What are the pharmacological actions adverse effects and uses of ACE inhibitors

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"ACE inhibitors"[MeSH Terms] AND "pharmacology"[MeSH Terms]

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ACE Inhibitors - Pharmacological Actions, Adverse Effects, and Uses

Source: Lippincott Illustrated Reviews: Pharmacology & Goodman and Gilman's Pharmacological Basis of Therapeutics

Mechanism of Action

ACE (Angiotensin-Converting Enzyme) inhibitors block the enzyme ACE, which normally cleaves angiotensin I (inactive) into angiotensin II (a potent vasoconstrictor). The result is a two-pronged vasodilatory effect:

RAAS pathway showing sites of action of ACE inhibitors, ARBs, renin inhibitors, and aldosterone antagonists

Figure: Effects of various drug classes on the renin-angiotensin-aldosterone system (RAAS). ACE inhibitors block the conversion of Angiotensin I → Angiotensin II.

Pharmacological Actions

Vasodilation (arteriolar and venous)
- Reduced angiotensin II → decreased vasoconstriction
- ACE also normally breaks down bradykinin; inhibiting ACE raises bradykinin levels, which stimulates production of nitric oxide and prostacyclin (both potent vasodilators)
- Net result: decreased peripheral vascular resistance → lower blood pressure
Reduced aldosterone secretion
- Less angiotensin II → less aldosterone → less sodium and water retention
- Reduces both preload and afterload, lowering myocardial workload
Renal hemodynamic effects
- Efferent arteriolar vasodilation → decreased intraglomerular pressure
- Slows progression of diabetic nephropathy; decreases albuminuria
Cardiac remodeling
- Sustained use leads to regression of left ventricular hypertrophy
- Improved ventricular remodeling after myocardial infarction
Neurohormonal effects
- Blunts the angiotensin II-mediated increase in epinephrine and aldosterone seen in heart failure
- Improves clinical signs/symptoms of HF and significantly improves survival in HFrEF (heart failure with reduced ejection fraction)

Therapeutic Uses

Indication	Notes
Hypertension	First-line; equally effective at equivalent doses across all ACE inhibitors
Heart failure (HFrEF)	Standard of care; all stages of LV failure; start low, titrate to target dose
Post-MI	Improve ventricular remodeling; indicated in all patients post-MI
Diabetic nephropathy	Slow disease progression, reduce albuminuria
Chronic kidney disease	First-line in hypertensive patients with CKD
Coronary artery disease	Patients at high cardiovascular risk benefit from long-term therapy
Left ventricular hypertrophy	Regression with chronic use
Asymptomatic LV dysfunction	Can be used even before overt HF symptoms develop

Adverse Effects

Figure 8.11: Common adverse effects of ACE inhibitors (Lippincott)

Adverse Effect	Mechanism / Notes
Dry cough	Most common (up to 10% of patients); due to raised bradykinin and substance P in the pulmonary tree; more frequent in women; resolves within days of stopping
Angioedema	Rare but life-threatening; swelling of lips, oral mucosa, throat; also bradykinin-mediated; contraindication to further use
Hyperkalemia	Reduced aldosterone → reduced K+ excretion; caution with K+ supplements, K+-sparing diuretics, and MRAs
Hypotension	Especially first-dose or postural; much more common if combined with a diuretic
Renal insufficiency / elevated creatinine	Efferent dilation can reduce GFR; a rise in creatinine up to 30% above baseline is acceptable and does not require discontinuation
Skin rash	More common with captopril (sulfhydryl group)
Dysgeusia (altered taste)	Particularly with captopril
Leukopenia / neutropenia	Rare; more common with captopril at high doses
Teratogenicity	Contraindicated in pregnancy - causes fetal renal anomalies, oligohydramnios, and fetal death (especially 2nd/3rd trimester)

Pharmacokinetics - Key Points

All ACE inhibitors are orally bioavailable as a drug or prodrug
Except captopril and lisinopril, all others are prodrugs requiring hepatic activation (these two may be preferred in severe hepatic impairment)
Fosinopril is the only ACE inhibitor with dual elimination (renal + fecal) - does not require dose adjustment in renal impairment
Enalaprilat is the only formulation available for IV administration
Captopril absorption is reduced by food - take on empty stomach
Half-lives of active compounds range from 2 to 12 hours, but ACE inhibition lasts much longer

Common Drugs in This Class

Drug	Brand Name	Notes
Captopril	Generic	Sulfhydryl group; rash/taste disturbance more common; taken on empty stomach
Enalapril	Vasotec	Prodrug; most widely used
Lisinopril	Prinivil, Zestril	Active drug (not prodrug); once daily
Ramipril	Altace	Prodrug; used in high-CV-risk patients (HOPE trial)
Fosinopril	Generic	Dual elimination; safe in renal impairment
Quinapril	Accupril	Prodrug
Perindopril	Generic	Prodrug
Enalaprilat	IV form	Only IV ACE inhibitor

Key Drug Interactions

Potassium-sparing diuretics / K+ supplements / MRAs: risk of severe hyperkalemia
Diuretics: increased risk of first-dose hypotension
NSAIDs: blunt antihypertensive effect; increase risk of renal dysfunction
ARBs or aliskiren: dual RAAS blockade - generally avoided due to increased risk of hypotension, hyperkalemia, and renal failure

Contraindications

Pregnancy (all trimesters - teratogenic)
History of angioedema with an ACE inhibitor
Bilateral renal artery stenosis (can precipitate acute kidney injury)
Severe hyperkalemia

Sources: Lippincott Illustrated Reviews: Pharmacology, 8th Ed., Ch. 8 & 10; Goodman & Gilman's The Pharmacological Basis of Therapeutics, Ch. 43.

Arb s

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Angiotensin Receptor Blockers (ARBs)

Sources: Lippincott Illustrated Reviews: Pharmacology | Katzung's Basic & Clinical Pharmacology | Goodman & Gilman's Pharmacological Basis of Therapeutics | Braunwald's Heart Disease

Mechanism of Action

ARBs are competitive antagonists at the AT1 (angiotensin type 1) receptor - the receptor subtype responsible for virtually all the harmful biological effects of angiotensin II. By blocking AT1 receptors, ARBs prevent angiotensin II from exerting its effects regardless of how angiotensin II was produced (via ACE or alternative pathways like chymase).

RAAS pathway showing sites of action of ACE inhibitors, ARBs, and renin inhibitors

Figure: RAAS pathway - ARBs block the AT1 receptor, downstream of the ACE inhibition site

Key distinction from ACE inhibitors:

ARBs do not inhibit ACE-mediated degradation of bradykinin or substance P
Therefore, they cause no cough and much less angioedema
They provide more complete blockade of angiotensin II effects (ACE inhibitors only block one enzyme; angiotensin II can still be made via other routes like chymase)
During AT1 blockade, increased angiotensin II stimulates unopposed AT2 receptors, which may produce additional vasodilation and antiproliferative effects

Pharmacological Actions

Action	Mechanism
Vasodilation (arterioles + veins)	Block AT1 → smooth muscle relaxation → reduced peripheral resistance
Reduced aldosterone	AT1 block → less aldosterone → increased Na+/water excretion
Reduced cardiac preload and afterload	Venodilatation + arteriolar dilation
Increased renal salt and water excretion	Reduced aldosterone + efferent arteriolar dilation
Reduced plasma volume	Natriuresis and diuresis
Anti-hypertrophic	Block AT1-mediated cardiac and vascular smooth muscle hypertrophy (important in HF remodeling)
Renoprotective	Reduce intraglomerular pressure; slow diabetic nephropathy progression
AT2 stimulation	Increased AngII (from lost AT1 feedback) stimulates AT2 → vasodilation, antiproliferative effects

Therapeutic Uses

1. Hypertension

First-line agents, especially with coexisting diabetes, heart failure, or CKD
Full antihypertensive effect typically reached after ~4 weeks
Most ARBs are effective with once-daily dosing (exception: losartan may need twice daily in some)
If BP not controlled with ARB alone, add a drug with different mechanism (diuretic or CCB)
Young/middle-aged Caucasians respond well; elderly African American patients are relatively more resistant

2. Heart Failure with Reduced EF (HFrEF)

Indicated when ACE inhibitors are not tolerated (cough/angioedema), as a substitute
Losartan, valsartan, and candesartan are most studied in HFrEF
Candesartan (CHARM-Alternative trial) significantly reduced all-cause mortality, CV death, and hospitalizations in ACE-intolerant HF patients
High-dose losartan (150 mg/day) is superior to low-dose (HEAAL trial)
Not recommended to combine ARB + ACE inhibitor due to increased hypotension, hyperkalemia, and renal dysfunction without added mortality benefit

3. Post-Myocardial Infarction

Valsartan was non-inferior to captopril for mortality in post-MI LV dysfunction (VALIANT trial)
An alternative to ACE inhibitors in post-MI patients who are ACE-intolerant

4. Diabetic Nephropathy

Slow progression; reduce proteinuria
Valsartan may reduce the incidence of new-onset diabetes in patients with impaired glucose tolerance

5. Chronic Kidney Disease

Renoprotective; first-line in hypertensive CKD patients

6. Marfan Syndrome

Losartan may be as effective as atenolol (standard treatment) by blocking AT1-mediated TGF-β signaling

Pharmacokinetics

Property	Details
Route	All orally active
Dosing	Once daily (most); valsartan: twice daily
Protein binding	Highly plasma protein bound
Losartan	Undergoes extensive first-pass hepatic metabolism → active metabolite (EXP-3174); other ARBs have inactive metabolites
Elimination	Urine and feces (dual route for most)
Onset of full effect	~4 weeks

Adverse Effects

ARBs have a similar adverse effect profile to ACE inhibitors, with two important differences:

Adverse Effect	Notes
Hypotension	Especially first-dose; increased risk if on diuretic
Hyperkalemia	Reduced aldosterone → K+ retention; monitor K+ levels; caution with K+-sparing diuretics/MRAs/K+ supplements
Renal insufficiency	Monitor creatinine; rise up to 30% above baseline acceptable
Teratogenicity	Contraindicated in pregnancy (all trimesters)
Cough	Significantly lower incidence than ACE inhibitors (no bradykinin accumulation)
Angioedema	Much rarer than with ACE inhibitors; still possible
Sprue-like enteropathy	A syndrome of chronic diarrhea with intestinal villous atrophy; notably associated with olmesartan
Dizziness/headache	Common at initiation

From the ON-TARGET trial (Goodman & Gilman): Telmisartan caused cough in 1.1% vs 4.2% with ramipril, and angioedema in 0.1% vs 0.3% - confirming much lower incidence of these bradykinin-mediated effects.

Contraindications

Pregnancy (teratogenic - renal dysgenesis, oligohydramnios, fetal death)
Bilateral renal artery stenosis
Severe hyperkalemia
Combination with ACE inhibitor (dual RAAS blockade not recommended - increases adverse effects without benefit)
Combination with aliskiren in patients with diabetes or renal impairment

Available ARBs

Drug	Brand Name	Notes
Losartan	Cozaar	First ARB approved; active metabolite (EXP-3174); may need twice daily; uricosuric (lowers uric acid)
Valsartan	Diovan	Twice daily; studied in HFrEF (Val-HeFT, VALIANT)
Candesartan	Atacand	Most studied in HF (CHARM trials); prodrug
Irbesartan	Avapro	Once daily; studied in diabetic nephropathy
Telmisartan	Micardis	Longest half-life; PPAR-γ agonism; studied in ON-TARGET
Olmesartan	Benicar	Associated with sprue-like enteropathy
Azilsartan	Edarbi	Most potent BP-lowering ARB
Eprosartan	Teveten	No longer marketed in the U.S.

ARBs vs ACE Inhibitors - Key Comparison

Feature	ACE Inhibitors	ARBs
Mechanism	Block ACE enzyme	Block AT1 receptor
Bradykinin effect	Increase (bradykinin accumulates)	No change
Cough	Common (up to 10%)	Much rarer
Angioedema	Rare but possible	Very rare
Completeness of AngII block	Partial (alternative pathways exist)	More complete
AT2 stimulation	Minimal	Yes (increased AngII stimulates AT2)
Efficacy in HF	Equivalent	Equivalent (as substitute)
Preferred if	Standard first choice	ACE inhibitor intolerance

Sources: Lippincott Illustrated Reviews: Pharmacology, 8th Ed., Ch. 8 & 10; Katzung's Basic & Clinical Pharmacology, 16th Ed., Ch. 11; Goodman & Gilman's Pharmacological Basis of Therapeutics, Ch. 30 & 43; Braunwald's Heart Disease, 12th Ed., Ch. 50

Difference and similarities between ace inhibitor and arb s

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ACE Inhibitors vs ARBs - Differences and Similarities

Sources: Lippincott Illustrated Reviews: Pharmacology | Katzung's Basic & Clinical Pharmacology 16e | Goodman & Gilman's Pharmacological Basis of Therapeutics | Braunwald's Heart Disease | Brenner & Rector's The Kidney

Quick Visual Overview

ACE inhibitors act at ACE (enzyme); ARBs act downstream at the AT1 receptor

SIMILARITIES

1. Mechanism - Both Block the RAAS

Both drug classes ultimately prevent angiotensin II from acting at the AT1 receptor, either by reducing its production (ACE inhibitors) or by blocking where it binds (ARBs).

2. Pharmacological Effects - Nearly Identical

Effect	ACE Inhibitors	ARBs
Arteriolar vasodilation	Yes	Yes
Venous vasodilation (reduced preload)	Yes	Yes
Reduced aldosterone secretion	Yes	Yes
Decreased sodium and water retention	Yes	Yes
Reduced cardiac afterload and preload	Yes	Yes
Anti-hypertrophic (LV regression)	Yes	Yes
Efferent arteriolar dilation (renal)	Yes	Yes

3. Therapeutic Indications - Essentially the Same

Hypertension - both are first-line agents with similar efficacy
Heart failure (HFrEF) - both reduce morbidity and mortality
Post-myocardial infarction - both improve LV remodeling
Diabetic nephropathy - both slow progression and reduce proteinuria
Chronic kidney disease - both renoprotective (reduce intraglomerular pressure)
Left ventricular hypertrophy - both cause regression with chronic use

From Brenner & Rector's The Kidney: "Although ACE inhibitors and ARBs differ significantly in their effects on the RAAS in ways that may be therapeutically relevant, experimental studies indicate that both treatments produce similar changes in glomerular hemodynamics (for a given blood pressure change)."

4. Adverse Effect Overlap

Adverse Effect	Both Cause?
Hypotension (especially first dose)	Yes
Hyperkalemia	Yes
Renal insufficiency / raised creatinine	Yes
Teratogenicity (contraindicated in pregnancy)	Yes
Dizziness	Yes

5. Drug Interactions - Same Cautions

Both require caution with potassium-sparing diuretics, K+ supplements, and MRAs (hyperkalemia risk)
Both potentiated by diuretics (hypotension)
Both blunted by NSAIDs
Should NOT be combined with each other - dual RAAS blockade increases hypotension, hyperkalemia, and renal impairment without mortality benefit (ON-TARGET trial)

6. Contraindications - Shared

Pregnancy
Bilateral renal artery stenosis
Severe hyperkalemia

DIFFERENCES

Feature	ACE Inhibitors	ARBs
Site of action	Block the ACE enzyme (prevents conversion of Ang I → Ang II)	Block AT1 receptor (prevent Ang II binding)
Completeness of AngII blockade	Incomplete - angiotensin II can still be produced via alternate enzymes (chymase, cathepsin, etc.)	More complete - blocks the receptor regardless of how Ang II was made
Effect on bradykinin	Increase bradykinin (ACE normally breaks it down)	No effect on bradykinin levels
Effect on substance P	Increase	No change
Dry cough	Common - up to 10% of patients (bradykinin + substance P in pulmonary tree)	Much rarer (no bradykinin accumulation)
Angioedema	Rare (~0.1-0.3%) but life-threatening	Very rare (~0.1%) - significantly lower
AT2 receptor stimulation	Minimal (Ang II levels fall)	Yes - Ang II rises (lost AT1 feedback) → stimulates AT2 → vasodilation, antiproliferative effects
Nitric oxide / prostacyclin	Increased (via raised bradykinin)	Not directly increased
First choice vs substitute	Primary / first choice	Substitute when ACE inhibitor not tolerated
Prodrug vs active	Most are prodrugs (except captopril, lisinopril)	Most are active drugs (losartan converts to active metabolite EXP-3174)
IV formulation	Yes (enalaprilat)	None available
Uricosuric effect	None	Losartan is uniquely uricosuric (lowers uric acid - useful in gout)
Sprue-like enteropathy	Not reported	Olmesartan specifically linked
Skin rash / dysgeusia	Yes (especially captopril - sulfhydryl group)	Not a significant feature
Effect on bradykinin-related vasodilation	Enhanced (therapeutic benefit contribution)	No direct bradykinin contribution
Renal protection - degree of evidence	Long-established	Equivalent (well-established in diabetic nephropathy)
Cost	Generally cheaper (generics widely available)	Slightly more expensive

Why Bradykinin Matters - The Key Difference Explained

ACE Inhibitors:
  Ang I  --[ACE blocked]-→  Ang II ↓
  Bradykinin --[ACE blocked]-→  NOT degraded → Bradykinin ↑
          ↓
  Nitric oxide ↑ + Prostacyclin ↑ → Vasodilation ✓
  BUT also: Cough, Angioedema ✗

ARBs:
  Ang I → Ang II (via ACE + chymase etc.) → AT1 receptor BLOCKED
  Bradykinin → degraded normally → No bradykinin accumulation
          ↓
  No cough ✓, No angioedema ✓
  BUT: No bradykinin-mediated vasodilation contribution

Clinical Decision - When to Choose Which?

Situation	Choice
Standard first-line hypertension	ACE inhibitor (cheaper, more established)
Hypertension + cough on ACE inhibitor	Switch to ARB
History of angioedema on ACE inhibitor	ARB (but use caution - angioedema can still rarely occur)
HFrEF	ACE inhibitor preferred; ARB if ACE-intolerant
Diabetic nephropathy	Either (evidence for both; ARBs slightly more studied in type 2 DM)
Hypertension + gout	Losartan (uricosuric effect)
Marfan syndrome	Losartan (reduces TGF-β signaling)
Hyperkalemia or renal insufficiency	Neither well-tolerated; re-evaluate dose
Pregnancy	Both absolutely contraindicated
Combination of both	Not recommended - no added benefit; more harm

Summary Table

Property	ACE Inhibitors	ARBs
Mechanism	Block ACE enzyme	Block AT1 receptor
BP lowering efficacy	Equal	Equal
Bradykinin effect	Raise	No change
Cough	Common (~10%)	Rare (<2%)
Angioedema	Rare (~0.3%)	Very rare (~0.1%)
Hyperkalemia	Yes	Yes
Teratogenicity	Yes	Yes
Renoprotection	Yes	Yes
Cardiac remodeling	Yes	Yes
Preferred role	First choice	ACE-intolerant substitute
IV form	Yes (enalaprilat)	No
Unique side effect	Cough, rash (captopril)	Sprue-like enteropathy (olmesartan)
Cost	Lower	Higher

Bottom line: ACE inhibitors and ARBs are clinically interchangeable for most indications with nearly identical efficacy. The primary reason to choose an ARB over an ACE inhibitor is intolerance to ACE inhibitor (cough in ~10%, angioedema). ARBs offer more complete blockade of angiotensin II but lose the bradykinin-mediated vasodilatory benefit. Combining both is not recommended.

Sources: Lippincott Illustrated Reviews: Pharmacology 8e, Ch. 8 & 10 | Katzung's Basic & Clinical Pharmacology 16e, Ch. 11 | Goodman & Gilman's 14e, Ch. 30 & 43 | Braunwald's Heart Disease 12e, Ch. 50 | Brenner & Rector's The Kidney

Create a comparison presentation on RAAS blockers

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// Legend note
s.addText("Blue arrows = drug blocks pathway | All RAAS blockers ultimately reduce blood pressure, cardiac remodeling, and renal damage", {
  x: 0.3, y: 3.45, w: 9.4, h: 0.35,
  fontSize: 10, italic: true, color: C.subtext, fontFace: "Calibri",
});

// ════════════════════════════════════════════════════════════════════════════
// SLIDE 3 — ACE INHIBITORS OVERVIEW
// ════════════════════════════════════════════════════════════════════════════
s = pres.addSlide();
slideHeader(s, "ACE Inhibitors — Overview", C.teal);

// Left panel
s.addShape(pres.ShapeType.rect, { x: 0.2, y: 0.85, w: 4.5, h: 4.6, fill: { color: "EBF5FB" }, line: { color: C.teal, width: 1.5 } });
pillBadge(s, 0.35, 0.92, 1.6, "MECHANISM", C.teal);
s.addText([
  { text: "Block ACE enzyme", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Prevent Ang I → Ang II conversion", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Bradykinin NOT degraded → accumulates", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "↑ Nitric oxide + Prostacyclin (vasodilation)", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "↓ Aldosterone → ↓ Na+/H₂O retention", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "↓ Cardiac preload AND afterload", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Efferent arteriolar dilation → ↓ intraglomerular pressure", options: { bullet: { code: "2022" } } },
], { x: 0.3, y: 1.3, w: 4.3, h: 2.5, fontSize: 11, color: C.dktext, fontFace: "Calibri", lineSpacingMultiple: 1.3 });

pillBadge(s, 0.35, 3.85, 1.2, "KEY DRUGS", C.teal);
s.addText("Captopril • Enalapril • Lisinopril\nRamipril • Fosinopril • Quinapril\nPerindopril • Trandolapril", {
  x: 0.3, y: 4.17, w: 4.3, h: 0.9,
  fontSize: 11, color: C.dktext, fontFace: "Calibri", italic: true,
});

// Right panel
s.addShape(pres.ShapeType.rect, { x: 4.9, y: 0.85, w: 4.9, h: 4.6, fill: { color: "EBF5FB" }, line: { color: C.teal, width: 1.5 } });
pillBadge(s, 5.05, 0.92, 1.5, "USES", C.teal);
const uses_ace = [
  "Hypertension (first-line)",
  "Heart failure / HFrEF",
  "Post-MI (ventricular remodeling)",
  "Diabetic nephropathy",
  "Chronic kidney disease",
  "LV hypertrophy regression",
  "Asymptomatic LV dysfunction",
  "High CV risk patients",
];
s.addText(uses_ace.map((u, i) => ({ text: u, options: { bullet: { code: "2022" }, breakLine: i < uses_ace.length - 1 } })),
  { x: 5.0, y: 1.3, w: 4.6, h: 2.5, fontSize: 11, color: C.dktext, fontFace: "Calibri", lineSpacingMultiple: 1.3 });

pillBadge(s, 5.05, 3.85, 1.8, "ADVERSE EFFECTS", C.crimson);
const ae_ace = [
  { text: "Dry cough (up to 10%)", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Angioedema (rare, life-threatening)", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Hyperkalemia", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Hypotension (first dose)", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Renal insufficiency", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Teratogenic (avoid in pregnancy)", options: { bullet: { code: "2022" } } },
];
s.addText(ae_ace, { x: 5.0, y: 4.2, w: 4.6, h: 1.8, fontSize: 10.5, color: C.dktext, fontFace: "Calibri", lineSpacingMultiple: 1.25 });

// ════════════════════════════════════════════════════════════════════════════
// SLIDE 4 — ARBs OVERVIEW
// ════════════════════════════════════════════════════════════════════════════
s = pres.addSlide();
slideHeader(s, "Angiotensin Receptor Blockers (ARBs) — Overview", C.crimson);

s.addShape(pres.ShapeType.rect, { x: 0.2, y: 0.85, w: 4.5, h: 4.6, fill: { color: "FDEDEC" }, line: { color: C.crimson, width: 1.5 } });
pillBadge(s, 0.35, 0.92, 1.6, "MECHANISM", C.crimson);
s.addText([
  { text: "Competitive antagonists at AT1 receptor", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Block Ang II regardless of how it was made", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "More complete Ang II blockade than ACEi", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Do NOT affect bradykinin levels", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "↑ Ang II → stimulates unopposed AT2 receptor", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "AT2 stimulation → vasodilation + antiproliferative", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "↓ Aldosterone, ↓ preload and afterload", options: { bullet: { code: "2022" } } },
], { x: 0.3, y: 1.3, w: 4.3, h: 2.5, fontSize: 11, color: C.dktext, fontFace: "Calibri", lineSpacingMultiple: 1.3 });

pillBadge(s, 0.35, 3.85, 1.2, "KEY DRUGS", C.crimson);
s.addText("Losartan • Valsartan • Candesartan\nIrbesartan • Telmisartan • Olmesartan\nAzilsartan • Eprosartan", {
  x: 0.3, y: 4.17, w: 4.3, h: 0.9,
  fontSize: 11, color: C.dktext, fontFace: "Calibri", italic: true,
});

s.addShape(pres.ShapeType.rect, { x: 4.9, y: 0.85, w: 4.9, h: 4.6, fill: { color: "FDEDEC" }, line: { color: C.crimson, width: 1.5 } });
pillBadge(s, 5.05, 0.92, 1.5, "USES", C.crimson);
const uses_arb = [
  "Hypertension (first-line)",
  "HFrEF (substitute for ACEi)",
  "Post-MI with LV dysfunction",
  "Diabetic nephropathy (Type 2 DM)",
  "Chronic kidney disease",
  "ACEi-intolerant patients",
  "Marfan syndrome (Losartan)",
  "LV hypertrophy",
];
s.addText(uses_arb.map((u, i) => ({ text: u, options: { bullet: { code: "2022" }, breakLine: i < uses_arb.length - 1 } })),
  { x: 5.0, y: 1.3, w: 4.6, h: 2.5, fontSize: 11, color: C.dktext, fontFace: "Calibri", lineSpacingMultiple: 1.3 });

pillBadge(s, 5.05, 3.85, 1.8, "ADVERSE EFFECTS", "922B21");
const ae_arb = [
  { text: "Hypotension (first dose)", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Hyperkalemia", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Renal insufficiency", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Cough — much rarer than ACEi", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Angioedema — very rare", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Olmesartan → sprue-like enteropathy", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Teratogenic (avoid in pregnancy)", options: { bullet: { code: "2022" } } },
];
s.addText(ae_arb, { x: 5.0, y: 4.2, w: 4.6, h: 1.8, fontSize: 10.5, color: C.dktext, fontFace: "Calibri", lineSpacingMultiple: 1.25 });

// ════════════════════════════════════════════════════════════════════════════
// SLIDE 5 — RENIN INHIBITORS + MRAs
// ════════════════════════════════════════════════════════════════════════════
s = pres.addSlide();
slideHeader(s, "Renin Inhibitors & Mineralocorticoid Receptor Antagonists (MRAs)", C.slate);

// Renin Inhibitors left
s.addShape(pres.ShapeType.rect, { x: 0.2, y: 0.85, w: 4.6, h: 4.6, fill: { color: "FEF9E7" }, line: { color: C.gold, width: 2 } });
pillBadge(s, 0.35, 0.9, 1.8, "RENIN INHIBITORS", C.gold, C.dktext);
s.addText("Aliskiren (Tekturna)", {
  x: 0.3, y: 1.29, w: 4.4, h: 0.35,
  fontSize: 13, bold: true, color: C.gold, fontFace: "Calibri",
});
s.addText([
  { text: "Mechanism", options: { bold: true, breakLine: true } },
  { text: "Directly inhibit renin enzyme", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Act earliest in RAAS cascade", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Block Angiotensinogen → Ang I step", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "", options: { breakLine: true } },
  { text: "Uses", options: { bold: true, breakLine: true } },
  { text: "Hypertension (monotherapy or add-on)", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "", options: { breakLine: true } },
  { text: "Adverse Effects", options: { bold: true, breakLine: true } },
  { text: "Diarrhea (especially high dose)", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Hyperkalemia, renal impairment", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Cough, angioedema (less than ACEi)", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "", options: { breakLine: true } },
  { text: "Contraindications", options: { bold: true, breakLine: true } },
  { text: "Pregnancy, diabetes + ACEi/ARB combo", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Renal insufficiency", options: { bullet: { code: "2022" } } },
], { x: 0.3, y: 1.65, w: 4.4, h: 3.6, fontSize: 10.5, color: C.dktext, fontFace: "Calibri", lineSpacingMultiple: 1.2 });

// MRAs right
s.addShape(pres.ShapeType.rect, { x: 5.1, y: 0.85, w: 4.7, h: 4.6, fill: { color: "F5EEF8" }, line: { color: C.purple, width: 2 } });
pillBadge(s, 5.25, 0.9, 1.2, "MRAs", C.purple);
s.addText("Spironolactone • Eplerenone • Finerenone", {
  x: 5.2, y: 1.29, w: 4.5, h: 0.35,
  fontSize: 12, bold: true, color: C.purple, fontFace: "Calibri",
});
s.addText([
  { text: "Mechanism", options: { bold: true, breakLine: true } },
  { text: "Block aldosterone at mineralocorticoid receptor", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Prevent Na+ retention and K+ excretion", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Prevent myocardial fibrosis and hypertrophy", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "", options: { breakLine: true } },
  { text: "Uses", options: { bold: true, breakLine: true } },
  { text: "Symptomatic HFrEF", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Post-MI with LV dysfunction + HF", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Resistant hypertension (add-on)", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Primary hyperaldosteronism", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "", options: { breakLine: true } },
  { text: "Adverse Effects", options: { bold: true, breakLine: true } },
  { text: "Hyperkalemia (monitor K+)", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Gynecomastia, dysmenorrhea (spironolactone)", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Eplerenone: selective → fewer endocrine SE", options: { bullet: { code: "2022" } } },
], { x: 5.2, y: 1.65, w: 4.5, h: 3.65, fontSize: 10.5, color: C.dktext, fontFace: "Calibri", lineSpacingMultiple: 1.2 });

// ════════════════════════════════════════════════════════════════════════════
// SLIDE 6 — HEAD-TO-HEAD COMPARISON TABLE: ACEi vs ARBs
// ════════════════════════════════════════════════════════════════════════════
s = pres.addSlide();
slideHeader(s, "ACE Inhibitors vs ARBs — Head-to-Head Comparison", C.navy);

const rows = [
  ["Feature", "ACE Inhibitors", "ARBs"],
  ["Site of Action", "ACE enzyme (blocks Ang I → Ang II)", "AT1 receptor (blocks Ang II binding)"],
  ["Bradykinin effect", "↑ Bradykinin accumulation", "No effect on bradykinin"],
  ["Completeness of AngII block", "Partial (chymase pathway remains)", "More complete"],
  ["Dry Cough", "Common (~10% patients)", "Rare (<2%)"],
  ["Angioedema", "Rare (~0.3%)", "Very rare (~0.1%)"],
  ["AT2 stimulation", "Minimal", "Yes — Ang II ↑ stimulates AT2"],
  ["Hyperkalemia", "Yes", "Yes"],
  ["Teratogenicity", "Yes — avoid in pregnancy", "Yes — avoid in pregnancy"],
  ["Preferred role", "First choice", "Substitute if ACEi not tolerated"],
  ["IV formulation", "Yes (Enalaprilat)", "None"],
  ["Unique effects", "Rash/dysgeusia (captopril)", "Sprue enteropathy (olmesartan); Uricosuric (losartan)"],
  ["Cost", "Generally lower", "Generally higher"],
];

const colW = [2.6, 3.4, 3.4];
const colX = [0.15, 2.75, 6.15];
const rowH = 0.33;
const startY = 0.82;

rows.forEach((row, ri) => {
  row.forEach((cell, ci) => {
    const isHeader = ri === 0;
    const isFeatureCol = ci === 0;
    const bg = isHeader ? C.navy : (ri % 2 === 0 ? "EBF5FB" : C.white);
    const textColor = isHeader ? C.gold : (isFeatureCol ? C.navy : C.dktext);
    s.addShape(pres.ShapeType.rect, {
      x: colX[ci], y: startY + ri * rowH, w: colW[ci], h: rowH,
      fill: { color: bg }, line: { color: C.ltgray, width: 0.5 },
    });
    s.addText(cell, {
      x: colX[ci] + 0.05, y: startY + ri * rowH, w: colW[ci] - 0.1, h: rowH,
      fontSize: isHeader ? 11 : 9.5,
      bold: isHeader || isFeatureCol,
      color: textColor, fontFace: "Calibri",
      valign: "middle", margin: 2,
    });
  });
});

// ════════════════════════════════════════════════════════════════════════════
// SLIDE 7 — FULL 4-WAY COMPARISON TABLE
// ════════════════════════════════════════════════════════════════════════════
s = pres.addSlide();
slideHeader(s, "All RAAS Blockers — 4-Way Comparison", C.slate);

const rows4 = [
  ["Property", "ACE Inhibitors", "ARBs", "Renin Inhibitors", "MRAs"],
  ["Target", "ACE enzyme", "AT1 receptor", "Renin enzyme", "Aldosterone receptor"],
  ["BP lowering", "✓✓✓", "✓✓✓", "✓✓", "✓✓"],
  ["Cough", "Common (~10%)", "Rare", "Rare", "No"],
  ["Angioedema", "Rare", "Very rare", "Rare", "No"],
  ["Hyperkalemia", "Yes", "Yes", "Yes", "Yes (main SE)"],
  ["Pregnancy", "CI", "CI", "CI", "CI"],
  ["Heart failure", "First-line", "ACEi substitute", "Not established", "First-line (add-on)"],
  ["Diabetic nephropathy", "Yes", "Yes", "Limited", "Yes (Finerenone)"],
  ["Unique SE", "Rash (captopril)", "Enteropathy (olmesartan)", "Diarrhea", "Gynecomastia (spiro)"],
];

const cW4 = [2.1, 1.95, 1.95, 1.95, 1.95];
const cX4 = [0.1, 2.2, 4.15, 6.1, 8.05];
const headerColors4 = [C.slate, C.teal, C.crimson, C.gold, C.purple];

rows4.forEach((row, ri) => {
  row.forEach((cell, ci) => {
    const isHeader = ri === 0;
    let bg;
    if (isHeader) {
      bg = headerColors4[ci];
    } else if (ci === 0) {
      bg = "D5DBDB";
    } else {
      bg = ri % 2 === 0 ? "F2F3F4" : C.white;
    }
    const textColor = (isHeader || ci === 0) ? (ci === 3 ? C.dktext : C.white) : C.dktext;
    s.addShape(pres.ShapeType.rect, {
      x: cX4[ci], y: 0.82 + ri * 0.46, w: cW4[ci], h: 0.46,
      fill: { color: bg }, line: { color: C.ltgray, width: 0.5 },
    });
    s.addText(cell, {
      x: cX4[ci] + 0.04, y: 0.82 + ri * 0.46, w: cW4[ci] - 0.08, h: 0.46,
      fontSize: isHeader ? 9.5 : 9,
      bold: isHeader || ci === 0,
      color: textColor, fontFace: "Calibri",
      valign: "middle", align: ci === 0 ? "left" : "center", margin: 2,
    });
  });
});

// CI note
s.addText("CI = Contraindicated | ✓✓✓ = Strong evidence | ✓✓ = Moderate evidence", {
  x: 0.1, y: 5.4, w: 9.8, h: 0.22,
  fontSize: 8, italic: true, color: C.subtext, fontFace: "Calibri",
});

// ════════════════════════════════════════════════════════════════════════════
// SLIDE 8 — PHARMACOKINETICS COMPARISON
// ════════════════════════════════════════════════════════════════════════════
s = pres.addSlide();
slideHeader(s, "Pharmacokinetics — Key Differences", C.slate);

// ACE inhibitors PK box
s.addShape(pres.ShapeType.rect, { x: 0.2, y: 0.85, w: 4.6, h: 4.6, fill: { color: "EBF5FB" }, line: { color: C.teal, width: 2 } });
s.addText("ACE Inhibitors", { x: 0.35, y: 0.9, w: 4.3, h: 0.38, fontSize: 14, bold: true, color: C.teal, fontFace: "Calibri" });
s.addText([
  { text: "Route: All orally bioavailable", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Prodrugs: Most (except captopril, lisinopril)", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "IV form: Enalaprilat only", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Renal elimination: Most (except fosinopril)", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Fosinopril: Dual renal + fecal — safe in renal impairment", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Captopril: Short-acting; take on empty stomach", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Half-life of active compounds: 2–12 hours", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "ACE inhibition lasts longer than plasma t½", options: { bullet: { code: "2022" } } },
], { x: 0.3, y: 1.33, w: 4.4, h: 3.9, fontSize: 11, color: C.dktext, fontFace: "Calibri", lineSpacingMultiple: 1.35 });

// ARBs PK box
s.addShape(pres.ShapeType.rect, { x: 5.1, y: 0.85, w: 4.7, h: 4.6, fill: { color: "FDEDEC" }, line: { color: C.crimson, width: 2 } });
s.addText("ARBs", { x: 5.25, y: 0.9, w: 4.5, h: 0.38, fontSize: 14, bold: true, color: C.crimson, fontFace: "Calibri" });
s.addText([
  { text: "Route: All orally active", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Dosing: Once daily (most); valsartan twice daily", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Highly plasma protein bound", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Losartan: Active metabolite EXP-3174 (extensive first-pass)", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Other ARBs: Inactive metabolites", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Elimination: Urine and feces (dual)", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "Full antihypertensive effect: ~4 weeks", options: { bullet: { code: "2022" }, breakLine: true } },
  { text: "No IV formulation available", options: { bullet: { code: "2022" } } },
], { x: 5.2, y: 1.33, w: 4.5, h: 3.9, fontSize: 11, color: C.dktext, fontFace: "Calibri", lineSpacingMultiple: 1.35 });

// ════════════════════════════════════════════════════════════════════════════
// SLIDE 9 — SIMILARITIES
// ════════════════════════════════════════════════════════════════════════════
s = pres.addSlide();
slideHeader(s, "ACE Inhibitors & ARBs — Shared Properties", C.slate);

const simCols = [
  {
    title: "Shared Pharmacology",
    color: C.teal,
    items: [
      "Arteriolar + venous vasodilation",
      "Reduce aldosterone secretion",
      "Reduce Na+/H₂O retention",
      "Reduce cardiac preload & afterload",
      "Anti-hypertrophic (LV regression)",
      "Efferent arteriolar dilation",
      "Renoprotective effects",
    ],
  },
  {
    title: "Shared Clinical Uses",
    color: C.crimson,
    items: [
      "Hypertension (first-line)",
      "Heart failure (HFrEF)",
      "Post-MI / LV remodeling",
      "Diabetic nephropathy",
      "Chronic kidney disease",
      "LV hypertrophy regression",
      "High cardiovascular risk",
    ],
  },
  {
    title: "Shared Adverse Effects",
    color: "6C3483",
    items: [
      "Hypotension (first-dose effect)",
      "Hyperkalemia",
      "Renal insufficiency",
      "Teratogenicity",
      "Bilateral renal artery stenosis risk",
    ],
  },
];

simCols.forEach((col, ci) => {
  const x = 0.2 + ci * 3.25;
  s.addShape(pres.ShapeType.rect, { x, y: 0.85, w: 3.1, h: 4.6, fill: { color: "F4F6F7" }, line: { color: col.color, width: 2 } });
  s.addShape(pres.ShapeType.rect, { x, y: 0.85, w: 3.1, h: 0.45, fill: { color: col.color } });
  s.addText(col.title, { x: x + 0.08, y: 0.85, w: 2.94, h: 0.45, fontSize: 12, bold: true, color: C.white, fontFace: "Calibri", valign: "middle" });
  s.addText(
    col.items.map((item, i) => ({ text: item, options: { bullet: { code: "2713" }, breakLine: i < col.items.length - 1 } })),
    { x: x + 0.08, y: 1.35, w: 2.94, h: 3.9, fontSize: 11, color: C.dktext, fontFace: "Calibri", lineSpacingMultiple: 1.45 }
  );
});

// Shared note at bottom
s.addShape(pres.ShapeType.rect, { x: 0.2, y: 5.22, w: 9.6, h: 0.32, fill: { color: "D6EAF8" }, line: { color: C.teal, width: 0.5 } });
s.addText("Both classes are NOT recommended in combination — dual RAAS blockade increases hyperkalemia, hypotension, and renal dysfunction without added mortality benefit (ON-TARGET trial)", {
  x: 0.35, y: 5.22, w: 9.3, h: 0.32,
  fontSize: 9, italic: true, color: C.navy, fontFace: "Calibri", valign: "middle",
});

// ════════════════════════════════════════════════════════════════════════════
// SLIDE 10 — WHEN TO CHOOSE WHICH
// ════════════════════════════════════════════════════════════════════════════
s = pres.addSlide();
slideHeader(s, "Clinical Decision Guide — When to Choose Which RAAS Blocker", C.navy);

const decisions = [
  { situation: "Standard hypertension, no comorbidities", choice: "ACE Inhibitor", reason: "First-line, cheaper, well-established", color: C.teal },
  { situation: "Hypertension + cough on ACEi", choice: "Switch to ARB", reason: "No bradykinin accumulation → no cough", color: C.crimson },
  { situation: "Angioedema on ACEi", choice: "ARB (with caution)", reason: "Much lower incidence of angioedema", color: C.crimson },
  { situation: "HFrEF (primary)", choice: "ACE Inhibitor", reason: "Most established; survival benefit proven", color: C.teal },
  { situation: "HFrEF + ACEi-intolerant", choice: "ARB (candesartan, valsartan)", reason: "Non-inferior to ACEi; CHARM-Alt trial", color: C.crimson },
  { situation: "Symptomatic HFrEF + tolerating ACEi/ARB", choice: "Switch to ARNI (sacubitril/valsartan)", reason: "Superior to ACEi in PARADIGM-HF trial", color: "1A5276" },
  { situation: "Hypertension + gout", choice: "Losartan (ARB)", reason: "Unique uricosuric effect lowers uric acid", color: C.crimson },
  { situation: "Marfan syndrome", choice: "Losartan (ARB)", reason: "Blocks AT1-mediated TGF-β signaling", color: C.crimson },
  { situation: "Symptomatic HFrEF on ACEi + BB", choice: "Add MRA (spironolactone/eplerenone)", reason: "Reduces mortality (RALES, EMPHASIS-HF)", color: C.purple },
  { situation: "Pregnancy", choice: "Both CONTRAINDICATED", reason: "Both are teratogenic", color: "C0392B" },
];

decisions.forEach((d, i) => {
  const y = 0.86 + i * 0.47;
  s.addShape(pres.ShapeType.rect, { x: 0.1, y, w: 3.6, h: 0.43, fill: { color: "EAF2FB" }, line: { color: C.ltgray, width: 0.5 } });
  s.addText(d.situation, { x: 0.15, y, w: 3.5, h: 0.43, fontSize: 9.5, color: C.dktext, fontFace: "Calibri", valign: "middle", bold: false });

  s.addShape(pres.ShapeType.rect, { x: 3.7, y, w: 2.5, h: 0.43, fill: { color: d.color }, line: { color: C.white, width: 0.5 } });
  s.addText(d.choice, { x: 3.75, y, w: 2.4, h: 0.43, fontSize: 9.5, bold: true, color: C.white, fontFace: "Calibri", valign: "middle" });

  s.addShape(pres.ShapeType.rect, { x: 6.2, y, w: 3.7, h: 0.43, fill: { color: "F4F6F7" }, line: { color: C.ltgray, width: 0.5 } });
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});

// Column headers
["Clinical Situation", "Drug Choice", "Reason"].forEach((h, i) => {
  const xs = [0.1, 3.7, 6.2];
  const ws = [3.6, 2.5, 3.7];
  s.addShape(pres.ShapeType.rect, { x: xs[i], y: 0.78, w: ws[i], h: 0.08, fill: { color: C.gold } });
});

// ════════════════════════════════════════════════════════════════════════════
// SLIDE 11 — CONTRAINDICATIONS
// ════════════════════════════════════════════════════════════════════════════
s = pres.addSlide();
slideHeader(s, "Contraindications & Cautions for RAAS Blockers", "922B21");

const ciData = [
  {
    drug: "ALL RAAS Blockers",
    color: "922B21",
    items: [
      "Pregnancy (all trimesters — teratogenic)",
      "Bilateral renal artery stenosis",
      "Severe hyperkalemia (K+ > 5.5 mEq/L)",
      "Combination ACEi + ARB (dual RAAS blockade)",
    ],
  },
  {
    drug: "ACE Inhibitors",
    color: C.teal,
    items: [
      "History of ACEi-induced angioedema",
      "Severe aortic stenosis (relative)",
      "Caution: severe renal impairment (most need dose adjustment, except fosinopril)",
    ],
  },
  {
    drug: "ARBs",
    color: C.crimson,
    items: [
      "History of ARB-induced angioedema",
      "Olmesartan: sprue-like enteropathy history",
      "Combination with aliskiren in diabetes/renal impairment",
    ],
  },
  {
    drug: "MRAs",
    color: C.purple,
    items: [
      "Severe renal impairment (GFR < 30)",
      "Hyperkalemia",
      "Spironolactone: caution in men (gynecomastia)",
    ],
  },
];

ciData.forEach((d, i) => {
  const col = i < 2 ? i : i - 2;
  const row = i < 2 ? 0 : 1;
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  const y = 0.85 + row * 2.4;
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  s.addShape(pres.ShapeType.rect, { x, y, w: 4.6, h: 0.4, fill: { color: d.color } });
  s.addText(d.drug, { x: x + 0.08, y, w: 4.44, h: 0.4, fontSize: 12, bold: true, color: i === 2 ? C.white : C.white, fontFace: "Calibri", valign: "middle" });
  s.addText(
    d.items.map((item, ii) => ({ text: item, options: { bullet: { code: "26A0" }, breakLine: ii < d.items.length - 1 } })),
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  );
});

// ════════════════════════════════════════════════════════════════════════════
// SLIDE 12 — KEY CLINICAL TRIALS
// ════════════════════════════════════════════════════════════════════════════
s = pres.addSlide();
slideHeader(s, "Landmark Clinical Trials for RAAS Blockers", C.navy);

const trials = [
  { trial: "HOPE (2000)", drug: "Ramipril (ACEi)", finding: "↓ CV death, MI, stroke by 22% in high-risk patients", color: C.teal },
  { trial: "SOLVD (1991)", drug: "Enalapril (ACEi)", finding: "↓ Mortality + HF hospitalizations in HFrEF", color: C.teal },
  { trial: "CHARM-Alt (2003)", drug: "Candesartan (ARB)", finding: "↓ Mortality/hospitalizations in ACEi-intolerant HF", color: C.crimson },
  { trial: "VALIANT (2003)", drug: "Valsartan (ARB)", finding: "Non-inferior to captopril in post-MI LV dysfunction", color: C.crimson },
  { trial: "HEAAL (2009)", drug: "Losartan (ARB)", finding: "High-dose (150mg) superior to low-dose (50mg) in HFrEF", color: C.crimson },
  { trial: "ON-TARGET (2008)", drug: "Telmisartan vs Ramipril", finding: "Equal efficacy; less cough & angioedema with ARB; combo not better", color: "7D6608" },
  { trial: "RALES (1999)", drug: "Spironolactone (MRA)", finding: "↓ Mortality by 30% in severe HFrEF", color: C.purple },
  { trial: "EMPHASIS-HF (2011)", drug: "Eplerenone (MRA)", finding: "↓ CV death/hospitalizations in mild symptomatic HFrEF", color: C.purple },
  { trial: "PARADIGM-HF (2014)", drug: "Sacubitril/Valsartan (ARNI)", finding: "Superior to enalapril → ↓ CV death/HF hospitalizations by 20%", color: "1A5276" },
];

trials.forEach((t, i) => {
  const y = 0.86 + i * 0.51;
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});

// ════════════════════════════════════════════════════════════════════════════
// SLIDE 13 — SUMMARY / CONCLUSION
// ════════════════════════════════════════════════════════════════════════════
s = pres.addSlide();
s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.navy } });
s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 0.06, fill: { color: C.teal } });
s.addShape(pres.ShapeType.rect, { x: 0, y: 5.565, w: 10, h: 0.06, fill: { color: C.crimson } });

s.addText("Key Takeaways", {
  x: 0.4, y: 0.25, w: 9.2, h: 0.65,
  fontSize: 28, bold: true, color: C.gold, fontFace: "Calibri", align: "center",
});

const takeaways = [
  { icon: "→", text: "All RAAS blockers ultimately reduce Ang II activity — but at different points in the cascade", color: C.teal },
  { icon: "→", text: "ACEi and ARBs have near-identical clinical efficacy across HTN, HF, and CKD", color: C.crimson },
  { icon: "→", text: "The key difference: ACEi raise bradykinin → cough (10%) and angioedema; ARBs do not", color: C.gold },
  { icon: "→", text: "ARBs are the preferred substitute when ACEi are not tolerated", color: C.crimson },
  { icon: "→", text: "MRAs (spironolactone/eplerenone) add mortality benefit in HFrEF on top of ACEi/ARB + beta-blocker", color: C.purple },
  { icon: "→", text: "ARNI (sacubitril/valsartan) is now preferred over ACEi in HFrEF when tolerated", color: "5DADE2" },
  { icon: "→", text: "All RAAS blockers are CONTRAINDICATED in pregnancy and bilateral renal artery stenosis", color: "E74C3C" },
  { icon: "→", text: "Do NOT combine ACEi + ARB — dual RAAS blockade causes more harm than benefit", color: "E74C3C" },
];

takeaways.forEach((t, i) => {
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    fontSize: 12, color: C.white, fontFace: "Calibri", valign: "middle",
  });
});

// ════════════════════════════════════════════════════════════════════════════
// WRITE FILE
// ════════════════════════════════════════════════════════════════════════════
pres.writeFile({ fileName: "/home/daytona/workspace/raas-blockers-ppt/RAAS_Blockers_Comparison.pptx" })
  .then(() => console.log("✅ Presentation saved successfully."))
  .catch(err => console.error("❌ Error:", err));

Running Command

cd /home/daytona/workspace/raas-blockers-ppt && node build.js 2>&1

Running Command

ls -lh /home/daytona/workspace/raas-blockers-ppt/RAAS_Blockers_Comparison.pptx

Your presentation is ready! Download it here:

RAAS Blockers Comparison

Presentation · PPTX

Here's what's inside the 13-slide deck (430 KB):

Slide	Content
1	Title slide — dark navy with teal/crimson/gold accents
2	RAAS Pathway Diagram — showing where each drug class acts
3	ACE Inhibitors — mechanism, uses, adverse effects, key drugs
4	ARBs — mechanism, uses, adverse effects, key drugs
5	Renin Inhibitors + MRAs — side-by-side overview
6	ACEi vs ARBs — detailed head-to-head comparison table
7	All 4 classes — 4-way comparison table
8	Pharmacokinetics — key differences (ACEi vs ARBs)
9	Similarities between ACEi and ARBs
10	Clinical Decision Guide — when to choose which drug
11	Contraindications and Cautions for all classes
12	Landmark Clinical Trials (HOPE, CHARM-Alt, RALES, PARADIGM-HF, etc.)
13	Key Takeaways — summary slide

Color coding used throughout:

🔵 Teal = ACE Inhibitors
🔴 Crimson = ARBs
🟡 Gold = Renin Inhibitors
🟣 Purple = MRAs

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