Clinical trial NCT01415934: Statin Discontinuation in Advanced Illness
Official title: Multisite Randomized Controlled Trial of Continuing vs. Discontinuing Statins
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Palliative Medicine
Cardiovascular Disease
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Institute of Nursing Research (NINR)
First posted: 2011-08-12
Enrollment: 381
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The purpose of this study is to determine if there is a difference in survival rate at 60 days after enrollment between patients with advanced life-limiting illness for whom statins are discontinued vs. for patients with advanced life-limiting illness who are maintained on the medication. Secondary outcomes of this study will determine the effects of medication cessation on overall survival, important cardiovascular events, quality of life (QOL), symptoms, performance status, polypharmacy issues, satisfaction with care, and costs.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of Deaths Within 60 Days of Enrollment.
timeFrame: Within 60 days of Subject Enrollment
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: San Diego
country: United States
facility: San Diego Hospice and the Institute for Palliative Medicine
state: California
city: Denver
country: United States
facility: University of Colorado, Denver
state: Colorado
city: Denver
country: United States
facility: Kaiser Permanente
state: Colorado
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina, Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Flat Rock
country: United States
facility: Four Seasons Hospice and Palliative Care
state: North Carolina
city: Cleveland
country: United States
facility: Hospice of Western Reserve
state: Ohio
city: Falls Church
country: United States
facility: Capital Caring
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: Duke University
name: Amy Abernethy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Jean Kutner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: McNeil MJ, Kamal AH, Kutner JS, Ritchie CS, Abernethy AP. The Burden of Polypharmacy in Patients Near the End of Life. J Pain Symptom Manage. 2016 Feb;51(2):178-83.e2. doi: 10.1016/j.jpainsymman.2015.09.003. Epub 2015 Sep 30.
citation: Tjia J, Kutner JS, Ritchie CS, Blatchford PJ, Bennett Kendrick RE, Prince-Paul M, Somers TJ, McPherson ML, Sloan JA, Abernethy AP, Furuno JP. Perceptions of Statin Discontinuation among Patients with Life-Limiting Illness. J Palliat Med. 2017 Oct;20(10):1098-1103. doi: 10.1089/jpm.2016.0489. Epub 2017 May 18.
citation: Portz JD, Kutner JS, Blatchford PJ, Ritchie CS. High Symptom Burden and Low Functional Status in the Setting of Multimorbidity. J Am Geriatr Soc. 2017 Oct;65(10):2285-2289. doi: 10.1111/jgs.15045. Epub 2017 Aug 30.
citation: Hochman MJ, Kamal AH, Wolf SP, Samsa GP, Currow DC, Abernethy AP, LeBlanc TW. Anticholinergic Drug Burden in Noncancer Versus Cancer Patients Near the End of Life. J Pain Symptom Manage. 2016 Nov;52(5):737-743.e3. doi: 10.1016/j.jpainsymman.2016.03.020. Epub 2016 Sep 20.
citation: Kutner JS, Blatchford PJ, Taylor DH Jr, Ritchie CS, Bull JH, Fairclough DL, Hanson LC, LeBlanc TW, Samsa GP, Wolf S, Aziz NM, Currow DC, Ferrell B, Wagner-Johnston N, Zafar SY, Cleary JF, Dev S, Goode PS, Kamal AH, Kassner C, Kvale EA, McCallum JG, Ogunseitan AB, Pantilat SZ, Portenoy RK, Prince-Paul M, Sloan JA, Swetz KM, Von Gunten CF, Abernethy AP. Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial. JAMA Intern Med. 2015 May;175(5):691-700. doi: 10.1001/jamainternmed.2015.0289.
citation: Murali KP, Yu G, Merriman JD, Vorderstrasse A, Kelley AS, Brody AA. Latent Class Analysis of Symptom Burden Among Seriously Ill Adults at the End of Life. Nurs Res. 2021 Nov-Dec 01;70(6):443-454. doi: 10.1097/NNR.0000000000000549.
citation: Schenker Y, Park SY, Jeong K, Pruskowski J, Kavalieratos D, Resick J, Abernethy A, Kutner JS. Associations Between Polypharmacy, Symptom Burden, and Quality of Life in Patients with Advanced, Life-Limiting Illness. J Gen Intern Med. 2019 Apr;34(4):559-566. doi: 10.1007/s11606-019-04837-7. Epub 2019 Feb 4.