For lipid-lowering therapies, outcomes data impact guidelines, clinical practice
PHILADELPHIA — Evidence for lipid-lowering therapies has evolved over the years, but what remains consistent is the impact of new evidence on guidelines and clinical practice, especially CV outcomes data, according to a speaker at the National Lipid Association Scientific Sessions.
Joseph Saseen, PharmD, BCPS, BCACP, CLS, FNLA, professor and vice chair of the department of clinical pharmacy and professor in the department of family medicine at University of Colorado Anschutz Medical Campus, provided a look at historical indications and prescribing of statins and the influence of data on ezetimibe (Zetia, Merck) on treatment of patients requiring lipid lowering.
Statin therapy over time
The 4S study, published in 1994, was the first to show an association between statins and positive clinical outcomes in high-risk patients. In that study, simvastatin reduced all-cause mortality and other CV outcomes compared with placebo in patients with CHD.
In 1998, the AFCAPS and TexCAPS studies showed lovastatin reduced risk for acute major coronary events in patients with elevated LDL. This was important because the population “represented a lot of patients we see that may not appear to be ill, until you see their lipoprotein package,” Saseen said.
Over time, other research demonstrated that statins benefited patients with a variety of CV conditions regardless of their baseline LDL, and that higher-intensity doses tended to have the greatest effect, he said.
“We see a push toward appreciating the effect of the potency of statin therapy, which should have been loud and clear in 2004 [when the National Cholesterol Education Panel Adult Treatment Panel III guidelines were published] and is even louder in the current day,” he said.
As a result, statins became a prominent therapy in guidelines and the first line of medical therapy in patients at high risk for CV events, he said.
“In the statin era, statins are the focus, but our earlier guidelines were much broader,” he said.
Road to other lipid-lowering agents
The story has been different for other lipid-lowering therapies.
Earlier studies demonstrated some benefits gemfibrozil, but this therapy was limited to studies that only included men, and is limited by interactions with other drugs, particularly statins. Other drugs showed promise for LDL reduction, but had an inadequate impact on clinical outcomes.
The life cycle of ezetimibe has been “schizophrenic” because evidence in favor of the therapy has been “up and down,” Saseen said.
The ENHANCE trial produced “confusing” data and the SEAS trial had a trend toward higher cancer rates in patients assigned ezetimibe — which was later shown to be a play of chance. The SHARP and IMPROVE-IT studies then showed ezetimibe was associated with reduced CV events and “have influenced some of our guidelines and expert recommendations and will continue to improve some of our guidelines,” he said.
That evidence led to an expert consensus decision pathway published by the American College of Cardiology, which suggests a 50% reduction in LDL for patients with atherosclerotic CVD and other comorbidities. According to the expert consensus decision pathway, statin therapy should be tried first, then ezetimibe should be considered if the goal is not met in patients with atherosclerotic CVS. Thereafter, PCSK9 inhibitors can be tried, he said.
“This [recommendation] was a direct response influenced by the IMPROVE-IT data,” Saseen said.
However, at the time, there were no clinical outcomes data for PCSK9 inhibitors. Due to rapidly accumulating data in recent years, the expert consensus decision pathway “is being updated by ACC currently,” he said. – by Erik Swain
Saseen J. Back to the future: Clinical experience with and access to lipid-lowering agents of the past, present and future. Presented at: National Lipid Association Scientific Sessions; May 18-21, 2017; Philadelphia.
Disclosure: Saseen reports no relevant financial disclosures.