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JUPITER update: Percent reduction of LDL relates to magnitude of risk reduction
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ORLANDO, Fla. — Percent reduction of LDL is related to the magnitude of reduction of risk for first CV event observed in patients on high-intensity statin therapy, according to new findings from the JUPITER trial presented at the American Heart Association Scientific Sessions.
“These data provide general support for the concept of introducing percent reduction in LDL into broader clinical practice, an approach consistent with that being advocated by current European, Canadian and U.S. guidelines,” Paul M. Ridker, MD, MPH, said during a presentation.
Paul M. Ridker
Ridker and colleagues analyzed results from the JUPITER trial (n = 17,802), which showed a reduction in CV events in those assigned rosuvastatin (Crestor, AstraZeneca) compared with those assigned placebo (HR = 0.56; 95% CI, 0.46-0.69), to determine the variability of percent reduction in LDL associated with high-intensity statin therapy and whether this variability might have implications for clinical care. Specifically, they evaluated how percent reduction in LDL affected the rate of first CV event, including MI, stroke, CV death and hospitalization for angina requiring coronary intervention.
The key question was “how did the percent reduction in LDL line up with the event rates, and were they different for different individuals in the trial,” said Ridker, senior physician at Brigham and Women’s Hospital and Eugene Braunwald professor of medicine at Harvard Medical School.
After adjustment for baseline lipid level, sex, smoking, age, hypertension, BMI and family history of CAD, event rates per 1,000 person-years in the JUPITER population were 11.2 for those assigned placebo (RR = 1), 9.2 for the rosuvastatin group who had no LDL reduction (RR = 0.86), 6.7 for the rosuvastatin group who had an LDL reduction of less than 50% (RR = 0.61), and 4.8 for the rosuvastatin group who had an LDL reduction of at least 50% (RR = 0.41; P for trend < .00001), Ridker said.
“Notice that the variability is exceptionally wide, from individuals with essentially no LDL reduction … all the way out to individuals with 75%, 80% or 85% reduction in LDL,” he said.
A similar trend was observed for reduction of non-HDL and reduction of apolipoprotein B (P for trend < .00001 for both), he said.
The data may offer insight into which patients on high-intensity statin therapy could also benefit from PCSK9 inhibitors, according to Ridker.
“The group with a 60% or greater LDL reduction … in theory might be a group where the PCSK9 inhibitors have the least benefit because we already have a 70% or 80% reduction in LDL; [they might be] a group where the residual risk is on the basis of inflammatory risk and not lipid risk. On the other hand, for the group with a small reduction in LDL, perhaps these are patients where we would want to target more aggressive care. This is the idea of bringing percent reduction into our guidelines.
“We found exceptionally wide variability in percent reduction in LDL, non-HDL and ApoB, yet the magnitude of that percent cholesterol reduction directly related to the magnitude of risk reduction,” he said. “These effects were robust.” – by Erik Swain
Reference:
Ridker PM, et al. CS.03: Managing risk factors for CAD – clinical trial updates. Presented at: American Heart Association Scientific Sessions; Nov. 7-11, 2015; Orlando, Fla.
Disclosure: Ridker reports receiving research grants from AstraZeneca, Novartis and Pfizer.