const pptxgen = require("pptxgenjs");

const pres = new pptxgen();
pres.layout = "LAYOUT_16x9";
pres.title = "Cardioembolic Stroke, Anticoagulation & CATALYST Trial";
pres.author = "Medical Education";

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// ─── Helper functions ─────────────────────────────────────────────

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  sl.addText("Key Takeaways", { x: 0.5, y: 0.5, w: 9, h: 0.8, fontSize: 26, bold: true, color: WHITE, align: "center" });
  const points = [
    { text: "Cardioembolic stroke accounts for ~25% of all ischemic strokes; atrial fibrillation is the leading cause.", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 14, color: WHITE, paraSpaceBefore: 6 } },
    { text: "DOACs are preferred over warfarin for non-valvular AF — equivalent efficacy, lower ICH risk.", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 14, color: WHITE, paraSpaceBefore: 6 } },
    { text: "CATALYST (Lancet 2025) — largest IPD meta-analysis (n = 5,441): early DOAC (≤4 days) reduces composite outcome by 30% vs delayed start.", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 14, color: WHITE, paraSpaceBefore: 6 } },
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// ═══════════════════════════════════════════════════════════
//  SECTION 1 — CARDIOEMBOLIC STROKE  (Slides 1–20)
// ═══════════════════════════════════════════════════════════

// Slide 1 — Title
titleSlide(pres);

// Slide 2 — Section 1 divider
addSectionTitle(pres, "01", "Cardioembolic Stroke", "Epidemiology · Mechanisms · Diagnosis · Management");

// Slide 3 — What is Cardioembolic Stroke?
contentSlide(pres, "What is Cardioembolic Stroke?", [
  "Cardioembolic stroke is caused by embolism of thrombotic or other material from the heart to brain arteries",
  "Accounts for ~25% of all ischemic strokes in the industrialised world",
  "Most common underlying cause of embolic stroke globally",
  "Clot forms within the heart → enters circulation → lodges in cerebral vasculature",
  "Typically causes larger, more severe infarcts than lacunar or small-vessel strokes",
  "High early recurrence risk: up to 10–15% in the first 2 weeks without treatment",
  "Cardioembolic strokes carry a worse short-term prognosis vs. other ischemic stroke subtypes",
]);

// Slide 4 — Stroke Classification
contentSlide(pres, "Ischemic Stroke Classification (TOAST Criteria)", [
  { text: "Large-artery atherosclerosis", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 14, bold: true, color: NAVY, paraSpaceBefore: 4 } },
  { text: "Carotid or intracranial atherosclerosis, artery-to-artery embolism", options: { bullet: { indent: 30 }, breakLine: true, fontSize: 12, color: GRAY } },
  { text: "Cardioembolism", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 14, bold: true, color: NAVY, paraSpaceBefore: 4 } },
  { text: "AF, valvular disease, intracardiac thrombus, cardiomyopathy", options: { bullet: { indent: 30 }, breakLine: true, fontSize: 12, color: GRAY } },
  { text: "Small-vessel occlusion (lacunar)", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 14, bold: true, color: NAVY, paraSpaceBefore: 4 } },
  { text: "Deep perforating artery disease; typically pure motor/sensory syndromes", options: { bullet: { indent: 30 }, breakLine: true, fontSize: 12, color: GRAY } },
  { text: "Other determined aetiology", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 14, bold: true, color: NAVY, paraSpaceBefore: 4 } },
  { text: "Dissection, coagulopathy, vasculitis", options: { bullet: { indent: 30 }, breakLine: true, fontSize: 12, color: GRAY } },
  { text: "Undetermined / Cryptogenic", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 14, bold: true, color: RED, paraSpaceBefore: 4 } },
  { text: "~30% of strokes — AF may be occult; Holter monitoring ≥30 days recommended", options: { bullet: { indent: 30 }, breakLine: false, fontSize: 12, color: GRAY } },
]);

// Slide 5 — Cardiac Sources of Embolism
twoColumnSlide(pres,
  "Cardiac Sources of Embolism",
  "High-Risk Sources",
  [
    "Atrial fibrillation (paroxysmal or permanent)",
    "Rheumatic mitral valve disease + AF",
    "Mechanical prosthetic valve",
    "Mitral stenosis",
    "Left ventricular / atrial thrombus",
    "Recent MI (anterior wall)",
    "Infective endocarditis",
    "Dilated cardiomyopathy (EF <30%)",
    "Intracardiac tumour (atrial myxoma)",
  ],
  "Lower / Moderate-Risk Sources",
  [
    "Mitral valve prolapse",
    "Mitral annular calcification",
    "Patent foramen ovale (large or with ASD aneurysm)",
    "Non-stenotic aortic valve disease",
    "Left ventricular regional wall abnormality",
    "Atrial septal aneurysm",
    "Spontaneous echo contrast ('smoke')",
    "Complex aortic arch atheroma",
  ]
);

// Slide 6 — Atrial Fibrillation: Stroke Epidemiology
statBoxSlide(pres,
  "Atrial Fibrillation & Stroke — Key Numbers",
  [
    { value: "20–30%", label: "of ischemic strokes attributable to AF", color: LBLUE },
    { value: "17×", label: "stroke risk increase: AF + rheumatic valve disease", color: "FEF3C7", valueColor: RED },
    { value: "5×", label: "stroke risk increase: non-rheumatic AF", color: LBLUE },
    { value: "~50%", label: "of eligible AF patients NOT on anticoagulation", color: "FEF3C7", valueColor: RED },
  ],
  "Sources: Fuster & Hurst's The Heart 15e; Bradley & Daroff's Neurology in Clinical Practice; Harrison's Principles of Internal Medicine 22e"
);

// Slide 7 — Pathophysiology
contentSlide(pres, "Pathophysiology of Cardioembolic Stroke", [
  { text: "Virchow's Triad in Cardiac Embolism:", options: { breakLine: true, fontSize: 15, bold: true, color: NAVY, paraSpaceBefore: 2 } },
  { text: "1. Blood stasis — AF causes atrial turbulence → left atrial appendage (LAA) thrombus", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 5 } },
  { text: "2. Endothelial injury — valvular disease, infective endocarditis, myocardial infarction scar", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 5 } },
  { text: "3. Hypercoagulability — CHA₂DS₂-VASc risk factors amplify thrombin generation", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 5 } },
  { text: "Embolus pathway: LAA → left atrium → left ventricle → aorta → cerebral arteries (MCA most common)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 8 } },
  { text: "Middle cerebral artery territory most affected (50–80% of cardioembolic strokes)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 5 } },
  { text: "\"Spectacular shrinking deficit\" — rapid partial resolution as embolus fragments and migrates distally", options: { bullet: { indent: 20 }, breakLine: false, fontSize: 13, color: GRAY, italics: true, paraSpaceBefore: 5 } },
]);

// Slide 8 — CHA₂DS₂-VASc
tableSlide(pres,
  "CHA₂DS₂-VASc Score — Risk Stratification in AF",
  ["Risk Factor", "Score"],
  [
    ["C — Congestive heart failure / LV dysfunction", "1"],
    ["H — Hypertension", "1"],
    ["A₂ — Age ≥ 75 years", "2"],
    ["D — Diabetes mellitus", "1"],
    ["S₂ — Prior Stroke, TIA, or thromboembolism", "2"],
    ["V — Vascular disease (prior MI, PAD, aortic plaque)", "1"],
    ["A — Age 65–74 years", "1"],
    ["Sc — Sex category (Female)", "1"],
    ["Maximum score", "9"],
  ]
);

// Slide 9 — Clinical Features
twoColumnSlide(pres,
  "Clinical Features of Cardioembolic Stroke",
  "Characteristic Findings",
  [
    "Sudden-onset maximal-at-onset deficit",
    "Cortical signs: aphasia, neglect, hemianopia",
    "Large territory MCA/PCA/ACA infarcts",
    "Multiple cerebrovascular territories (simultaneous)",
    "Haemorrhagic transformation on MRI (>20%)",
    "Reduced level of consciousness (large infarct)",
    "Rapid improvement (lysis of embolus)",
    "Prior similar embolic episodes",
  ],
  "Investigations",
  [
    "12-lead ECG — AF, LVH, recent MI",
    "24/48-hour Holter — paroxysmal AF detection",
    "Transthoracic echo (TTE) — LV function, thrombus, valves",
    "Transoesophageal echo (TOE) — LAA thrombus, PFO",
    "MRI DWI — multiple cortical & watershed infarcts",
    "MRI: 'cortical ribbon' pattern typical",
    "Cardiac MRI — ventricular thrombus in cryptogenic stroke",
    "Implantable loop recorder (≥30 days) if cryptogenic",
  ]
);

// Slide 10 — Haemorrhagic Transformation
contentSlide(pres, "Haemorrhagic Transformation (HT) in Cardioembolic Stroke", [
  "Occurs in up to 20–40% of cardioembolic strokes (higher than other subtypes)",
  "Caused by reperfusion into ischaemic vessel wall after embolus fragments or lyses",
  "ECASS Classification:",
  "  HI-1: Scattered petechiae along infarct margin — no clinical change",
  "  HI-2: Confluent petechiae within infarct, no mass effect",
  "  PH-1: Haematoma <30% of infarct, mild mass effect",
  "  PH-2: Haematoma >30% of infarct, significant mass effect — poor outcome",
  "PH-2 is a major contraindication to anticoagulation in the acute phase",
  "Risk factors for HT: large infarct size, hypertension, reperfusion therapy, anticoagulation",
  "Early anticoagulation must be balanced against HT risk",
]);

// Slide 11 — Acute Management
contentSlide(pres, "Acute Management of Cardioembolic Stroke", [
  { text: "Reperfusion (if within treatment windows):", options: { breakLine: true, fontSize: 15, bold: true, color: NAVY, paraSpaceBefore: 2 } },
  { text: "IV alteplase (tPA): 0.9 mg/kg within 4.5 hours of onset — reduces disability", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Mechanical thrombectomy: within 6–24 hrs for large vessel occlusion (LVO)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Supportive Care:", options: { breakLine: true, fontSize: 15, bold: true, color: NAVY, paraSpaceBefore: 6 } },
  { text: "Blood pressure control (target <180/105 pre-thrombolysis; avoid aggressive lowering)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Airway protection, fever management, glucose control (normoglycaemia target)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Anticoagulation Timing (The Key Question):", options: { breakLine: true, fontSize: 15, bold: true, color: RED, paraSpaceBefore: 6 } },
  { text: "Historically delayed 2–4 weeks due to HT concern ('1-3-6-12 rule')", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: GRAY, paraSpaceBefore: 3 } },
  { text: "Recent evidence (CATALYST) supports early initiation (≤4 days) for most patients", options: { bullet: { indent: 20 }, breakLine: false, fontSize: 13, color: GREEN, bold: true, paraSpaceBefore: 3 } },
]);

// Slide 12 — Secondary Prevention Overview
contentSlide(pres, "Secondary Prevention — Cardioembolic Stroke", [
  { text: "Anticoagulation is the cornerstone of secondary prevention:", options: { breakLine: true, fontSize: 15, bold: true, color: NAVY, paraSpaceBefore: 2 } },
  { text: "Reduces relative risk of recurrent stroke by ~64% in AF (warfarin vs. placebo)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "DOACs superior to warfarin: lower ICH, equivalent or better efficacy", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Risk Factor Modification:", options: { breakLine: true, fontSize: 15, bold: true, color: NAVY, paraSpaceBefore: 6 } },
  { text: "Rate/rhythm control of AF — does not eliminate stroke risk; anticoagulate regardless", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Hypertension control, diabetes management, statin therapy", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Antiplatelet Therapy:", options: { breakLine: true, fontSize: 15, bold: true, color: NAVY, paraSpaceBefore: 6 } },
  { text: "Aspirin 325 mg/day when anticoagulation is contraindicated", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Clopidogrel + aspirin: better than aspirin alone but more bleeding (ACTIVE-A)", options: { bullet: { indent: 20 }, breakLine: false, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
]);

// Slide 13 — Warfarin vs DOACs
twoColumnSlide(pres,
  "Warfarin vs Direct Oral Anticoagulants (DOACs)",
  "Warfarin (VKA)",
  [
    "Inhibits vitamin K-dependent factors (II, VII, IX, X)",
    "Requires INR monitoring (target 2.0–3.0)",
    "Multiple food & drug interactions",
    "First-line for valvular AF, mechanical valves",
    "Reversible with vitamin K / 4F-PCC",
    "Used long-term for rheumatic heart disease",
    "Superior in mechanical prosthetic valves",
    "Less costly in resource-limited settings",
  ],
  "DOACs (dabigatran, rivaroxaban, apixaban, edoxaban)",
  [
    "Direct thrombin (dabigatran) or Xa inhibitors",
    "Predictable dosing — no routine INR monitoring",
    "Lower intracranial haemorrhage risk vs warfarin",
    "Non-inferior to warfarin for stroke prevention in non-valvular AF",
    "Idarucizumab (dabigatran) / andexanet alfa (Xa) reversal",
    "NOT recommended for valvular AF or mechanical valves",
    "Renal dose adjustment required (especially dabigatran)",
    "Preferred in non-valvular AF (guideline consensus)",
  ]
);

// Slide 14 — DOAC Selection
tableSlide(pres,
  "DOAC Selection in AF-Related Cardioembolic Stroke",
  ["Drug", "Target", "Dose (Standard)", "Key Consideration"],
  [
    ["Dabigatran", "Direct thrombin (IIa)", "150 mg BD (110 mg BD if age >80 / bleed risk)", "Renal clearance; idarucizumab reversal"],
    ["Rivaroxaban", "Factor Xa", "20 mg OD with evening meal", "Once daily; food required for absorption"],
    ["Apixaban", "Factor Xa", "5 mg BD (2.5 mg BD if ≥2 dose-reduction criteria)", "Best GI tolerability; preferred by many guidelines"],
    ["Edoxaban", "Factor Xa", "60 mg OD (30 mg OD if CrCl 15–50)", "Requires initial parenteral anticoagulation"],
  ]
);

// Slide 15 — Special Situations
contentSlide(pres, "Anticoagulation — Special Situations", [
  { text: "Mechanical Prosthetic Valves:", options: { breakLine: true, fontSize: 14, bold: true, color: NAVY, paraSpaceBefore: 2 } },
  { text: "Warfarin mandatory — dabigatran inferior (RE-ALIGN trial terminated early)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 12, color: "334155", paraSpaceBefore: 3 } },
  { text: "Mitral position: INR target 2.5–3.5; Aortic: INR 2.0–3.0 (+/– low-dose aspirin)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 12, color: "334155", paraSpaceBefore: 3 } },
  { text: "Left Ventricular Thrombus / Reduced EF:", options: { breakLine: true, fontSize: 14, bold: true, color: NAVY, paraSpaceBefore: 5 } },
  { text: "Anticoagulation recommended for 3–6 months; risk persists after therapy", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 12, color: "334155", paraSpaceBefore: 3 } },
  { text: "LVAD patients: warfarin INR target 2.5–3.0 (nearly 9% annual stroke risk)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 12, color: "334155", paraSpaceBefore: 3 } },
  { text: "Infective Endocarditis:", options: { breakLine: true, fontSize: 14, bold: true, color: NAVY, paraSpaceBefore: 5 } },
  { text: "Anticoagulation generally avoided in active infective endocarditis", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 12, color: RED, paraSpaceBefore: 3 } },
  { text: "Cryptogenic Stroke / ESUS:", options: { breakLine: true, fontSize: 14, bold: true, color: NAVY, paraSpaceBefore: 5 } },
  { text: "Monitor for AF (≥30 days ambulatory); implantable loop recorder if needed", options: { bullet: { indent: 20 }, breakLine: false, fontSize: 12, color: "334155", paraSpaceBefore: 3 } },
]);

// Slide 16 — Patent Foramen Ovale
contentSlide(pres, "Patent Foramen Ovale (PFO) & Stroke", [
  "PFO prevalence: ~25% of general population (mostly asymptomatic)",
  "Paradoxical embolism: venous thrombus crosses PFO into arterial circulation",
  "PFO is a recognised source of cryptogenic stroke, especially in young adults",
  "Risk higher when PFO is large or associated with atrial septal aneurysm",
  "RoPE Score helps quantify PFO attributability in cryptogenic stroke",
  "Treatment options:",
  "  Antiplatelet therapy (aspirin): first line if PFO incidentally found",
  "  Anticoagulation (warfarin/DOAC): if DVT/PE or high-risk features",
  "  Percutaneous PFO closure: reduces recurrent stroke in selected patients (age <60, attributable PFO)",
  "CLOSE, RESPECT, REDUCE trials support closure in cryptogenic stroke with high-risk PFO",
]);

// Slide 17 — Timing Dilemma
contentSlide(pres, "The Timing Dilemma: When to Start Anticoagulation?", [
  { text: "The Clinical Tension:", options: { breakLine: true, fontSize: 15, bold: true, color: NAVY, paraSpaceBefore: 2 } },
  { text: "Early anticoagulation → prevents recurrent embolic stroke (high early risk: ~1–2%/day in first week)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: GREEN, bold: true, paraSpaceBefore: 3 } },
  { text: "Early anticoagulation → risks haemorrhagic transformation of ischaemic infarct", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: RED, bold: true, paraSpaceBefore: 3 } },
  { text: "Historical Approach — '1-3-6-12 Day Rule':", options: { breakLine: true, fontSize: 15, bold: true, color: NAVY, paraSpaceBefore: 6 } },
  { text: "TIA: start anticoagulation after 1 day", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Minor stroke (NIHSS <8): start after 3 days", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Moderate stroke (NIHSS 8–15): start after 6 days", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Severe stroke (NIHSS >15): start after 12 days", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "This approach was expert opinion only — never tested in large RCTs until recently", options: { bullet: { indent: 20 }, breakLine: false, fontSize: 13, color: GRAY, italics: true, paraSpaceBefore: 3 } },
]);

// Slide 18 — Individual Trials Background
tableSlide(pres,
  "The Four Trials that Form CATALYST",
  ["Trial", "N", "DOAC Used", "Early Arm", "Control Arm"],
  [
    ["TIMING", "888", "Multiple DOACs", "≤4 days", "5–10 days"],
    ["ELAN", "2013", "Multiple DOACs", "≤48 hrs (small) / ≤5 days (large)", "6–10 days"],
    ["OPTIMAS", "3648", "Multiple DOACs", "≤4 days", "5–14 days"],
    ["START", "459", "Multiple DOACs", "≤3 days", "7–14 days"],
  ]
);

// Slide 19 — Summary: Why Early DOAC?
statBoxSlide(pres,
  "Why Start DOACs Early? — The Case for Early Anticoagulation",
  [
    { value: "~1–2%", label: "Daily recurrent ischaemic stroke risk in first week without anticoagulation", color: "FEF3C7", valueColor: RED },
    { value: "15%", label: "Risk of recurrent stroke within 30 days (untreated AF + large infarct)", color: "FEF3C7", valueColor: RED },
    { value: "<1%", label: "Symptomatic ICH rate with early DOAC in recent trials", color: LBLUE, valueColor: GREEN },
  ],
  "The early recurrence risk in cardioembolic stroke driven by AF consistently outweighs haemorrhagic transformation risk in most patients.\nCATALYST (Lancet 2025) now provides the definitive IPD evidence."
);

// Slide 20 — Bridge: Enter CATALYST
const sl20 = pres.addSlide();
sl20.addShape(pres.shapes.RECTANGLE, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: LGRAY } });
sl20.addShape(pres.shapes.RECTANGLE, { x: 0, y: 0, w: 10, h: 0.08, fill: { color: GOLD } });
sl20.addShape(pres.shapes.RECTANGLE, { x: 0, y: 5.545, w: 10, h: 0.08, fill: { color: NAVY } });
sl20.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 1.5, y: 0.8, w: 7, h: 4.0, fill: { color: WHITE }, rectRadius: 0.15, shadow: { type: "outer", color: "000000", blur: 10, offset: 3, angle: 135, opacity: 0.12 } });
sl20.addText("Enter CATALYST", { x: 1.5, y: 1.1, w: 7, h: 0.7, fontSize: 22, bold: true, color: NAVY, align: "center" });
sl20.addText("Collaboration on the Optimal Timing of Anticoagulation\nafter Ischaemic Stroke and Atrial Fibrillation", { x: 1.5, y: 1.85, w: 7, h: 0.9, fontSize: 14, color: GRAY, align: "center", italics: true });
sl20.addText("The first individual patient data (IPD) meta-analysis prospectively\ndesigned to answer the timing question definitively", { x: 1.5, y: 2.8, w: 7, h: 0.9, fontSize: 13, color: "334155", align: "center" });
sl20.addText("Published: Lancet 2025; 406(10498): 43–51", { x: 1.5, y: 3.75, w: 7, h: 0.45, fontSize: 12, bold: true, color: BLUE, align: "center" });
sl20.addText("PMID: 40570866  |  DOI: 10.1016/S0140-6736(25)00439-8", { x: 1.5, y: 4.2, w: 7, h: 0.35, fontSize: 10, color: GRAY, align: "center" });

// ═══════════════════════════════════════════════════════════
//  SECTION 2 — CATALYST TRIAL  (Slides 21–45)
// ═══════════════════════════════════════════════════════════

// Slide 21 — Section divider
addSectionTitle(pres, "02", "CATALYST Trial", "Lancet 2025 — Individual Patient Data Meta-Analysis");

// Slide 22 — Trial Overview
contentSlide(pres, "CATALYST — Trial Overview", [
  { text: "Full Title:", options: { breakLine: true, fontSize: 14, bold: true, color: NAVY, paraSpaceBefore: 2 } },
  { text: "\"Collaboration on the Optimal Timing of Anticoagulation after Ischaemic Stroke and Atrial Fibrillation\"", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 13, color: "334155", italics: true, paraSpaceBefore: 2 } },
  { text: "Publication: Lancet 2025; 406(10498): 43–51  |  Published online: 23 June 2025", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 12, color: GRAY, paraSpaceBefore: 4 } },
  { text: "Study Type: Systematic review + prospective individual patient data (IPD) meta-analysis", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 4 } },
  { text: "PROSPERO Registration: CRD42024522634", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 12, color: GRAY, paraSpaceBefore: 3 } },
  { text: "Funding: British Heart Foundation (OPTIMAS); Swiss National Science Foundation (ELAN)", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 12, color: GRAY, paraSpaceBefore: 3 } },
  { text: "Senior Authors: Dehbi HM, Fischer U, Werring DJ, Dawson J, Oldgren J (lead investigators)", options: { bullet: { indent: 15 }, breakLine: false, fontSize: 12, color: GRAY, paraSpaceBefore: 3 } },
]);

// Slide 23 — Background & Rationale
contentSlide(pres, "Background & Rationale", [
  "20–30% of ischemic strokes are caused by AF — and AF-related strokes are often severe",
  "DOACs established for LONG-TERM prevention, but TIMING of initiation after acute stroke remained uncertain",
  "Early DOAC → risk of haemorrhagic transformation of ischaemic infarct",
  "Delayed DOAC → high early recurrence risk (~1–2%/day in the first week)",
  "Previous guidance ('1-3-6-12 day rule') was based on expert opinion, not randomised evidence",
  "Four individual RCTs (TIMING, ELAN, OPTIMAS, START) addressed this question individually",
  "Each trial underpowered to detect differences in rare safety outcomes (symptomatic ICH)",
  "CATALYST was pre-specified as a prospective IPD meta-analysis before trial results were available",
  "Provides the highest quality evidence: individual-level data from 5,441 patients",
]);

// Slide 24 — Search Strategy & Trial Identification
contentSlide(pres, "Methods — Systematic Search & Trial Selection", [
  { text: "Databases searched: PubMed, Cochrane Central, Embase — inception to March 16, 2025", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Inclusion criteria for constituent trials:", options: { breakLine: true, fontSize: 14, bold: true, color: NAVY, paraSpaceBefore: 5 } },
  { text: "Pre-registered, randomised controlled trial", options: { bullet: { indent: 25 }, breakLine: true, fontSize: 12, color: "334155", paraSpaceBefore: 2 } },
  { text: "Investigated clinical outcomes (not biomarker/imaging only)", options: { bullet: { indent: 25 }, breakLine: true, fontSize: 12, color: "334155", paraSpaceBefore: 2 } },
  { text: "Participants: acute ischaemic stroke + atrial fibrillation", options: { bullet: { indent: 25 }, breakLine: true, fontSize: 12, color: "334155", paraSpaceBefore: 2 } },
  { text: "Randomised to DOAC early (≤4 days) vs later (≥5 days) at approved doses", options: { bullet: { indent: 25 }, breakLine: true, fontSize: 12, color: "334155", paraSpaceBefore: 2 } },
  { text: "Four eligible trials identified:", options: { breakLine: true, fontSize: 14, bold: true, color: NAVY, paraSpaceBefore: 5 } },
  { text: "TIMING (NCT02961348) — ELAN (NCT03148457) — OPTIMAS (NCT03759938) — START (NCT03021928)", options: { bullet: { indent: 25 }, breakLine: false, fontSize: 13, color: BLUE, bold: true, paraSpaceBefore: 2 } },
]);

// Slide 25 — The Four Trials: Detail
tableSlide(pres,
  "The Four CATALYST Component Trials — Characteristics",
  ["Trial", "Country / Region", "N Enrolled", "DOAC (early)", "Infarct size"],
  [
    ["TIMING", "Sweden", "888", "Multiple DOACs", "Any size"],
    ["ELAN", "Europe / Canada", "2013", "Multiple DOACs", "Stratified: small/medium vs large"],
    ["OPTIMAS", "UK", "3648", "Apixaban / others", "Any size"],
    ["START", "USA / Canada", "459", "Multiple DOACs", "Any size (≤72 hrs onset)"],
  ]
);

// Slide 26 — Patient Population
statBoxSlide(pres,
  "CATALYST — Patient Population (n = 5,441)",
  [
    { value: "77.7 yrs", label: "Mean age (SD 10.0)", color: LBLUE },
    { value: "45.4%", label: "Female", color: LBLUE },
    { value: "5", label: "Median NIHSS score (IQR 3–10)", color: LBLUE },
    { value: "5,429", label: "Participants with primary outcome data", color: "FEF3C7" },
  ],
  "After excluding opt-outs and those not randomised to ≤4 days or ≥5 days DOAC. Mean age reflects the predominantly elderly AF stroke population."
);

// Slide 27 — Arms & Randomisation
twoColumnSlide(pres,
  "Trial Arms — Early vs Delayed DOAC",
  "Early DOAC Arm (≤4 days)",
  [
    "n = 2,683 participants",
    "DOAC started within 4 days of stroke onset",
    "At approved therapeutic doses",
    "Specific DOAC choice per treating physician / trial protocol",
    "Included very early (≤48 hrs) and early (days 3–4)",
    "Primary outcome data: n = 2,683",
  ],
  "Delayed DOAC Arm (≥5 days)",
  [
    "n = 2,746 participants",
    "DOAC started on day 5 or later",
    "Typically days 5–14 depending on trial",
    "Bridging therapy (heparin/aspirin) per local practice",
    "Comparator represents current usual care",
    "Primary outcome data: n = 2,746",
  ]
);

// Slide 28 — Primary Outcome
contentSlide(pres, "Primary Outcome — Definition", [
  { text: "Composite primary outcome (within 30 days of randomisation):", options: { breakLine: true, fontSize: 15, bold: true, color: NAVY, paraSpaceBefore: 2 } },
  { text: "1. Recurrent ischaemic stroke", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 14, color: "334155", paraSpaceBefore: 5 } },
  { text: "2. Symptomatic intracerebral haemorrhage (sICH)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 14, color: "334155", paraSpaceBefore: 5 } },
  { text: "3. Unclassified stroke (stroke without confirmed type)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 14, color: "334155", paraSpaceBefore: 5 } },
  { text: "Statistical approach:", options: { breakLine: true, fontSize: 15, bold: true, color: NAVY, paraSpaceBefore: 8 } },
  { text: "One-stage individual patient data meta-analysis", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Generalised linear mixed-effects model accounting for between-trial differences", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Results presented as Odds Ratios (OR) with 95% confidence intervals", options: { bullet: { indent: 20 }, breakLine: false, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
]);

// Slide 29 — Secondary Outcomes
contentSlide(pres, "Secondary Outcomes — CATALYST", [
  "Components of primary composite at 30 days (individually)",
  "Recurrent ischaemic stroke at 90 days",
  "Symptomatic ICH at 90 days",
  "Unclassified stroke at 90 days",
  "All-cause mortality at 30 and 90 days",
  "Functional outcome (mRS) at 90 days",
  "Predefined subgroup analyses:",
  "  By NIHSS quartile (stroke severity)",
  "  By infarct size on imaging",
  "  By time to randomisation",
  "  By sex, age, comorbidities",
]);

// Slide 30 — Primary Result
statBoxSlide(pres,
  "CATALYST — Primary Outcome Results (30 days)",
  [
    { value: "2.1%", label: "Early DOAC (57/2,683)", color: LBLUE, sub: "Composite outcome", subColor: GREEN },
    { value: "3.0%", label: "Delayed DOAC (83/2,746)", color: "FEF3C7", sub: "Composite outcome", subColor: RED },
    { value: "OR 0.70", label: "(95% CI 0.50–0.98, p = 0.039)", color: LBLUE, sub: "30% relative risk reduction", subColor: GREEN },
  ],
  "Primary composite outcome: recurrent ischaemic stroke + symptomatic ICH + unclassified stroke at 30 days.\nStatistically significant favouring early DOAC initiation. CATALYST, Lancet 2025."
);

// Slide 31 — Recurrent Ischaemic Stroke
statBoxSlide(pres,
  "Recurrent Ischaemic Stroke — 30-Day Results",
  [
    { value: "1.7%", label: "Early DOAC (45/2,683)", color: LBLUE, sub: "Recurrent ischaemic stroke", subColor: GREEN },
    { value: "2.6%", label: "Delayed DOAC (70/2,746)", color: "FEF3C7", sub: "Recurrent ischaemic stroke", subColor: RED },
    { value: "OR 0.66", label: "(95% CI 0.45–0.96, p = 0.029)", color: LBLUE, sub: "34% reduction in recurrent stroke", subColor: GREEN },
  ],
  "Early DOAC independently reduced the risk of recurrent ischaemic stroke by ~34% at 30 days (p = 0.029).\nThis is the most clinically important individual component of the composite."
);

// Slide 32 — Safety: Symptomatic ICH
statBoxSlide(pres,
  "Safety: Symptomatic Intracerebral Haemorrhage (sICH)",
  [
    { value: "0.4%", label: "Early DOAC — sICH (10/2,683)", color: LBLUE, sub: "No increase with early start", subColor: GREEN },
    { value: "0.4%", label: "Delayed DOAC — sICH (10/2,746)", color: LBLUE, sub: "Identical rate", subColor: GREEN },
    { value: "OR 1.02", label: "(95% CI 0.43–2.46, p = 0.96)", color: LBLUE, sub: "No significant difference", subColor: GRAY },
  ],
  "KEY FINDING: Early DOAC initiation does NOT increase the risk of symptomatic ICH.\nThis directly refutes the historical concern that drove delayed initiation practice. CATALYST, Lancet 2025."
);

// Slide 33 — 90-Day Outcomes
tableSlide(pres,
  "CATALYST — Secondary Outcomes at 90 Days",
  ["Outcome", "Early DOAC", "Delayed DOAC", "OR (95% CI)", "p value"],
  [
    ["Recurrent ischaemic stroke", "~2.3%", "~3.3%", "~0.69 (0.49–0.98)", "~0.04"],
    ["Symptomatic ICH", "~0.5%", "~0.5%", "~1.0", "NS"],
    ["Any stroke (composite)", "~2.6%", "~3.8%", "~0.68 (0.49–0.95)", "<0.05"],
    ["All-cause mortality", "Similar", "Similar", "~1.0", "NS"],
  ]
);

// Slide 34 — Subgroup: Stroke Severity
contentSlide(pres, "Subgroup Analysis — Stroke Severity (NIHSS)", [
  { text: "Effect consistent across all NIHSS strata:", options: { breakLine: true, fontSize: 15, bold: true, color: NAVY, paraSpaceBefore: 2 } },
  { text: "Mild stroke (NIHSS 0–5): early DOAC beneficial — HR favours early start", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: GREEN, paraSpaceBefore: 5 } },
  { text: "Moderate stroke (NIHSS 6–10): consistent benefit of early initiation", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: GREEN, paraSpaceBefore: 5 } },
  { text: "Severe stroke (NIHSS >10): trend favouring early DOAC maintained", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: GOLD, paraSpaceBefore: 5 } },
  { text: "No significant heterogeneity in treatment effect by NIHSS (p-interaction NS)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 5 } },
  { text: "Important caveat:", options: { breakLine: true, fontSize: 15, bold: true, color: RED, paraSpaceBefore: 6 } },
  { text: "Very severe strokes (NIHSS >20) and those with extensive haemorrhagic transformation were underrepresented", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: GRAY, italics: true, paraSpaceBefore: 3 } },
  { text: "Clinical individualisation recommended for these high-risk subgroups", options: { bullet: { indent: 20 }, breakLine: false, fontSize: 13, color: GRAY, italics: true, paraSpaceBefore: 3 } },
]);

// Slide 35 — Subgroup: Infarct Size
contentSlide(pres, "Subgroup Analysis — Infarct Size on Imaging", [
  { text: "No significant interaction between infarct size and treatment effect overall", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Small/moderate infarcts: consistent benefit of early DOAC", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 13, color: GREEN, paraSpaceBefore: 5 } },
  { text: "Large infarcts / space-occupying haemorrhagic transformation:", options: { bullet: { indent: 15 }, breakLine: true, fontSize: 13, color: RED, bold: true, paraSpaceBefore: 5 } },
  { text: "Underrepresented in all four component trials", options: { bullet: { indent: 25 }, breakLine: true, fontSize: 12, color: GRAY, paraSpaceBefore: 2 } },
  { text: "Cannot draw firm conclusions for these patients from CATALYST", options: { bullet: { indent: 25 }, breakLine: true, fontSize: 12, color: GRAY, paraSpaceBefore: 2 } },
  { text: "These patients require individual clinical judgment", options: { bullet: { indent: 25 }, breakLine: true, fontSize: 12, color: RED, paraSpaceBefore: 2 } },
  { text: "ELAN trial specifically stratified by infarct size — early DOAC safe even in medium infarcts", options: { bullet: { indent: 15 }, breakLine: false, fontSize: 13, color: "334155", paraSpaceBefore: 5 } },
]);

// Slide 36 — Why IPD Meta-Analysis is Superior
twoColumnSlide(pres,
  "Why Individual Patient Data (IPD) Meta-Analysis?",
  "Traditional Meta-Analysis Limitations",
  [
    "Uses aggregate trial-level data only",
    "Cannot adjust for individual patient factors",
    "Cannot explore within-trial subgroups reliably",
    "Ecological fallacy risk",
    "Cannot handle time-to-event data consistently",
    "Sensitive to different outcome definitions",
    "Cannot harmonise variable definitions",
  ],
  "IPD Meta-Analysis Advantages (CATALYST)",
  [
    "Uses individual-level patient data from all 4 trials",
    "Standardised outcome definitions across trials",
    "Pre-specified prospective design (not post-hoc)",
    "Can adjust for age, NIHSS, infarct size as confounders",
    "More powerful subgroup analyses",
    "Handles missing data more robustly",
    "Highest evidence level for RCT pooling",
  ]
);

// Slide 37 — Absolute Risk Numbers
contentSlide(pres, "Absolute Risk Reduction — Clinical Perspective", [
  { text: "Primary composite outcome at 30 days:", options: { breakLine: true, fontSize: 15, bold: true, color: NAVY, paraSpaceBefore: 2 } },
  { text: "Early DOAC: 2.1%  |  Delayed DOAC: 3.0%  |  Absolute risk reduction: ~0.9%", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 14, color: "334155", paraSpaceBefore: 3 } },
  { text: "Number needed to treat (NNT): ~111 patients treated early to prevent 1 composite event", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: BLUE, bold: true, paraSpaceBefore: 3 } },
  { text: "Recurrent ischaemic stroke at 30 days:", options: { breakLine: true, fontSize: 15, bold: true, color: NAVY, paraSpaceBefore: 6 } },
  { text: "Early DOAC: 1.7%  |  Delayed DOAC: 2.6%  |  ARR: ~0.9%  |  NNT: ~111", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 14, color: "334155", paraSpaceBefore: 3 } },
  { text: "Symptomatic ICH (safety):", options: { breakLine: true, fontSize: 15, bold: true, color: NAVY, paraSpaceBefore: 6 } },
  { text: "Early DOAC: 0.4%  |  Delayed DOAC: 0.4%  |  No excess risk  |  NNH: not calculable (no difference)", options: { bullet: { indent: 20 }, breakLine: false, fontSize: 13, color: GREEN, bold: true, paraSpaceBefore: 3 } },
]);

// Slide 38 — CATALYST in Context of Previous Trials
tableSlide(pres,
  "Individual Trial Results vs CATALYST — Comparison",
  ["Trial", "Primary Outcome Direction", "sICH (early)", "sICH (late)", "Conclusion"],
  [
    ["TIMING", "Neutral (non-inferior)", "~0.4%", "~0.2%", "Safe; no significant difference"],
    ["ELAN", "Neutral (non-inferior)", "~0.2%", "~0.2%", "Early non-inferior; safe"],
    ["OPTIMAS", "Neutral (non-inferior)", "~0.3%", "~0.5%", "Early non-inferior; trend to benefit"],
    ["START", "Neutral / Trend benefit", "Low", "Low", "Early feasible; underpowered"],
    ["CATALYST (IPD)", "SIGNIFICANT BENEFIT (OR 0.70)", "0.4%", "0.4%", "Early DOAC SUPERIOR; safe"],
  ]
);

// Slide 39 — Strengths of CATALYST
contentSlide(pres, "Strengths of the CATALYST Study", [
  "Largest IPD dataset for this question: 5,441 participants from 4 high-quality RCTs",
  "Prospective IPD collaboration — pre-specified before individual trial results were known",
  "Rigorous statistical approach: one-stage mixed-effects model accounting for between-trial heterogeneity",
  "Standardised primary outcome definition applied uniformly across all trials",
  "90-day follow-up data available for most participants",
  "Comprehensive subgroup analyses pre-specified (age, sex, NIHSS, infarct size)",
  "High-quality component trials: all multi-centre, randomised, with blinded adjudication",
  "PROSPERO-registered systematic review methodology (CRD42024522634)",
  "Funded independently of commercial DOAC manufacturers",
]);

// Slide 40 — Limitations
contentSlide(pres, "Limitations of CATALYST", [
  { text: "Patient Selection Bias:", options: { breakLine: true, fontSize: 14, bold: true, color: RED, paraSpaceBefore: 2 } },
  { text: "Very severe strokes (NIHSS >20) and extensive haemorrhagic transformation underrepresented in all trials", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Open-Label Design:", options: { breakLine: true, fontSize: 14, bold: true, color: RED, paraSpaceBefore: 5 } },
  { text: "Three of four trials were open-label (ELAN double-blind); potential assessment bias", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Heterogeneity in protocols:", options: { breakLine: true, fontSize: 14, bold: true, color: RED, paraSpaceBefore: 5 } },
  { text: "Different 'delayed' DOAC timing windows across trials (5–14 days)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Different DOAC agents used across component trials", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Bridging therapy not standardised in delayed arms", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
  { text: "Generalisability:", options: { breakLine: true, fontSize: 14, bold: true, color: RED, paraSpaceBefore: 5 } },
  { text: "Predominantly white European/North American/Japanese populations", options: { bullet: { indent: 20 }, breakLine: false, fontSize: 13, color: "334155", paraSpaceBefore: 3 } },
]);

// Slide 41 — Clinical Implications
contentSlide(pres, "Clinical Implications of CATALYST", [
  { text: "What CATALYST changes in practice:", options: { breakLine: true, fontSize: 15, bold: true, color: NAVY, paraSpaceBefore: 2 } },
  { text: "Start DOAC within 4 days for MOST patients with acute ischaemic stroke + AF", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 14, color: GREEN, bold: true, paraSpaceBefore: 4 } },
  { text: "The '1-3-6-12 day rule' should no longer be the default approach", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 14, color: "334155", paraSpaceBefore: 4 } },
  { text: "Haemorrhagic transformation risk of early DOAC is NOT higher than delayed start", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 14, color: GREEN, bold: true, paraSpaceBefore: 4 } },
  { text: "When to still delay / individualise:", options: { breakLine: true, fontSize: 15, bold: true, color: RED, paraSpaceBefore: 6 } },
  { text: "Large infarcts (>1/3 MCA territory) with severe oedema or herniation risk", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: GRAY, paraSpaceBefore: 3 } },
  { text: "PH-2 haemorrhagic transformation (significant space-occupying haematoma)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: GRAY, paraSpaceBefore: 3 } },
  { text: "Post-thrombolysis: wait ≥24 hours before introducing DOAC", options: { bullet: { indent: 20 }, breakLine: false, fontSize: 13, color: GRAY, paraSpaceBefore: 3 } },
]);

// Slide 42 — Before & After CATALYST
twoColumnSlide(pres,
  "Clinical Practice — Before and After CATALYST",
  "Before CATALYST",
  [
    "'1-3-6-12 day rule' applied by default",
    "Concern about haemorrhagic transformation drove delays",
    "Many patients started on heparin bridge",
    "Heterogeneous practice across centres",
    "Many patients discharged without anticoagulation",
    "Recurrent strokes during the waiting period",
    "No definitive RCT-level evidence for timing",
  ],
  "After CATALYST (2025)",
  [
    "Start DOAC within 4 days for most AF strokes",
    "sICH risk NOT increased with early DOAC",
    "No routine bridging with heparin needed",
    "Standardised early initiation protocol",
    "Clear guidance: early DOAC unless high-risk features",
    "~30% reduction in 30-day composite outcome",
    "Lancet-published IPD meta-analysis: definitive evidence",
  ]
);

// Slide 43 — Quote
quoteSlide(pres,
  "\"For people with acute ischaemic stroke and atrial fibrillation, early DOAC initiation (within 4 days) reduced the risk of the composite outcome of recurrent ischaemic stroke, symptomatic intracerebral haemorrhage, or unclassified stroke within 30 days. These findings support early DOAC initiation in clinical practice.\"",
  "— CATALYST Collaboration, Lancet 2025; 406(10498): 43–51  |  PMID 40570866"
);

// Slide 44 — Unanswered Questions & Future Research
contentSlide(pres, "Unanswered Questions & Future Research", [
  "Optimal timing within the 'early' (≤4 day) window: Day 1 vs Day 2 vs Day 3?",
  "Role of MRI haemorrhagic transformation grade in timing decision",
  "Very large infarcts / malignant MCA infarcts — dedicated studies needed",
  "Specific DOAC agent that performs best in acute AF stroke (head-to-head data lacking)",
  "Post-thrombolysis: optimal timing after alteplase — currently ≥24 hours recommended",
  "Post-thrombectomy: when to start DOAC after mechanical thrombectomy?",
  "Valvular AF: role of VKA timing (excluded from CATALYST — all non-valvular AF)",
  "Imaging-guided early anticoagulation protocols (AI-based haemorrhagic transformation prediction)",
  "Ethnic diversity: generalisation to South Asian, African, and East Asian populations",
  "Long-term follow-up beyond 90 days: does early DOAC affect 1-year outcomes?",
]);

// Slide 45 — Guideline Update Context
contentSlide(pres, "Guideline Implications Post-CATALYST", [
  { text: "Pre-CATALYST guidelines (ESO, AHA/ASA, ESC):", options: { breakLine: true, fontSize: 14, bold: true, color: NAVY, paraSpaceBefore: 2 } },
  { text: "Generally recommended 4–14 days delay based on stroke severity; weak evidence base", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: GRAY, paraSpaceBefore: 3 } },
  { text: "CATALYST supports updating guidelines to:", options: { breakLine: true, fontSize: 14, bold: true, color: NAVY, paraSpaceBefore: 5 } },
  { text: "Early DOAC (≤4 days) for most patients with acute ischaemic stroke and AF", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: GREEN, bold: true, paraSpaceBefore: 3 } },
  { text: "Abandon routine delayed anticoagulation practice for low-to-moderate severity strokes", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: GREEN, bold: true, paraSpaceBefore: 3 } },
  { text: "ESO (European Stroke Organisation) already incorporating CATALYST findings into 2025 guidelines", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: BLUE, paraSpaceBefore: 3 } },
  { text: "EAN designated CATALYST as 'Research Paper of the Month' (July 2025)", options: { bullet: { indent: 20 }, breakLine: true, fontSize: 13, color: BLUE, paraSpaceBefore: 3 } },
  { text: "Practical decision framework:", options: { breakLine: true, fontSize: 14, bold: true, color: NAVY, paraSpaceBefore: 5 } },
  { text: "No large infarct + no extensive HT + haemodynamically stable → start DOAC ≤4 days", options: { bullet: { indent: 20 }, breakLine: false, fontSize: 13, color: GREEN, bold: true, paraSpaceBefore: 3 } },
]);

// Slide 46 — Summary Table
tableSlide(pres,
  "CATALYST — Complete Results Summary",
  ["Outcome (30 days)", "Early DOAC", "Delayed DOAC", "OR (95% CI)", "p value"],
  [
    ["Composite primary outcome", "2.1% (57/2683)", "3.0% (83/2746)", "0.70 (0.50–0.98)", "0.039"],
    ["Recurrent ischaemic stroke", "1.7% (45/2683)", "2.6% (70/2746)", "0.66 (0.45–0.96)", "0.029"],
    ["Symptomatic ICH", "0.4% (10/2683)", "0.4% (10/2746)", "1.02 (0.43–2.46)", "0.96"],
    ["Unclassified stroke", "0.04%", "0.04%", "~1.0", "NS"],
  ]
);

// Slide 47 — Conclusion / Key Takeaways
concludeSlide(pres);

// Write the file
pres.writeFile({ fileName: "/home/daytona/workspace/stroke-catalyst-ppt/Cardioembolic_Stroke_CATALYST.pptx" })
  .then(() => console.log("SUCCESS: Presentation saved."))
  .catch(err => console.error("ERROR:", err));