Less than 30% of women and men with familial hypercholesterolemia achieve their LDL cholesterol treatment targets, according to new research.

Published data show that heterozygous familial hypercholesterolemia (FH) is the most common codominant monogenic dyslipidemia, affecting approximately 1 in 250 people. “FH can be caused by various types of genetic mutations that can lead to high LDL cholesterol levels from birth onward,” explains Jeanine E. Roeters van Lennep, MD, PhD. “Lifelong elevations of LDL cholesterol can increase risks for developing premature CVD.” Studies have shown that patients with FH who experience a CVD event have a more than two-fold risk for a recurrent event within 1 year.

Timely and adequate LDL cholesterol-lowering therapy is critically important to reducing CVD risks in patients with FH. Statins are the cornerstone treatment to reach recommended targets, but previous research suggests that most patients with FH do not reach their LDL cholesterol goal with a statin alone. Other lipid-lowering medications can be added when target LDL cholesterol levels are not reached, such as ezetimibe and PCSK9 inhibitors. “Importantly, women with FH are less likely than men to achieve LDL cholesterol treatment goals, which is concerning since the impact of FH on CVD morbidity is higher for women than men,” says Dr. Roeters van Lennep.

LDL Cholesterol Goal Attainment: Trends & Sex Differences

For a study published in Atherosclerosis, Dr. Roeters van Lennep and colleagues investigated attainment of, and determinants for, LDL cholesterol goal attainment—as well as reasons for not reaching these goals—in women and men with FH at five hospitals. “In a real-world setting, we wanted to see how many patients were reaching their treatment targets and determine if sex differences were present,” Dr. Roeters van Lennep says. Clinical characteristics and information about lipid-lowering therapy, lipid levels, and reasons for not being on LDL cholesterol treatment or reaching treatment goal were retrospectively collected from electronic medical records.

Of 3,178 patients with FH in the analysis, 53.9% were women. “Our results showed that fewer than 30% of men and women with FH reached their LDL cholesterol target,” says Dr. Roeters van Lennep. Among individuals with CVD, only about 17% of women and 26% of men with FH reached their LDL cholesterol target. “Patients with a history of CVD and those with high untreated LDL cholesterol levels had significantly lower odds of reaching their LDL target,” adds Dr. Roeters van Lennep. Conversely, patients with FH using ezetimibe and those using PCSK9-inhibitors had a higher likelihood of reaching their LDL cholesterol target (Table).

In sex-specific analyses, women with FH had higher LDL cholesterol levels before treatment but were less likely to receive high-intensity statins and ezetimibe. “The most common reasons for not achieving the LDL cholesterol target were insufficient effects from using maximum lipid-lowering therapy and side effects, a finding seen more frequently in women than men,” Dr. Roeters van Lennep says. “Regardless of CVD status, women were more likely than men to fail to reach their LDL cholesterol target due to side effects.” Administration of a maximum dose of lipid-lowering therapy was more often reported as a reason for not reaching LDL cholesterol targets in patients with CVD and in men.

Patient Education Critical to Uptake of Lipid-Lowering Therapy

Based on the study findings, alternative lipid-lowering therapies, such as ezetimibe or PCSK9-inhibitors, should be considered if statin treatment is insufficient at helping patients with FH reach target LDL cholesterol goals.

“It’s critically important for healthcare providers to take time to educate patients with FH, especially women, about the benefits of statin treatment and their long-term effects on CVD risk reduction,” says Dr. Roeters van Lennep. “We also need to reassure patients about the safety of statins and explain to them that most perceived side effects are in fact ‘nocebo’ effects and are not caused by statins. If these measures are taken and LDL cholesterol levels are still uncontrolled, combination therapy should be considered.”