Low-dose methotrexate,
does it really help with Prevention of major cardiovascular events in high-risk coronary disease?
research showsGrade D, 34 points. In 4,786 CIRT participants, the original primary composite occurred in 170 versus 167 patients, HR 1.01 (95% CI 0.82 to 1.25), with absolute rates 3.46 versus 3.43 per 100 person-years. The lower limit still allows up to 18% relative benefit, so absence of benefit was not conclusively established.
ads claimRheumatology efficacy and an anti-inflammatory label do not establish coronary-event prevention.
Useful facts when choosing a product
- Target dose was 15 to 20 mg weekly with folate.
- Liver enzyme, blood count, infection, and skin-cancer concerns were reported.
What the research actually shows
Four-gate review: ① Interim-boundary early stop ② listed item ③ the independent DSMB stopped the trial after crossing a prespecified futility boundary ④ not investigator misconduct and difficult to avoid, but this is the sole rule exception and is counted because early stopping can bias estimates. ① At least 15% attrition ② listed item ③ survival censoring is not attrition and no fixed-time missingness of 15% or more was established ④ criterion not met.
Why this is classified as D (34)
One large publicly funded null hard-outcome trial without replicated refutation or precise exclusion gives D, 34.
Counterpoint. The interval permits up to 18% relative benefit.
Rejudgment record. Source checked — Large publicly funded hard-outcome RCT, null result, and prespecified futility stop
| Endpoint | H | Hard endpoint - actual events such as death |
| Replication | R1 | Single confirmatory trial |
| Independence | I1 | Mixed funding sources |
| Effect size | E0 | Null |
| Precision | C0 | The confidence interval leaves room for benefit |
The scoring table and the verdict agree (D).
Sub-claim grades by effect
This ingredient is marketed for several effects. A single overall grade blends strong and weak claims together, so each effect is graded separately here. The overall grade reflects the strongest disconfirming or core claim.
| Effect (sub-claim) | Grade | Basis |
|---|---|---|
| Prevention of major cardiovascular events | D | HR was 1.01. |
Cross-check — AI research and Codex final gate
Evidence Table
| Study | Design | Sample | Funding | Endpoint | Result | Weight |
|---|---|---|---|---|---|---|
| Study 1 | Randomized double-blind placebo-controlled trial | 4,786 | NHLBI public funding; Teva and Amneal supplied study medicines | Nonfatal MI, nonfatal stroke, or cardiovascular death | 170 vs 167; HR 1.01 (95% CI 0.82 to 1.25); 3.46 vs 3.43 per 100 person-years | Large hard-outcome RCT |
Receipt — 1 References
All 1 cited sources were verified for existence at the original page (as of 2026-08-26).
Final verification and publication gate: Codex · Verification cutoff: 2026-08-26 · Corrections: none
Cite this verdict
[Chamgap] No Benefit of Low-Dose Methotrexate for Preventing Major Cardiovascular Events in High-Risk Coronary Disease — Evidence Grade D·34. 1 cited sources checked. Source: https://chamgap.com/en/verdicts/heart/low-dose-methotrexate-cardiovascular-event-prevention/ · CC BY 4.0CC BY 4.0 — free to use with attribution; do not distort grades, numbers, or verdict meaning.
What this document does and does not do
Chamgap is an information source. It reports what research has and has not confirmed; it does not tell readers what to take or buy. That decision belongs to readers and, when needed, medical or legal professionals. This verdict reflects literature available up to the search date and may change as new research appears. Nothing here is medical advice.