Hypertension

Disease Introduction

Hypertension (HTN) is a chronic medical condition characterized by persistently elevated systemic arterial blood pressure. It represents the most prevalent modifiable risk factor for cardiovascular disease, stroke, heart failure, atrial fibrillation, chronic kidney disease, cognitive decline, and premature death. According to the World Health Organization, hypertension affects approximately 1.3 billion people globally, with prevalence increasing with age. The condition is often asymptomatic until complications develop, earning it the moniker “the silent killer.”

Harrison’s Principles of Internal Medicine defines hypertension as systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg based on multiple properly measured readings. The pathophysiology involves complex interactions between genetic predisposition, environmental factors, neurohormonal systems, and vascular biology. Management requires a comprehensive approach including accurate diagnosis, risk stratification, lifestyle modifications, and pharmacotherapy tailored to individual patient characteristics and comorbidities.

Primary (Essential) Hypertension

Epidemiology & Risk Factors

Primary hypertension accounts for 90-95% of all hypertension cases. Prevalence increases with age, affecting >60% of individuals over 60 years. Major risk factors include:

  • Non-modifiable: Age (>45 men, >55 women), male sex, family history of premature CVD, genetic polymorphisms affecting renal sodium handling, African ancestry
  • Modifiable: Obesity (BMI ≥30 kg/m²), excessive sodium intake (>2.3g/day), inadequate potassium intake, physical inactivity, excessive alcohol consumption, smoking, chronic stress, sleep apnea
  • Comorbidities: Diabetes mellitus, dyslipidemia, chronic kidney disease

Prerequisite Normal Physiology & Anatomy

Blood Pressure Determinants

Blood pressure = Cardiac Output × Systemic Vascular Resistance (BP = CO × SVR)

  • Cardiac Output (CO): Stroke Volume × Heart Rate (normal 4-8 L/min)
  • Stroke Volume: Determined by preload, afterload, and contractility
  • Systemic Vascular Resistance: Primarily determined by arteriolar tone
Regulatory Systems
  • Renin-Angiotensin-Aldosterone System (RAAS): Renin (kidney) converts angiotensinogen to angiotensin I → ACE converts to angiotensin II → vasoconstriction + aldosterone release → sodium/water retention
  • Sympathetic Nervous System: α₁-receptors (vasoconstriction), β₁-receptors (increased HR/contractility), β₂-receptors (vasodilation)
  • Endothelial Function: Nitric oxide (vasodilation), Endothelin-1 (vasoconstriction), Prostacyclin (vasodilation)
  • Natriuretic Peptides: ANP, BNP promote natriuresis and vasodilation
  • Baroreceptor Reflex: Carotid sinus and aortic arch sensors for rapid BP adjustment (seconds to minutes)

Pathophysiology of Primary Hypertension

Early Phase Mechanisms
  • Increased Sympathetic Tone: Enhanced norepinephrine release, reduced neuronal reuptake, increased receptor sensitivity
  • Sodium Retention: Genetic defects in renal sodium handling (30-50% of cases), reduced nephron number
  • RAAS Activation: Inappropriate renin secretion despite normal/high BP, increased angiotensin II sensitivity
  • Endothelial Dysfunction: Reduced nitric oxide bioavailability, increased endothelin-1 production
Established Hypertension Mechanisms
  • Vascular Remodeling: Media hypertrophy, reduced lumen diameter, increased wall-to-lumen ratio
  • Pressure Natriuresis Reset: Kidneys excrete sodium at higher BP levels
  • Structural Changes: Arteriolar hyalinization, reduced capillary density
  • Inflammation: Increased cytokines (IL-6, TNF-α), oxidative stress, immune cell infiltration
Genetic Contributions

Polygenic inheritance with >100 identified loci. Key genes involve:

  • Renal sodium handling (WNK kinases, SLC12A3, SCNN1)
  • RAAS components (ACE, AGT, AGTR1)
  • Endothelial function (NOS3, EDN1)
  • Adrenergic receptors (ADRB1, ADRB2)
Clinical Presentation

Most patients are asymptomatic. When symptoms occur, they may include:

  • Non-specific: Headache (typically occipital, morning), dizziness, fatigue, epistaxis
  • Target Organ Damage:
    • Cardiac: Angina, dyspnea, palpitations
    • Cerebrovascular: TIA symptoms, cognitive impairment
    • Renal: Nocturia, edema
    • Vascular: Intermittent claudication
    • Retinal: Visual changes (rare)
Physical Examination Findings
  • Accurate BP Measurement: Proper cuff size (bladder encircling ≥80% arm circumference), patient seated with back support, feet flat, arm at heart level, no caffeine/exercise 30 minutes prior, quiet environment
  • Hypertensive Retinopathy: Keith-Wagener-Barker Classification:
    • Grade I: Arteriolar narrowing, increased light reflex
    • Grade II: AV nicking, copper/silver wiring
    • Grade III: Flame hemorrhages, cotton wool spots
    • Grade IV: Papilledema (malignant hypertension)
  • Cardiac Exam: Sustained PMI, S4 gallop (diastolic dysfunction), aortic regurgitation murmur (aortic root dilation)
  • Vascular: Carotid/renal/femoral bruits, delayed/absent peripheral pulses
Diagnostic Evaluation
  • Confirm Diagnosis: ≥2 elevated readings on ≥2 occasions (office, home, or ABPM)
  • Ambulatory BP Monitoring: Gold standard for diagnosis; indications: white coat HTN, masked HTN, resistant HTN, hypotensive symptoms, autonomic dysfunction
  • Home BP Monitoring: ≥135/85 mmHg threshold for hypertension
  • Laboratory Tests:
    • Basic: CBC, CMP (Na, K, Cl, CO2, BUN, Cr, glucose, Ca), lipids, urinalysis, spot urine albumin:creatinine ratio
    • Selected patients: TSH, uric acid, plasma aldosterone/renin ratio (if hypokalemic, resistant HTN)
  • ECG: LVH (Sokolow-Lyon: SV1 + RV5/V6 >3.5 mV; Cornell: RaVL + SV3 >2.8 mV men, >2.0 mV women)
  • Echocardiography: If symptoms/signs of heart disease, LVH on ECG, assess LV mass, systolic/diastolic function
BP Category Systolic (mmHg) Diastolic (mmHg) Recommended Follow-up
Normal <120 and <80 Recheck in 1 year
Elevated 120-129 and <80 Recheck in 3-6 months, lifestyle modifications
Stage 1 HTN 130-139 or 80-89 Confirm within 1 month, lifestyle modifications, consider pharmacotherapy if ASCVD risk ≥10% or diabetes/CKD
Stage 2 HTN ≥140 or ≥90 Confirm within 1 month, initiate pharmacotherapy (2 drugs usually)

Comprehensive Treatment Protocol (ACC/AHA 2017)

1
Diagnosis & Risk Stratification

Confirm BP ≥130/80 mmHg on ≥2 occasions. Calculate 10-year ASCVD risk (Pooled Cohort Equations). Assess target organ damage: LVH, CKD (eGFR <60 or albuminuria), cerebrovascular disease, PAD, retinopathy.

2
Lifestyle Modifications (All Patients)

DASH Diet: Fruits, vegetables, whole grains, low-fat dairy, reduced saturated fat/cholesterol. Sodium Restriction: <2.3g/day (ideally <1.5g). Weight Loss: Goal BMI 18.5-24.9 kg/m², waist circumference <40 inches men, <35 inches women. Physical Activity: ≥150 min/week moderate-intensity or 75 min/week vigorous. Alcohol: ≤1 drink/day women, ≤2 drinks/day men. Smoking Cessation: Complete cessation.

3
Pharmacotherapy Initiation

Stage 1 HTN: Monotherapy if 10-year ASCVD risk ≥10% OR clinical CVD, diabetes, CKD, age ≥65. First-line: ACEI, ARB, CCB, or thiazide. Stage 2 HTN: Start with 2-drug combination (usually ACEI/ARB + CCB or thiazide). Compelling Indications:

  • CAD/post-MI: Beta- blocker + ACEI
  • HFrEF: ACEI/ARB/ARNI + beta-blocker + MRA + SGLT2i
  • CKD with proteinuria: ACEI/ARB
  • Diabetes: ACEI/ARB preferred
  • Recurrent stroke prevention: ACEI + thiazide

4
Medication Titration & Monitoring

Titrate to target BP <130/80 mmHg. Recheck BP every 2-4 weeks during titration. Monitor electrolytes, renal function 1-2 weeks after starting/changing ACEI/ARB/diuretic. Assess adherence, side effects, orthostatic hypotension in elderly. Add third drug if BP uncontrolled on 2 drugs at moderate-high doses.

5
Resistant HTN Management

Defined as BP ≥130/80 despite 3 drugs of different classes (including diuretic) at optimal doses. Evaluate for:

  • Non-adherence (pill counts, pharmacy records)
  • White coat effect (ABPM)
  • Drug interactions (NSAIDs, steroids, decongestants, stimulants)
  • Suboptimal regimen (inadequate diuretic, inappropriate combinations)
  • Secondary causes
Add fourth drug: Spironolactone 12.5-25mg daily (if eGFR >45, K+ <4.5). Consider referral to hypertension specialist.

Comprehensive Medication Guide with Dosages

Drug Class Mechanism Representative Drugs Starting Dose Maximum Dose Key Side Effects Contraindications Special Considerations
ACE Inhibitors Inhibit ACE → ↓Ang II → vasodilation, ↓aldosterone Lisinopril, Enalapril, Ramipril Lisinopril 10mg daily
Enalapril 5mg BID		 Lisinopril 40mg daily
Enalapril 40mg daily		 Dry cough (10-20%), angioedema (0.1-0.7%), hyperkalemia, acute kidney injury Pregnancy, bilateral renal artery stenosis, history of angioedema Monitor Cr/K+ 1-2 weeks after start/dose increase. Better renal protection than ARBs in proteinuric CKD.
ARBs Block AT1 receptor → vasodilation, ↓aldosterone Losartan, Valsartan, Candesartan Losartan 50mg daily
Valsartan 80mg daily		 Losartan 100mg daily
Valsartan 320mg daily		 Hyperkalemia, dizziness, rarely angioedema Pregnancy, bilateral renal artery stenosis Alternative to ACEI if cough. Losartan has uricosuric effect (good for gout).
CCBs (Dihydropyridine) Block L-type Ca²⁺ channels → arterial vasodilation Amlodipine, Nifedipine XL Amlodipine 5mg daily
Nifedipine 30mg daily		 Amlodipine 10mg daily
Nifedipine 120mg daily		 Peripheral edema (10-30%), headache, flushing, reflex tachycardia None absolute Excellent for isolated systolic HTN in elderly. Less edema with amlodipine vs nifedipine.
CCBs (Non-DHP) Block cardiac/AV nodal Ca²⁺ channels → ↓HR, ↓contractility Diltiazem, Verapamil Diltiazem ER 120mg daily
Verapamil SR 120mg daily		 Diltiazem ER 540mg daily
Verapamil SR 480mg daily		 Constipation (verapamil), bradycardia, heart block, HF exacerbation Sick sinus syndrome, 2°/3° AV block, HFrEF (especially verapamil) Good for HTN + AFib rate control. Avoid with beta-blockers (bradycardia risk).
Thiazide Diuretics Block Na⁺-Cl⁻ cotransporter in DCT → natriuresis, volume depletion Hydrochlorothiazide, Chlorthalidone HCTZ 12.5-25mg daily
Chlorthalidone 12.5mg daily		 HCTZ 50mg daily
Chlorthalidone 25mg daily		 Hypokalemia, hyponatremia, hyperuricemia, hyperglycemia, hypercalcemia, ↑LDL Gout, severe hyponatremia Chlorthalidone more potent/longer acting than HCTZ. Monitor K+ 1-2 weeks after start.
Loop Diuretics Block Na⁺-K⁺-2Cl⁻ cotransporter in TAL → potent diuresis Furosemide, Torsemide, Bumetanide Furosemide 20-40mg daily Furosemide 600mg daily (in HF) Hypokalemia, ototoxicity (high dose IV), hypovolemia Anuria, hepatic coma Use in CKD stage ≥4 (eGFR <30) or volume overload states. Less effective than thiazides for HTN alone.
Beta-blockers Block β₁-receptors → ↓HR, ↓CO, ↓renin Metoprolol, Atenolol, Bisoprolol Metoprolol 25-50mg BID
Bisoprolol 2.5-5mg daily		 Metoprolol 200mg daily
Bisoprolol 10mg daily		 Fatigue, bradycardia, bronchospasm, erectile dysfunction, masking hypoglycemia Asthma/COPD (non-selective), decompensated HF, bradycardia, heart block Preferred in HTN + CAD, HFrEF, arrhythmias. Avoid as monotherapy in elderly (inferior stroke prevention).
Alpha-blockers Block α₁-receptors → arterial/venous dilation Doxazosin, Prazosin Doxazosin 1mg daily
Prazosin 1mg BID/TID		 Doxazosin 16mg daily
Prazosin 20mg daily		 First-dose syncope, orthostatic hypotension, dizziness, headache None absolute Good for HTN + BPH. Not first-line for HTN alone (ALLHAT trial). Start at bedtime.
Mineralocorticoid Receptor Antagonists Block aldosterone receptor → natriuresis, K⁺ retention Spironolactone, Eplerenone Spironolactone 12.5-25mg daily
Eplerenone 25mg daily		 Spironolactone 50mg daily
Eplerenone 100mg daily		 Hyperkalemia, gynecomastia (spironolactone 10%), menstrual irregularities eGFR <30, K+ >5.0, Addison’s disease Fourth-line for resistant HTN. Eplerenone less anti-androgen effects.
ACE Inhibitors (Lisinopril)
Start: 10mg daily, Max: 40mg daily. Monitor Cr/K+. Cough side effect 10-20%.
ARBs (Losartan)
Start: 50mg daily, Max: 100mg daily. Alternative to ACEI if cough.
CCBs (Amlodipine)
Start: 5mg daily, Max: 10mg daily. Peripheral edema 10-30%. Good for isolated systolic HTN.
Thiazides (Chlorthalidone)
Start: 12.5mg daily, Max: 25mg daily. Monitor K+, uric acid, glucose. More potent than HCTZ.
Beta-blockers (Metoprolol)
Start: 25mg BID, Max: 200mg daily. Avoid in asthma/COPD. Good for HTN + CAD/HF.
MRA (Spironolactone)
Start: 12.5-25mg daily, Max: 50mg daily. Monitor K+ closely. Gynecomastia 10%.
Special Populations Management

Elderly (>65 years): Start with half usual dose, monitor for orthostasis. Goal BP <130/80 if tolerated. CCBs and thiazides particularly effective for isolated systolic HTN. Avoid centrally acting agents (clonidine, methyldopa) due to CNS side effects.

Diabetes: Target BP <130/80. ACEI/ARB first-line for renal protection. Monitor Cr/K+ closely, especially with NSAID use or volume depletion.

Chronic Kidney Disease: Target BP <130/80, <120/80 if proteinuria >1g/day. ACEI/ARB first-line regardless of race. May need loop diuretic if eGFR <30. Monitor for hyperkalemia, AKI.

Black Patients: CCBs and thiazides more effective as monotherapy. ACEI/ARB less effective as monotherapy but still indicated if proteinuria, HF, post-MI. Usually require combination therapy.

Pregnancy: Methyldopa, labetalol, nifedipine are safe. Avoid ACEI/ARB (teratogenic), thiazides (↓ placental perfusion). Target BP <140/90 to prevent progression to preeclampsia.

Secondary Hypertension

When to Suspect Secondary Hypertension
  • Age <30 or >55 years at onset
  • Severe HTN (BP >180/110)
  • Resistant HTN (≥3 drugs at optimal doses)
  • Accelerated/malignant HTN (retinopathy grade III/IV)
  • Sudden onset or worsening of previously controlled HTN
  • Hypokalemia without diuretic use
  • Abdominal bruit, flank mass
  • Significant target organ damage disproportionate to duration/severity of HTN
  • Paroxysmal symptoms (headache, sweating, palpitations)
Cause Prevalence Pathophysiology Diagnostic Clues Confirmatory Tests
Primary Aldosteronism 5-10% of HTN Autonomous aldosterone production → Na⁺ retention, K⁺ wasting Hypokalemia, metabolic alkalosis, resistant HTN, adrenal incidentaloma Elevated aldosterone/renin ratio (>20-30), saline suppression test, adrenal CT, adrenal vein sampling
Renal Artery Stenosis 1-5% of HTN Renal ischemia → ↑renin → ↑Ang II → vasoconstriction + aldosterone Abdominal/flank bruit, flash pulmonary edema, worsening renal function with ACEI/ARB, asymmetric kidney size >1.5cm Renal duplex ultrasound (peak velocity >200 cm/s), CTA, MRA, captopril renal scan, renal angiography
Pheochromocytoma 0.1-0.6% of HTN Catecholamine- secreting tumor → α/β stimulation Paroxysmal HTN, headache, sweating, palpitations, pallor, weight loss Plasma free metanephrines (sensitivity 99%), 24-hr urine metanephrines/catecholamines, adrenal CT/MRI, MIBG scan
Cushing’s Syndrome 0.1-0.6% of HTN Cortisol excess → mineralocorticoid effect + increased vascular reactivity Central obesity, moon face, buffalo hump, purple striae, glucose intolerance, proximal weakness 24-hr urine free cortisol, overnight dexamethasone suppression test, late-night salivary cortisol, ACTH level
Coarctation of Aorta Rare in adults Mechanical obstruction → ↑afterload proximal to stenosis Radio- femoral delay, upper extremity HTN, systolic murmur (collaterals), rib notching on CXR Echo (gradient), CTA/MRA of aorta, cardiac catheterization
Renal Parenchymal Disease 2-5% of HTN Volume overload, RAAS activation, sympathetic overactivity Edema, abnormal urinalysis (proteinuria, hematuria, casts), elevated Cr Urinalysis, urine albumin:creatinine ratio, renal ultrasound, kidney biopsy if indicated
Obstructive Sleep Apnea 30-50% of HTN Intermittent hypoxia → sympathetic activation, oxidative stress, endothelial dysfunction Snoring, witnessed apneas, daytime sleepiness, obesity, neck circumference >17″ men, >16″ women Sleep study (AHI ≥5), Epworth Sleepiness Scale >10

Hypertensive Crisis

Definitions
  • Hypertensive Urgency: Severe HTN (BP >180/120) WITHOUT evidence of acute target organ damage. Can be managed with oral medications over 24-48 hours.
  • Hypertensive Emergency: Severe HTN WITH evidence of acute or progressive target organ damage. Requires immediate BP reduction (not necessarily to normal) with IV medications in ICU.
Target Organ Damage in Hypertensive Emergency
  • Neurologic: Hypertensive encephalopathy, intracerebral hemorrhage, acute ischemic stroke, subarachnoid hemorrhage
  • Cardiac: Acute coronary syndrome, acute pulmonary edema, aortic dissection
  • Renal: Acute kidney injury, acute glomerulonephritis
  • Obstetric: Eclampsia, severe preeclampsia
  • Other: Microangiopathic hemolytic anemia, retinopathy grade III/IV
IV Medication Mechanism Dose Onset/Duration Indications Cautions
Nitroprusside NO donor → arterial/venous dilation 0.25-10 mcg/kg/min IV Seconds/1-2 min Most hypertensive emergencies, especially aortic dissection (with beta-blocker) Cyanide/thiocyanate toxicity (>72h, renal/hepatic impairment), light sensitive
Nicardipine Dihydropyridine CCB → arterial dilation 5-15 mg/hr IV 5-10 min/1-4 h Most emergencies except acute HF, safe in renal failure Reflex tachycardia, headache, nausea
Labetalol α/β-blocker 20-80 mg bolus q10min or 0.5-2 mg/min infusion 5-10 min/3-6 h Most except acute HF, aortic dissection (with vasodilator) Avoid in asthma, decompensated HF, heart block
Esmolol Cardioselective β-blocker 500 mcg/kg load, then 50-300 mcg/kg/min 1-2 min/10-30 min Aortic dissection (with vasodilator), perioperative HTN Short duration, avoid in asthma/decompensated HF
Fenoldopam Dopamine-1 agonist → vasodilation, natriuresis 0.1-0.3 mcg/kg/min IV 5 min/30 min Renal impairment, no cyanide risk Reflex tachycardia, ↑ intraocular pressure
Nitroglycerin Venodilation (low dose), arterial dilation (high dose) 5-100 mcg/min IV 2-5 min/5-10 min ACS, acute pulmonary edema Tolerance, headache, methemoglobinemia
Hydralazine Direct arterial vasodilator 10-20 mg IV q4-6h 10-30 min/2-6 h Eclampsia, preeclampsia Reflex tachycardia, lupus-like syndrome, unpredictable response
Management Protocol for Hypertensive Emergency
1
Immediate Assessment

ABCs, IV access, cardiac monitor, BP in both arms, targeted history/physical for target organ damage. STAT labs: CBC, CMP, troponin, urinalysis, ECG, CXR.

2
IV Medication Selection

Choose based on specific emergency:

  • Aortic dissection: Esmolol + nitroprusside (target SBP 100-120, HR 60)
  • ACS/pulmonary edema: Nitroglycerin
  • Stroke: Cautious reduction (15-25% in first 24h), avoid precipitous drops
  • Eclampsia: Magnesium sulfate + labetalol/hydralazine

3
BP Reduction Goals

Reduce MAP by 10-20% in first hour, then additional 5-15% over next 23 hours. Avoid normalizing BP too rapidly (risk of cerebral/renal/coronary hypoperfusion). For aortic dissection: target SBP 100-120 mmHg within 20 minutes.

4
Transition to Oral Therapy

Once BP stable for 12-24 hours, start oral agents while tapering IV. Usually need 2-3 oral drugs. Ensure close follow-up within 1 week.

Hypertension Complications

Cardiovascular Complications
  • Left Ventricular Hypertrophy: Concentric (pressure overload) → diastolic dysfunction → HFpEF. Eccentric (volume overload) → systolic dysfunction → HFrEF. Regression occurs with effective treatment.
  • Coronary Artery Disease: Accelerated atherosclerosis, endothelial dysfunction, increased myocardial oxygen demand. HTN present in 75% of patients with CAD.
  • Heart Failure: 90% of HF patients have history of HTN. Mechanisms: pressure overload → LVH → diastolic dysfunction; coronary ischemia → systolic dysfunction; neurohormonal activation.
  • Atrial Fibrillation: HTN present in 60-80% of AFib cases. Mechanisms: LA enlargement from LVH/diastolic dysfunction, fibrosis, inflammation.
  • Aortic Dissection: Medial degeneration from chronic pressure stress. Most common in ascending aorta (type A).
Cerebrovascular Complications
  • Stroke: HTN is strongest modifiable risk factor (RR 3-4). Mechanisms: lacunar infarcts (lipohyalinosis of penetrating arteries), large artery atherosclerosis, cardioembolism (AFib), intracerebral hemorrhage (Charcot-Bouchard aneurysms).
  • Vascular Dementia: Small vessel disease → white matter hyperintensities, lacunes → cognitive impairment.
  • Hypertensive Encephalopathy: Acute severe HTN → breakthrough autoregulation → cerebral edema → headache, confusion, seizures, coma.
Renal Complications
  • Hypertensive Nephrosclerosis: Afferent arteriolar hyalinosis, glomerular ischemia, interstitial fibrosis. Second leading cause of ESRD after diabetes.
  • Albuminuria: Early marker of endothelial dysfunction. Microalbuminuria (30-300 mg/day) predicts CVD risk.
  • Renal Artery Stenosis: Atherosclerotic (elderly men, ostial) or fibromuscular dysplasia (young women, mid-distal).
Other Complications
  • Retinopathy: Grades I-IV as described. Vision loss from macular edema, retinal detachment, optic neuropathy.
  • Peripheral Arterial Disease: HTN present in 40% of PAD patients. Ankle-brachial index <0.9.
  • Erectile Dysfunction: Endothelial dysfunction, atherosclerosis of pudendal arteries, medication side effects.
Key Clinical Pearls – Hypertension
  • Proper BP measurement technique is critical: correct cuff size, patient position, quiet environment.
  • White coat HTN affects 15-30% of patients; consider ABPM for diagnosis.
  • Masked HTN (normal office, elevated out-of-office) carries similar risk as sustained HTN.
  • Orthostatic hypotension common in elderly, diabetics, autonomic dysfunction. Check lying/standing BP.
  • Morning BP surge (6am-10am) associated with increased cardiovascular events.
  • Nocturnal non-dipping pattern (failure of BP to drop ≥10% at night) predicts target organ damage.
  • Pseudoresistance common: improper measurement, white coat effect, non-adherence, inadequate diuretic.
  • Drug- induced HTN: NSAIDs, steroids, decongestants, stimulants, erythropoietin, cyclosporine.
  • J-curve phenomenon: Excessive BP lowering (<110-120/70) may increase events in high-risk patients.
  • BP variability (visit-to-visit, day-to-day) independently predicts CVD risk beyond mean BP.
High-Yield Exam Points:
  • ACC/AHA 2017 classification thresholds (130/80 for Stage 1)
  • Primary aldosteronism: Hypokalemia, metabolic alkalosis, elevated aldosterone:renin ratio
  • Pheochromocytoma: Triad of headache, sweating, palpitations with paroxysmal HTN
  • Renal artery stenosis: Flash pulmonary edema, worsening renal function with ACEI
  • Hypertensive emergency: IV labetalol, nitroprusside, nicardipine
  • Compelling indications: CAD → beta-blocker + ACEI; CKD → ACEI/ARB; Diabetes → ACEI/ARB
  • Resistant HTN: Spironolactone as fourth-line (PATHWAY-2 trial)
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Ischemic Heart Disease

Disease Introduction

Ischemic Heart Disease (IHD), also known as coronary artery disease (CAD), encompasses a spectrum of clinical syndromes resulting from myocardial ischemia – an imbalance between myocardial oxygen supply and demand. It remains the leading cause of death globally, responsible for approximately 9 million deaths annually according to WHO data. The clinical manifestations range from chronic stable angina to acute coronary syndromes (unstable angina, non-ST-elevation myocardial infarction, ST-elevation myocardial infarction).

According to Harrison’s Principles of Internal Medicine, the fundamental pathophysiology is atherosclerosis of the epicardial coronary arteries, with acute coronary syndromes typically resulting from plaque rupture or erosion with superimposed thrombosis. Risk factors include both traditional factors (age, male sex, hypertension, dyslipidemia, diabetes, smoking, family history) and emerging factors (inflammatory markers, psychosocial stress, sedentary lifestyle, diet). Management focuses on both symptom relief and modification of atherosclerotic disease progression through lifestyle interventions, pharmacotherapy, and revascularization when indicated.

Prerequisite Normal Coronary Physiology & Anatomy

Coronary Anatomy
  • Left Main Coronary Artery: Originates from left aortic sinus, bifurcates into LAD and LCx
  • Left Anterior Descending (LAD): Supplies anterior LV, anterior 2/3 septum, apex. Diagonal branches supply anterolateral wall.
  • Left Circumflex (LCx): Supplies lateral LV, obtuse marginal branches. In 10-15%, gives rise to PDA (left dominant).
  • Right Coronary Artery (RCA): Supplies right ventricle, inferior LV, posterior 1/3 septum (via PDA), SA node (55%), AV node (90%).
  • Coronary Dominance: Right dominant (85% – PDA from RCA), left dominant (8% – PDA from LCx), co-dominant (7%).
Myocardial Oxygen Supply-Demand Balance

Myocardial O₂ demand = Heart Rate × Contractility × Wall Stress (Laplace’s Law: wall stress ∝ [pressure × radius] / [2 × thickness])

Myocardial O₂ supply = Coronary Blood Flow × Arterial O₂ Content

Coronary Blood Flow Regulation
  • Autoregulation: Maintains constant flow over perfusion pressure 60-140 mmHg
  • Metabolic Regulation: Adenosine, H⁺, K⁺, CO₂, lactate induce vasodilation during increased demand
  • Endothelial Regulation: NO (shear stress), prostacyclin (vasodilation); Endothelin-1 (vasoconstriction)
  • Neural Regulation: α-adrenergic (vasoconstriction), β₂-adrenergic (vasodilation), cholinergic (vasodilation)
Coronary Flow Reserve

Maximum increase in coronary flow above resting level. Normally 4-5 fold. Reduced in endothelial dysfunction, microvascular disease, epicardial stenosis.

Atherosclerosis Pathophysiology

Initiation Phase (Response-to-Injury Hypothesis)
  • Endothelial Dysfunction: Reduced NO bioavailability, increased adhesion molecules (VCAM-1, ICAM-1)
  • LDL Entry & Modification: LDL particles enter intima, become oxidized (ox-LDL)
  • Monocyte Recruitment: Chemoattractants (MCP-1) recruit monocytes → macrophages
  • Foam Cell Formation: Macrophages take up ox-LDL via scavenger receptors → foam cells → fatty streak
Progression Phase
  • Smooth Muscle Cell Migration: PDGF, TGF-β recruit SMCs from media to intima
  • Extracellular Matrix Production: SMCs produce collagen, elastin, proteoglycans → fibrous cap
  • Plaque Growth: Continued lipid accumulation, neovascularization, intraplaque hemorrhage
Vulnerable Plaque Characteristics
  • Large lipid core (>40% of plaque volume)
  • Thin fibrous cap (<65 μm)
  • Macrophage infiltration (inflammation)
  • Reduced SMC content
  • Positive remodeling (expansive, lumen preserved)
  • Neovascularization (microvessels prone to hemorrhage)
Plaque Rupture vs Erosion
  • Plaque Rupture (60-75%): Fibrous cap fissure exposes lipid core → tissue factor exposure → platelet adhesion/activation → thrombus
  • Plaque Erosion (25-30%): Endothelial denudation without cap rupture → platelet adhesion to intimal matrix → thrombus
  • Calcified Nodule (2-7%): Eruptive calcification → thrombus

Stable Angina Pectoris

Definition & Epidemiology

Stable angina is characterized by predictable chest discomfort provoked by exertion or emotional stress and relieved by rest or nitroglycerin. It results from fixed coronary stenosis (typically >70%) limiting flow during increased myocardial oxygen demand. Prevalence increases with age: 2-4% in men aged 45-54, 10-15% in men aged 65-74.

Clinical Features
  • Location: Substernal, may radiate to neck, jaw, shoulders, arms (left > right), epigastrium, back
  • Quality: Pressure, tightness, squeezing, heaviness, burning; NOT sharp, stabbing, pleuritic
  • Duration: 2-10 minutes, builds gradually, relieved by rest/nitrates within 1-5 minutes
  • Precipitants: Exertion, emotional stress, cold exposure, heavy meals, sexual activity
  • Relieving Factors: Rest, nitroglycerin (1-3 minutes)
  • Associated Symptoms: Dyspnea, diaphoresis, nausea, fatigue
  • Atypical Presentation: More common in women, elderly, diabetics (silent ischemia)
Physical Examination
  • May be completely normal between episodes
  • During pain: Diaphoresis, pallor, tachycardia, hypertension, S4 gallop
  • Evidence of risk factors: Xanthelasma, corneal arcus, diabetic retinopathy, peripheral vascular disease
  • Carotid/abdominal/femoral bruits, diminished peripheral pulses
Class Description Functional Limitation
I Ordinary physical activity does not cause angina No limitation
II Slight limitation of ordinary activity Angina with walking >2 blocks, climbing >1 flight stairs at normal pace
III Marked limitation of ordinary physical activity Angina with walking 1-2 blocks, climbing 1 flight stairs at normal pace
IV Inability to carry on any physical activity without discomfort Angina at rest or with minimal activity
Diagnostic Approach
Initial Evaluation
  • Resting ECG: May show Q waves (old MI), ST-T changes, LVH. Normal in 50% of patients with CAD.
  • Basic Labs: CBC, CMP, lipids, HbA1c if diabetes suspected, TSH if symptoms suggest
  • Chest X-ray: Usually normal. May show cardiomegaly, pulmonary congestion, aortic calcification.
Non-Invasive Testing (Risk Stratification)
  • Exercise ECG (Stress Test): Sensitivity 68%, specificity 77%. Diagnostic if ≥1mm horizontal/downsloping ST depression. Duke Treadmill Score = Exercise time – (5 × ST deviation) – (4 × angina index: 0=none, 1=non- limiting, 2=limiting). Score ≥+5: low risk (1% annual mortality); -10 to +4: intermediate; ≤-11: high risk (5% annual mortality).
  • Stress Imaging: Indicated if baseline ECG abnormalities (LBBB, LVH, digoxin), prior revascularization, indeterminate exercise test.
    • Stress Echocardiography: Sensitivity 85%, specificity 81%. New regional wall motion abnormality indicates ischemia.
    • Myocardial Perfusion Imaging (SPECT): Sensitivity 88%, specificity 77%. Reversible perfusion defect = ischemia; fixed defect = infarct.
  • Coronary CT Angiography: Sensitivity 95%, specificity 83%. Rule out CAD if low-intermediate pretest probability. Calcium score: 0 = very low risk, >400 = high risk.
Invasive Coronary Angiography

Indications: High-risk features on non-invasive testing, CCS class III-IV despite medical therapy, suspected left main/3-vessel disease, survived sudden cardiac death, HF with angina.

Comprehensive Management Protocol

1
Acute Angina Attack

Sublingual nitroglycerin 0.3-0.6mg, repeat every 5 minutes ×3 max. Stop activity, sit or lie down. Seek emergency care if pain persists >10 minutes or worsens despite 3 nitroglycerin doses.

2
Lifestyle & Risk Factor Modification

Smoking: Complete cessation. Diet: Mediterranean-style (fruits, vegetables, whole grains, fish, olive oil), limit saturated fat <7% calories, trans fat <1%. Exercise: 30-60 minutes moderate intensity ≥5 days/week. Weight: Goal BMI 18.5-24.9. Blood Pressure: Target <130/80. Lipids: High-intensity statin (atorvastatin 40-80mg, rosuvastatin 20-40mg). Diabetes: HbA1c <7% (individualized).

3
Pharmacotherapy for Symptom Relief

First-line: Beta-blocker (metoprolol 25-100mg BID, bisoprolol 2.5-10mg daily) or CCB (amlodipine 5-10mg daily, diltiazem ER 120-360mg daily). Second-line: Add long-acting nitrate (isosorbide mononitrate 30-60mg daily with 8-12h nitrate-free period) or ranolazine (500-1000mg BID). Alternative: Ivabradine if sinus rhythm, HR >70 on beta-blocker (5-7.5mg BID).

4
Secondary Prevention (All Patients)

Anti- platelet: Aspirin 81-325mg daily lifelong (if not contraindicated). Consider adding clopidogrel 75mg daily if aspirin-intolerant. Statin: High-intensity regardless of LDL level. ACEI/ARB: If diabetes, CKD, LVEF ≤40%, hypertension. Beta- blocker: Post-MI, LVEF ≤40%. Ranolazine: Consider if persistent symptoms.

5
Revascularization Consideration

Refer for coronary angiography if:

  • CCS class III-IV despite optimal medical therapy
  • High-risk non-invasive test (large area ischemia, LVEF <50%, stress-induced hypotension/arrhythmia)
  • Clinical high-risk features: HF, survived sudden death
  • Occupational requirements (pilot, bus driver)
Choice: PCI for 1-2 vessel disease, CABG for left main, 3- vessel disease, diabetes with multivessel disease.

Comprehensive Medication Guide for Stable Angina

Drug Class Mechanism in Angina Representative Drugs Dosage Key Side Effects Contraindications Special Considerations
Beta-blockers ↓HR, ↓contractility, ↓BP → ↓MVO₂ Metoprolol, Atenolol, Bisoprolol, Carvedilol Metoprolol 25-100mg BID
Atenolol 25-100mg daily
Bisoprolol 2.5-10mg daily		 Fatigue, bradycardia, bronchospasm, erectile dysfunction, depression, masking hypoglycemia Asthma/COPD (relative), decompensated HF, bradycardia (<50), 2°/3° AV block, sick sinus syndrome First-line for effort angina. Target HR 55-60 bpm. Avoid abrupt withdrawal (rebound angina/MI). Carvedilol has α-blocking properties (↓afterload).
Calcium Channel Blockers (DHP) Arterial vasodilation → ↓afterload → ↓MVO₂; coronary vasodilation → ↑supply Amlodipine, Nifedipine XL, Felodipine Amlodipine 5-10mg daily
Nifedipine XL 30-120mg daily		 Peripheral edema (dose-dependent), headache, flushing, reflex tachycardia, gingival hyperplasia None absolute; caution in severe aortic stenosis, HFrEF Good for vasospastic angina. Amlodipine better tolerated than nifedipine. Combine with beta-blocker to prevent reflex tachycardia.
Calcium Channel Blockers (Non-DHP) ↓HR, ↓contractility, ↓BP → ↓MVO₂; coronary vasodilation Diltiazem, Verapamil Diltiazem ER 120-540mg daily
Verapamil SR 120-480mg daily		 Constipation (verapamil), bradycardia, AV block, HF exacerbation, headache Sick sinus syndrome, 2°/3° AV block, HFrEF (especially verapamil), WPW with AFib (verapamil) Good for angina + AFib rate control. Avoid combining with beta-blockers (excessive bradycardia). Diltiazem preferred in COPD/asthma.
Nitrates Venodilation → ↓preload → ↓MVO₂; coronary vasodilation → ↑supply Nitroglycerin SL, Isosorbide Dinitrate/Mononitrate NTG SL: 0.3-0.6mg PRN (max 3 in 15min)
ISMN: 30-60mg daily
ISDN: 10-40mg TID		 Headache, hypotension, flushing, tolerance (with continuous use) Hypotension, RV infarction, phosphodiesterase inhibitor use (sildenafil, tadalafil) within 24-48h Must have 8-12h nitrate-free period daily to prevent tolerance. ISMN once daily provides this automatically. Sublingual for acute attacks only.
Ranolazine Inhibits late Na⁺ current → ↓intracellular Ca²⁺ overload → ↓diastolic tension, ↓MVO₂ Ranolazine 500-1000mg BID Dizziness, nausea, constipation, QT prolongation (dose-dependent) Cirrhosis (Child-Pugh C), concomitant QT-prolonging drugs, congenital long QT Does not affect HR/BP. Add-on therapy when symptoms persist on beta-blocker/CCB. Monitor ECG for QTc >500ms.
Ivabradine Inhibits Iₓ current in SA node → ↓HR without affecting contractility/BP Ivabradine 5-7.5mg BID Phosphenes (visual brightness), bradycardia, AFib (increased risk) Acute decompensated HF, sick sinus syndrome, 3°/2° AV block, pacemaker-dependent, HR <60, hepatic impairment Only if sinus rhythm, HR >70 on maximally tolerated beta-blocker. Not first-line. SIGNIFY trial showed no mortality benefit.
Trimetazidine Inhibits fatty acid oxidation → shifts to glucose oxidation (more efficient ATP production per O₂) Trimetazidine 35mg BID Parkinsonism, tremor, restless legs (reversible) Parkinson’s disease, movement disorders, severe renal impairment Metabolic anti-ischemic agent. Limited data. Not available in US. Used as add-on therapy.
Beta-blockers (Metoprolol)
25-100mg BID. First-line for effort angina. ↓HR, ↓contractility, ↓BP. Target HR 55-60.
CCBs (Amlodipine)
5-10mg daily. Arterial vasodilation → ↓afterload. Peripheral edema common. Good for vasospastic angina.
Nitrates (ISMN)
30-60mg daily. Venodilation → ↓preload. Must have 8-12h nitrate-free period. SL NTG for acute attacks only.
Ranolazine
500-1000mg BID. Inhibits late Na⁺ current. Add-on therapy. Monitor QTc. No effect on HR/BP.
Ivabradine
5-7.5mg BID. ↓HR via Iₓ current inhibition. Only if sinus rhythm, HR >70 on beta-blocker. Phosphenes side effect.

Acute Coronary Syndromes

Spectrum & Definitions
  • Unstable Angina (UA): Ischemic chest discomfort at rest (>20 min), new onset (CCS III-IV), or accelerating pattern without troponin elevation.
  • Non-ST-Elevation MI (NSTEMI): Ischemic symptoms with troponin elevation but without persistent ST elevation.
  • ST-Elevation MI (STEMI): Ischemic symptoms with persistent (≥20 min) ST elevation in ≥2 contiguous leads or new LBBB.
Pathophysiology of ACS
  • Plaque Disruption: Rupture (60-75%), erosion (25-30%), calcified nodule (2-7%)
  • Thrombus Formation: Platelet adhesion (vWF, GP Ib) → activation (ADP, TxA₂, thrombin) → aggregation (GP IIb/IIIa) → fibrin formation → occlusive/non-occlusive thrombus
  • Vasoconstriction: Serotonin, thromboxane A₂, endothelin-1 from platelets; loss of NO from endothelium
  • Microembolization: Distal embolization of platelet aggregates → microvascular obstruction
Clinical Presentation
  • Typical: Substernal pressure/discomfort radiating to jaw/arm, associated with dyspnea, diaphoresis, nausea, anxiety
  • Atypical (more common in women, elderly, diabetics): Epigastric pain, indigestion, fatigue, syncope, confusion
  • Silent MI: 20-30% of MIs are clinically unrecognized, more common in diabetics, elderly

ST-Elevation Myocardial Infarction

ECG Diagnosis Criteria
  • New ST elevation at J-point: ≥2mm in men or ≥1.5mm in women in leads V₂-V₃ and/or ≥1mm in other leads
  • Contiguous Leads:
    • Anterior: V₁-V₄ (LAD)
    • Lateral: I, aVL, V₅-V₆ (LCx/diagonals)
    • Inferior: II, III, aVF (RCA/LCx)
    • Posterior: V₇-V₉ (reciprocal ST depression V₁-V₃, tall R in V₁-V₂)
    • Right ventricular: V₄R (RCA proximal)
  • New LBBB: Consider STEMI equivalent if clinical presentation consistent
  • Hyperacute T waves: Early sign (minutes), tall, broad-based
Localization of STEMI
Infarct Location Involved Coronary Artery ECG Leads Complications
Anterior LAD (proximal) V₁-V₄ LV dysfunction, cardiogenic shock, ventricular arrhythmias
Anteroseptal LAD (septal branches) V₁-V₃ Conduction abnormalities (RBBB, LAFB)
Anterolateral LAD (diagonals) or LCx I, aVL, V₅-V₆ Mitral regurgitation (papillary muscle dysfunction)
Inferior RCA (80%), LCx (20%) II, III, aVF Bradycardia (inferoposterior ischemia → vagal), RV infarction (if proximal RCA)
Posterior RCA or LCx (PDA) V₇-V₉ Often missed, reciprocal changes in V₁-V₃
Right Ventricular RCA (proximal) V₄R Hypotension with clear lungs, Kussmaul’s sign, avoid nitrates/diuretics
STEMI Management Protocol
1
Immediate Assessment (First 10 Minutes)

MONA: Morphine 2-4mg IV PRN pain (caution in inferior/RV MI), Oxygen if SpO₂ <90%, Nitroglycerin SL/IV (avoid if RV MI, hypotension), Aspirin 162-325mg chewable. IV access, cardiac monitor, 12-lead ECG. Activate catheterization lab for primary PCI.

2
Reperfusion Strategy

Primary PCI: Gold standard if available within 90 minutes of first medical contact. Door-to-balloon time <90 minutes. Fibrinolysis: If PCI not available within 120 minutes and symptom onset <12 hours. Door-to-needle time <30 minutes. Contraindications: active bleeding, intracranial hemorrhage history, ischemic stroke <3 months, aortic dissection, severe hypertension.

3
Adjunctive Pharmacotherapy

P2Y₁₂ Inhibitor: Ticagrelor 180mg load then 90mg BID (preferred) OR Clopidogrel 600mg load then 75mg daily (if ticagrelor/prasugrel contraindicated). Anticoagulation: Bivalirudin (0.75mg/kg bolus then 1.75mg/kg/h) OR UFH (60-70 U/kg bolus, max 5000U, then 12-15 U/kg/h, max 1000U/h). Beta-blocker: If hemodynamically stable (no HF, shock, bradycardia). Metoprolol 5mg IV q5min ×3 then oral. ACEI/ARB: Start within 24h if no hypotension, especially anterior MI, LVEF <40%. Statin: High-intensity (atorvastatin 80mg) regardless of LDL.

4
Monitoring & Complications Management

Admit to CCU. Monitor for:

  • Arrhythmias: VT/VF (defibrillate), bradycardia (atropine, pacing)
  • Heart Failure: Diuretics, afterload reduction
  • Cardiogenic Shock: IABP, inotropes, consider mechanical circulatory support
  • Mechanical Complications: VSD, free wall rupture, papillary muscle rupture (emergent surgery)

5
Long-term Management

DAPT: Continue for 12 months (ticagrelor/prasugrel) or clopidogrel if CABG. Beta-blocker: Continue indefinitely if no contraindication. ACEI/ARB: Indefinitely if LVEF ≤40% or anterior MI. MRA: Eplerenone if LVEF ≤40% + HF symptoms/diabetes (start 3-14 days post-MI). Statin: High-intensity lifelong. Cardiac rehab: Refer all patients.

NSTEMI/Unstable Angina

Risk Stratification
  • TIMI Risk Score: Age ≥65, ≥3 CAD risk factors, known CAD (stenosis ≥50%), ASA use in past 7d, severe angina (≥2 episodes in 24h), ST changes ≥0.5mm, positive cardiac markers. Score 0-2: low risk (4.7% event rate); 3-4: intermediate (8.3%); 5-7: high risk (13.2%).
  • GRACE Risk Score: More comprehensive, predicts in-hospital and 6-month mortality. Variables: age, HR, SBP, Cr, cardiac arrest, ST changes, elevated enzymes, Killip class.
  • High-Risk Features: Recurrent ischemia, dynamic ST changes, elevated troponin, HF, hemodynamic instability, malignant arrhythmias.
ECG Findings in NSTEMI
  • ST depression ≥0.5mm in ≥2 contiguous leads
  • T-wave inversion ≥2mm in ≥2 contiguous leads
  • Transient ST elevation (<20 minutes)
  • May be normal initially (repeat if symptoms recur)
Troponin Interpretation
  • High-sensitivity troponin (hs-cTn): Detectable in most healthy individuals
  • Rise and/or fall pattern necessary for diagnosis of acute MI
  • Peaks at 12-24 hours, returns to baseline over 5-14 days
  • Level correlates with infarct size and prognosis
  • Elevated troponin without ACS: PE, HF, sepsis, renal failure, myocarditis, cardiac contusion
NSTEMI/UA Management Protocol
1
Initial Stabilization

Aspirin 162-325mg chewable. Nitroglycerin SL/IV for ischemia. Morphine 2-4mg IV PRN pain. Oxygen if SpO₂ <90%. ECG, serial troponins, risk stratification (TIMI/GRACE).

2
Antithrombotic Therapy

P2Y₁₂ Inhibitor: Ticagrelor 180mg load then 90mg BID (preferred) OR Clopidogrel 300-600mg load then 75mg daily. Defer if CABG likely. Anticoagulation: Enoxaparin 1mg/kg SC q12h (preferred) OR UFH IV bolus 60-70 U/kg then 12-15 U/kg/h. Continue until PCI or for 48h. GP IIb/IIIa Inhibitor: High-risk patients undergoing PCI: Epitifibatide or tirofiban.

3
Early Invasive vs Ischemia-Guided Strategy

Early Invasive (within 24-48h): Indicated for: GRACE score >140, dynamic ST changes, elevated troponin, recurrent ischemia, HF, hemodynamic instability, LVEF <40%, prior CABG, PCI within 6 months. Ischemia-Guided: Low-risk patients (TIMI 0-2, normal troponin, no ECG changes).

4
Medical Therapy

Beta-blocker: If no contraindications (HF, shock, bradycardia). ACEI/ARB: If LVEF ≤40%, diabetes, hypertension, CKD. High-intensity statin: Start immediately. Nitrates: For ongoing ischemia. MRA: Consider if LVEF ≤40% and HF/diabetes.

5
Long-term Management

DAPT: 12 months minimum (extended therapy considered in high ischemic/low bleeding risk). Beta-blocker: Indefinitely. ACEI/ARB: Indefinitely if LVEF ≤40%. Statin: High-intensity lifelong. Cardiac rehab: Refer all. Risk factor modification: Aggressive lifestyle changes.

Unstable Angina

Definition & Diagnosis

Unstable angina is defined as ischemic chest discomfort with one of three features: (1) Occurring at rest or with minimal exertion and usually lasting >20 minutes; (2) Severe and new onset (within 1 month); (3) Occurring with a crescendo pattern (more severe, prolonged, or frequent than previously). Unlike NSTEMI, cardiac biomarkers (troponin) remain normal.

Biological Markers of Plaque Instability
  • High-sensitivity CRP: Marker of inflammation, predicts future events
  • Myeloperoxidase: Leukocyte enzyme, indicates plaque inflammation
  • Lipoprotein-associated phospholipase A₂: Enzyme in LDL, hydrolyzes oxidized phospholipids → pro-inflammatory products
  • Growth-differentiation factor-15: Stress-responsive cytokine, prognostic in ACS
Management Principles

Similar to NSTEMI but lower risk if troponin negative. All patients require anti-ischemic therapy, antithrombotic therapy, and risk stratification. Early invasive strategy generally reserved for high-risk features. Stress testing prior to discharge if managed conservatively.

ACS Pharmacotherapy Guide

Medication Class STEMI Dose NSTEMI/UA Dose Duration Key Trials
Aspirin 162-325mg chewable load, then 81-325mg daily 162-325mg chewable load, then 81-325mg daily Lifelong ISIS-2: 23% mortality reduction
Clopidogrel 600mg load, then 75mg daily 300-600mg load, then 75mg daily 12 months minimum CURE: 20% RR reduction vs aspirin alone in NSTEMI
Ticagrelor 180mg load, then 90mg BID 180mg load, then 90mg BID 12 months minimum PLATO: 16% RR reduction vs clopidogrel
Prasugrel 60mg load, then 10mg daily 60mg load, then 10mg daily 12 months minimum TRITON-TIMI 38: 19% RR reduction vs clopidogrel in ACS-PCI
Enoxaparin 30mg IV bolus, then 1mg/kg SC q12h 1mg/kg SC q12h 48h to 8 days EXTRACT-TIMI 25: Superior to UFH in STEMI
Fondaparinux 2.5mg SC daily 2.5mg SC daily Up to 8 days OASIS-5: Similar efficacy, less bleeding vs enoxaparin
Bivalirudin 0.75mg/kg bolus, then 1.75mg/kg/h infusion 0.75mg/kg bolus, then 1.75mg/kg/h infusion During PCI ± 4h post HORIZONS-AMI: Less bleeding vs UFH+GPIIb/IIIa
Abciximab 0.25mg/kg bolus, then 0.125 mcg/kg/min infusion (max 10 mcg/min) 0.25mg/kg bolus, then 0.125 mcg/kg/min infusion 12h infusion ADMIRAL: Better outcomes in STEMI-PCI
Aspirin
162-325mg chewable load, then 81-325mg daily lifelong. ISIS-2: 23% mortality reduction.
Ticagrelor
180mg load, then 90mg BID ×12 months minimum. PLATO: 16% RR reduction vs clopidogrel.
Enoxaparin
1mg/kg SC q12h ×48h-8 days. EXTRACT-TIMI 25: Superior to UFH in STEMI.
Bivalirudin
0.75mg/kg bolus, then 1.75mg/kg/h during PCI. HORIZONS-AMI: Less bleeding.
Mechanical Complications of MI
Papillary Muscle Rupture
  • Timing: 2-7 days post-MI
  • Presentation: Sudden pulmonary edema, holosystolic murmur (may be soft if LV failure), cardiogenic shock
  • Diagnosis: Echocardiography shows flail mitral leaflet, severe MR
  • Treatment: Emergent surgery (valve repair/replacement + CABG), IABP for stabilization
Ventricular Septal Rupture
  • Timing: 3 -5 days post-MI
  • Presentation: New holosystolic murmur (loud, harsh), HF, shock
  • Diagnosis: Echo with Doppler shows left-to-right shunt, step-up in O₂ saturation from RA to RV
  • Treatment: Emergent surgical repair, IABP, vasodilators (nitroprusside) to ↓afterload
Free Wall Rupture
  • Timing: 1-5 days post-MI, most fatal complication
  • Presentation: Sudden hemodynamic collapse, electromechanical dissociation (pulseless electrical activity)
  • Diagnosis: Echocardiography shows pericardial effusion with tamponade
  • Treatment: Emergent pericardiocentesis, surgical repair (rarely survived)
Left Ventricular Aneurysm
  • Timing: Weeks to months post-MI
  • Presentation: HF, angina, ventricular arrhythmias, systemic embolism
  • Diagnosis: Echo shows dyskinetic/akinetic segment with diastolic deformity, ECG shows persistent ST elevation
  • Treatment: Anticoagulation (if thrombus present), antiarrhythmics, aneurysmectomy if refractory symptoms
Key Clinical Pearls – Ischemic Heart Disease
  • Typical angina: Substernal pressure radiating to jaw/left arm, provoked by exertion, relieved by rest/nitrates.
  • Atypical presentations more common in women, diabetics, elderly: epigastric pain, indigestion, fatigue.
  • Silent ischemia: 20-30% of MIs are clinically unrecognized, especially in diabetics.
  • Non-cardiac chest pain: Pleuritic (worsens with breathing), positional (worsens with certain positions), reproducible by palpation, sharp/stabbing.
  • Early repolarization: Normal variant with J-point elevation, concave ST segment, notched J point, stable over time.
  • Pericarditis: Diffuse ST elevation (concave up), PR depression, pericardial rub, pain relief with sitting forward.
  • Takotsubo cardiomyopathy: Emotional/physical stress, apical ballooning, minimal troponin elevation relative to wall motion abnormalities.
  • Rule of 300: For ST elevation, the number of QRS complexes between R waves multiplied by 300 gives heart rate.
  • Wellens’ syndrome: Biphasic or deeply inverted T waves in V₂-V₃ indicates critical LAD stenosis, high risk for anterior MI.
  • de Winter pattern: ST depression in V₁-V₄ with tall symmetrical T waves = acute LAD occlusion (STEMI equivalent).
High-Yield Exam Points – IHD:
  • STEMI ECG criteria: ≥2mm ST elevation in V₂-V₃ (men), ≥1.5mm (women), ≥1mm in other leads in ≥2 contiguous leads.
  • Right ventricular MI: ST elevation in V₄R, treat with fluids, avoid nitrates/diuretics.
  • Posterior MI: ST depression in V₁-V₃, tall R in V₁-V₂, confirm with posterior leads V₇-V₉.
  • Door-to-balloon time: <90 minutes for primary PCI.
  • Door-to-needle time: <30 minutes for fibrinolysis.
  • TIMI risk score for NSTEMI: 7 variables, high risk if ≥5.
  • GRACE risk score: More accurate for mortality prediction in NSTEMI.
  • DAPT duration post-ACS: 12 months minimum (ticagrelor/prasugrel preferred over clopidogrel).
  • Mechanical complications post-MI: Papillary muscle rupture (acute MR), VSD (new harsh murmur), free wall rupture (PEA).
  • Takotsubo: Apical ballooning, emotional stress, minimal enzyme elevation, usually reversible.