This article is more than 5 years old. Information may no longer be current.
Late-breaking clinical trials in CVD prevention: Where are the events?
by Parag H. Joshi, MD, MHS
CHICAGO — The cold weather in Chicago seems to have led to increased attendance at talks, if for nothing else than to stay warm. An exciting, packed session on Monday, Nov. 17, focused on late-breaking clinical trials in the realm of primary and secondary prevention of CVD events.
Two negative studies in primary prevention highlighted an important point: The event rates were low in both studies, yielding no detectable differences by the interventions that were tested. Both trials, based on designs established more than 7 years ago, “suffered” from event rates that were much lower than expected. Importantly, these low event rates in primary prevention populations suggests to me that we are doing a better job of reducing risk in primary prevention. Also, it will take a large effect size of an intervention, something that reduces risk dramatically, in order to show a difference in these trials. Alternatively, perhaps trials should seek to enroll the highest-risk primary prevention population, such as those with high burdens of subclinical atherosclerosis who have not yet suffered from a CV event.
Parag H. Joshi
The clear main event in the session was the long-awaited results from the IMPROVE-IT trial, which showed that CV events were significantly reduced when adding ezetimibe to simvastatin therapy (Vytorin, Merck) in a high-risk secondary prevention population.
This is incredibly exciting, particularly on the heels of the lipid treatment guidelines from 2013. As the first trial to show benefit of lipid-lowering on hard CV outcomes when added to statin therapy, it appears that ezetimibe (Zetia, Merck) should be considered for treatment of high-risk secondary prevention patients to achieve a lower LDL cholesterol level. Patients included in the ezetimibe/simvastatin group achieved an LDL level of 54 mg/dL, while those in the simvastatin only (Zocor, Merck) group had an LDL level of nearly 70 mg/dL.
For me, after confirming the results when the full manuscript is published, this will potentially change my practice. I can envision treating post-ACS patients with high-intensity statins like atorvastatin 80 mg daily, and if they don’t achieve an LDL in the 50s, I may recommend the addition of ezetimibe. An important consideration for my practice is that the absolute difference in risk over 7 years was 2%, translating to a number needed to treat of 50 patients to prevent one event. Is this cost effective? Fortunately ezetimibe will come off patent in 2 years and should be more affordable.
The results of IMPROVE-IT generated incredible buzz at the sessions and has been the highlight of the conference for me so far … and a welcome distraction from the cold weather in Chicago.
Parag H. Joshi, MD, MHS, is a clinical fellow at The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease and a member of the Cardiology Today Fellows Advisory Board.
Disclosure: Joshi reports no relevant financial disclosures.