Cardiovascular Event Risk Increases in Year After Statin Discontinuation

Yaw B. Owusu, PharmD, MSc

Credit: Qatar University

A recent systematic review of available literature reported an elevated rate of statin discontinuation and a subsequently increased risk of adverse cardiovascular outcomes within the first year of stopping the medication.¹

The analysis, involving more than 4 million participants, revealed the rate of statin discontinuation within the first year of initiation ranged from 0.8% to 70.5%, with patient factors including male sex, non-White descent, and lack of prescription insurance linked to higher discontinuation rates.

“These factors, especially modifiable factors such as smoking and lack of insurance coverage, must be addressed, and patients at risk of discontinuation should be regularly assessed for adherence,” wrote the investigative team, led by Yaw B. Owusu, PharmD, MSc, department of clinical pharmacy and practice, college of pharmacy, QU Health, Qatar University.

In 2013, clinical practice guidelines from the American College of Cardiology (ACC) and American Heart Association (AHA) on the management of blood cholesterol to lower atherosclerotic cardiovascular disease (ASCVD) risk were updated to focus on lifestyle changes and expand the eligibility of statin therapy.²

Statin use significantly increased in subsequent years, reflecting its use as a first-line pharmacotherapy for primary and secondary ASCVD prevention.³ However, a notable amount of statin users often discontinue the medication, with significant variation by setting, population, and country of study.

Causes of discontinuation can range from socioeconomic issues to low health literature or side effects related to statin use. In this systematic review, Owusu and colleagues searched published literature to determine the discontinuation rate of statins within the first year of initiation and the involved risk factors, and estimate the risk of cardiovascular events in this period.¹

From inception to December 2022, the team searched PubMed, EMBASE, ScienceDirect, SCOPUS, and Google Scholar to identify relevant studies of patients with or at risk of CV events who discontinued statin therapy. Overall, the analysis included 52 studies, predominantly cohort studies (n = 38), with a total of 4,277,061 participants.

Most studies (n = 44) included individuals who had newly started statin therapy. Across the studies, the highest mean age was 82.5 years, while the lowest mean age was 52.5 years. A total of 39 studies included participants who received statins for primary and secondary prevention.

Upon analysis, the prevalence of statin discontinuation within the first year of initiation ranged from 0.8% to 70.5%. Among 4 studies evaluating the difference in discontinuation between primary and secondary prevention, a higher discontinuation rate was observed in the primary prevention group.

Multiple sociodemographic factors were linked to a higher likelihood of statin discontinuation, including male sex, non-White ethnicity, smoking status, and having no insurance. A lower likelihood of statin discontinuation was identified in patients with ASCVD who received secondary prevention statin therapy and those with polypharmacy.

Owusu and colleagues noted age exhibited a varied and mixed association with statin discontinuation across age groups. Among 5 studies reporting the cardiovascular risk of statin discontinuation, the team identified a significantly elevated risk of 1-year all-cause mortality (adjusted hazard ratio [aHR], 1.36; 95% CI, 1.08–1.70; P = .008).

In their summary, Owusu and colleagues pointed to the need for further study to determine the specific causes of statin discontinuation and the adverse consequences of poor adherence on an individual’s health.

“Some consequences of statin discontinuation, such as the recurrence of major adverse cardiovascular events, are serious and require prompt intervention to improve adherence and improve sequelae,” they wrote.

References

1. _{Ageeb SA, Abdelmoghith A, ElGeed H, Awaisu A, ElMansor A, Owusu YB. Prevalence, Associated Risk Factors, and Adverse Cardiovascular Outcomes of Statins Discontinuation: A Systematic Review. Pharmacoepidemiol Drug Saf. 2024;33(8):e5879. doi:10.1002/pds.5879}
2. _{Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published correction appears in J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):3024-3025] [published correction appears in J Am Coll Cardiol. 2015 Dec 22;66(24):2812]. J Am Coll Cardiol. 2014;63(25 Pt B):2889-2934. doi:10.1016/j.jacc.2013.11.002}
3. _{Pencina MJ, Navar-Boggan AM, D'Agostino RB Sr, et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med. 2014;370(15):1422-1431. doi:10.1056/NEJMoa1315665}