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RECENT PUBLICATIONS ON RESIDUAL RISK

2017

Congress News : 66th Annual Scientific Sessions of the American College of Cardiology, Washington DC, 17-19 March
PCSK9 Inhibition tops the bill; HDL fails again

This year’s ACC Sessions highlighted PCSK9 inhibition, with evidence from two studies with PCSK9 monoclonal antibody therapy - FOURIER and SPIRE-2 with the prematurely terminated bococizumab – that lowering low-density lipoprotein cholesterol (LDL-C) levels far beyond current LDL-C targets reduces cardiovascular events in very high risk patients (1,2). As shown by the SPIRE-2 study, the magnitude of benefit appeared to be greater in patients with higher LDL-C levels at baseline, and thus at higher LDL-related risk, consistent with the regression line shown for statin therapy in the Cholesterol Treatment Trialists’ Collaboration meta-analysis (3). While FOURIER was an event-driven trial, the short duration of follow-up (median 2.2 years) has led to some controversy regarding the lack of benefit on cardiovascular mortality. Additionally, it is relevant that adding evolocumab to maximally tolerated lipid lowering therapy did not eliminate the risk of cardiovascular events in very high risk patients, thus underlying the importance of other risk factors, both lipid and non-lipid related, that contribute to this residual risk. Data are also awaited on subgroup analyses evaluating the effects of evolocumab added to maximal lipid-lowering therapy in diabetes patients.
 
Regarding other lipids and lipoproteins, there was disappointing news (yet again) for targeting high-density lipoprotein (HDL) from the proof-of concept CER-001 Atherosclerosis Regression Acute Coronary Syndrome Trial (CARAT) study (4). Short-term treatment with the HDL mimetic CER-001 did not produce a significant effect on coronary disease progression, as measured by intravascular ultrasonography (IVUS), against a background of contemporary therapy in the acute coronary syndrome (ACS) setting. Thus these findings from CARAT suggest that CER-001 is not a promising strategy for ACS patients. Whether HDL-targeted therapy can impact plaque or clinical events remains a persistent question for researchers.
 
References
1. Sabatine MS, Giugliano RP, Keech AC et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017 Mar 17. doi: 10.1056/NEJMoa1615664. [Epub ahead of print]
2. Ridker PM, Revkin J, Amarenco P et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N Engl J Med 2017 Mar 17. doi: 10.1056/NEJMoa1701488. [Epub ahead of print]
3. Collins R, Reith C, Emberson J et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet 2016 Nov 19;388(10059):2532-56.
4. Nicholls SJ, Andrews J, Kastelein JJP et al. Results of the CARAT Study. Effect of serial infusions of CER-001, a pre-beta high-density lipoprotein mimetic on coronary atherosclerosis. Available at http://clintrialresults.org/Slides/ACC2017/CARAT_Nicholls.pdf