β-blockers, calcium antagonists, and mortality in stable coronary artery disease: an international cohort study
Key result
Baseline beta-blocker use shows no 5-year mortality benefit in stable CAD.
- HR 0.94
- 95% CI 0.84-1.06
- P=0.30
- n=22,006
Why the study?
The effect of first-line antianginal agents, β-blockers, and calcium antagonists on clinical outcomes in stable CAD remains uncertain.
Does the use of β-blockers or calcium antagonists reduce mortality in patients with stable coronary artery disease?
Population
22 006 stable CAD patients across 45 countries in the CLARIFY registry
Comparison
Use vs non-use of β-blockers or calcium antagonists
Design
International cohort study
Follow-up
5 years
Authors
Discussion
Loading...
Member takes
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“systematic use of beta-blockers is not mandated for all patients with stable coronary artery disease, especially in the absence of previous myocardial infarction”
Implication
β-Blocker use was not associated with lower mortality in stable CAD overall; leaves open whether benefit is confined to recent MI and requires prospective confirmation.
Key Points
- To evaluate the association of first-line antianginal agents, specifically beta-blockers and calcium antagonists, with all-cause mortality and cardiovascular outcomes in stable coronary artery disease.
- Prospective international cohort study using the CLARIFY registry across 45 countries, analyzing 22 006 patients with stable coronary artery disease enrolled between 2009 and 2010 and followed annually up to 5 years.
- Multivariable-adjusted Cox proportional hazards models assessed associations between baseline and time-updated medication use and outcomes including all-cause death, cardiovascular death, and cardiovascular death/non-fatal myocardial infarction.
- Baseline beta-blocker use was not associated with lower all-cause death [1345 (7.8%) in users vs. 407 (8.4%) in non-users; HR 0.94, 95% CI 0.84-1.06; P = 0.30], cardiovascular death [861 (5.0%) vs. 262 (5.4%); HR 0.91, 95% CI 0.79-1.05; P = 0.20], or cardiovascular death/non-fatal MI [1272 (7.4%) vs. 340 (7.0%); HR 1.03, 95% CI 0.91-1.16; P = 0.66].
- Among patients enrolled within one year of a myocardial infarction, beta-blocker use was associated with lower all-cause death [205 (7.0%) vs. 59 (10.3%); HR 0.68, 95% CI 0.50-0.91; P = 0.01] and lower cardiovascular death [132 (4.5%) vs. 49 (8.5%); HR 0.52, 95% CI 0.37-0.73; P = 0.0001].
- Calcium antagonist use showed no association with all-cause death [493 (8.4%) vs. 1259 (7.8%); HR 1.02, 95% CI 0.91-1.13; P = 0.76] or cardiovascular death [311 (5.3%) vs. 812 (5.0%); HR 1.01, 95% CI 0.88-1.16; P = 0.87], regardless of prior myocardial infarction history.
Study Design
Type
Cohort (n=22,006)
Multicenter
Yes
Structured PICO
Does the use of β-blockers or calcium antagonists reduce mortality in patients with stable coronary artery disease?
P
Population
22,006 outpatients with stable coronary artery disease, with a mean age of 63.8 years and 21.8% female, followed annually for up to 5 years.
E
Exposure
Baseline use of β-blockers or calcium antagonists (assessed at baseline and yearly)
C
Comparator
Non-use of β-blockers or calcium antagonists at baseline
O
Outcome
All-cause mortality at up to 5 years follow-uphard clinical
Main Result
Hazard Ratio: 0.94 (95% CI 0.84–1.06)
Absolute Event Rate: 7.8% vs 8.4%
p-value: p=0.30
In patients with stable coronary artery disease, routine use of β-blockers or calcium antagonists is not associated with improved survival, except for β-blockers in the first year following a myocardial infarction.
Limitations
- Analyses were not formally prespecified before data collection and the methods of analysis were not prospectively defined.
- Outcomes were not adjudicated.
- Residual confounding from measured or unmeasured variables cannot be excluded (related to both contraindication and indication bias).
- Enrolment and follow-up did not start at the time of treatment initiation or at the time of diagnosis, which can cause bias.
- Analyses were not formally prespecified before data collection
- Excluded patients with severe heart failure or life-threatening arrhythmias
- Outcomes were not adjudicated
- Residual confounding from measured or unmeasured variables (indication and contraindication bias)
- Enrolment and follow-up did not start at the time of treatment initiation or diagnosis
Cite This Study
Sorbets et al. (2018) conducted a cohort in Stable coronary artery disease (CAD) (n=22,006). β-blockers vs. Non-users was evaluated on All-cause mortality (HR 0.94, 95% CI 0.84-1.06, p=0.30). Baseline use of β-blockers in patients with stable coronary artery disease was not associated with lower all-cause mortality at 5 years compared to non-users (HR 0.94, 95% CI 0.84-1.06, P=0.30).