Heart Failure Drugs: Types, How They Work & Side Effects

What Are Heart Failure Medications and Why Are They Important?

Heart failure medications are drugs that help the heart pump more efficiently, reduce its workload, remove excess fluid from the body, and prevent harmful hormonal responses. Modern drug therapy can reduce the risk of death by up to 50% and significantly decrease hospital admissions when multiple medication classes are used together.

Heart failure is a chronic condition where the heart cannot pump blood effectively enough to meet the body's needs. This leads to symptoms like shortness of breath, fatigue, and fluid retention causing swelling in the legs and ankles. Without treatment, heart failure progressively worsens over time, leading to increasingly severe symptoms, frequent hospitalizations, and reduced life expectancy.

The good news is that heart failure treatment has advanced dramatically over the past few decades. We now have multiple classes of medications that work through different mechanisms to improve heart function and outcomes. Clinical trials have consistently shown that patients who receive optimal medical therapy - meaning the right combination of medications at appropriate doses - have significantly better quality of life and longer survival compared to those who receive incomplete treatment.

The concept of "guideline-directed medical therapy" (GDMT) has become central to heart failure management. This refers to using all four major drug classes that have been proven to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF). These four pillars include ACE inhibitors or ARNIs, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors. Each class works differently, and their benefits are additive when used together.

Understanding your medications is crucial for successful heart failure management. When you know why each drug is prescribed and what to expect, you're more likely to take them consistently and report any problems to your healthcare team. This collaborative approach between patients and healthcare providers leads to better outcomes and helps you maintain the best possible quality of life.

How Heart Failure Medications Work Together

Heart failure triggers a cascade of harmful responses in the body. The heart, sensing that it's not pumping effectively, activates the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. While these responses are meant to be protective in the short term, chronic activation causes further damage to the heart and blood vessels.

Different medication classes target different parts of this harmful cycle. ACE inhibitors and ARBs block the RAAS, reducing strain on the heart. Beta-blockers slow the heart rate and reduce the effects of adrenaline. MRAs block aldosterone, a hormone that causes fluid retention and heart damage. SGLT2 inhibitors work through multiple mechanisms that are still being fully understood but provide additional protection beyond what other drugs offer.

What Are ACE Inhibitors and How Do They Help Heart Failure?

ACE inhibitors (such as enalapril, ramipril, and lisinopril) are foundational heart failure medications that block the production of angiotensin II, a hormone that constricts blood vessels and increases blood pressure. By relaxing blood vessels and reducing strain on the heart, ACE inhibitors improve symptoms, prevent disease progression, and reduce mortality by approximately 20-25%.

ACE inhibitors were among the first medications proven to improve survival in heart failure patients, and they remain a cornerstone of treatment today. The landmark CONSENSUS and SOLVD trials in the late 1980s and early 1990s demonstrated that enalapril significantly reduced deaths and hospitalizations in patients with heart failure. Since then, ACE inhibitors have become one of the most important drug classes for managing this condition.

When you have heart failure, your body produces excess amounts of a hormone called angiotensin II. This hormone causes blood vessels to constrict, increases blood pressure, and stimulates the release of aldosterone, which causes salt and water retention. All of these effects make the heart work harder and contribute to disease progression. ACE inhibitors work by blocking the enzyme that converts angiotensin I to angiotensin II, thereby reducing these harmful effects.

Patients taking ACE inhibitors typically notice improvements in their symptoms over several weeks. Shortness of breath often decreases, and exercise tolerance improves as the heart doesn't have to work as hard to pump blood through relaxed blood vessels. Beyond symptom relief, ACE inhibitors also slow down the structural changes that occur in the failing heart, a process called cardiac remodeling.

Your doctor will usually start ACE inhibitors at a low dose and gradually increase it over time. This approach helps minimize side effects while eventually reaching the doses that were shown to be most effective in clinical trials. It's important to reach these target doses whenever possible, as studies show that higher doses provide greater benefits than lower doses.

Common Side Effects of ACE Inhibitors

The most common side effect of ACE inhibitors is a dry, persistent cough, which occurs in about 5-20% of patients. This cough is caused by the buildup of substances called bradykinins and typically doesn't respond to cough suppressants. If the cough becomes intolerable, your doctor may switch you to an ARB or ARNI instead, which work similarly but rarely cause coughing.

Other potential side effects include dizziness or lightheadedness, especially when standing up quickly. This occurs because ACE inhibitors lower blood pressure. Taking your medication at bedtime and rising slowly from sitting or lying positions can help minimize this effect. Elevated potassium levels (hyperkalemia) can also occur, particularly in patients with kidney problems, which is why your doctor will monitor your blood tests regularly.

Rarely, ACE inhibitors can cause a condition called angioedema, where swelling occurs in the lips, tongue, or throat. This is a medical emergency that requires immediate treatment. If you experience any facial or throat swelling, seek emergency care immediately and do not take any more of the medication.

ARBs as an Alternative

Angiotensin receptor blockers (ARBs) such as losartan, valsartan, and candesartan work similarly to ACE inhibitors but block the receptor for angiotensin II rather than its production. ARBs are an excellent alternative for patients who cannot tolerate ACE inhibitors, particularly those with persistent cough. Clinical trials have shown that ARBs provide similar benefits to ACE inhibitors in heart failure.

What Is ARNI (Sacubitril/Valsartan) and Why Is It Revolutionary?

ARNI (angiotensin receptor-neprilysin inhibitor) combines valsartan with sacubitril to provide dual protection for the heart. The PARADIGM-HF trial showed that sacubitril/valsartan (Entresto) reduced cardiovascular death and heart failure hospitalization by 20% compared to enalapril, making it the preferred choice over ACE inhibitors in many patients with heart failure with reduced ejection fraction.

Sacubitril/valsartan represents one of the most significant advances in heart failure treatment in recent decades. This medication combines an ARB (valsartan) with a new type of drug called a neprilysin inhibitor (sacubitril). By inhibiting neprilysin, the drug increases levels of beneficial natriuretic peptides that help the body eliminate sodium and water while reducing stress on the heart.

The PARADIGM-HF trial, published in 2014, compared sacubitril/valsartan to enalapril in over 8,000 patients with heart failure and reduced ejection fraction. The results were so striking that the trial was stopped early because it was deemed unethical to continue giving patients the less effective treatment. Patients receiving sacubitril/valsartan had a 20% lower risk of cardiovascular death or heart failure hospitalization, along with improvements in quality of life.

Current guidelines now recommend sacubitril/valsartan as the preferred therapy over ACE inhibitors in patients who remain symptomatic despite treatment with ACE inhibitors, beta-blockers, and MRAs. Many experts also support starting sacubitril/valsartan as initial therapy in newly diagnosed patients, given its superior efficacy. Your doctor will consider your individual circumstances when deciding the best approach.

When switching from an ACE inhibitor to sacubitril/valsartan, there must be a washout period of at least 36 hours between stopping the ACE inhibitor and starting the ARNI. This prevents a rare but serious condition called angioedema. If you're switching medications, your doctor will provide specific instructions about timing.

Side Effects of Sacubitril/Valsartan

The side effects of sacubitril/valsartan are similar to those of ARBs, including low blood pressure, elevated potassium, and kidney function changes. Unlike ACE inhibitors, it rarely causes cough. Some patients experience symptomatic low blood pressure, particularly when starting the medication, which often improves with time or dose adjustment.

How Do Beta-Blockers Help the Failing Heart?

Beta-blockers (such as bisoprolol, carvedilol, and metoprolol succinate) protect the heart by slowing the heart rate, reducing blood pressure, and blocking harmful stress hormones like adrenaline. Despite initially seeming counterintuitive for a weakened heart, beta-blockers have been proven to improve heart function over time and reduce mortality by approximately 30% in heart failure patients.

For many years, beta-blockers were thought to be dangerous in heart failure because they reduce the heart's pumping strength. Doctors worried that blocking the effects of adrenaline would make a weakened heart pump even less effectively. However, landmark clinical trials in the 1990s and 2000s completely changed this understanding and revealed that beta-blockers are actually among the most beneficial heart failure medications.

When you have heart failure, your body chronically activates the sympathetic nervous system, releasing excess adrenaline and noradrenaline. While this is meant to compensate for reduced heart function, prolonged exposure to these stress hormones is toxic to heart cells and accelerates disease progression. Beta-blockers protect the heart from this harmful hormonal exposure.

Patients starting beta-blockers may initially feel slightly worse for the first few weeks as the body adjusts. This is normal and expected. Over time, typically 3-6 months, the heart begins to recover and strengthen. Studies using cardiac imaging have shown that beta-blockers can actually reverse some of the structural damage in the heart, improving its pumping ability. This recovery, called reverse remodeling, is one of the most remarkable effects of modern heart failure therapy.

Three beta-blockers have been specifically proven to benefit heart failure patients: bisoprolol, carvedilol, and metoprolol succinate (the extended-release form). Not all beta-blockers are equally effective for heart failure, so it's important to use one of these evidence-based options. Your doctor will start at a low dose and gradually increase it over several weeks to months.

Common Side Effects of Beta-Blockers

The most common side effects of beta-blockers include fatigue, particularly in the first few weeks of treatment. Many patients find this improves as their body adjusts to the medication. Cold hands and feet can occur because beta-blockers reduce blood flow to the extremities. Slow heart rate (bradycardia) is expected and usually beneficial, but if your heart rate becomes too slow or you feel dizzy, contact your doctor.

Beta-blockers can worsen symptoms in some patients with asthma, although many patients with mild asthma or COPD can take them safely with careful monitoring. They can also affect blood sugar control in diabetics. Sexual dysfunction, particularly erectile dysfunction in men, can occur but is often reversible with dose adjustment or switching to a different beta-blocker.

What Are Diuretics and How Do They Relieve Heart Failure Symptoms?

Diuretics (water pills) such as furosemide, bumetanide, and torasemide remove excess fluid from the body by increasing urine production. While they don't improve long-term survival like other heart failure medications, diuretics provide rapid relief from symptoms like shortness of breath and swelling, making them essential for managing acute symptoms and fluid overload.

Heart failure causes the kidneys to retain salt and water, leading to fluid buildup in the lungs (causing shortness of breath) and in the tissues (causing swelling in the legs, ankles, and abdomen). This fluid overload, called congestion, is responsible for many of the symptoms that make heart failure so debilitating. Diuretics directly address this problem by helping the kidneys eliminate excess fluid.

Loop diuretics like furosemide (Lasix) are the most commonly used diuretics in heart failure. They work on a part of the kidney called the loop of Henle, blocking the reabsorption of sodium and water. The effect is rapid - you'll typically notice increased urination within an hour of taking the medication, and symptoms like breathlessness can improve within days.

Unlike ACE inhibitors, beta-blockers, and other disease-modifying medications, diuretics primarily treat symptoms rather than improving long-term outcomes. They don't reverse the underlying heart damage or prevent disease progression. However, they remain essential for managing congestion and keeping patients comfortable. Many patients need ongoing diuretic therapy, while others only need them during episodes of fluid retention.

The dose of diuretics often needs adjustment based on symptoms and weight. Your doctor may teach you to adjust your diuretic dose at home based on daily weight monitoring. Weight gain of more than 2 kg in 2-3 days often indicates fluid retention and may require increasing your diuretic dose. Always follow your doctor's specific instructions about dose adjustments.

Thiazide Diuretics

Thiazide diuretics like hydrochlorothiazide and metolazone work on a different part of the kidney and are sometimes added to loop diuretics for patients who develop resistance to loop diuretics alone. This combination can be very effective but requires careful monitoring because it can cause significant electrolyte losses.

Side Effects of Diuretics

The most common side effect of diuretics is frequent urination, which is expected as this is how the medication works. Taking your diuretic in the morning helps avoid disrupting sleep. Diuretics can cause electrolyte imbalances, particularly low potassium (hypokalemia), low sodium, and low magnesium. Your doctor will monitor your blood tests and may prescribe supplements if needed.

Dehydration and low blood pressure can occur if diuretic doses are too high or if you become ill with vomiting or diarrhea. Signs of dehydration include thirst, dizziness, and reduced urine output. During hot weather or illness, you may need to temporarily reduce your diuretic dose - consult your doctor for guidance.

What Are MRAs and Why Are They Called Potassium-Sparing Diuretics?

Mineralocorticoid receptor antagonists (MRAs) such as spironolactone and eplerenone block the hormone aldosterone, which causes salt retention and heart damage. Despite their diuretic properties, MRAs are considered one of the four pillars of heart failure therapy because they significantly reduce mortality - the RALES trial showed spironolactone reduced deaths by 30% in severe heart failure.

Aldosterone is a hormone produced by the adrenal glands that causes the kidneys to retain sodium and excrete potassium. In heart failure, aldosterone levels become chronically elevated, contributing to fluid retention, potassium loss, and direct damage to the heart muscle. This damage includes fibrosis (scarring) and inflammation that worsen heart function over time.

MRAs block the receptors that aldosterone binds to, preventing these harmful effects. The RALES trial, published in 1999, demonstrated that adding spironolactone to standard therapy reduced mortality by 30% in patients with severe heart failure. Later, the EMPHASIS-HF trial showed similar benefits for eplerenone in patients with milder symptoms. These dramatic results established MRAs as a core component of heart failure therapy.

Unlike traditional diuretics that cause potassium loss, MRAs actually raise potassium levels, which is why they're called "potassium-sparing." This effect requires careful monitoring, especially in patients with kidney problems or those taking other medications that raise potassium (like ACE inhibitors or ARBs). Your doctor will check your potassium levels regularly and adjust doses accordingly.

Spironolactone is less expensive and has been used longer, but it can cause breast enlargement (gynecomastia) in men and breast tenderness in women due to its effects on sex hormone receptors. Eplerenone is more selective and causes fewer hormonal side effects, but it's more expensive. Your doctor will help choose the most appropriate option for your situation.

Important Monitoring with MRAs

Regular blood tests are essential when taking MRAs to monitor potassium levels and kidney function. High potassium (hyperkalemia) can be dangerous, causing heart rhythm problems. You should limit high-potassium foods (like bananas, oranges, and potatoes) and avoid potassium supplements unless specifically prescribed. Report symptoms like muscle weakness or irregular heartbeat to your doctor immediately.

What Are SGLT2 Inhibitors and Why Are They Game-Changers for Heart Failure?

SGLT2 inhibitors (dapagliflozin and empagliflozin) are the newest class of heart failure medications, originally developed for diabetes but now proven to benefit all heart failure patients regardless of diabetes status. The DAPA-HF trial showed a 26% reduction in cardiovascular death or worsening heart failure, with benefits appearing within just weeks of starting treatment.

The discovery that SGLT2 inhibitors benefit heart failure patients is one of the most exciting developments in cardiovascular medicine in recent years. These medications were initially developed to lower blood sugar in type 2 diabetes by blocking glucose reabsorption in the kidneys, causing excess sugar to be excreted in urine. However, cardiovascular outcome trials revealed unexpected and dramatic heart benefits that were independent of their glucose-lowering effects.

The DAPA-HF trial, published in 2019, tested dapagliflozin in over 4,700 patients with heart failure with reduced ejection fraction, including both diabetic and non-diabetic patients. The results were remarkable: a 26% reduction in the combined endpoint of cardiovascular death or worsening heart failure, with benefits seen in both diabetic and non-diabetic patients. The EMPEROR-Reduced trial showed similar benefits for empagliflozin.

What makes SGLT2 inhibitors particularly exciting is that they provide benefits on top of existing therapies. Even patients already taking ACE inhibitors, beta-blockers, and MRAs experienced additional reductions in hospitalizations and death when SGLT2 inhibitors were added. This additive benefit has led to SGLT2 inhibitors becoming the fourth pillar of heart failure therapy.

The exact mechanisms by which SGLT2 inhibitors benefit the heart are still being studied, but they appear to work through multiple pathways including reducing fluid overload, improving heart metabolism, reducing inflammation, and protecting heart cells from damage. Benefits appear quickly - improvements in symptoms and reduced hospitalizations are seen within weeks of starting treatment.

Which Patients Should Receive SGLT2 Inhibitors?

Current guidelines recommend SGLT2 inhibitors for all patients with heart failure with reduced ejection fraction (HFrEF), regardless of whether they have diabetes. Recent trials have also shown benefits in heart failure with preserved ejection fraction (HFpEF), expanding the eligible population. Your doctor will determine if SGLT2 inhibitors are appropriate for your specific situation.

Side Effects of SGLT2 Inhibitors

Because SGLT2 inhibitors cause sugar to be excreted in the urine, they increase the risk of genital fungal infections (yeast infections), particularly in women and uncircumcised men. Good hygiene and prompt treatment of any infections can help manage this side effect. Urinary tract infections may also be slightly more common.

SGLT2 inhibitors have a mild diuretic effect, so they can cause low blood pressure and dehydration, especially when combined with other diuretics. Your doctor may need to reduce your loop diuretic dose when starting an SGLT2 inhibitor. Rare but serious side effects include diabetic ketoacidosis (even in non-diabetics) and Fournier's gangrene (a rare genital infection).

What Other Medications Might Be Used for Heart Failure?

Beyond the four core drug classes, other medications may be used for specific situations: digoxin can help with symptoms and reduce hospitalizations, hydralazine/nitrates provide an alternative for patients who can't take ACE inhibitors, ivabradine slows heart rate in patients with rapid heartbeat despite beta-blockers, and vericiguat may benefit high-risk patients after hospitalization.

Digoxin

Digoxin is one of the oldest heart medications, derived from the foxglove plant. While it doesn't improve survival, digoxin can reduce symptoms and decrease hospitalizations in patients with heart failure. It works by strengthening heart contractions and slowing the heart rate, particularly in patients with atrial fibrillation. Digoxin requires careful dosing because too much can be toxic, so blood levels and kidney function are monitored regularly.

Hydralazine and Isosorbide Dinitrate

This combination of a vasodilator (hydralazine) and a nitrate (isosorbide dinitrate) is an alternative for patients who cannot tolerate ACE inhibitors or ARBs. The A-HeFT trial showed particular benefit in Black patients with heart failure, and guidelines recommend considering this combination in addition to standard therapy for this population.

Ivabradine

Ivabradine slows the heart rate through a different mechanism than beta-blockers. It's used in patients who have a resting heart rate above 70 beats per minute despite maximally tolerated beta-blocker doses. By further slowing the heart rate, ivabradine can reduce hospitalizations for worsening heart failure. It can only be used in patients who are in normal sinus rhythm (not atrial fibrillation).

Vericiguat

Vericiguat is a newer medication that enhances the effects of nitric oxide on blood vessels. The VICTORIA trial showed that vericiguat reduced cardiovascular death or heart failure hospitalization in high-risk patients who had recently been hospitalized or needed intravenous diuretics. It's generally reserved for patients with progressive symptoms despite optimal therapy.

When Should You Contact Your Doctor About Your Medications?

Contact your doctor if you experience significant weight gain (more than 2 kg in 2-3 days), worsening shortness of breath, increased swelling, persistent dizziness, fainting, irregular heartbeat, or any severe side effects. For severe chest pain, inability to breathe, or loss of consciousness, seek emergency care immediately by calling your local emergency number.

Monitoring your symptoms and knowing when to seek help is an essential part of living with heart failure. Most day-to-day fluctuations are normal and don't require immediate medical attention. However, certain warning signs indicate that your condition may be worsening or that your medications need adjustment.

Daily weight monitoring is one of the most important things you can do. Weigh yourself every morning, after urinating and before eating, wearing similar clothing. Record your weight and look for trends. A sudden increase of more than 2 kg (about 4-5 pounds) in 2-3 days usually indicates fluid retention and should prompt a call to your healthcare provider. They may advise you to increase your diuretic dose or come in for evaluation.

Worsening shortness of breath, especially if it's new at rest or wakes you from sleep, is another important warning sign. The same applies to increasing swelling in your legs, ankles, or abdomen. These symptoms suggest fluid buildup that needs to be addressed.

Medication side effects should also be reported, even if they seem minor. Sometimes what feels like a side effect might actually be a sign that your heart failure is worsening, and your doctor can help distinguish between the two. Don't stop taking medications on your own because of side effects - your doctor may be able to adjust doses or switch to alternatives.

What Are the Best Tips for Taking Heart Failure Medications?

Success with heart failure medications depends on taking them consistently as prescribed, monitoring your weight daily, attending regular follow-up appointments, understanding each medication's purpose, and communicating openly with your healthcare team about any concerns or side effects you experience.

Managing multiple medications can be challenging, but developing good habits makes it much easier. Here are practical strategies that help patients succeed with their heart failure treatment:

Establish a Routine

Take your medications at the same time each day, linking them to a regular activity like breakfast or brushing your teeth. Use a pill organizer to keep track of multiple medications and make it easy to see if you've taken your doses. Set phone alarms or use medication reminder apps if helpful.

Understand Your Medications

Know the name, dose, and purpose of each medication you take. Understand why each one is important - this knowledge increases motivation to take them consistently. Keep an updated medication list in your wallet and share it with all your healthcare providers.

Monitor and Record

Weigh yourself daily and record the results. Note any symptoms you experience, including when they occur and what makes them better or worse. This information is valuable during doctor visits and helps identify patterns that might indicate the need for treatment adjustments.

Communicate with Your Healthcare Team

Don't hesitate to report side effects, concerns, or difficulties with your treatment. Your doctor can often adjust doses, change timing, or switch to alternative medications to address problems. Ask questions if you don't understand something - your healthcare team wants you to be an informed partner in your care.

Never Stop Medications Abruptly

Even if you feel better, continue taking your medications as prescribed. Heart failure is a chronic condition, and medications prevent it from worsening. If you need to stop a medication for any reason, your doctor will guide you on how to do so safely.