Optimal threshold of adherence to lipid lowering drugs in predicting acute coronary syndrome, stroke, or mortality: A cohort study
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Published on: November 10, 2017
Arsène Zongo1,2,3, Scot Simpson4, Jeffrey A Johnson1
1School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
Insights
Optimal adherence to lipid-lowering drugs (LLD) varies by outcome in hypertensive patients. Around 50% adherence may prevent cardiovascular events, while 80% is needed for mortality reduction.
Area of Science:
- Cardiology
- Pharmacology
- Public Health
Background:
- Medication adherence thresholds are often not evidence-based.
- A common assumption is that 80% adherence is needed for improved outcomes.
- The optimal adherence threshold for lipid-lowering drugs (LLD) in hypertensive patients is unclear.
Purpose of the Study:
- To determine the optimal adherence threshold of LLDs for predicting cardiovascular-related (CV) outcomes in patients with hypertension.
- To evaluate if the standard 0.8 adherence threshold is appropriate for LLDs in this population.
Main Methods:
- A cohort study of new LLD users with hypertension was conducted using healthcare administrative data (2008-2016).
- Adherence was measured as proportion of days covered (PDC).
- Optimal thresholds were identified using Contal and O'Quigley method, minimum distance method, and Youden's J index, with Cox regressions and Akaike information criteria for analysis.
Main Results:
- The study included 52,229 patients.
- Optimal adherence thresholds varied by outcome: 0.52 for acute coronary syndrome (ACS)/stroke, 0.79 for CV-related mortality, and 0.84 for all-cause mortality.
- Results were consistent in patients aged ≥ 65 years.
Conclusions:
- For hypertensive patients initiating LLDs, approximately 50% adherence may suffice to prevent long-term ACS or stroke.
- A higher adherence threshold, around 0.80, appears necessary to reduce the risk of all-cause or CV-related mortality.
- These findings suggest outcome-specific adherence targets for LLDs in hypertension management.
Objective:
Thresholds defining medication adherence are rarely evidence-based. A threshold of 0.8 is typically presumed to achieve improved outcomes. We aimed to assess the optimal threshold of adherence to lipid-lowering drugs (LLD) in predicting cardiovascular-related (CV) outcomes in patients with hypertension.
Design:
Cohort study of new users of LLDs.
Setting:
Comprehensive healthcare administrative databases of the province of Alberta (Canada) from 2008 to 2016.
Participants:
Patients with hypertension, who were new users of LLDs. Patients who had the outcomes prior to the initiation of LLD were excluded.
Main Outcomes Measures:
Hospitalization for acute coronary syndrome (ACS)/stroke, CV-related mortality and all-cause mortality.
Statistical Analysis:
Adherence to LLDs was assessed as the proportion of days covered (PDC) by any LLD, from drug initiation to censoring, outcome, or study end. Three methods were used to assess the threshold: Contal and O'Quigley method, minimum distance method, and Youden's J index. Cox regressions were used to assess the risk associated with each method-specific threshold and Akaike information criteria were used to retain the optimal threshold after adjustment.
Results:
52229 patients were included; 4.0% were hospitalized for ACS/stroke, 3.4% died, and 1.3% died from CV-related cause. In predicting ACS/stroke, CV-related and all-cause mortality, the optimal adherence threshold was 0.52 (range: 0.51-0.54), 0.79 (0.45-0.87), and 0.84 (0.79-0.89), respectively. These results were consistent among patients aged ≥ 65 years (n = 19804). However, the results varied among those aged < 65 years, where the incidence rates of outcomes were low.
Conclusion:
In new-users of LLDs with hypertension, approximately 50% days covered by LLDs may be enough to prevent long-term occurrence of ACS, or stroke. However, a threshold near 0.80 may be needed to prevent or reduce the risk of all-cause or CV-related mortality.
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