Secondary Prevention Statin Adherence and Major Adverse Cardiovascular Events

By Michael H. Crawford, MD, Editor

SYNOPSIS: A study of adherence to statin therapy after an atherosclerotic cardiovascular event demonstrated full adherence for five years was associated with significantly lower major adverse cardiovascular events, although only 5% of these patients achieved full compliance for five years.

SOURCE: May HT, Knowlton KU, Anderson JL, et al. High-statin adherence over 5 years of follow-up is associated with improved cardiovascular outcomes in patients with atherosclerotic cardiovascular disease: Results from the IMPRES study. Eur Heart J Qual Care Clin Outcomes 2022;8:352-360.

Reducing low-density lipoprotein (LDL) cholesterol levels with a statin drug after an atherosclerotic cardiovascular disease (ASCVD) event can improve long-term outcomes, but patients do not always adhere to statin medications for secondary prevention. Investigators from Intermountain Healthcare (IMHC), with 22 hospitals and 185 clinics in Utah and Idaho, analyzed their hospital and pharmacy database to determine the adherence to statins and the association of adherence with outcomes.

A total of 7,339 patients were seen from 1999 through 2013. Each had been diagnosed with ASCVD, survived for one year, and were prescribed a statin during the first year. The patients were followed for at least five years. The primary outcome was major ASCVD events (major adverse cardiovascular events [MACE], mortality, myocardial infarction, stroke) and revascularization. The main metric was the proportion of days covered (PDC) by a statin prescription as determined by IMHC pharmacy records. Fully covered was defined as a PDC of ≥ 80%. Five percent of patients were fully covered for five years, 6% for one to three years, 12% for the first year only, 18% for one year out of years 2 through 5, and 61% were non-adherent for all five years. MACE was progressively related to compliance: 12% in those fully compliant and 26% in those totally non-compliant. Mortality was 5% in the fully compliant and 16% in the totally non-compliant. Stroke was 1% in the compliant and 4% in the totally non-compliant. The MACE hazard ratio for those fully compliant was 0.51 (95% CI, 0.37-0.71), although a certain degree of compliance provided some benefit. Full compliance was more likely in young white men whose index event was coronary, who were not depressed, not smokers, and were on statins before the index event. There was no association with LDL levels or diabetes. The authors concluded that long-term adherence to statins after an ASCVD event was associated with a decrease in MACE compared to those with lesser degrees of compliance.

COMMENTARY

The low adherence rate is remarkable because there were no pharmacy cost issues in this health plan, and all the patients were given a prescription for a statin after the index ASCVD event. Only 5% were fully compliant for five years, and almost two-thirds were non-compliant the entire time. Adherence declined markedly after the first year, when it was 21%, and then almost half stopped statins after five years. The reasons for non-adherence are unknown for this study. Some of the possibilities the authors suggested — no doubt from talking to patients — were a fear of statin side effects, a belief that the drugs are needed only temporarily, faith that a change in lifestyle obviates their need, and that they are taking too many medications. Whether studies like this can overcome this prejudice against statins is unclear. The advent of PCSK-9 inhibitors has not reversed this trend, which is not totally surprising since they must be given subcutaneously. Perhaps future LDL cholesterol-lowering drugs will have better luck winning the hearts of patients.

The major limitation of this study was its observational nature, so the reason for non-adherence is unknown. Also, any medical care or prescriptions acquired outside IMHC would not be captured, but this is unlikely to be a big factor. In addition, the adherence rates in this comprehensive health plan may not apply everywhere. Finally, the racial ethnic breakdown of the patients is not given but is likely to be mainly white and Hispanic, given the geographic location of IMHC.

Non-adherence to statins is common, even in high-risk populations that would benefit most from them. Physicians must pay close attention to this attrition in compliance and try to nullify it. Perhaps the results of this study and others will help.