{
  "release_id": "5dcd9b263fe17744",
  "id": "cardio:hfref-four-medicine-regimen",
  "owner": "cardio",
  "kind": "intervention",
  "slug": "hfref-four-medicine-regimen",
  "name": "Four-class medicine regimen in heart failure (guideline-directed medical therapy)",
  "aliases": [
    "Guideline-directed medical therapy",
    "GDMT"
  ],
  "atlases": [
    "cardio"
  ],
  "summary_plain": "The four classes of medicine that an ACC summary of the 2022 heart failure guideline from the AHA, ACC and HFSA calls guideline-directed medical therapy: renin-angiotensin system inhibition (an ARNI, ACE inhibitor or angiotensin receptor blocker), beta blockers, mineralocorticoid receptor antagonists and SGLT2 inhibitors. The summary says everyone with heart failure now or in the past, whatever their ejection fraction, should be considered for this therapy. It says an ARNI is now the first choice within the first class when the ejection fraction is reduced.",
  "summary_technical": "Regimen record. The source is the ACC key-perspectives summary of the guideline (hash only, cite only), not the guideline text. The summary gives no doses, no schedule, no starting order and no class of recommendation for the four-class statement, so none is recorded and the page does not say the classes are started together. The first component stands for the ARNI class, using the only ARNI record in this atlas as the example; an ACE inhibitor or an angiotensin receptor blocker is the alternative the summary names when an ARNI is not feasible. The id keeps the HFrEF wording of the plan, but the summary states the four classes for heart failure in general, and its own class 1a statements for the first and fourth classes are limited to reduced ejection fraction. No recommendation link is written for the regimen as a whole. PubMed lists three corrections to the guideline; their text was not read.",
  "editorial_state": "draft",
  "last_substantive_edit": "2026-10-15",
  "last_evidence_check": "2026-10-15",
  "next_review_due": null,
  "identifiers": [],
  "navigation": {
    "cardio": {
      "system": [
        "heart"
      ],
      "condition-area": [
        "heart-failure"
      ]
    }
  },
  "payload": {
    "subtype": "regimen",
    "mechanism": "Four medicine classes that the ACC summary of the 2022 guideline lists as guideline-directed medical therapy; it gives no combined mechanism.",
    "components": [
      {
        "entity": "cardio:sacubitril-valsartan",
        "role": "First-line renin-angiotensin system inhibitor (an ARNI) when the ejection fraction is reduced; an ACE inhibitor or an angiotensin receptor blocker is used when an ARNI is not feasible",
        "dose_text": null,
        "schedule_text": null,
        "snapshot": "cardio:acc-hf2022-key-perspectives-2026-10-15"
      },
      {
        "entity": "cardio:beta-blockers",
        "role": "One of the four classes of guideline-directed medical therapy",
        "dose_text": null,
        "schedule_text": null,
        "snapshot": "cardio:acc-hf2022-key-perspectives-2026-10-15"
      },
      {
        "entity": "cardio:mineralocorticoid-receptor-antagonists",
        "role": "One of the four classes of guideline-directed medical therapy",
        "dose_text": null,
        "schedule_text": null,
        "snapshot": "cardio:acc-hf2022-key-perspectives-2026-10-15"
      },
      {
        "entity": "cardio:sglt2-inhibitors",
        "role": "One of the four classes of guideline-directed medical therapy; recommended in symptomatic chronic HFrEF whether or not there is type 2 diabetes",
        "dose_text": null,
        "schedule_text": null,
        "snapshot": "cardio:acc-hf2022-key-perspectives-2026-10-15"
      }
    ]
  },
  "content_digest": "f380bf36eff217413bf9895b8917398ace607e006a8c49e6547d066902d878f4",
  "review": {
    "content_digest": "f380bf36eff217413bf9895b8917398ace607e006a8c49e6547d066902d878f4",
    "current": [],
    "conflicting": [],
    "stale": [],
    "inactive": []
  },
  "claims": [
    {
      "release_id": "5dcd9b263fe17744",
      "id": "cardio:claim-aha-acc-hfsa-2022-gdmt-four-classes",
      "owner": "cardio",
      "subject_entity_id": "cardio:hfref-four-medicine-regimen",
      "category": "descriptive",
      "statement": "An ACC summary of the 2022 heart failure guideline of the AHA, ACC and HFSA says that guideline-directed medical therapy now has four classes: renin-angiotensin system inhibition (with an angiotensin receptor-neprilysin inhibitor, an ACE inhibitor or an angiotensin receptor blocker), beta blockers, mineralocorticoid receptor antagonists and SGLT2 inhibitors. It says everyone with heart failure now or in the past, whatever their ejection fraction, should be considered for this therapy.",
      "context": {
        "id": "cardio:ctx-aha-acc-hfsa-2022-heart-failure-any-ef",
        "label": "Patients with current or prior heart failure, any ejection fraction (2022 AHA/ACC/HFSA, as summarized by the ACC)",
        "recipient": "unknown",
        "population": "Patients with current or prior heart failure, whatever their ejection fraction, who according to the ACC summary should be considered for guideline-directed therapy. The summary gives no age limits.",
        "care_setting": "Not stated in the ACC summary.",
        "geography": "Not stated in the ACC summary (issued by American societies; jurisdiction not verified)",
        "life_stage_note": "Not stated in the ACC summary",
        "life_stage_terms": null,
        "gestational_age_min_days": null,
        "gestational_age_max_days": null,
        "gestational_age_basis": null,
        "postnatal_age_min_days": null,
        "postnatal_age_max_days": null,
        "gestational_age_status": null,
        "postnatal_age_status": null,
        "followup_description": "Not applicable (guideline context)",
        "eligibility": {
          "inclusion": [
            "Current or prior heart failure, at any ejection fraction (to be considered for the therapy)"
          ],
          "exclusion": []
        }
      },
      "evidence_stage": "guidance",
      "certainty": "not_assessed",
      "certainty_method": null,
      "limitations": "The source is the ACC key-perspectives summary of the guideline (ACC content, hash only), not the guideline text. This is a description of what the therapy consists of and a statement that patients should be considered for it, not a recommendation to use all four classes at every ejection fraction. The statements in the summary itself limit the first-line ARNI statement and the class 1a SGLT2 inhibitor statement to heart failure with reduced ejection fraction, and give SGLT2 inhibitors class 2a in mildly reduced and preserved ejection fraction. It gives no class of recommendation for the four-class statement, no doses and no order of starting, so none is recorded and nothing here says the classes are started together. PubMed lists three corrections to the guideline; their text was not read, so it is not known whether they change anything stated here.",
      "editorial_state": "draft",
      "checked_at": "2026-10-15",
      "next_review_due": null,
      "valid_from": null,
      "valid_to": null,
      "citations": [
        {
          "evidence_role": "supports",
          "locator": "Key perspective 2, sentence 1, fragments 1 to 3",
          "applicability_note": "The four classes of guideline-directed medical therapy.",
          "snapshot": {
            "id": "cardio:acc-hf2022-key-perspectives-2026-10-15",
            "retrieved_at": "2026-10-15T13:50:22Z",
            "content_hash": "9bf3f8d91011b793cc049e80db09ae5624271eb6cdb688f5331c7f8aa1556cad",
            "source_effective_date": null,
            "public_archive_url": null,
            "source_state": "corrected"
          },
          "source": {
            "id": "cardio:aha-acc-hfsa-2022-heart-failure",
            "source_type": "guideline",
            "title": "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines",
            "canonical_url": "https://doi.org/10.1161/CIR.0000000000001063",
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                "scheme": "pmid",
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            ],
            "publication_date": "2022-05-03",
            "publisher": "Circulation",
            "edition": "Published in Circulation 145(18):e895-e1032 (issue date 2022-05-03; electronic publication 2022-04-01). PubMed abstract and bibliographic data only. PubMed lists no PMC copy. The guideline text was not read. PubMed lists 3 corrections to the guideline; their text was not read. The same source also holds a snapshot of the ACC key-perspectives summary page of the guideline (dated Apr 01, 2022), which is an ACC summary and not the guideline text. The recommendation text for this atlas comes from that page. The publisher field is the journal title as PubMed gives it.",
            "reuse_basis": "PubMed record and ACC page. PubMed record fetched through NCBI E-utilities on 2026-10-15. Only the hash of the bytes is kept; nothing is committed. Bibliographic metadata and short quotations from the PubMed abstract, under 25 words each. The full text was not redistributed and the societies' reuse terms were not reviewed.  ACC web page fetched with a plain Mozilla/5.0 user agent on 2026-10-15. Only the hash of the bytes is kept; nothing is committed. The ACC's reuse terms were not read, so public text is cite_only: public pages state the summary in the atlas's own words, with a citation and a link, and use no ACC wording. Quote rows are short evidence fragments for the reviewer.",
            "public_text": "cite_only"
          }
        },
        {
          "evidence_role": "supports",
          "locator": "Key perspective 1, last sentence",
          "applicability_note": "Anyone with current or past HF should be considered for this therapy.",
          "snapshot": {
            "id": "cardio:acc-hf2022-key-perspectives-2026-10-15",
            "retrieved_at": "2026-10-15T13:50:22Z",
            "content_hash": "9bf3f8d91011b793cc049e80db09ae5624271eb6cdb688f5331c7f8aa1556cad",
            "source_effective_date": null,
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            "source_state": "corrected"
          },
          "source": {
            "id": "cardio:aha-acc-hfsa-2022-heart-failure",
            "source_type": "guideline",
            "title": "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines",
            "canonical_url": "https://doi.org/10.1161/CIR.0000000000001063",
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            "publication_date": "2022-05-03",
            "publisher": "Circulation",
            "edition": "Published in Circulation 145(18):e895-e1032 (issue date 2022-05-03; electronic publication 2022-04-01). PubMed abstract and bibliographic data only. PubMed lists no PMC copy. The guideline text was not read. PubMed lists 3 corrections to the guideline; their text was not read. The same source also holds a snapshot of the ACC key-perspectives summary page of the guideline (dated Apr 01, 2022), which is an ACC summary and not the guideline text. The recommendation text for this atlas comes from that page. The publisher field is the journal title as PubMed gives it.",
            "reuse_basis": "PubMed record and ACC page. PubMed record fetched through NCBI E-utilities on 2026-10-15. Only the hash of the bytes is kept; nothing is committed. Bibliographic metadata and short quotations from the PubMed abstract, under 25 words each. The full text was not redistributed and the societies' reuse terms were not reviewed.  ACC web page fetched with a plain Mozilla/5.0 user agent on 2026-10-15. Only the hash of the bytes is kept; nothing is committed. The ACC's reuse terms were not read, so public text is cite_only: public pages state the summary in the atlas's own words, with a citation and a link, and use no ACC wording. Quote rows are short evidence fragments for the reviewer.",
            "public_text": "cite_only"
          }
        },
        {
          "evidence_role": "context",
          "locator": "CommentsCorrectionsList, three ErratumIn entries",
          "applicability_note": "Shows that corrections exist. What they change is unknown.",
          "snapshot": {
            "id": "cardio:pubmed-35363499-2026-10-15",
            "retrieved_at": "2026-10-15T13:48:58Z",
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          "source": {
            "id": "cardio:aha-acc-hfsa-2022-heart-failure",
            "source_type": "guideline",
            "title": "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines",
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            "publication_date": "2022-05-03",
            "publisher": "Circulation",
            "edition": "Published in Circulation 145(18):e895-e1032 (issue date 2022-05-03; electronic publication 2022-04-01). PubMed abstract and bibliographic data only. PubMed lists no PMC copy. The guideline text was not read. PubMed lists 3 corrections to the guideline; their text was not read. The same source also holds a snapshot of the ACC key-perspectives summary page of the guideline (dated Apr 01, 2022), which is an ACC summary and not the guideline text. The recommendation text for this atlas comes from that page. The publisher field is the journal title as PubMed gives it.",
            "reuse_basis": "PubMed record and ACC page. PubMed record fetched through NCBI E-utilities on 2026-10-15. Only the hash of the bytes is kept; nothing is committed. Bibliographic metadata and short quotations from the PubMed abstract, under 25 words each. The full text was not redistributed and the societies' reuse terms were not reviewed.  ACC web page fetched with a plain Mozilla/5.0 user agent on 2026-10-15. Only the hash of the bytes is kept; nothing is committed. The ACC's reuse terms were not read, so public text is cite_only: public pages state the summary in the atlas's own words, with a citation and a link, and use no ACC wording. Quote rows are short evidence fragments for the reviewer.",
            "public_text": "cite_only"
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      "review": {
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        "current": [],
        "conflicting": [],
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        "inactive": []
      },
      "api_path": "api/v1/claims/cardio--claim-aha-acc-hfsa-2022-gdmt-four-classes.json"
    }
  ],
  "decisions": [],
  "milestones": [],
  "relationships": {
    "outgoing": [
      {
        "predicate": "related_to",
        "label": "Medicine classes the ACC summary lists for heart failure",
        "clinical_claim_not_fact": false,
        "family": "navigation",
        "other_entity_id": "cardio:heart-failure",
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  "page_path": "interventions/hfref-four-medicine-regimen/",
  "context_path": "api/v1/context/cardio--hfref-four-medicine-regimen.md"
}