Comparative effectiveness of ARB and ACEi for cardiovascular outcomes and risk of angioedema among different ethnic groups in England: an analysis in the UK Clinical Practice Research Datalink with emulation of a reference trial (ONTARGET)
Bibliographic record
Abstract
Objective To study the comparative effectiveness of angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEi) in ethnic minority groups in the UK. Design Observational cohort study using a reference trial emulation approach benchmarked against the ONTARGET trial. Setting UK Clinical Practice Research Datalink Aurum data from 01/01/2001-31/07/2019. Participants Black, South Asian, or White patients with a prescription for an ARB/ACEi who met the ONTARGET trial criteria. Main outcome measures The primary composite outcome was: cardiovascular-related death, myocardial infarction, stroke, or hospitalisation for heart failure with individual components studied as secondary outcomes. Angioedema was a safety endpoint. We assessed outcomes using a propensity-score-weighted Cox proportional hazards model for ARB vs ACEi with heterogeneity by ethnicity assessed on the relative and absolute scale. Results 17,593 Black, 30,805 South Asian, and 524,623 White patients were included. We benchmarked results against ONTARGET comparing ARB with ACEi for the primary outcome (hazard ratio [HR] 0.96, 95% CI: 0.95 to 0.98) and found no evidence of treatment effect heterogeneity( P int =0.422). Results were consistent for most secondary outcomes. However, for cardiovascular-related death, there was strong evidence of heterogeneity ( P int =0.002), with ARB associated with more events in Black individuals and with fewer events in White individuals compared to ACEi, and no differences in South Asian individuals. For angioedema, HR 0.56 (95% CI: 0.46 to 0.67) for ARB vs ACEi ( P int =0.306). Absolute risks were higher in Black individuals, for ARB vs ACEi number-needed-to-treat was 204 in Black individuals compared with 2000 in South Asian individuals and 1667 in White individuals ( P int =0.023). Conclusions These results demonstrate variation in drug effects of ACEi and ARB by ethnicity and suggest the potential for adverse consequences from current UK guideline recommendations for ARB in preference to ACEi for Black individuals.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.057 | 0.154 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.005 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.003 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".