What is the drug of choice for accelerated hypertension in a patient with coronary artery disease (CAD) and acute coronary syndrome (ACS)?

Drug of Choice for Accelerated Hypertension in CAD with ACS

For patients with acute coronary syndrome and accelerated hypertension, intravenous nitroglycerin is the first-line agent, followed by intravenous beta-blockers (esmolol or metoprolol) if there are no contraindications such as hemodynamic instability, heart failure, or bradycardia. 1

Initial Management: Nitroglycerin

Intravenous nitroglycerin should be considered first-line to lower blood pressure and relieve ongoing ischemia or pulmonary congestion in patients with ACS and hypertension (Class I; Level of Evidence C). 1

• Nitroglycerin is particularly useful when there is ongoing ischemia or pulmonary congestion, as it reduces myocardial oxygen demand without negative inotropic effects 1, 2
• Start with sublingual or intravenous nitroglycerin, which can be transitioned to longer-acting preparations once stable 1
• Critical contraindications include suspected right ventricular infarction, hemodynamic instability, and use of phosphodiesterase-5 inhibitors within 24-48 hours 1, 3

Beta-Blocker Therapy: Second-Line or Adjunctive

If there is no contraindication, initial therapy should include a short-acting β1-selective beta-blocker without intrinsic sympathomimetic activity (metoprolol tartrate or bisoprolol), typically initiated orally within 24 hours (Class I; Level of Evidence A). 1

For Severe Hypertension or Ongoing Ischemia:

• Intravenous esmolol can be considered for patients with severe hypertension or ongoing ischemia (Class IIa; Level of Evidence B) 1
• Esmolol offers the advantage of ultra-short action, allowing rapid titration and quick reversal if complications develop 4
• Beta-blockers reduce heart rate and blood pressure, thereby decreasing myocardial oxygen demand and reducing reinfarction risk 1, 5

Critical Contraindications to Beta-Blockers:

Beta-blocker therapy should be delayed until stabilization in hemodynamically unstable patients or when decompensated heart failure exists (Class I; Level of Evidence A). 1

• Absolute contraindications include bradycardia (<60 bpm), marked first-degree heart block (PR >0.24 seconds), second- or third-degree heart block, severe bronchospastic disease, decompensated heart failure, and hypotension 1, 2, 6
• The COMMIT trial demonstrated increased cardiogenic shock risk (5.0% vs 3.9%) with early intravenous beta-blockers, particularly in hemodynamically unstable patients 1
• Early intravenous beta-blocker therapy should be used selectively and restricted to patients with significant hypertension or tachycardia and those at low risk for hemodynamic compromise 1

Alternative Agents When Beta-Blockers Are Contraindicated

If there is a contraindication to beta-blockers or intolerable side effects, a nondihydropyridine calcium channel blocker (verapamil or diltiazem) may be substituted for patients with ongoing ischemia, provided that left ventricular dysfunction or heart failure is not present (Class IIa; Level of Evidence B). 1

Nicardipine as Alternative:

• Intravenous nicardipine is recommended as the best alternative if nitroglycerin is ineffective or not tolerated, as it reduces afterload without affecting heart rate or conduction 2, 7
• Nicardipine produces significant decreases in systemic vascular resistance and has been shown to improve left ventricular function in patients with coronary artery disease 7
• In patients with coronary artery disease, nicardipine improves perfusion and aerobic metabolism in ischemic areas 7

Long-Term Management Considerations

An ACE inhibitor (Class I; Level of Evidence A) or ARB (Class I; Level of Evidence B) should be added if the patient has anterior MI, persistent hypertension, left ventricular dysfunction, heart failure, or diabetes mellitus. 1

• The combination of beta-blocker, ACE inhibitor or ARB, and thiazide diuretic provides complementary actions on the sympathetic nervous system and renin-angiotensin-aldosterone system 1, 8
• These agents have established evidence for risk reduction in ACS beyond their blood pressure-lowering effects 1

Critical Pitfalls to Avoid

• Avoid hypotension, which risks worsening myocardial ischemia 1
• Do not use short-acting nifedipine, which has been associated with increased mortality in post-MI patients 1
• Uncontrolled hypertension increases bleeding risk with antiplatelet and anticoagulation therapy, particularly hemorrhagic stroke risk, providing rationale for aggressive blood pressure control 1
• Never initiate beta-blockers on the day of surgery in beta-blocker-naïve patients (Class III: Harm; Level of Evidence B-NR) 1
• Avoid abrupt discontinuation of chronically administered beta-blockers, which can precipitate severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias 6

Monitoring Requirements

• Continuous cardiac monitoring for heart rate, rhythm, and blood pressure 2
• Assess for signs of ongoing ischemia (chest pain, ECG changes, troponin elevation) during blood pressure reduction 2
• Target blood pressure reduction should be gradual to avoid compromising coronary perfusion 1