Looking beyond ‘typical’ factors of nonadherence to lipid lowering therapies

12 Apr 2022

Experts say there needs to be more focus on adherence and persistence to lipid-lowering therapies in order to achieve the degree of cardiovascular risk reduction shown possible through atherosclerotic cardiovascular disease (ASCVD) clinical trials.1 Despite this, adherence rates continue to languish in Australia.2,3 Speaking to the limbic, Professor David Hare says that cardiologists have the ability to promote better adherence by connecting with patients and providing advice from a position of authority.

How hope for the future may help adherence to therapy

Prof. Hare believes that a positive message about potential life expectancy after an acute coronary syndrome can be transformative when delivered by a cardiologist. “We have systems in place in both hospital and outpatient rehabilitation programs that provide the ancillary support for the patient, which includes education, exercise, and guidelines for lifestyle. These are good, but nothing’s as powerful as an authority figure saying ‘You’re going to be fine,’” he says.

If the message is linked to the benefit of ongoing medication, then adherence may be improved, says Prof. Hare. “On a coronary care ward round, I will often say to the patient,You had cholesterol blocking up the arteries. As well as the stents we have put in, we are going to put you on cholesterol tablets, and you have to take these tablets every day for at least the next thirty years.’” He explains that this gives the patients two important pieces of information that are linked together: “One is that the patient needs to keep doing something [taking the medication], and the second is the patient thinking, ‘I’m going to survive another 30 years? I was wondering if I was going to survive another week or a year!’” By offering hope for the future, which is linked to taking the medication, Prof. Hare believes patients are more likely to be more adherent.

Statin persistence is low in Australia

A study conducted over a decade ago using data from the Pharmaceutical Benefit Scheme (PBS) claim records of patients initiated on a statin from April 2005 to March 2010 (n=77,867)2 found that 43% of patients discontinued statin therapy within 6 months of initiation, with 23% of patients failing to collect their first repeat at one month.2 Median persistence time was 11 months across the patient population, but higher (19 months) in patients aged 65–74 years of age. In those younger than 55 years of age, persistence was only 3–6 months. The study authors concluded, “Unsatisfactory long term persistence on statin therapy has changed little over the past 10 years.”2

It seems that little has changed in the 10 years since this analysis. A retrospective cohort study of PBS claims data from the start of 2015 to the end of 2019 (n=141,062)3 found that 58.8% of patients discontinued statins (defined as a 90-day gap in prescriptions), of whom just over half (55.2%) restarted therapy at some stage. The proportion of people found to be nonadherent was 24.0% at 6 months and 49.0% at 5 years. People on low and moderate intensity statins were more likely to discontinue compared to those on high intensity statins (hazard ratio [HR] 1.20, 95% CI 1.09–1.31 for low to moderate intensity; HR 1.28, 95% CI 1.14 – 1.42 for high intensity). The authors concluded, “Long-term persistence and adherence to statins remains generally poor among Australians, which limits the effectiveness of these medicines.”3

Early adherence data emerges for PCSK9 inhibitors

While larger studies are required to confirm the findings,4 there is some observational data from small data sets to suggest adherence to PCSK9 inhibitors may be higher than with statins.4,5,6,7

One Italian study assessing adherence, persistence, and concomitant lipid lowering therapies in the first six months of therapy for patients who started treatment with a PCSK9 inhibitor in the Tuscany region of Italy during the first year of reimbursement (July 2017 to June 2018). In a total of 269 individuals initiated on PCSK9 inhibitors, 79.9% were adherent to therapy and 73.3% were persistent over the one-year period. In the six months before being initiated on a PCSK9 inhibitor, the majority of patients (61.3%) had received at least one prescription of ezetimibe or high-intensity statin, and 45.7% of patients were found to be persistent to these therapies.7

Other studies have found interruptions in therapy occur in up to half of patients taking PCSK9 inhibitor therapy,8,9 and PCSK9 inhibitor initiation has been shown to lead to a discontinuation of other concomitant lipid lowering therapy.8

Factors related to non-adherence

A recent systematic review of reviews10 looked at factors that affect adherence to lipid-lowering therapies, particularly statins. Factors associated with adherence included high socioeconomic and educational position and middle age. Factors contributing to non-adherence included female sex, older age (≥70 years), younger age (<50 years), non-white race, low socioeconomic position, high medication co-payments, being a new statin user, comorbidities, side effects, regimen complexity, high intensity statin doses, smoking, alcohol consumption, imperceptible benefits, and medical distrust.10

Looking beyond ‘typical factors’ for non-adherence

Although studies have helped elucidate factors linked to non-adherence, the authors of an Australian meta-analysis11 investigating this issue suggest that a focus on “typical” factors (i.e. the patient, condition, healthcare system or socioeconomic factors) may miss other potential influences.

The meta-analysis used data from five studies, including eight datasets of a total 76,867 patients, and looked for factors that influenced adherence. By pooling patient groups according to adherence levels, the investigators found no clear patterns in relation to factors for non-adherence. They suggest, “The lack of pattern in the typical factors of non-adherence suggests that other factors, such as patients’ beliefs about their conditions and medications, may be playing a stronger role in their non-adherence than clinical or sociodemographic factors.”11

Authors of a recent cross-sectional survey of patients in the United States who had never started taking their prescribed statin12 agree that patient attitudes are an important consideration when addressing adherence issues, and suggest that this needs to be considered upfront when therapy is initiated. The authors studied attitudes of a cohort of patients who were prescribed a statin but didn’t take it (n = 173), of which 57.2% never had their prescription dispensed, and the remainder had the statin prescription dispensed but didn’t take it. “Addressing patient attitudes, beliefs, and willingness to start a statin before prescribing a statin may be more successful than prescribing a statin and then trying to address nonadherence afterwards,” they say.

Prof. Hare notes that simply providing information does not always lead to attitude and behaviour change. “Information doesn’t necessarily turn to knowledge. Knowledge doesn’t necessarily change attitudes or behaviour. And if behaviour does change, it doesn’t necessarily lead to maintenance of behaviour change. So at every level, information doesn’t necessarily change behaviour,12he says.

Prof. David Hare’s ‘Three R’s of adherence’

Prof. Hare, who often delivers lectures on the issue of adherence, explains that cardiologists are in a strong position to influence adherence in their patients once trust is established. “I have a slide that talks about the three most most important things about adherence. Number one: Relationships. Number two: Relationships. And number three: Relationships.”

Trust is so important,” explains Prof. Hare. “You need to make statements from a position of authority that [the patient is] going to be fine. And then you need to identify with them, make human connections, and create trust,” he says.


This article was sponsored by Novartis. Any views expressed in the article are those of the expert alone and do not necessarily reflect the views of the sponsor. Before prescribing, please review the Leqvio product information via the TGA website. Treatment decisions based on these data are the responsibility of the prescribing physician.


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