THE IMPACT OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS ON MULTIPLE CARDIOVASCULAR OUTCOMES: A SYSTEMATIC REVIEW AND META-ANALYSIS
Bibliographic record
Abstract
Objective: Meta-analyses of randomized controlled trials exploring the cardiovascular (CV) protective effects of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) on CV outcomes report conflicting results. We performed a systematic review and meta-analysis including only double-blind, placebo-controlled trials and excluding heart failure (HF) trials to explore the impact of ACE-Is and ARBs on CV, renal, and cerebrovascular outcomes in patients at high/very high CV risk, irrespective of the presence of hypertension. Design and method: The protocol for the systematic review was registered on PROSPERO (CRD42023452406). Sixteen trials (9 ACE-Is and 7 ARBs, N=86,003) were included in a random-effects meta-analysis to estimate summary hazard ratios (HR) and 95% confidence intervals (CI). Results: The event rates for all-cause mortality, CV mortality and major CV events (MACEs) did not differ in the placebo arm of ACE-I and ARB trials, suggesting similar CV disease and mortality risks at baseline. The average blood pressure (BP) was higher in ARBs (147/84mmHg) vs ACE-I trials (135/80mmHg) at baseline, while final BP values were similar (ARBs: 138/78mmHg vs ACE-I: 134/78mmHg). Compared to placebo, ACE-Is reduced the rate of CV mortality (HR=0.88; 95%CI=0.78-0.99]), all-cause mortality (HR=0.92; 95%CI=0.85-0.99), myocardial infarction (MI) (HR=0.83; 95%CI=0.73-0.94), HF (HR=0.77; 95%CI=0.69-0.85), stroke (HR=0.82; 95%CI=0.71-0.96), MACEs (HR=0.90; 95%CI=0.81-1.00), new-onset diabetes (HR=0.82; 95%CI=0.70–0.96). Compared to placebo, ARBs did not reduce the rate of CV mortality (HR=1.03; 95%CI=0.95-1.11), all-cause mortality (HR=1.00; 95%CI=0.94-1.06), MI (HR=0.91; 95%CI=0.77-1.07), while a reduction in the rate of MACEs (HR=0.94; 95%CI=0.89-0.99), stroke (HR=0.85; 95%CI=0.77-0.94), HF (HR=0.87; 95%CI=0.76-1.00) and new-onset diabetes (HR=0.86; 95%CI=0.80-0.92) was observed. Limited studies were available to explore the impact of ACE-Is and ARBs on peripheral artery disease and end-stage renal failure. The heterogeneity test showed a greater reduction of CV mortality with ACE-Is vs ARBs (chi2=4.59; p-value=0.03). Conclusions: In double-blind, placebo-controlled randomized trials including patients at high/very high CV risk, ACE-Is reduce the rate of all-cause and CV mortality, MI, whereas ARBs do not, despite similar achieved BP and baseline CV risk. The benefits of ACE-Is in reducing CV mortality over ARBs support their preferential use for comprehensive CV protection.
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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 | 0.021 | 0.039 |
| Meta-epidemiology (narrow) | 0.004 | 0.002 |
| Meta-epidemiology (broad) | 0.026 | 0.051 |
| Bibliometrics | 0.009 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| 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".