Placebo Adherence and Its Association with Morbidity and Mortality in the Studies of Left Ventricular Dysfunction
Open accessAbstract
BACKGROUND: A provocative finding from several double-blind clinical trials has been the association between greater adherence to placebo study medication and better health outcomes. We used data from the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial (SOLVD-TT) and the SOLVD Prevention Trial (SOLVD-PT) to examine whether such associations could be validated and to examine several sources of bias and potential confounding. METHODS: Survival analytic methods were used to estimate the association between placebo adherence and several health outcomes, employing a number of modeling techniques to test for the existence of alternative explanations for the association. Higher adherence was defined as having taken ≥75% of prescribed study medication. RESULTS: Higher placebo adherence was associated with improved overall survival in both SOLVD-TT and SOLVD-PT [hazard ratio (HR) = 0.52, 95% confidence interval (CI): 0.35 to 0.79 and HR = 0.52, 95%CI: 0.38 to 0.71, respectively]. Associations were similar for fatal or non-fatal cardiovascular or coronary heart disease events. Adjustment for both modifiable and non-modifiable cardiac risk factors (including age, gender, diabetes, blood pressure, smoking, weight, alcohol use, and levels of education) had minimal effect on the strength of the association. Little evidence of bias was found as an explanation for this relationship. CONCLUSIONS: In these two trials, better adherence to placebo was associated with markedly superior health outcomes, including total in-study mortality and incident cardiovascular events. No important confounders were identified. These data suggest there may exist strong but unrecognized determinants of health outcomes for which placebo adherence is a marker.
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Medical studies have shown that adherence is associated with better outcomes, regardless of whether patients received placebo or active interventions.
“Medical studies have shown that adherence is associated with better outcomes, regardless of whether patients received placebo or active interventions [78,79].”
From A Systematic Review of the Impact of Adherence on the Effectiveness of e-Therapies (2011) · cites this paper as [78]
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- Authors
- Avins, A. L., Pressman, A., Ackerson, L., Rudd, P., Neuhaus, J., & Vittinghoff, E.
- Affiliations
- San Francisco VA Medical Center (US)
- Kaiser Permanente (US)
- Stanford Medicine (US)
- University of California, San Francisco (US)
- Corresponding author
- Avins, Andrew L.
- Venue
- Journal of General Internal Medicine
- Published
- 2010-08-13
- Volume
- 25
- Issue
- 12
- Pages
- 1275-1281
- ISSN
- 0884-8734 (ISSN-L)
- 1525-1497
- PMC
- PMC2988150
- OpenAlex
- W2073244283
- Cited by
- 33
- References
- 32
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 1 · 2021: 6 · 2020: 2 · 2019: 1 · 2018: 1 · 2016: 1 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 5
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Journal of General Internal Medicine (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL081195)
- Topics
- Health Sciences › Medicine › Family Practice › Medication Adherence and Compliance
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Keywords
- placebo effect, left ventricular dysfunction, overall survival, cardiovascular events, coronary artery disease, confounding, bias in clinical trials, SOLVD trial
- MeSH terms
- Adult, Aged, Double-Blind Method, Enalapril, Female, Follow-Up Studies, Heart Failure, Humans, Male, Middle Aged, Morbidity, Patient Compliance, Placebo Effect, Treatment Outcome, Ventricular Dysfunction, Left
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