IMPROVE-IT Study Results: An Incremental Improvement

The results of the IMPROVE-IT trial were finally revealed this November during the American HeartAssociation (AHA) Scientific Sessions in Chicago. The trial itself remains highly controversial, and its long-awaited results may set precedence for new therapies in the future and possibly even changes to the clinicalguideline recommendations.

So what does this mean for people affected with Familial Hypercholesterolemia (FH)? Many individualsaffected with the disorder are prescribed multiple drugs just in hopes to get their LDL levels below 200 mg/dL(according to the Mayo Clinic, an LDL-C measurement of below 70 mg/dL is considered ideal for patients atvery high risk of heart). From this study, evidence shows that FH patients may not only cut their cholesterollevels, but also lower their lifetime exposure for high LDL levels and lower their risk for cardiovascularevents—beyond using statins alone. According to the study, the lower the LDL levels, the better.

Background

Cardiovascular prevention has, in the past, mainly involved the process of lowering LDL cholesterol (LDL-C).Statins are a class of drugs that lower cholesterol levels, and numerous established trials have shown statinsreduce morbidity and mortality from cardiovascular events. AHA/ACC Guidelines emphasize the use of statintherapy. Additionally, there have been no lipid-modifying therapies included with statin that demonstrateclinical benefit until the IMPROVE-IT study.

Ezetimibe is a non-statin agent that blocks cholesterol absorption in the small intestine, which in turn increasesLDL-cholesterol receptors in the liver. Though a successful drug with regards to worldwide sales, ezetimibe’sreputation has been surrounded with controversy—the ENHANCE trial, which compared the effect ofezetimibe with simvastatin versus simvastatin alone in patients with heterozygous FH, found no significantpositive effects of the drug. The ENHANCE trial itself is controversial due to a delayment of its results. As ofmid-2014, the AHA and ACC do not recognize nor recommend the use of non-statin cholesterol lowering drugslike ezetimibe. This has made access to drugs such as Zetia (ezetimibe), difficult for FH patients.

The IMPROVE-IT Trial

The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is a randomizedcontrol study established to examine the clinical benefit and safety of Vytorin (ezetimibe/simvastatin) versussimvastatin alone in high-risk patients with post acute coronary syndrome. Additional study goals includeddetermining if lowering LDL-C with the non-statin agent ezetimibe would reduce cardiac events, and if “evenlower” LDL-C levels are “even better.”

After seven years and over 18,000 patients from 39 countries, results were positive: compared to patients treatedwith simvastatin alone, patients treated with both ezetimibe and simvastatin had a 20% decrease in cholesteroland experienced a statistically significant 6.4% reduction in cardiovascular event risk.

Therefore, according to the study, non-statin lowering LDL-C with ezetimibe reduces cardiovascular events,“even lower” LDL-C levels is “even better,” and the study reaffirms the LDL hypothesis that reducing LDL-Cprevents cardiovascular events. Moreover, no issues arose in patients using ezetimibe, confirming the drug’s safety.

Though further studies need to be conducted for more insight and evidence, the study provides evidence thatadding a non-statin medication on top of statin can provide additional medical benefit. This significant studywill set precedence for new, non-statin therapies, further evidence-based medication, and possibly bring up theneed to update the statin-centric AHA/ACC prevention guidelines.

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