Statin Discontinuation in Advanced Illness

Cardiovascular Disease Clinical Trial

Official title:

Multisite Randomized Controlled Trial of Continuing vs. Discontinuing Statins

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01415934
• Other study ID #: 11-0314
• Secondary ID: UC4NR012584
• Status: Completed
• Phase: N/A
• Start date: June 3, 2011
• Est. completion date: July 15, 2013

Study information

• Verified date: August 2018
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 381
• Est. completion date: July 15, 2013
• Est. primary completion date: July 15, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Palliative Medicine

Intervention

Other:
• discontinue statins
patients will be randomized to either continue taking statins or discontinue.

Locations

Country	Name	City	State
United States	University of Alabama, Birmingham	Birmingham	Alabama
United States	University of North Carolina, Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Hospice of Western Reserve	Cleveland	Ohio
United States	Kaiser Permanente	Denver	Colorado
United States	University of Colorado, Denver	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Capital Caring	Falls Church	Virginia
United States	Four Seasons Hospice and Palliative Care	Flat Rock	North Carolina
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Beth Israel Medical Center	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University	Saint Louis	Missouri
United States	San Diego Hospice and the Institute for Palliative Medicine	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Institute of Nursing Research (NINR)

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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, Ogunse — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Deaths Within 60 Days of Enrollment.	To determine, among patients with life-limiting illness, if there is a difference in the proportion who die within 60 days after enrollment between patients for whom statins are discontinued vs. patients who are maintained on the medication.	Within 60 days of Subject Enrollment