Cholesterol absorption inhibitor added benefit?

Ezetimibe and intense statin therapy for LDL are considered here.

Some would say–really? Is intense statin therapy that good, and now we worry about something that inhibits digestion and absorption.
So the report goes.
With commentary by a cardiologist lipid expert.
No Incremental Benefit Seen With Ezetimibe
Benjamin Morgan Scirica MD
The “cholesterol hypothesis” is one of the most elegant stories in modern medicine. “Bedside” observations that elevated cholesterol levels increase cardiovascular risk, followed by laboratory work elucidating the fundamentals in cholesterol metabolism, led to targeted drug design (of statins), now the cornerstone in the management of atherosclerosis. In the case of LDL, in marked contrast to HDL, the story has been straightforward. Lower levels of LDL, regardless of how you achieve them, are associated with a lower risk of cardiovascular events. The benefit of statins, the most powerful method to reduce LDL, has been demonstrated in dozens of well-controlled, randomized clinical trials across the spectrum of atherosclerotic disease and, accordingly, assigned the highest recommendation in current practice guidelines.
What is not known is whether additional LDL lowering on top of potent statin use will result in additional clinical benefit. Other lipid-lowering agents, including ezetimibe, a cholesterol absorption inhibitor, provides a relatively mild LDL lowering (~10%), and are only used in patients with persistently elevated LDL levels despite statins or in the statin-intolerant patient. (Other agents in development, such as cholesterol ester transfer protein (CETP) inhibitors and, even more so, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, are much more potent.) Despite the widespread uses of ezetimibe, we still lack long-term randomized data regarding its clinical efficacy when added to statins. For that, we must await the IMPROVE-IT trial, an 18,000 patient study projected to end in 2014.
With that, it is understandable that researchers look for other sources to evaluate the benefit of ezetimibe, as Pauriah and colleagues have done in an observational, retrospective study of over 9000 patients in a UK research database.1 In their study, they found that patients who received potent statin therapy were at lowest risk of recurrent events compared with patients treated with standard-dose statins. The addition of ezetimibe was not associated with any incremental benefit on top of statins.

These results, however, must be considered in the context of the study design. Observational studies cannot prove causal relationships. Without randomization, it is impossible to tease out the differences between the groups and therefore determine whether the observed differences were due to inherent imbalances or the actual drugs. Even with exquisite statistical modeling, residual confounding is always present. The example of estrogen, once touted as beneficial until a randomized trial demonstrated actual harm, is a prime example.
Thus these data are of interest, but should not change practice. We await the IMPROVE-IT study for the “final” word on ezetimibe. And we should follow the most recent guidelines, which recommend the highest tolerated statin dose for those at the greatest cardiovascular risk.
References
Pauriah M, Elder DH, Ogston S, et al. High-Potency Statin and Ezetimibe Use and Mortality in Survivors of an Acute Myocardial Infarction: A Population-Based Study [ published online ahead of print February 19, 2014]. Heart. doi: 10.1136/heartjnl-2013-304678.
Related Items
Mortality With High-Potency Statin and Ezetimibe After Acute Myocardial Infarction