Houston, Texas, USA : In a clinical trial involving 18,924 patients from 57 countries who had suffered a recent heart attack or threatened heart attack, researchers at the University of Colorado Anschutz Medical Campus and fellow scientists around the world have found that the cholesterol-lowering drug alirocumab reduced the chance of having additional heart problems or stroke.
The study was published today in the New England Journal of Medicine.
Alirocumab is in the class of drugs called PCSK9 antibodies.
“It works by increasing receptors on the liver that attract particles of LDL cholesterol from the blood and break them down. The result is that blood levels of LDL or ‘bad’ cholesterol decrease by approximately 50 percent, even when patients are already taking a statin,” explained Gregory Schwartz MD, Ph.D., co-author of the study and professor of medicine at the University of Colorado School of Medicine.
The trial looked at patients who were at least 40-years-old, had been hospitalized with a heart attack or threatened heart attack (unstable angina), and had levels of LDL cholesterol of at least 70 mg per deciliter despite taking high doses of statins.
Half of the patients received alirocumab by self-injection under the skin every two weeks, and the other half received placebo injections. The patients were followed for an average of nearly three years. During that time, LDL cholesterol levels averaged 40 to 66 mg per deciliter in patients given alirocumab, compared with 93 to 103 mg per deciliter with placebo. Death from coronary heart disease, another heart attack or episode of unstable angina, or a stroke occurred in 903 patients given alirocumab, compared with 1052 patients given the placebo, corresponding to a 15% reduction in risk.
“Statins have been the main cholesterol-lowering drugs for heart patients for more than 30 years, and they are very effective,” Schwartz said. “Now we know that we can improve the outcomes after a heart attack by adding alirocumab to statins in selected patients.”
In the trial, alirocumab was safe and generally well-tolerated. The only common side effect with alirocumab was itching, redness, or swelling at the injection site which was usually mild. It occurred in 3.8 percent of those given alirocumab, compared with 2.1 percent of patients who received the placebo.
Alirocumab was approved by the Food and Drug Administration in 2015 as a treatment for high cholesterol, but it has only now been shown to also reduce the risk of heart disease events and stroke.
A second clinical trial found that alirocumab reduces cardiovascular events after acute coronary syndrome.
Alirocumab reduces cardiovascular events after acute coronary syndrome.
Among patients with persistently high cholesterol despite high-intensity statin therapy, the proprotein convertase subtilisin-kexin 9 (PCSK9) inhibitor alirocumab reduced rates of major adverse cardiovascular events (MACE) by 15 percent compared with placebo, in a study presented at the American College of Cardiology’s 67th Annual Scientific Session. The drug’s effect was even greater for patients at highest risk—those who started the study with LDL, or “bad” cholesterol, of 100 mg/dL or higher—who saw a 24 percent reduction in cardiovascular events, including heart attack and stroke, compared with placebo.
Researchers enrolled nearly 19,000 patients at more than 1,300 centers in 57 countries. All patients had ACS within one month to one year before enrolling in the study. The trial included those whose LDL cholesterol remained 70 mg/dL or above, non-HDL cholesterol 100 mg/dL or above, or apolipoprotein B 80 mg/dL or above despite treatment with a high or maximum-tolerated dose of a high-potency statin (atorvastatin or rosuvastatin).
Patients were randomly assigned to receive injections of either alirocumab or placebo every two weeks. Neither patients nor doctors knew who received the drug. To mimic the adjustments a doctor might make when using the drug, those patients randomized to receive alirocumab had their doses adjusted in a blinded fashion (neither patients nor doctors were aware of the adjustments) in efforts to reach LDL cholesterol levels of 25-50 mg/dL. If LDL cholesterol levels dropped consistently below 15 mg/dL, the patient was switched to placebo, again in a blinded fashion.
Patients were tracked for at least two years, with 44 percent tracked for three years or more. Overall, the primary endpoint occurred in 9.5 percent of those receiving alirocumab and 11.1 percent of those receiving placebo, while 3.5 percent of those receiving alirocumab and 4.1 percent of those receiving placebo died. When researchers looked at causes of death separately, there was no significant difference between the two groups in terms of coronary heart disease and cardiovascular disease deaths. However, Steg noted there may not have been enough events in each subcategory to show a definite difference.
Patients starting the trial with LDL cholesterol levels above 100 mg/dL saw improvements in all outcomes that were assessed, including rates of heart attack, stroke, unstable angina requiring hospitalization, coronary heart disease death, cardiovascular death and death from any cause. Among these patients, the primary endpoint occurred in 11.5 percent of those receiving alirocumab and 14.9 percent of those receiving placebo, while 4.1 percent of those receiving alirocumab and 5.7 percent of those receiving placebo died.
In terms of safety and tolerability, the only significant difference between the two study groups was minor local site reactions (mild itching, redness or swelling) at the injection site, which occurred in 3.1 percent of those receiving alirocumab and 2.1 percent of those receiving placebo.
Researchers will use the trial data to evaluate the cost-effectiveness of alirocumab. PCSK9 inhibitors cost tens of thousands of dollars per year and are often not covered by insurers.
“Now that we have two trials that consistently show benefits from PCSK9 inhibitors, and given the mortality benefit that we are reporting here for the first time, I think these results may change the equation for these drugs,” Steg said. “We’re not just talking about preventing nonfatal events such as heart attacks but actually preserving life.”
Researchers will continue to track patient outcomes for up to 10 years to determine whether the benefits continue after stopping the drug.