4.1 Cardiovascular Disorders

Why Cardiovascular Therapeutics Dominates the NAPLEX

The Person-Centered Assessment and Treatment Planning domain is 40% of the NAPLEX, and cardiovascular disease appears throughout it because nearly every adult patient vignette carries a cardiometabolic comorbidity. You will be asked to select guideline-concordant therapy, recommend monitoring, identify a clinically significant interaction, and adjust regimens for organ dysfunction. The exam rewards reasoning from patient-specific factors rather than memorized first-line lists.

Approach every cardiovascular case the same way: confirm the diagnosis and severity, check for compelling indications and contraindications, choose evidence-based therapy, and define what you will monitor for efficacy and toxicity.

Hypertension

Hypertension is sustained elevation of arterial blood pressure that increases risk of stroke, myocardial infarction, heart failure, and chronic kidney disease (CKD). Therapy selection is driven by compelling indications: comorbid conditions that make one drug class preferred independent of blood pressure alone.

First-Line Drug Classes

For most patients without a compelling indication, first-line therapy is chosen from three classes, often started as two agents when blood pressure is markedly above goal.

A renin-angiotensin system blocker (ACEi or ARB) plus a CCB or thiazide is a preferred two-drug combination. An ACE inhibitor and an ARB are not used together because the combination increases hyperkalemia, acute kidney injury, and hypotension without added benefit.

Compelling Indications

• Diabetes or albuminuric CKD: ACEi or ARB for kidney protection.
• Heart failure with reduced ejection fraction: beta-blocker plus renin-angiotensin blockade plus an MRA (see HFrEF below).
• Post-myocardial infarction or stable ischemic heart disease: beta-blocker plus ACEi/ARB.
• Black patients without HF or CKD: a CCB or thiazide is often more effective than renin-angiotensin blockade as initial monotherapy.

Hypertensive Emergency vs Urgency

A hypertensive emergency is severely elevated blood pressure with acute target-organ damage and requires intravenous therapy in a monitored setting with controlled blood pressure lowering. Hypertensive urgency is severe elevation without acute organ damage and is managed with oral agents and close follow-up; abrupt large reductions can cause ischemic complications.

Heart Failure with Reduced Ejection Fraction (HFrEF)

HFrEF is a clinical syndrome of impaired ventricular filling or ejection with a reduced left ventricular ejection fraction. Modern guideline-directed medical therapy is built on four foundational pillars that each independently reduce mortality and hospitalization. The current standard is to initiate all four classes early and titrate to target or maximally tolerated doses.

Supportive agents include loop diuretics (furosemide, torsemide, bumetanide) for congestion and symptom control, and additional agents such as hydralazine-isosorbide dinitrate or ivabradine in selected patients. Loop diuretics relieve symptoms but are not mortality-reducing pillars.

Clinical pearl: The single most tested HFrEF interaction is the ARNI-ACEi overlap. Switching a patient from lisinopril to sacubitril-valsartan requires holding the ACE inhibitor for 36 hours before the first ARNI dose because overlapping neprilysin and ACE inhibition markedly increases bradykinin-mediated angioedema risk.

Acute Coronary Syndrome and Ischemic Heart Disease

Acute coronary syndrome (ACS) spans unstable angina and myocardial infarction caused by acute coronary plaque disruption. Acute management classically includes antiplatelet therapy, anticoagulation, anti-ischemic therapy, and reperfusion when indicated.

Antiplatelet and Secondary Prevention Therapy

• Dual antiplatelet therapy (DAPT): aspirin plus a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) after ACS, with duration individualized by ischemic and bleeding risk.
• High-intensity statin: initiated for plaque stabilization and long-term LDL-C lowering.
• Beta-blocker and ACEi/ARB: reduce remodeling and recurrent events, especially with reduced ejection fraction.
• Nitrates: relieve anginal symptoms; sublingual nitroglycerin for acute angina.

High-yield interaction: Phosphodiesterase-5 inhibitors (for example, sildenafil, tadalafil) are contraindicated with any nitrate because the combination causes profound, potentially fatal hypotension. This is one of the most consistently tested cardiovascular contraindications.

For chronic stable ischemic heart disease, antianginal therapy includes beta-blockers, calcium channel blockers, and long-acting nitrates, with ranolazine as an add-on; all patients receive aspirin and a statin for secondary prevention unless contraindicated.

Atrial Fibrillation and Anticoagulation

Atrial fibrillation (AF) is an irregular supraventricular arrhythmia that increases thromboembolic stroke risk. Management has three components: rate or rhythm control, and stroke prevention.

Stroke Risk Stratification

The CHA2DS2-VASc score estimates annual stroke risk and drives anticoagulation decisions. A higher score generally favors oral anticoagulation; bleeding risk is assessed separately and is used to manage modifiable risk factors rather than to withhold anticoagulation outright.

For most patients with nonvalvular AF, a DOAC is preferred over warfarin because of more predictable pharmacokinetics, fewer dietary interactions, and lower intracranial bleeding rates. Warfarin remains the agent of choice for mechanical heart valves and moderate-to-severe mitral stenosis. Rate control commonly uses beta-blockers or non-dihydropyridine CCBs (diltiazem, verapamil); the latter are avoided in HFrEF because of negative inotropy.

Dyslipidemia

Dyslipidemia is an abnormal lipid profile that drives atherosclerotic plaque formation. Treatment intensity is matched to overall ASCVD risk rather than to LDL-C alone.

• Statins are first-line; high-intensity statins are used for established ASCVD and other high-risk groups.
• Ezetimibe is the usual first add-on when LDL-C remains above goal on a maximally tolerated statin.
• PCSK9 inhibitors and additional non-statin agents are reserved for very high-risk patients not at goal.

Monitoring: Check a baseline lipid panel and repeat after initiation or dose change to assess response and adherence. Statin myopathy risk increases with interacting CYP3A4 inhibitors; counsel patients to report new muscle pain or weakness.