Addition of anacetrapib to statins lowers coronary events in ASCVD: REVEAL trial
UK: E Sammons, University of Oxford, Oxford, UK, and colleagues have found in a randomized controlled trial REVEAL that addition of cholesteryl ester transfer protein inhibitor therapy anacetrapib to intensive statin therapy lowers the risk of major coronary events in patients with atherosclerotic vascular disease.
The study has been published in the European Heart Journal.
Based on the analysis, they found that with longer follow-up the beneficial effects of anacetrapib on major coronary events increased, and no adverse effects emerged on non-vascular mortality or morbidity. The findings suggest that trials of lipid-modifying agents should have the sufficiently long treatment and follow-up durations in order to fully assess the benefits and harms of treatment.
The researchers conducted this study to determine the long-term effects of anacetrapib on atherosclerotic vascular disease based on follow-up of the REVEAL randomized controlled trial.
30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo along with open-label atorvastatin therapy. 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation after stopping the randomly allocated treatment.
The first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) was the primary outcome during the in-trial and post-trial treatment periods, with analysis by intention-to-treat.
Salient findings of the study include:
- Allocation to anacetrapib conferred a 9% 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% reduction.
- Overall, there was a 12% proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% 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.
"Extended follow-up of the REVEAL trial showed that the addition of anacetrapib to effective statin therapy resulted in an absolute reduction in major coronary events of about 50% larger at 6 years than it had been at the end of the 4-year treatment period," wrote the authors. "Although the manufacturers of anacetrapib decided not to pursue regulatory approval or commercialization of anacetrapib,20 these results still have important implications."
Reference:
The HPS3/TIMI55-REVEAL Collaborative Group Writing Committee:, E Sammons, J C Hopewell, F Chen, W Stevens, K Wallendszus, E Valdes-Marquez, R Dayanandan, C Knott, K Murphy, E Wincott, A Baxter, R Goodenough, M Lay, M Hill, S Macdonnell, G Fabbri, D Lucci, M Fajardo-Moser, S Brenner, D Hao, H Zhang, J Liu, B Wuhan, S Mosegaard, W Herrington, C Wanner, C Angermann, G Ertl, A Maggioni, P Barter, B Mihaylova, Y Mitchel, R Blaustein, S Goto, J Tobert, P DeLucca, Y Chen, Z Chen, A Gray, R Haynes, J Armitage, C Baigent, S Wiviott, C Cannon, E Braunwald, R Collins, L Bowman, M Landray, on behalf of the REVEAL Collaborative Group, Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease, European Heart Journal, 2021;, ehab863, https://doi.org/10.1093/eurheartj/ehab863
