Lower Statin Adherence Linked to Higher Mortality Risk, Even Among Patients With Established ASCVD

Patients with atherosclerotic cardiovascular disease (ASCVD) who are inconsistent in taking their statins over the long term may face a 30% greater risk of death compared to their more adherent counterparts, according to a new study.

Moreover, women and minorities, as well adults both younger and older than the median age, were less likely to adhere to statins, which underscores the importance of getting the adherence message to these harder-to-reach groups, its authors say.

“These findings suggest there is a substantial opportunity for improvement in the secondary prevention of ASCVD through optimization of statin adherence,” they write.

While prior research has explored statin adherence and its impact on mortality, many of the studies have focused on adherence after a single cardiac event, with follow-up of around 1 year, said lead author Fatima Rodriguez, MD, MPH (Stanford University, CA). “We know that adherence for those patients is very low and 50% of those patients are not on the drug in a year and even less so after that.”

By selecting patients with a stable statin prescription and an average high level of adherence and at least two ASCVD events, researchers hoped to tease out associations between lower adherence and mortality risk. They also assessed how statin adherence related to patient demographics.

The study, published this week in JAMA Cardiology, included patients with myocardial infarction, stroke, or peripheral arterial disease treated within the Veterans Affairs Health System between January 1, 2013, and April 1, 2014. Researchers selected patients who had classified ASCVD codes at two visits in the past 2 years. Patients were excluded if their statin prescription had changed in intensity or if they stopped filling prescriptions altogether. Researchers defined statin adherence through medical possession ratio (MPR), a calculation of the patient’s access to daily doses of medication over the study period.

The total study cohort consisted of 374,104 patients, with a mean age of 71 years. Nearly all patients were men, 81.9% were white, 10.4% were African-American, and 4.7% were Hispanic. During the mean follow-up of 2.9 years, 85,930 patients died—nearly a quarter of the cohort.

Decreasing Statin Adherence Worsened Outcomes

Researchers found that decreased statin adherence was correlated with increased risk of death. Compared to the most-adherent patients, who had an MPR of 90% or above, patients with the lowest statin adherence (< 50%) had a 30% higher risk of death. As statin adherence increased, risk of morality decreased.

Death Risk vs MPR ≥90%

To help control for the “healthy adherer effect”—where more-adherent patients are more likely to engage in beneficial behaviors that may improve outcomes—researchers factored in other cardiac medications the patients could be taking, including beta-blockers and ACE inhibitors. While adjusting for this effect did attenuate morality risk, the differences between the groups were still pronounced.

“Even if you took the LDL effect out of the equation, taking the statin more consistently is associated with lower mortality,” said Tracy Wang, MD (Duke University Clinical Research Institute, Durham), who commented on the study for TCTMD. “This basically says there is a benefit to statin therapy independent of what kind of person you are, what kind of patient behaviors you exhibit, and how much LDL is removed from your system.”

Rodriguez et al also found that lower adherence to high-intensity statins was associated with a greater risk of death compared to moderate- or low-intensity statins.

Death Risk by Statin Intensity: Adjusted HR vs MPR ≥90%

While previous studies have found that an MPR greater than 80% is sufficient to see benefit, these new data tell a slightly different story, said Rodriguez, where target adherence should be at or above 90% to see optimal outcomes.

Over 36% of the study cohort had MPR adherence levels lower than 90%, the authors note. Women and nonwhite patients were less likely to adhere to their statin prescriptions, consistent with previous research. Women were 11% less likely than men to regularly take their statin medication (OR 0.89, 95% CI 0.84-0.94). Black patients were 42% less likely to have high statin adherence (MPR > 80%) than non-Hispanic white patients; Hispanic and Asian patients were 27% less likely (OR 0.73; 95% CI 0.70-0.75) and 18% less likely (OR 0.82; 95% CI 0.71-0.93) to regularly take statin medication, respectively.

Adherence Is Key

Rodriguez emphasized the importance of prioritizing patient adherence in clinical settings. “I don't think we do enough as clinicians to address the issue of [low] adherence, but it's pervasive,” she said. “Particularly for the drugs that are chronic medications such as statins, it's hard to get people to take a medicine basically forever.”

Both Rodriguez and Wang agree that the best way to help patients understand adherence is by starting a dialogue about medication use during clinic visits. “If you don't know that you have a problem, you can't treat the problem,” Wang said. By talking with the patient, physicians can identify potential barriers that could be preventing someone from consistent adherence, whether it be cost, pharmacy access, or even remembering to take the medication, she continued. “The fundamental step is understanding if we have a problem and then trying to get at the root cause of that problem.”

“In cardiology, we have many drugs that are very effective and cheap,” added Rodriguez, “but if the patient doesn't take them, they don't work.”