CHAMGAP
APPROVEDReviewed and approved by the Chamgap Editorial Team (2026-08-01). The draft was written by AI, the existence of all 1 cited sources was verified at the original page, and the verdict passed blind grading and adversarial audit. Methodology v0.6.
Verdict No. 1928 · Search date 2026-08-01 · Methodology v0.6

Sacubitril/valsartan,
does it really help with Reduction in cardiovascular death, heart-failure hospitalization, or outpatient heart failure after acute myocardial infarction?

30-Second Summary
D
Evidence Grade D · 32 · Safety caution
Superiority over ramipril for first heart-failure events or cardiovascular death after acute myocardial infarction was not established
Hypotension, worsening kidney function, hyperkalemia, and angioedema require monitoring, and concomitant ACE-inhibitor use is contraindicated. Blood pressure, kidney function, and potassium should be checked around treatment initiation.
What the
research shows
The grade is D. PARADISE-MI randomized and analyzed by intention to treat 5,661 high-risk patients after acute myocardial infarction. The primary composite of cardiovascular death, first heart-failure hospitalization, or outpatient heart failure failed: 11.9% versus 13.2%, HR 0.90 (95% CI 0.78 to 1.04), P=0.17. The lower bound still allows a 22% relative reduction, so the result is D with 32 points rather than F.
What the
ads claim
Results differ in chronic heart failure with reduced ejection fraction. Verdict 732 is B with 77 points in that population, whereas this verdict addresses event prevention immediately after acute myocardial infarction. Success in one population cannot be transferred to another.
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Useful facts when choosing a product

  • PARADISE-MI used standard ACE-inhibitor ramipril rather than placebo as comparator.
  • All 5,661 randomized participants entered the primary intention-to-treat analysis.
  • Supportive recurrent-event analyses do not reverse the failed first-event primary endpoint.
Gap Measurement · Verdict 1928 · D 32
What advertising claims
What independent, higher-quality research supports
△ GAP
01

What the research actually shows

PARADISE-MI assigned 5,661 participants to sacubitril/valsartan, 2,830, or ramipril, 2,831, in a multicenter double-blind active-comparator superiority trial. The primary intention-to-treat analysis included all randomized participants. The composite occurred in 338 (11.9%) versus 373 (13.2%), HR 0.90 (95% CI 0.78 to 1.04), P=0.17. Novartis sponsored the trial, and the executive committee worked with the sponsor on design, conduct, and analysis.

02

Why this is classified as D (32)

A large hard-outcome trial exists, but its primary endpoint was null and the interval retained meaningful benefit, giving D with 32 points.

Counterpoint. D does not deny efficacy in chronic HFrEF; it applies only to superiority over ramipril after acute myocardial infarction.

Rejudgment record. Cross-check applied — Failed first-event primary endpoint in 5,661 intention-to-treat participants with a confidence interval allowing up to 22% relative reduction

Scoring profile behind this grade
EndpointHHard endpoint - actual events such as death
ReplicationR1Single confirmatory trial
IndependenceI0Evidence comes only from manufacturer studies
Effect sizeE0Null
PrecisionC0The 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)GradeBasis
Reduction in cardiovascular deathDThe failed primary composite does not support superiority based on an individual component.
Reduction in first heart-failure hospitalizationDThe primary composite had HR 0.90 and P=0.17, without established superiority.
Reduction in outpatient heart-failure eventsDAs a component of the failed primary composite, it cannot independently establish success.

Cross-check — Codex and Claude

This verdict was drafted by Codex through literature review and source-existence checks, cross-checked through blind grading and adversarial audit, and settled by reapplying the methodology boundary rules. Cases with split grades were resolved through rejudgment.
03

Evidence Table

StudyDesignSampleFundingEndpointResultWeight
Study 1Multicenter double-blind ramipril-controlled superiority randomized trial2,831NovartisPrimary composite of cardiovascular death, first heart-failure hospitalization, or outpatient heart failure338 (11.9%) versus 373 (13.2%), HR 0.90 (95% CI 0.78 to 1.04), P=0.17.Only large confirmatory trial; failed primary endpoint
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Receipt — 1 References

All 1 cited sources were verified for existence at the original page (as of 2026-08-01).

Pfeffer MA, Claggett B, Lewis EF, et al. Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction. N Engl J Med. 2021;385:1845-1855. DOI: 10.1056/NEJMoa2104508.
checked
Draft and rewrite: Codex (AI) · Verification: Codex blind grading and adversarial audit · Final adjudication: Claude
Reviewed and approved: Chamgap Editorial Team · Approval date: 2026-08-01 · Corrections: none

Cite this verdict

Sacubitril/valsartan x prevention of heart-failure events after myocardial infarction Evidence Grade D card
[Chamgap] Sacubitril/valsartan x prevention of heart-failure events after myocardial infarction — Evidence Grade D·32. 1 cited sources checked. Source: https://chamgap.com/en/verdicts/heart/sacubitril-valsartan-post-mi-heart-failure-events/ · CC BY 4.0

CC BY 4.0 — free to use with attribution; do not distort grades, numbers, or verdict meaning.

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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.