A review of STRIDE‐2 and STRIDE‐2X: the case for selective endothelin receptor blockade
Bibliographic record
Abstract
BACKGROUND: Pulmonary arterial hypertension remains incurable and has previously required difficult parenteral therapy. Endothelin-1(ET-1) is an important mediator of pulmonary arterial hypertension. The recent availability of oral therapies, including endothelin receptor antagonists, has improved ease of use for patients, but most patients remain symptomatic to a significant degree. Two classes of ET-1 receptors have been described, ET(A) and ET(B). It has previously been unclear whether both receptors must be blocked in pulmonary arterial hypertension, or only the ET(A) receptor. MATERIALS AND METHODS: The Sitaxsentan To Relieve ImpaireD Exercise-2 (STRIDE-2) study followed by STRIDE-2X exposed patients with pulmonary arterial hypertension to the highly selective ET(A) antagonist sitaxsentan (n = 145), or to bosentan (n = 84), a nonselective ET(A) and ET(B) antagonist. The total exposure duration and follow-up period was 1 year. Pre-specified comparisons included time to discontinuation of monotherapy, time to clinical worsening, incidence of elevated hepatic transaminase levels > 3 x upper limit of normal and survival. RESULTS: Sitaxsentan therapy showed significant benefit over bosentan with respect to discontinuation of monotherapy at 1 year (24% vs. 43%, P = 0.002), clinical worsening at 1 year (28% vs. 39%, P = 0.0425), elevated hepatic transaminases at 1 year (4% vs. 14%, P = 0.014) and 1-year survival (96% vs. 88%, P = 0.028). CONCLUSIONS: STRIDE-2 and its extension, STRIDE-2X, suggest significant benefit of sitaxsentan compared with bosentan, in terms of efficacy and reduced hepatotoxicity. The former may be related to the high ET(A) receptor selectivity of sitaxsentan.
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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 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.004 | 0.004 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".