Candesartan Cilexetil is not Associated with Cough in Patients with Enalapril-induced Cough
Bibliographic record
Abstract
Treatment with angiotensin-converting enzyme (ACE) inhibitors is frequently associated with persistent dry cough. This side effect is thought to be due to the non-specific action of ACE inhibitors, which, in addition to suppressing the renin-angiotensin system (RAS), leads to the accumulation of kinins, encephalins and other biologically active peptides. Candesartan cilexetil is a new, long-acting angiotensin II type 1 (AT 1 ) receptor blocker, which offers a more specific means of suppressing the RAS than can be achieved with ACE inhibitors. In this study, we compared the incidence and severity of cough during treatment with candesartan cilexetil, enalapril and placebo in patients with hypertension and enalapril-induced cough. Men and women, aged 20-80 years, with a history of medically treated primary hypertension and ACE-inhibitor-related cough were enrolled. The presence of cough was confirmed during a 4-week challenge period with enalapril, 10 mg, which abated during a subsequent 4-week washout period with placebo. Patients with confirmed ACE-inhibitor-related cough were then randomized to double-blind treatment with candesartan cilexetil, 8 mg once daily ( n = 62), enalapril, 10 mg once daily ( n = 66), or placebo ( n = 26). Baseline blood pressure was similar in all groups. Although blood pressure was recorded during the study, this was for safety monitoring, and the measurements were not standardized in relation to study drug intake or time of day. The frequency of dry cough was recorded on a visual analogue scale (VAS). For each assessment, patients marked a cross on a straight horizontal 100 mm line, rating cough frequency from 'none of the time( at one end of the line to 'all of the time( at the other end. The impact of treatment on quality of life was also studied, using the Symptom Assessment (SA) questionnaire and the Minor Symptom Evaluation (MSE) profile. The SA questionnaire assessed the severity of nine symptoms, including dry cough, by means of a five-graded Likert scale (not at all, a little, moderately, quite a bit, extremely). Changes in the three dimensions of the MSE profile - contentment, vitality and sleep - were recorded using a VAS. Candesartan cilexetil was superior to enalapril regarding the change in frequency ( p = 0.001) and severity ( p < 0.001) of dry cough. After 8 weeks of treatment, the proportions of patients with cough were 26.9% for placebo, 35.5% for candesartan cilexetil and 68.2% for enalapril ( p < 0.001, candesartan cilexetil versus enalapril; p > 0.20, candesartan cilexetil versus placebo). Treatment with candesartan cilexetil did not compromise patients' well-being. Compared with placebo, candesartan cilexetil was superior in terms of its effect on contentment; similar trends were noted for vitality and sleep, although the differences were not significant. When all adverse events were considered, candesartan cilexetil was very well tolerated. No serious adverse events occurred in the candesartan cilexetil or placebo groups, while three patients in the enalapril group reported serious adverse events (chest pain, agranulocytosis, accidental fracture). No treatment-related changes of clinical relevance could be found with regard to laboratory variables, ECG or vital signs/physical findings, except the anticipated blood pressure reduction in the active treatment groups. In conclusion, candesartan cilexetil is not associated with cough in hypertensive patients with previous ACE-inhibitor-induced cough. The incidence of dry cough in patients treated with candesartan cilexetil was similar to that of placebo and lower than that of enalapril.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".