19.6 Adjunct Medications Used in Heart Failure

Adjunct Medications in Heart Failure Treatment

Key Adjunct Medications for Heart Failure

Heart failure management often requires layering several drugs on top of the foundational therapies (ACE inhibitors, beta-blockers, diuretics). The adjunct medications below each address a specific piece of the heart failure puzzle.

Digoxin is a cardiac glycoside used in heart failure and atrial fibrillation. It increases cardiac contractility by inhibiting the sodium-potassium ATPase pump, which ultimately raises intracellular calcium levels. Digoxin also slows heart rate through vagal stimulation, reducing the workload on the heart. It does not improve mortality but can reduce symptoms and hospitalizations.

Hydralazine and isosorbide dinitrate (BiDil) is a vasodilator combination that reduces cardiac workload and improves cardiac output. Hydralazine is an arterial vasodilator that lowers afterload. Isosorbide dinitrate is a venous vasodilator that lowers preload. Together, they lighten the load on both sides of the heart. This combination is particularly important for African American patients with HFrEF, where clinical trials have shown significant mortality benefit.

Ivabradine (Corlanor) is a selective sinus node inhibitor that lowers heart rate without affecting contractility or blood pressure. It works by blocking hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the sinoatrial node. It's used in patients with HFrEF who have a resting heart rate ≥70 bpm despite being on maximally tolerated beta-blocker doses.

Vericiguat (Verquvo) is a soluble guanylate cyclase (sGC) stimulator. It enhances production of cyclic guanosine monophosphate (cGMP), which promotes vasodilation and reduces cardiac remodeling. Vericiguat is indicated for patients with worsening chronic heart failure (typically after a recent hospitalization or need for IV diuretics) to reduce the risk of further hospitalization and cardiovascular death.

Foundational Heart Failure Medications (Brief Review)

These are the core therapies you'll see adjunct drugs added onto:

• ACE inhibitors reduce angiotensin II production, causing vasodilation and decreased cardiac workload. They improve survival and reduce hospitalizations.
• Beta-blockers slow heart rate and reduce myocardial oxygen demand, improving left ventricular function over time. Particularly beneficial in heart failure with reduced ejection fraction (HFrEF).
• Diuretics manage fluid overload by increasing urine output, relieving congestion symptoms like shortness of breath and edema. They improve symptoms but have not been shown to improve mortality.
• Aldosterone antagonists (spironolactone, eplerenone) block aldosterone's effects, reducing fluid retention and harmful cardiac remodeling. Useful in severe heart failure and post-MI patients.
• Natriuretic peptides (BNP, NT-proBNP) are not medications but biomarkers. Elevated levels indicate increased cardiac wall stress and help diagnose heart failure, gauge severity, and guide treatment decisions.

Mechanisms of Adjunct Heart Failure Drugs

Digoxin works through a three-step chain reaction:

1. It inhibits the sodium-potassium ATPase pump on cardiac cell membranes.
2. Intracellular sodium rises, which reduces the sodium-calcium exchange, so calcium accumulates inside the cell.
3. Higher intracellular calcium strengthens myocardial contractions (positive inotropic effect).

Digoxin also stimulates the vagus nerve, which slows conduction through the AV node and reduces heart rate.

Hydralazine and isosorbide dinitrate work on two different parts of the vasculature:

• Hydralazine relaxes arterial smooth muscle, lowering peripheral vascular resistance (afterload).
• Isosorbide dinitrate releases nitric oxide, which dilates veins, increasing venous capacitance (reducing preload).
• The combined reduction in preload and afterload improves cardiac output while decreasing myocardial oxygen demand.

Ivabradine targets the "funny current" ($I_f$) in sinoatrial node pacemaker cells:

• HCN channels drive the spontaneous depolarization that sets heart rate.
• Blocking these channels slows the rate of depolarization, reducing heart rate.
• Because it only acts on the SA node, it does not lower blood pressure or reduce contractility.

Vericiguat works downstream of nitric oxide signaling:

1. It directly stimulates soluble guanylate cyclase, even when nitric oxide levels are low (common in heart failure).
2. This increases conversion of GTP to cGMP.
3. Elevated cGMP promotes vascular smooth muscle relaxation, vasodilation, and reduced cardiac remodeling.

Side Effects of Adjunct Heart Failure Medications

Digoxin

• GI symptoms: nausea, vomiting, loss of appetite
• Visual disturbances: blurred vision, characteristic yellow-green halos around lights
• Cardiac arrhythmias, especially when potassium is low (hypokalemia potentiates toxicity)
• CNS effects: confusion, disorientation, delirium, particularly in older adults or patients with renal impairment (digoxin is renally cleared)

Hydralazine and Isosorbide Dinitrate

• Headache, dizziness, and lightheadedness from vasodilation
• Reflex tachycardia as the body compensates for lower blood pressure
• Flushing, skin rash, and itching
• With long-term hydralazine use: drug-induced lupus-like syndrome (rare but important to know)

Ivabradine

• Bradycardia, especially in patients with pre-existing conduction disorders or those on other rate-lowering drugs
• Visual disturbances called phosphenes (brief flashes or increased brightness, often triggered by sudden changes in light)
• Atrial fibrillation, which can paradoxically increase heart rate and undermine ivabradine's benefit

Vericiguat

• Hypotension, particularly when combined with other vasodilators or antihypertensives
• Headache and dizziness from vasodilation
• Anemia due to potential effects on erythropoiesis and hemoglobin levels

Nursing Considerations for Adjunct Therapies

Digoxin

• Check the apical pulse for a full 60 seconds before administration. Hold the dose and notify the provider if the heart rate is below 60 bpm (or per facility protocol).
• Monitor serum digoxin levels regularly. The therapeutic range is narrow, and levels above 2.0 ng/mL significantly increase toxicity risk.
• Track potassium, magnesium, and calcium levels. Hypokalemia and hypomagnesemia increase sensitivity to digoxin toxicity, even at "therapeutic" drug levels.
• Teach patients to recognize toxicity signs: nausea, visual changes, new palpitations, or confusion. Emphasize the importance of keeping follow-up lab appointments.
• Know that digoxin immune Fab (Digibind) is the antidote for severe digoxin toxicity.

Hydralazine and Isosorbide Dinitrate

• Monitor blood pressure and heart rate closely during dose titration.
• Isosorbide dinitrate requires a nitrate-free interval (typically 10–12 hours overnight) to prevent tolerance. Doses are usually scheduled asymmetrically (e.g., 8 AM, 1 PM, 6 PM rather than every 8 hours).
• Warn patients not to stop the medication abruptly, as rebound hypertension or angina can occur.
• Instruct patients to rise slowly from sitting or lying positions to minimize orthostatic hypotension.

Ivabradine

• Assess heart rate and rhythm regularly. Ivabradine should generally be avoided if resting heart rate drops below 60 bpm.
• Take ivabradine with food, as this improves absorption.
• Educate patients that phosphenes (visual brightness or flashes) are usually transient and not harmful, but should be reported.
• Monitor for new-onset atrial fibrillation, which may require stopping ivabradine or adding rate-control therapy.
• Avoid grapefruit juice, which inhibits CYP3A4 and can increase ivabradine levels.

Vericiguat

• Monitor blood pressure closely when starting therapy or adjusting doses.
• Check hemoglobin levels periodically to catch developing anemia early.
• Vericiguat is contraindicated with other sGC stimulators (e.g., riociguat) and with PDE5 inhibitors (e.g., sildenafil) due to risk of severe hypotension.
• Teach patients to report dizziness, lightheadedness, or unusual fatigue.

General Considerations for All Adjunct Therapies

• Assess medication adherence at every visit. Practical tools like pill organizers, phone alarms, or pharmacy sync programs can help.
• Reinforce lifestyle modifications: sodium restriction (typically <2 g/day), daily weight monitoring, appropriate physical activity, and fluid management as prescribed.
• Regularly reassess the patient's NYHA functional classification (Class I–IV) to track disease progression and guide therapy adjustments.
• Encourage patients to report any new or worsening symptoms promptly, including increased shortness of breath, weight gain of more than 2–3 lbs in a day (or 5 lbs in a week), or new edema.