Statin Negligence Associated with Greater Cardiovascular Mortality

A 300,000-plus patient cohort analysis showed patients with atherosclerotic cardiovascular disease are at a significantly greater risk of death if they don't adhere to statin prescriptions.

Fatima Rodriguez, MD, MPH

Use of the treatment is highly advocated, but now it is even more evidenced: low statin therapy adherence in patients with atherosclerotic cardiovascular disease (ASCVD) is associated with a greater risk of death.

A retrospective cohort analysis assessing nearly 350,000 adults in the Veterans Affairs Health System (VAHS) with ASCVD has found a link between decreasing statin medication possession ratio (MPR) and increased mortality hazard ratio (HR). The study—conducted by a team of investigators at Stanford University—also identified patient demographics least likely to adhere to statin treatment, and bolstered the precedent to improve statin use among cardiovascular disease patients.

Statins have been repeatedly advised in guidelines from the American College of Cardiology (ACC), American Heart Association (AHA), and other organizations as a go-to cholesterol management therapy in patients with ASCVD. Despite this, their use is frequently limited by treatment misinterpretation or fear of adverse effects. As James Underberg, MD, president of the National Lipid Association, noted to MD Magazine®, the perceived or realistic rate of statin effects have hindered their benefit for patients with cardiovascular disease risk.

“The important thing for patients to understand is that while there is certainly a lot of information out there about potential side effects of statins, that has to be countered by the benefits,” Underberg said. “In general, statins are safe and effective.”

Investigators, led by Fatima Rodriguez, MD, MPH, of Stanford’s Division of Cardiovascular Medicine and Cardiovascular Institute, noted that previous clinical trials have shown that as much as one-third of high-risk patients ASCVD patients prescribed statins discontinued treatment, often because of patient preference and without cause of adverse effects.

“In real-world clinical registries, adherence to statin therapy is even lower, with adherence rates less than 50% at 1 year after starting therapy, declining to 30% at 2 years,” the team noted.

To assess patient risk of death in association with statin discontinuation, investigators assessed 347,104 adults aged 21 to 85 years old treated within the (VAHS) between January 2013 and April 2014. Qualified patients had classified ASCVD codes on 2 or more dates within the past 2 years, without changes in statin prescription intensity.

The team defined adherence with MPR, categorizing levels of adherence as MPR of <50%, 50% to 69%, 70% to 89%, and ≥90%. Adherence was defined as an MPR of ≥80% for dichotomous analyses.

Patient population was 1.6% (n= 5472) women, with a majority (n= 284,150; 81.9%) being white. The remaining population was African American (10.4%), Hispanic (4.7%), Pacific Islander (1.2%), Native American (0.4%), and Asian (0.3%).

Patients prescribed to a moderate-intensity statin regimen were found to be more adherent than patients prescribed high-intensity therapy (OR 1.18; 95% CI: 1.16-1.20). Women and minorities, though both constituting small portions of the patient population, were less adherent. Adults aged 65 to 74 years old were more likely to be adherent to their statin regimen than patients younger or older than them.

Investigators reported 85,930 patient deaths (24.8%) through a mean 2.9 years of follow-up. When compared to the patients with an adherence of ≥90% MPR, patients least adherent (<50%) had a hazard ratio (HR) of 1.30 (95% CI: 1.27-1.34). Patients with an MPR between 50% and 69% had an HR of 1.21 (95% CI: 1.18-1.24), and those with an MPR of 70% to 89% had an HR of 1.08 (95% CI: 1.06-1.09).

The association between mortality risk and reduced statin adherence was most pronounced in patients prescribed high-intensity statins, the team observed. Lower adherence was also associated with greater low-density lipoprotein (LDL)-C levels and rates of hospitalization for stroke and ischemic heart disease, as investigators anticipated. They suggested higher statin adherence may simply indicate a more overall healthy patient, though.

“Although this healthy adherer effect may partially confound the association between statin adherence and overall mortality, it can help clinicians identify patients who are more likely to benefit from statin adherence and maintaining a healthy lifestyle,” Rodriguez and colleagues wrote.

In an editorial accompanying the study results, Ann Marie Navar, MD, PhD, of the Duke Clinical Research Institute, praised the study’s novel, comprehensive attempt to distinguish between statin therapeutic benefit and healthy adherer bias when associating treatment adherence with mortality risk.

She expressed disappointment with the current trend of efforts to bolster statin adherence in ASCVD patients—if any are commonly practiced. Follow-up lipid testing rates are low in physician practices, despite guideline recommendations, and clinical performance puts emphasis on statin prescription—not adherence.

“Although research (and common sense) supports the concept that greater adherence to effective therapies improves outcomes, strategies to improve medication adherence remain elusive,” Navar wrote.

Noting the public has put hundreds of millions of dollars investment towards research focused on statin’s benefits for cardiovascular disease, Navar concluded that such great efforts to find benefits would be negated by continued neglection to treatment.

The study, “Association of Statin Adherence With Mortality in Patients With Atherosclerotic Cardiovascular Disease,” was published online in JAMA Cardiology.