Mr. Susman is a freelance medical writer based in Florida, USA. He travels worldwide to report from medical conferences, writing regularly for wire services, internet websites, and medical journals such as the Journal of the National Cancer Institute and AIDS.
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AMSTERDAM, the Netherlands – In a studio devoid of a live audience, researchers at the virtual European Society of Cardiology described new studies that may improve the heart health of people across the age spectrum.
For example, an international team of doctors reported that children diagnosed with heterozygous familial hypercholesterolemia were able to reduce their low density lipoprotein (LDL) by more than 40%, and significantly more than placebo, if they were administered the PSCK9-inhibitor evolocumab.
In the clinical trial, children ages 10-17 received monthly injections of evolocumab, and lowered their LDL an average of 77 mg/dL from a baseline mean of 130 mg/dL – a 44.5% decrease over 24 weeks, reported Raul Santos, MD, director of the Lipid Clinic at the Heart Institute and associate professor of the University of São Paulo Medical School, Brazil.
The reduction in LDL seen among the patients on evolocumab was in contrast to the patients who had been assigned to placebo. The placebo patients had a reduction of 6.3%. the difference between the groups was highly statistically significant (P<0.001), Dr. Santos reported.
The reduction in LDL cholesterol was accomplished without an increase in side effects, he reported at the meeting and, simultaneously, online in the New England Journal of Medicine.
“Throughout the present 6-month trial, 153 of 157 patients (97%) received all planned doses of evolocumab or placebo, and among the 104 who received evolocumab, binding or neutralizing antibodies developed in no patients,” Dr. Santos reported. “No trends indicative of clinically important treatment-related laboratory or vital-sign abnormalities, abnormal physical examination findings (including findings on growth and pubertal development), or cognitive changes were observed. Moreover, there was no evidence of clinically relevant effects of evolocumab on steroid hormone biosynthesis or on levels of vitamins (A, D, E, and K).”
Both the evolocumab and placebo groups received subcutaneous injections every 4 weeks, the researchers reported. They noted that were were no dropouts related to adverse events related to injection.
“Heterozygous familial hypercholesterolemia is genetic condition characterized by an elevated plasma concentration of LDL cholesterol starting at birth and an increased risk of premature atherosclerotic cardiovascular disease,” Santos explained. “With an estimated prevalence of 1 in 250 in the general population, heterozygous familial hypercholesterolemia is the most frequent monogenic disorder and a major heritable cause of atherosclerotic cardiovascular disease worldwide.”
The researchers enrolled children who had been diagnosed with heterozygous familial hypercholesterolemia, and who were following a low-fat diet. All the subjects in the trial were required to be receiving stable lipid-lowering therapy for at least 4 weeks before screening. Patients were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of either
evolocumab (420 mg) or placebo for 24 weeks. Patients underwent screening and randomization at 47 sites across 23 countries in North America, Latin America, Europe, and the Asia–Pacific region.
The mean age of the subjects was 13.7 years, and about 55% of the group were girls. More than 80% of the study population were white. About 30% of the children in the evolocumab cohort had a family history of premature cardiovascular disease; about 40% of the children in the placebo group had a family history of premature cardiovascular disease, the researchers noted.
Treating the Very Old
Older Japanese patients diagnosed with atrial fibrillation controlled their risk of stroke and avoid feared bleeding risks by taking low dose edoxaban, researchers reported.
The annualized rate of stroke or systemic embolism was 2.3% in the edoxaban group and 6.7% in the placebo group [HR 0.34 (95% CI 0.19-0.61; P<0.001), and the annualized rate of major bleeding was 3.3% in the edoxaban group and 1.8% in the placebo group [HR 1.87 (95% CI 0.90-3.89; P=0.09), reported Ken Okumura, MD, PhD, chief technical advisor, Saiseikai Kumamoto Hospital Cardiovascular Center, in Japan.
After a median of 36 months in the trial, 15 patients – 12 with stroke and 3 with systemic embolism – experienced the primary efficacy endpoint in the edoxaban arm of the ELDERCARE-AF trial, compared with 44 patients in the placebo patients, Dr. Okumura reported. There was one fatal stroke in the edoxaban patients and 3 fatal strokes in the placebo patients.
He and colleagues also reported there were substantially more events of gastrointestinal bleeding in the edoxaban group than in the placebo, but there was no substantial between-group difference in death from any cause – 9.9% among the patients assigned to edoxaban and 10.2% in the patients who were on placebo.
Major bleeding was observed in 30 patients on edoxaban and in 18 patients on placebo, the researchers reports. They reported that 66 patients in the edoxaban died from any cause; 69 deaths of any cause were recorded in the placebo group.
“In very elderly Japanese patients with nonvalvular atrial fibrillation who were not appropriate candidates for standard doses of oral anticoagulants, a once-daily 15-mg dose of edoxaban was superior to placebo in preventing stroke or systemic embolism and did not result in a significantly higher incidence of major bleeding than placebo,” wrote Dr. Okumura, in reporting the results of the ELDERCARE-AF trial at the virtual meeting and simultaneously online in the New England Journal of Medicine.
The ELDERCARE-AF trial was restricted to a population over the age of 80, and, in fact the mean age of the population in the trial was 86 years. Eligible patients, in addition to their age, were required to have had a history of nonvalvular atrial fibrillation documented on an electrocardiogram or on a monitor recording obtained within 1 year before consent was given, and had a CHADS2 score of 2 or higher. Eligible patients were also considered to be inappropriate candidates for oral anticoagulants or at approved doses because of kidney impairment, a history of bleeding, low body weight, continuous use of nonsteroidal antiinflammatory drugs, or current use of an antiplatelet drug.
The researchers were able to enroll 492 patients in both the edoxaban group and in the placebo group. A majority of the patients in the study were women – 42.6% were men; the mean body mass index for the entire population was 22mg/m2; the mean CHADS2 score was 3.1.
Low Dose Colchicine Helpful
Colchicine, an old and inexpensive medicine often used to treat gout, appears to prevent cardiac events in patients with diagnosed heart disease.
In the randomized clinical trial, 187 patients – about 6.8% of the 2,762 assigned to colchicine experienced the composite endpoint which translated to an incidence of 2.5 per 100-person-years compared with 264 (9.6%) of patients on placebo or 3.6 events per 100 person-years (HR 0.69 (95% CI 0.57-0.83), P<0.001), reported Stefan (Mark) Nidorf, MD, MBBS, consultant cardiologist at GenesisCare Western Australia in Perth.
“The results of our trial show that among patients with chronic coronary disease, most of whom were already receiving proven secondary prevention therapies, the occurrence of cardiovascular events was significantly lower with low-dose colchicine than with placebo,” he reported at the meeting and in the New England Journal of Medicine.
“Compared with placebo, cardiac events were reduced more than 30% with colchicine,” Nidorf said.
“The results of LoDoCo2 provide strong evidence that support re-purposing colchicine for routine secondary prevention in patients with coronary disease,” he said.
The primary end point was a composite of cardiovascular death, spontaneous (non-procedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. With a successful finding that colchicine was superior to placebo, the secondary end points, which were tested in hierarchical fashion.
In the key secondary endpoint – the composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke, Nidorf said that treatment with colchicine was again superior to placebo. That composite endpoint was experienced by 115 patients (4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group [HR 0.72 (95% CI 0.57-0.92; P = 0.007)].
Treatment with colchicine was also superior to placebo:
- In respect to the composite of spontaneous myocardial infarction or ischemia-driven coronary revascularization.
- The composite of cardiovascular death or spontaneous myocardial infarction;
- Ischemia-driven coronary revascularization;
- Spontaneous myocardial infarction.
The incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group with an incidence of 0.7 events per 100 person-years among the colchicine patients versus 0.5 events per 100 person-years among the placebo patients [HR 1.51 (95% CI, 0.99-2.31)], a difference that failed to reach statistical significance.