Adverse Effects of Combination Angiotensin II Receptor Blockers Plus Angiotensin-Converting Enzyme Inhibitors for Left Ventricular Dysfunction
Bibliographic record
Abstract
BACKGROUND: We performed a meta-analysis of randomized controlled trials to assess ongoing concerns about the safety profile of combination angiotensin II receptor blockers (ARBs) plus angiotensin-converting enzyme (ACE) inhibitors in symptomatic left ventricular dysfunction. METHODS: MEDLINE (January 1966-December 2006) and Web sites for the National Institute of Health Clinical Trials and the Food and Drug Administration were searched for eligible RCTs that included 500 or more subjects, had a follow-up of 3 months or longer, and reported adverse effects. We used a random effects model to calculate the relative risk (RR) and 95% confidence interval (CI) for the following outcome measures: medication discontinuations because of adverse effects, worsening renal function (an increase in serum creatinine level of > 0.5 mg/dL [to convert to micromoles per liter, multiply by 88.4]), hyperkalemia (serum potassium level > 5.5 mEq/L [to convert to millimoles per liter, multiply by 1]), and symptomatic hypotension. RESULTS: Four studies (N = 17 337; mean follow-up, 25 months [range, 11-41 months]) were selected. Combination ARB plus ACE inhibitor vs control treatment that included ACE inhibitors was associated with significant increases in medication discontinuations because of adverse effects in patients with chronic heart failure (RR, 1.38 [95% CI, 1.22-1.55]) or in patients with acute myocardial infarction with symptomatic left ventricular dysfunction (RR, 1.17 [95% CI, 1.03-1.34]), and for both conditions there were significant increases in worsening renal function (RR, 2.17 [95% CI, 1.59-2.97] and RR, 1.61 [95% CI, 1.31-1.98], respectively), hyperkalemia (RR, 4.87 [95% CI, 2.39-9.94] and RR, 1.33 [95% CI, 0.90-1.98], respectively; the latter was not significant), and symptomatic hypotension (RR, 1.50 [95% CI, 1.09-2.07], and RR, 1.48 [95% CI, 1.33-3.18], respectively). CONCLUSION: Combination ARB plus ACE inhibitor therapy in subjects with symptomatic left ventricular dysfunction was accompanied by marked increases in adverse effects.
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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 | 0.044 | 0.060 |
| Meta-epidemiology (narrow) | 0.004 | 0.002 |
| Meta-epidemiology (broad) | 0.016 | 0.054 |
| Bibliometrics | 0.006 | 0.005 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.001 |
| 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".