain. We set out to determine the effect of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition on the risk of VTE, explore potential mechanisms, and examine the efficacy in subgroups with clinically and genetically defined risk.We performed a post hoc analysis of the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) testing whether evolocumab reduces the risk of VTE events (deep venous thrombosis or pulmonary embolism). Data from FOURIER and ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment with Alirocumab) were then combined in a meta-analysis to assess the class effect of PCSK9 inhibition on the risk of VTE. We also analyzed baseline lipids in FOURIER to investigate potential mechanisms explaining the reduction in VTE with evolocumab. Last, an exploratory genetic analysis was performed in FOURIER to determine whether a VTE polygenic risk score could identify high-risk patients who would derive the greatest VTE reduction from evolocumab.METHODSWe performed a post hoc analysis of the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) testing whether evolocumab reduces the risk of VTE events (deep venous thrombosis or pulmonary embolism). Data from FOURIER and ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment with Alirocumab) were then combined in a meta-analysis to assess the class effect of PCSK9 inhibition on the risk of VTE. We also analyzed baseline lipids in FOURIER to investigate potential mechanisms explaining the reduction in VTE with evolocumab. Last, an exploratory genetic analysis was performed in FOURIER to determine whether a VTE polygenic risk score could identify high-risk patients who would derive the greatest VTE reduction from evolocumab.In FOURIER, the hazard ratio (HR) for VTE with evolocumab was 0.71 (95% CI, 0.50-1.00; P=0.05), with no effect in the 1st year (HR, 0.96 [95% CI, 0.57-1.62]) but a 46% reduction (HR, 0.54 [95% CI, 0.33-0.88]; P=0.014) beyond 1 year. A meta-analysis of FOURIER and ODYSSEY OUTCOMES demonstrated a 31% relative risk reduction in VTE with PCSK9 inhibition (HR, 0.69 [95% CI, 0.53-0.90]; P=0.007). There was no relation between baseline low-density lipoprotein cholesterol levels and magnitude of VTE risk reduction. In contrast, in patients with higher baseline lipoprotein(a) (Lp[a]) levels, evolocumab reduced Lp(a) by 33 nmol/L and risk of VTE by 48% (HR, 0.52 [95% CI, 0.30-0.89]; P=0.017), whereas, in patients with lower baseline Lp(a) levels, evolocumab reduced Lp(a) by only 7 nmol/L and had no effect on VTE risk (Pinteraction 0.087 for HR; Pheterogeneity 0.037 for absolute risk reduction). Modeled as a continuous variable, there was a significant interaction between baseline Lp(a) concentration and magnitude of VTE risk reduction (Pinteraction=0.04). A polygenic risk score identified patients who were at >2-fold increased risk for VTE and who derived greater relative (Pinteraction=0.04) and absolute VTE reduction (Pheterogeneity=0.009) in comparison with those without high genetic risk.RESULTSIn FOURIER, the hazard ratio (HR) for VTE with evolocumab was 0.71 (95% CI, 0.50-1.00; P=0.05), with no effect in the 1st year (HR, 0.96 [95% CI, 0.57-1.62]) but a 46% reduction (HR, 0.54 [95% CI, 0.33-0.88]; P=0.014) beyond 1 year. A meta-analysis of FOURIER and ODYSSEY OUTCOMES demonstrated a 31% relative risk reduction in VTE with PCSK9 inhibition (HR, 0.69 [95% CI, 0.53-0.90]; P=0.007). There was no relation between baseline low-density lipoprotein cholesterol levels and magnitude of VTE risk reduction. In contrast, in patients with higher baseline lipoprotein(a) (Lp[a]) levels, evolocumab reduced Lp(a) by 33 nmol/L and risk of VTE by 48% (HR, 0.52 [95% CI, 0.30-0.89]; P=0.017), whereas, in patients with lower baseline Lp(a) levels, evolocumab reduced Lp(a) by only 7 nmol/L and had no effect on VTE risk (Pinteraction 0.087 for HR; Pheterogeneity 0.037 for absolute risk reduction). Modeled as a continuous variable, there was a significant interaction between baseline Lp(a) concentration and magnitude of VTE risk reduction (Pinteraction=0.04). A polygenic risk score identified patients who were at >2-fold increased risk for VTE and who derived greater relative (Pinteraction=0.04) and absolute VTE reduction (Pheterogeneity=0.009) in comparison with those without high genetic risk.PCSK9 inhibition significantly reduces the risk of VTE. Lp(a) reduction may be an important mediator of this effect, a finding of particular interest given the ongoing development of potent Lp(a) inhibitors.CONCLUSIONSPCSK9 inhibition significantly reduces the risk of VTE. Lp(a) reduction may be an important mediator of this effect, a finding of particular interest given the ongoing development of potent Lp(a) inhibitors. The relationship between cholesterol levels and risk of venous thromboembolism (VTE) is uncertain. We set out to determine the effect of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition on the risk of VTE, explore potential mechanisms, and examine the efficacy in subgroups with clinically and genetically defined risk. We performed a post hoc analysis of the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) testing whether evolocumab reduces the risk of VTE events (deep venous thrombosis or pulmonary embolism). Data from FOURIER and ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment with Alirocumab) were then combined in a meta-analysis to assess the class effect of PCSK9 inhibition on the risk of VTE. We also analyzed baseline lipids in FOURIER to investigate potential mechanisms explaining the reduction in VTE with evolocumab. Last, an exploratory genetic analysis was performed in FOURIER to determine whether a VTE polygenic risk score could identify high-risk patients who would derive the greatest VTE reduction from evolocumab. In FOURIER, the hazard ratio (HR) for VTE with evolocumab was 0.71 (95% CI, 0.50-1.00; =0.05), with no effect in the 1st year (HR, 0.96 [95% CI, 0.57-1.62]) but a 46% reduction (HR, 0.54 [95% CI, 0.33-0.88]; =0.014) beyond 1 year. A meta-analysis of FOURIER and ODYSSEY OUTCOMES demonstrated a 31% relative risk reduction in VTE with PCSK9 inhibition (HR, 0.69 [95% CI, 0.53-0.90]; =0.007). There was no relation between baseline low-density lipoprotein cholesterol levels and magnitude of VTE risk reduction. In contrast, in patients with higher baseline lipoprotein(a) (Lp[a]) levels, evolocumab reduced Lp(a) by 33 nmol/L and risk of VTE by 48% (HR, 0.52 [95% CI, 0.30-0.89]; =0.017), whereas, in patients with lower baseline Lp(a) levels, evolocumab reduced Lp(a) by only 7 nmol/L and had no effect on VTE risk ( 0.087 for HR; 0.037 for absolute risk reduction). Modeled as a continuous variable, there was a significant interaction between baseline Lp(a) concentration and magnitude of VTE risk reduction ( =0.04). A polygenic risk score identified patients who were at >2-fold increased risk for VTE and who derived greater relative ( =0.04) and absolute VTE reduction ( =0.009) in comparison with those without high genetic risk. PCSK9 inhibition significantly reduces the risk of VTE. Lp(a) reduction may be an important mediator of this effect, a finding of particular interest given the ongoing development of potent Lp(a) inhibitors. |
| Author | Giugliano, Robert P Sabatine, Marc S Gurmu, Yared Keech, Anthony C Ruff, Christian T Marston, Nicholas A Sever, Peter S Ellinor, Patrick T Gencer, Baris Roselli, Carolina Bonaca, Marc Pedersen, Terje R Melloni, Giorgio E M Lubitz, Steven A O'Donoghue, Michelle L |
| Author_xml | – sequence: 1 givenname: Nicholas A surname: Marston fullname: Marston, Nicholas A organization: TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.A.M., Y.G., G.E.M.M., B.G., M.L.O., R.P.G., C.T.R., M.S.S.) – sequence: 2 givenname: Yared surname: Gurmu fullname: Gurmu, Yared organization: TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.A.M., Y.G., G.E.M.M., B.G., M.L.O., R.P.G., C.T.R., M.S.S.) – sequence: 3 givenname: Giorgio E M surname: Melloni fullname: Melloni, Giorgio E M organization: TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.A.M., Y.G., G.E.M.M., B.G., M.L.O., R.P.G., C.T.R., M.S.S.) – sequence: 4 givenname: Marc surname: Bonaca fullname: Bonaca, Marc organization: CPC Clinical Research, Department of Medicine, Cardiovascular Division, University of Colorado School of Medicine, Aurora (M.B.) – sequence: 5 givenname: Baris surname: Gencer fullname: Gencer, Baris organization: TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.A.M., Y.G., G.E.M.M., B.G., M.L.O., R.P.G., C.T.R., M.S.S.) – sequence: 6 givenname: Peter S surname: Sever fullname: Sever, Peter S organization: National Heart and Lung Institute, Imperial College London, United Kingdom (P.S.S.) – sequence: 7 givenname: Terje R surname: Pedersen fullname: Pedersen, Terje R organization: Oslo University Hospital, Ulleval and Medical Faculty, University of Oslo, Norway (T.R.P.) – sequence: 8 givenname: Anthony C surname: Keech fullname: Keech, Anthony C organization: Sydney Medical School, National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Australia (A.C.K.) – sequence: 9 givenname: Carolina surname: Roselli fullname: Roselli, Carolina organization: University Medical Center Groningen, University of Groningen, The Netherlands (C.R.) – sequence: 10 givenname: Steven A surname: Lubitz fullname: Lubitz, Steven A organization: Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., P.T.E.) – sequence: 11 givenname: Patrick T surname: Ellinor fullname: Ellinor, Patrick T organization: Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., P.T.E.) – sequence: 12 givenname: Michelle L surname: O'Donoghue fullname: O'Donoghue, Michelle L organization: TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.A.M., Y.G., G.E.M.M., B.G., M.L.O., R.P.G., C.T.R., M.S.S.) – sequence: 13 givenname: Robert P surname: Giugliano fullname: Giugliano, Robert P organization: TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.A.M., Y.G., G.E.M.M., B.G., M.L.O., R.P.G., C.T.R., M.S.S.) – sequence: 14 givenname: Christian T surname: Ruff fullname: Ruff, Christian T organization: TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.A.M., Y.G., G.E.M.M., B.G., M.L.O., R.P.G., C.T.R., M.S.S.) – sequence: 15 givenname: Marc S surname: Sabatine fullname: Sabatine, Marc S organization: TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.A.M., Y.G., G.E.M.M., B.G., M.L.O., R.P.G., C.T.R., M.S.S.) |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32223429$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkNtKw0AQhhepWFt9BVnv6kXa7G5OexlCtaHFljb1NuQwoavJbs0mYt_eLVYQZpgf5p-PmRmhgVQSEHok9pQQj8yieBvtV2ESr1_DRTgl1J7ajse4f4VuiUsdy3EZH_zTQzTS-t22bY_57g0aMkopcyi_RV1yADyvKig6rCq8iXZLjiebVh1b1YGQOFLyC9ou04B3fd6JWmghZ0v4Nr3kdATMn3AsDyIXnVASm-gMcSv0x5n3BlL1GieHVjW5ApNmvrlD11VWa7i_1DHaP8-TaGGt1i9xFK6swg0C38q4m3msoE4ZFFBV1LcZ515ZAKOZF3gZKxl3oczBIX5eFgHPGS88lxlzDgwCOkaTX6455rMH3aWN0AXUdSbBrJVSFjgB4YycrQ8Xa583UKbHVjRZe0r_PkV_AOVab_I |
| CitedBy_id | crossref_primary_10_1097_MS9_0000000000001601 crossref_primary_10_3389_fcvm_2021_711923 crossref_primary_10_1016_j_jtha_2023_08_004 crossref_primary_10_1016_j_thromres_2022_03_021 crossref_primary_10_1097_FJC_0000000000001160 crossref_primary_10_1161_CIRCULATIONAHA_120_049350 crossref_primary_10_1182_blood_2023022522 crossref_primary_10_1093_ehjacc_zuaf109 crossref_primary_10_1007_s11883_022_01053_3 crossref_primary_10_3389_fphys_2020_595819 crossref_primary_10_2337_dc20_2842 crossref_primary_10_1093_eurheartj_ehae492 crossref_primary_10_1080_21556660_2020_1801452 crossref_primary_10_1007_s11239_025_03108_z crossref_primary_10_1093_eurjpc_zwab052 crossref_primary_10_1016_j_thromres_2020_07_049 crossref_primary_10_3390_life11060466 crossref_primary_10_1055_s_0042_1757562 crossref_primary_10_3390_ijms22115880 crossref_primary_10_1007_s11883_021_00918_3 crossref_primary_10_1161_CIRCULATIONAHA_120_050174 crossref_primary_10_1093_cvr_cvab032 crossref_primary_10_1161_JAHA_120_019395 crossref_primary_10_1093_eurjpc_zwab167 crossref_primary_10_2147_VHRM_S275739 crossref_primary_10_1016_j_mehy_2020_110452 crossref_primary_10_1093_eurheartj_ehae361 crossref_primary_10_1016_j_mayocp_2023_08_013 crossref_primary_10_1055_a_2674_5114 crossref_primary_10_3390_biomedicines12122729 crossref_primary_10_3389_fcvm_2021_639727 crossref_primary_10_1093_eurheartj_ehaa1080 crossref_primary_10_1016_j_jacc_2023_12_031 crossref_primary_10_1093_eurheartj_ehab875 crossref_primary_10_1016_j_thromres_2021_06_012 crossref_primary_10_1097_MOL_0000000000000763 crossref_primary_10_3389_fcvm_2024_1339487 crossref_primary_10_1111_jcmm_18370 crossref_primary_10_1016_j_medj_2024_02_015 crossref_primary_10_1093_cvr_cvab144 crossref_primary_10_1093_eurheartj_ehac361 crossref_primary_10_1016_j_jaut_2022_102832 crossref_primary_10_1002_pul2_70043 crossref_primary_10_1136_rmdopen_2024_005129 crossref_primary_10_3390_ph16091197 crossref_primary_10_1093_ehjcvp_pvae076 crossref_primary_10_1097_MD_0000000000040770 crossref_primary_10_3390_jcm11133625 crossref_primary_10_1093_ehjcvp_pvae077 crossref_primary_10_1093_eurjpc_zwaa063 crossref_primary_10_3390_nu12072024 crossref_primary_10_1007_s11883_021_00951_2 crossref_primary_10_3390_cells11192972 crossref_primary_10_1002_clc_23456 crossref_primary_10_1016_j_vph_2021_106931 crossref_primary_10_1016_j_vph_2022_106977 crossref_primary_10_12688_f1000research_27115_1 crossref_primary_10_3390_metabo12030226 crossref_primary_10_1097_MOL_0000000000000830 crossref_primary_10_3390_metabo14070388 crossref_primary_10_1007_s10557_024_07599_5 crossref_primary_10_2174_1381612829666230412105238 crossref_primary_10_3390_jcm13102744 crossref_primary_10_52420_umj_24_4_55 crossref_primary_10_1093_europace_euac030 crossref_primary_10_1016_j_atherosclerosis_2022_04_020 crossref_primary_10_1186_s12916_023_02844_4 crossref_primary_10_1016_j_jacc_2021_04_102 crossref_primary_10_3390_ijms24031966 crossref_primary_10_1002_joa3_12717 crossref_primary_10_1055_a_1472_1457 crossref_primary_10_3390_jcdd12090355 crossref_primary_10_3892_ijmm_2024_5381 crossref_primary_10_1016_j_hrthm_2022_03_1225 crossref_primary_10_4274_balkanmedj_galenos_2023_2023_10_17 crossref_primary_10_1016_j_ajpc_2024_100651 crossref_primary_10_1186_s12944_023_01926_9 crossref_primary_10_3389_fcvm_2021_637366 |
| ContentType | Journal Article |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1161/CIRCULATIONAHA.120.046397 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Medicine Anatomy & Physiology |
| EISSN | 1524-4539 |
| ExternalDocumentID | 32223429 |
| Genre | Meta-Analysis Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NHLBI NIH HHS grantid: L30 HL143770 – fundername: NHLBI NIH HHS grantid: R01 HL139731 – fundername: NHLBI NIH HHS grantid: F32 HL144029 – fundername: NHLBI NIH HHS grantid: R01 HL092577 – fundername: NHLBI NIH HHS grantid: K08 HL153950 – fundername: NHLBI NIH HHS grantid: K24 HL105780 |
| GroupedDBID | --- .-D .3C .XZ .Z2 01R 0R~ 0ZK 18M 1J1 29B 2FS 2WC 354 40H 4Q1 4Q2 4Q3 53G 5GY 5RE 5VS 6PF 71W 77Y 7O~ AAAAV AAAXR AAGIX AAHPQ AAIQE AAJCS AAMOA AAMTA AAQKA AARTV AASCR AASOK AASXQ AAUEB AAWTL AAXQO ABASU ABBUW ABDIG ABJNI ABOCM ABPMR ABQRW ABVCZ ABXVJ ABZAD ACDDN ACEWG ACGFO ACGFS ACIJW ACILI ACLDA ACOAL ACRKK ACWDW ACWRI ACXJB ACXNZ ADBBV ADCYY ADGGA ADHPY AE3 AE6 AEBDS AENEX AFCHL AFDTB AFEXH AFSOK AFUWQ AGINI AHMBA AHOMT AHQNM AHRYX AHVBC AIJEX AINUH AJCLO AJIOK AJNWD AJZMW AKCTQ AKULP ALKUP ALMA_UNASSIGNED_HOLDINGS ALMTX AMJPA AMKUR AMNEI AOHHW ASPBG AVWKF AWKKM AYCSE AZFZN BAWUL BOYCO BQLVK BYPQX C45 CGR CS3 CUY CVF DIK DIWNM DU5 E3Z EBS ECM EEVPB EIF ERAAH EX3 F2K F2L F2M F2N F5P FCALG GNXGY GQDEL GX1 H0~ HLJTE HZ~ IKREB IKYAY IN~ IPNFZ JF9 JG8 JK3 K-A K-F K8S KD2 KMI KQ8 L-C L7B N9A NPM N~7 N~B O9- OAG OAH OBH OCB ODA ODMTH OGEVE OHH OHYEH OJAPA OK1 OL1 OLB OLG OLH OLU OLV OLW OLY OLZ OPUJH OVD OVDNE OVIDH OVLEI OVOZU OWBYB OWU OWV OWW OWX OWY OWZ OXXIT P2P PQQKQ RAH RHF RIG RLZ S4R S4S T8P TEORI TR2 TSPGW UPT V2I VVN W2D W3M W8F WH7 WOQ WOW X3V X3W XXN XYM YFH YOC YSK YYM YZZ ZFV ZY1 ~H1 7X8 AAFWJ ABPXF ABXYN ABZZY ACDOF ACZKN ADKSD ADSXY AFBFQ AFMBP AFNMH AHQVU AOQMC |
| ID | FETCH-LOGICAL-c5887-a95a63c24d8ceff2703996dce32a686a3d395edbe417bdc89b39c653cefbe3e82 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 82 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=00003017-202005190-00002&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1524-4539 |
| IngestDate | Mon Sep 08 06:10:20 EDT 2025 Wed Feb 19 02:02:28 EST 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 20 |
| Keywords | numbers needed to treat cholesterol, LDL PCSK9 protein, human venous thromboembolism evolocumab |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c5887-a95a63c24d8ceff2703996dce32a686a3d395edbe417bdc89b39c653cefbe3e82 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.046397 |
| PMID | 32223429 |
| PQID | 2384819318 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2384819318 pubmed_primary_32223429 |
| PublicationCentury | 2000 |
| PublicationDate | 2020-May-19 |
| PublicationDateYYYYMMDD | 2020-05-19 |
| PublicationDate_xml | – month: 05 year: 2020 text: 2020-May-19 day: 19 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Circulation (New York, N.Y.) |
| PublicationTitleAlternate | Circulation |
| PublicationYear | 2020 |
| References | 33104398 - Circulation. 2020 Oct 27;142(17):e262-e263 33104403 - Circulation. 2020 Oct 27;142(17):e264 |
| References_xml | – reference: 33104403 - Circulation. 2020 Oct 27;142(17):e264 – reference: 33104398 - Circulation. 2020 Oct 27;142(17):e262-e263 |
| SSID | ssj0006375 |
| Score | 2.587239 |
| SecondaryResourceType | review_article |
| Snippet | The relationship between cholesterol levels and risk of venous thromboembolism (VTE) is uncertain. We set out to determine the effect of PCSK9 (proprotein... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 1600 |
| SubjectTerms | Aged Antibodies, Monoclonal, Humanized - adverse effects Antibodies, Monoclonal, Humanized - therapeutic use Anticholesteremic Agents - adverse effects Anticholesteremic Agents - therapeutic use Biomarkers - blood Cholesterol, LDL - blood Clinical Trials as Topic Dyslipidemias - blood Dyslipidemias - diagnosis Dyslipidemias - drug therapy Dyslipidemias - epidemiology Female Humans Incidence Lipoprotein(a) - blood Male Middle Aged PCSK9 Inhibitors Pulmonary Embolism - diagnosis Pulmonary Embolism - epidemiology Pulmonary Embolism - prevention & control Risk Assessment Risk Factors Serine Proteinase Inhibitors - adverse effects Serine Proteinase Inhibitors - therapeutic use Time Factors Treatment Outcome Venous Thromboembolism - diagnosis Venous Thromboembolism - epidemiology Venous Thromboembolism - prevention & control Venous Thrombosis - diagnosis Venous Thrombosis - epidemiology Venous Thrombosis - prevention & control |
| Title | The Effect of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibition on the Risk of Venous Thromboembolism |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/32223429 https://www.proquest.com/docview/2384819318 |
| Volume | 141 |
| WOSCitedRecordID | wos00003017-202005190-00002&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1JS8QwFH64IV7c94UIInqoziRtmpxEiqKow-DG3IYmTbDotDodRP-9L2nFkyAIbS9pSkhf3vc2vgewh7BjhKUyoFyKIJSWBZLrKIhVWzlAawmb-mYTcacjej3ZbQJuVVNW-a0TvaLOSu1i5McILSGiF4rgyetb4LpGuexq00JjHCYZmjLuYMa9H7ZwzjzRLkJUGIQRk9Ow65UEbx8nl7fJw3VNOHvhIoKtI8edJePfLU2POOdz_13rPMw2tiY5rYVjAcZMsQhLpwX62YNPsk989acPqy_C9E2TZF-CEYoOqVmNSWlJN7m7kuSgOyw9p0NekMRVqqPVXhmCemeUv-QVutdX5gPHnF9L5CG5LJ5y5cvBCF5oZZLbvHp233v0rLDk_mlYDlRp8Mb5g2V4OD-7Ty6CpjlDoCOnmFIZpZxpGmZCG2spag50nTJtGE254CnLmIxMpkzYjlWmhVRMah4xfFkZZgRdgYmiLMwaEMuNNFqhZohaocqEYBanILIytOVoStdh93ub-yj8LqORFgaX2v_Z6HVYrf9V_7Vm6ei7FBJDtN34w-xNmKHOj3asrHILJi0efbMNU_p9lFfDHS9V-Ox0b74AxaDV5A |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Effect+of+PCSK9+%28Proprotein+Convertase+Subtilisin%2FKexin+Type+9%29+Inhibition+on+the+Risk+of+Venous+Thromboembolism&rft.jtitle=Circulation+%28New+York%2C+N.Y.%29&rft.au=Marston%2C+Nicholas+A&rft.au=Gurmu%2C+Yared&rft.au=Melloni%2C+Giorgio+E+M&rft.au=Bonaca%2C+Marc&rft.date=2020-05-19&rft.eissn=1524-4539&rft.volume=141&rft.issue=20&rft.spage=1600&rft_id=info:doi/10.1161%2FCIRCULATIONAHA.120.046397&rft_id=info%3Apmid%2F32223429&rft_id=info%3Apmid%2F32223429&rft.externalDocID=32223429 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1524-4539&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1524-4539&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1524-4539&client=summon |