IMPROVE-IT Proves that with LDL, Lower is Most Definitely Better

The IMPROVE-IT verdict is in and it will change the practice of cardiovascular disease prevention. For the first time, a non-statin medication has been shown to reduce cardiovascular events (including stroke and MI) when added to a statin. Achieving an LDL level of 53 vs 70 by the end of the trial’s first year translated into a significant ASCVD risk reduction. The risk reduction is so substantial that in this patient population the “number needed to teat” was only 50. That means that for every 50 patients treated with Zetia on top of a statin, a serious/life-threatening event was prevented. And, there were no safety issues associated with adding Zetia. Thus, a downside was not present. There are so many ramifications of this trial; I will highlight a few:

As believed by most lipid (cholesterol) specialists, lower LDL is definitely better.
Ezetimibe should be added to statins in appropriate patients.
The hotly debated 2013 ACC/AHA Cholesterol Guidelines now require an addendum adding Ezetimibe to front line therapy.
Many insurance companies will have to revisit their denials of Zetia – it has now been shown to be highly effective and must be a part of doctors’ armamentaria. Other emerging medications that dramatically lower cholesterol – the PCSK9 inhibitors and possibly the CETP inhibitors – will likely lower ASCVD events in the right patients.
In patients with severe genetically caused high cholesterol – specifically those with Familial Hypercholesterolemia – doctors will try even harder to use varied tools to lower LDL as much as possible. This includes using LDL apheresis, a procedure that has frequently been denied coverage by many insurance carriers, even after experts have testified about its efficacy.
We have learned that an understanding of biology and pathophysiology, in the context of clinical experience and careful observation, should not be dismissed solely because of the absence of a large randomized controlled trial (RCT). Though it took an RCT to prove this point, those of us who have been using Zetia religiously for many years have borne witness to its efficacy. We did not need this trial to tell us how important the medication is in the management of ASCVD, but it surely makes us feel better (and a bit vindicated as well). Most consequentially, it is heartwarming to consider the vast numbers of patients we’ve helped avoid experiencing heart attacks and strokes as a result of our well-considered and steadfast convictions.