Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease
<p><strong>Aims</strong></p> REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up b...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2021
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| _version_ | 1797108341896380416 |
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| author | Sammons, E Hopewell, JC Chen, F Stevens, W Wallendszus, K Valdes-Marquez, E Dayanandan, R Knott, C Murphy, K Wincott, E Baxter, A Goodenough, R Lay, M Hill, M Macdonnell, S Fabbri, G Lucci, D Fajardo-Moser, M Brenner, S Hao, D Zhang, H Liu, J Wuhan, B Mosegaard, S Herrington, W Wanner, C Angermann, C Ertl, G Maggioni, A Barter, P Mihaylova, B Mitchel, Y Blaustein, R Goto, S Tobert, J DeLucca, P Chen, Y Chen, Z Gray, A Haynes, R Armitage, J Baigent, C Wiviott, S Cannon, C Braunwald, E Collins, R Bowman, L Landray, M |
| author2 | HPS3/TIMI55-REVEAL Collaborative Group |
| author_facet | HPS3/TIMI55-REVEAL Collaborative Group Sammons, E Hopewell, JC Chen, F Stevens, W Wallendszus, K Valdes-Marquez, E Dayanandan, R Knott, C Murphy, K Wincott, E Baxter, A Goodenough, R Lay, M Hill, M Macdonnell, S Fabbri, G Lucci, D Fajardo-Moser, M Brenner, S Hao, D Zhang, H Liu, J Wuhan, B Mosegaard, S Herrington, W Wanner, C Angermann, C Ertl, G Maggioni, A Barter, P Mihaylova, B Mitchel, Y Blaustein, R Goto, S Tobert, J DeLucca, P Chen, Y Chen, Z Gray, A Haynes, R Armitage, J Baigent, C Wiviott, S Cannon, C Braunwald, E Collins, R Bowman, L Landray, M |
| author_sort | Sammons, E |
| collection | OXFORD |
| description | <p><strong>Aims</strong></p>
REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period.
<p><strong>Methods and results</strong></p>
A total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3–15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10–29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7–17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0–2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants.
<p><strong>Conclusion</strong></p>
The beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms.
<p><strong>Trial registration</strong></p>
International Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18. |
| first_indexed | 2024-03-07T07:27:50Z |
| format | Journal article |
| id | oxford-uuid:bd77e1c6-ebb2-4c6b-93b2-c4aa5e502d74 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:27:50Z |
| publishDate | 2021 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:bd77e1c6-ebb2-4c6b-93b2-c4aa5e502d742022-11-29T13:00:26ZLong-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular diseaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bd77e1c6-ebb2-4c6b-93b2-c4aa5e502d74EnglishSymplectic ElementsOxford University Press2021Sammons, EHopewell, JCChen, FStevens, WWallendszus, KValdes-Marquez, EDayanandan, RKnott, CMurphy, KWincott, EBaxter, AGoodenough, RLay, MHill, MMacdonnell, SFabbri, GLucci, DFajardo-Moser, MBrenner, SHao, DZhang, HLiu, JWuhan, BMosegaard, SHerrington, WWanner, CAngermann, CErtl, GMaggioni, ABarter, PMihaylova, BMitchel, YBlaustein, RGoto, STobert, JDeLucca, PChen, YChen, ZGray, AHaynes, RArmitage, JBaigent, CWiviott, SCannon, CBraunwald, ECollins, RBowman, LLandray, MHPS3/TIMI55-REVEAL Collaborative Group<p><strong>Aims</strong></p> REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period. <p><strong>Methods and results</strong></p> A total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3–15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10–29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7–17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0–2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants. <p><strong>Conclusion</strong></p> The beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms. <p><strong>Trial registration</strong></p> International Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18. |
| spellingShingle | Sammons, E Hopewell, JC Chen, F Stevens, W Wallendszus, K Valdes-Marquez, E Dayanandan, R Knott, C Murphy, K Wincott, E Baxter, A Goodenough, R Lay, M Hill, M Macdonnell, S Fabbri, G Lucci, D Fajardo-Moser, M Brenner, S Hao, D Zhang, H Liu, J Wuhan, B Mosegaard, S Herrington, W Wanner, C Angermann, C Ertl, G Maggioni, A Barter, P Mihaylova, B Mitchel, Y Blaustein, R Goto, S Tobert, J DeLucca, P Chen, Y Chen, Z Gray, A Haynes, R Armitage, J Baigent, C Wiviott, S Cannon, C Braunwald, E Collins, R Bowman, L Landray, M Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease |
| title | Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease |
| title_full | Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease |
| title_fullStr | Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease |
| title_full_unstemmed | Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease |
| title_short | Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease |
| title_sort | long term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease |
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