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Randomized Controlled Trial
. 2022 Dec 2;18(11):e888-e896.
doi: 10.4244/EIJ-D-22-00735.

Effects of routine early treatment with PCSK9 inhibitors in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a randomised, double-blind, sham-controlled trial

Shamir R Mehta  1   2   3 , Guillaume Pare  1   2   3   4 , Eva M Lonn  1   2   3 , Sanjit S Jolly  1   2   3 , Madhu K Natarajan  1   2   3 , Natalia Pinilla-Echeverri  1   2   3 , Jon-David Schwalm  1   2   3 , Tej N Sheth  1   2   3 , Matthew Sibbald  2   3 , Michael Tsang  2   3 , Nicholas Valettas  2   3 , James L Velianou  2   3 , Shun Fu Lee  1 , Tahsin Ferdous  1 , Sadia Nauman  3 , Helen Nguyen  1 , Tara McCready  1 , Matthew J McQueen  1   2   3   4
Affiliations
Randomized Controlled Trial

Effects of routine early treatment with PCSK9 inhibitors in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a randomised, double-blind, sham-controlled trial

Shamir R Mehta et al. EuroIntervention. .

Abstract

Background: In patients with ST-segment elevation myocardial infarction (STEMI), early initiation of high-intensity statin therapy, regardless of low-density lipoprotein (LDL) cholesterol levels, is the standard of practice worldwide. Aims: We sought to determine the effect of a similar early initiation strategy, using a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor added to the high-intensity statin, on LDL cholesterol in acute STEMI.

Methods: In a randomised, double-blind trial we assigned 68 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) to early treatment with alirocumab 150 mg subcutaneously or to a matching sham control. The first injection was given before primary PCI regardless of the baseline LDL level, then at 2 and 4 weeks. The primary outcome was the percent reduction in direct LDL cholesterol up to 6 weeks, analysed using a linear mixed model. Results: High-intensity statin use was 97% and 100% in the alirocumab and sham-control groups, respectively. At a median of 45 days, the primary outcome of LDL cholesterol decreased by 72.9% with alirocumab (2.97 mmol/L to 0.75 mmol/L) versus 48.1% with the sham control (2.87 mmol/L to 1.30 mmol/L), for a mean between-group difference of -22.3% (p<0.001). More patients achieved the European Society of Cardiology/European Atherosclerosis Society dyslipidaemia guideline target of LDL ≤1.4 mmol/L in the alirocumab group (92.1% vs 56.7%; p<0.001). Within the first 24 hours, LDL declined slightly more rapidly in the alirocumab group than in the sham-control group (-0.01 mmol/L/hour; p=0.03) with similar between-group mean values. Conclusions: In this randomised trial of routine early initiation of PCSK9 inhibitors in patients undergoing primary PCI for STEMI, alirocumab reduced LDL cholesterol by 22% compared with sham control on a background of high-intensity statin therapy. A large trial is needed to determine if this simplified approach followed by long-term therapy improves cardiovascular outcomes in patients with acute STEMI. (ClinicalTrials.gov: NCT03718286).

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Conflict of interest statement

S.R. Mehta reports an unrestricted grant from Sanofi to Hamilton Health Sciences for the present study and consulting fees from Amgen, Sanofi, and Novartis. E.M. Lonn reports grants from Amgen, Novartis, Boehringer Ingelheim, the Montreal Heart Institute, and Vifor Pharma; consulting fees from Amgen, Sanofi, HLS Therapeutics, Novartis, Alnylam Pharmaceuticals, Novo Nordisk, and Bayer; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Amgen, HLS Therapeutics, Servier, Novartis, and Bayer; participation on a DSMB or advisory board for Novartis, Resvirologix, and LIB Therapeutics. G. Pare reports grants from Bayer and Lilly; consulting fees from Amgen, Bayer, and Sanofi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Amgen, Sanofi, and Novartis. N. Pinilla-Echeverri reports consulting fees from Abbott Vascular and Conavi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbott Vascular, Conavi, Novartis, and Amgen; payment for expert testimony from Conavi; support for attending meetings and/or travel from Abbott Vascular; and participation on an advisory board for Abbott and Philips. J.D. Schwalm reports consulting fees from Novartis and payment for an educational event from Novartis. M. Sibbald reports grants from Abbott Vascular and Philips. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. CONSORT diagram.
LDL: low-density lipoprotein
Central illustration
Central illustration. Direct LDL levels at follow-up.
BL: baseline; CI: confidence interval; LDL: low-density lipoprotein; sc: subcutaneous
Figure 2
Figure 2. Reduction in LDL at each timepoint after discharge.
CI: confidence interval; LDL: low-density lipoprotein
Figure 3
Figure 3. Proportion in the alirocumab and sham-control groups achieving various LDL cholesterol targets at a median follow-up of 45 days.
CI: confidence interval; LDL: low-density lipoprotein; OR: odds ratio
Figure 4
Figure 4. Scatter plot of very early effect of alirocumab vs sham control on direct LDL levels.
LDL: low-density lipoprotein
See this image and copyright information in PMC

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