Statin Discontinuation in Advanced Illness

Currently, over 80% of the population is expected to die of chronic life-limiting illnesses,
predominant among which are the various manifestations of cardiovascular disease, cancer,
dementia, and chronic lung disease. Patients with high cholesterol and those potentially at
risk for atherosclerotic heart disease and stroke are often treated preventively with HMG
Co-A reductase inhibitors (a.k.a., statins). Clinical trial evidence supports the use of
statins for patients with hyperlipidemia and established ischemic heart disease to reduce
risk of future cardiovascular events and mortality, and to reduce risk of future
cardiovascular events in patients with multiple cardiac risk factors. Beneficial outcomes are
evident in these trials after 3-6 years of treatment. Hence, statins are among the most
prescribed medications in the world. In the United States, over 25% of Medicare beneficiaries
take a statin medication. Statin medications are frequently continued until the patient can
no longer eat or swallow at the end of life, because there are no evidence-based guidelines
regarding when or how to discontinue medications for co-morbidities. The risks and costs vs.
benefits of statins for palliative care patients, for whom prognosis is limited, remains a
genuine clinical uncertainty. Meanwhile, medications for symptoms and other concerns
accumulate as illness progresses, and therefore polypharmacy and compounding medication side
effects are troublesome problems in the setting of advanced life-limiting illness. While
multiple studies have demonstrated the benefit of long-term preventive statin use for
patients at cardiovascular risk, other studies have supported the discontinuation of
medications (specifically statins) in end-stage disease. A rational approach to medication
discontinuation, specifically statin discontinuation, therefore has the potential to reduce
patient burden, polypharmacy, and side effects, while also preserving healthcare resources
for more beneficial interventions.

This study is a multi-site randomized controlled trial of discontinuing vs. continuing statin
medications in patients with advanced life-limiting illness. Eligible participants are adults
with advanced life-limiting illness with an estimated prognosis of 1-6 months who are on
statins for primary or secondary prevention of cardiovascular events. The primary outcome is
survival rate at 60 days; secondary outcomes address cardiovascular events, polypharmacy,
medication adverse effects, quality of life (QOL), and measures of the patient's
health-related experience. The primary hypothesis is that discontinuing statins will not
influence survival. Secondary hypotheses are that discontinuation of statins will not
adversely affect cardiovascular events or overall QOL, but will improve statin-related
symptoms and decrease polypharmacy.

Inclusion Criteria:

- age >18 years old;

- have an advanced life-limiting illness;

- have a life expectancy of >1 month, AND patient exhibits declining functional status,
defined as a reduction in Australia-modified Karnofsky Performance Status (AKPS)22
score to <80% in the previous 3 months;

- be on a statin medication for primary or secondary prevention of cardiovascular
disease for ≥3 months;

- have adequately intact cognitive status to provide informed consent and complete the
baseline assessment, as evidenced by a Short Portable Mental Status Questionnaire
(SPMSQ)23 score of ≥6;

- provide informed consent; and,

- speak and read English at or above a grade 5 level (per patient or caregiver report).

Exclusion Criteria:

- primary treating physician/care provider estimates their life expectancy as < 1 month;

- under the care of a primary treating physician/primary care provider who is unwilling
to have the patient enrolled;

- not consenting;

- having known active cardiovascular disease or sufficient risk of active cardiovascular
disease to require ongoing therapy with statin drugs, in the opinion of the treating
physician; OR,

- exhibiting obvious symptoms of myositis, known liver function test (LFT) abnormalities
of >2.5x the upper limit of normal (ULN), known creatine kinase (CK) abnormalities of
>2.5x ULN, or other contraindications to continuing statins, in the opinion of the
treating physician.