Morbidity and mortality reduction with ramipril: the latest results of the HOPE trial
Bibliographic record
Abstract
The HOPE Study randomised 9500 high risk individuals aged >55 years, to Vitamin E (400 mg od) and/or Ramipril (10 mg od) or matching placebos, over 18 months from 267 centres in 19 countries. The trial was funded by the Canadian MRC, Hoechst Marion Roussel, Astra and Vitamin E manufacturers. The trial was stopped early by the DMSB, after a mean of 4–5 year follow-up because of significant benefit in the Ramipril arm. Non-trial baseline treatment: was 76% aspirin, 30% lipid lowering agents, 40% on beta blockade, 47% on calcium blockers, and 15% on diuretics. Baseline BP was 138/79 mmHg, which fell modestly (by 3.3/1.5 mmHg) on Ramipril. The primary outcome of death, MI or stroke was reduced by 22% (with tight confidence intervals) from 17.5% Ramipril to 13.9% Placebo (p = 0.0000002). The separate end points were also each significantly reduced (by 25%, 20% and 32% respectively). Revascularisation was reduced by 15% (p = 0.0013) and heart failure hospitalisation by 16% (p = 0.12). The results were particularly impressive in the 3518 diabetics, with CV death reduced 38%, MI 21%, stroke 32%, and all cause mortality 25%. The primary outcome was reduced from 19.6% Placebo to 15.3% Ramipril. The overall results were remarkably consistent across many pre-specified sub groups, divided by age, sex, and the presence/absence of diabetes, cardiovascular disease, coronary disease, or hypertension. The results were similar in those taking either beta blockers, calcium blockers, or diuretics compared with those not taking the respective drug. The benefit was greater in those with higher usual systolic BP at baseline, but benefit was apparent down to baseline SBP of 125–130 mmHg. Only about half the stroke benefit and one quarter of the MI benefit could be attributed to BP reduction by Ramipril. Ramipril rapidly reduces the risk of serious events in patients with evidence of prior vascular disease, or in diabetics with some additional risk factor; this result was seen on top of high use of current treatments for hypertension or ischaemia. There was a 5% drop out from side effects (mainly cough). There was neither benefit, nor harm from Vitamin E. New data from sub studies in diabetic patients, and of changes in the carotid wall, support an effect which is independent of blood pressure.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".