In analyses led by the TIMI Study Group at Brigham and Women’s Hospital (BWH), researchers provide evidence that suggests that evolocumab, a medication in a new class of drugs called PCSK9 inhibitors, may reduce the number of cardiovascular events in patients with high cholesterol. These findings are presented at the American College of Cardiology’s 64th Annual Scientific Session and simultaneously published in the New England Journal of Medicine.
More than 70 million American adults have high LDL (“bad”) cholesterol, and elevated LDL cholesterol is a known risk factor for cardiovascular disease. PCSK9 is a protein that binds to the receptor for LDL cholesterol, and prevents it from being available to clear LDL cholesterol from the blood. Evolocumab is a drug that inhibits PCSK9, thereby allowing LDL receptors to clear more bad cholesterol from the blood. Previous research in relatively short-term trials has shown that evolocumab can reduce LDL cholesterol by approximately 60 percent. However, what is not well understood is whether that reduction in LDL cholesterol has an effect on cardiovascular events.
Now, by using data from a longer-term study of evolocumab, researchers observed that patients treated with evolocumab had half the rate of death or major cardiovascular events.
“This is an exciting class of drugs that has been shown to be extremely effective in reducing LDL cholesterol,” said Marc S. Sabatine, MD, MPH, chairman of the TIMI Study Group at BWH and lead researcher of this trial. “As we await the results of a large cardiovascular outcomes trial we are currently conducting, this analysis, which explores the available data to date, provides support for the concept that this class of drug may be effective in reducing cardiovascular events.”
In this analysis, 4,465 patients who participated in previous clinical trials involving evolocumab were recruited to a long-term extension study and randomized to receive evolocumab (140mg every 2 weeks or 420mg monthly as subcutaneous injections) plus standard of care or standard of care alone. Over approximately 11 months, researchers followed patients and tracked cholesterol levels, safety events, and cardiovascular events including death, coronary events, and strokes.
When compared to standard of care alone, evolocumab reduced LDL cholesterol by 61 percent. Researchers documented 60 cardiovascular events during this time period and report that the rate of these events was 2.11 percent in the standard of care group but only 0.95 percent in the evolocumab group. The reduction was consistent for the different types of major cardiovascular events (death, heart attack, hospitalization for worsening angina, or angioplasty, and major or minor strokes).
“Over approximately one year of therapy, evolocumab significantly and substantially reduced major adverse cardiovascular events, and we observed no major safety concerns,” Sabatine said. “We are encouraged by these findings and look forward to larger outcomes trials to confirm them .”
The TIMI Study Group is conducting an ongoing trial of 27,500 patients to investigate evolocumab’s effect on cardiovascular outcomes with results expected in 2017.