Prof. Peter Barlis

Professor Peter Barlis (MBBS, MPH, PhD, FESC, FACC, FSCAI, FRACP) is an Interventional Cardiologist and the founding editor of Heart Matters. With expertise in coronary artery disease, advanced cardiac imaging, and interventional cardiology — and fellowships of the European Society of Cardiology, the American College of Cardiology, and the Royal Australasian College of Physicians — he brings the highest level of clinical authority to everything published on this site. Heart Matters was founded on Professor Barlis's belief that patients who understand their condition are less frightened and better equipped to make decisions about their care. Every article on this site reflects that commitment.

The Timing of Cholesterol-Lowering Medications: Does Nighttime Dosing Make a Difference?

April 17, 2026

Should you take your statin at night, or does the timing not really matter? The answer depends on which statin you are on.

The hs-CRP Test: Inflammation, Heart Risk, and Why Context Matters

April 17, 2026April 16, 2026

Blood test tube labelled hs-CRP Test held by a gloved hand in a laboratory

The hs-CRP test measures inflammation in the blood — but it is not a diagnostic test for heart disease. Here is what it can and cannot tell us about cardiovascular risk.

Nitrates for Angina: GTN Spray, Patches, and Long-Acting Tablets Explained

April 15, 2026

Key points

Nitrates are one of the oldest and most effective treatments for angina, the chest pain or tightness caused by reduced blood flow to the heart
They come in several forms: a spray or tablet under the tongue for fast relief, skin patches for all-day protection, and long-acting tablets taken once or twice daily
The most important side effect is a sudden drop in blood pressure causing headache, flushing, or dizziness, these are common and manageable, not dangerous
Nitrates must never be taken with erectile dysfunction medicines such as sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra), the combination can cause a dangerous and potentially life-threatening drop in blood pressure
Tolerance can develop with long-acting nitrates, your doctor will advise a nitrate-free period each day to keep the medication working effectively

If you have been prescribed a small spray or tablet to carry with you for chest pain, you are holding one of the most effective medicines in cardiovascular care, and one with a history stretching back more than 150 years.

Nitrates have been used to treat angina since the 1870s. They remain a cornerstone of treatment today not because medicine hasn’t moved on, but because they work, quickly, reliably, and in a way that no other class of medication quite replicates. Understanding what they do, how to use them correctly, and what to watch for will help you feel confident with a medicine that may become an important part of your daily life.

What nitrates do

Angina occurs when the heart muscle is not receiving enough blood, usually because the coronary arteries that supply it have become narrowed by coronary artery disease. The heart muscle is working hard but not getting enough oxygen to meet the demand. The result is chest pain, pressure, tightness, or heaviness, often brought on by exertion and relieved by rest.

Nitrates work by relaxing the walls of blood vessels. They cause the veins throughout the body to widen, a process called vasodilation which reduces the amount of blood returning to the heart with each beat. This reduces the workload the heart muscle has to perform, lowering its oxygen demand and relieving the mismatch between supply and demand that causes angina.

Nitrates also cause the coronary arteries themselves to relax and widen, improving blood flow to the heart muscle directly. This dual effect, reducing demand and improving supply simultaneously, is what makes them so effective.

Nitrates do not treat the underlying coronary artery disease. They manage symptoms by making the heart’s workload more manageable. This is an important distinction, and one worth discussing with your cardiologist if you are relying on them frequently.

The different types of nitrates

Nitrates come in several forms, each suited to a different purpose. Some are designed to act within minutes for immediate relief. Others release slowly throughout the day to provide ongoing protection against angina episodes.

Sublingual glyceryl trinitrate, the spray or tablet under the tongue

Glyceryl trinitrate GTN, is the fast-acting form most people associate with angina. It comes as a small spray applied under the tongue, or as a small tablet placed under the tongue to dissolve. Both forms work within one to three minutes and last for approximately 20 to 30 minutes.

GTN is used in two ways. First, as an immediate treatment when an angina episode occurs, used at the onset of symptoms for rapid relief. Second, as a preventive measure before activities you know are likely to trigger angina, climbing stairs, walking uphill, or any exertion that has provoked symptoms before. Used this way, GTN can allow you to undertake activities that would otherwise cause discomfort.

Your cardiologist or pharmacist will give you specific instructions on how and when to use your GTN, including how many doses are appropriate and at what point you should call an ambulance rather than continuing to wait. It is important to have that conversation before you need it, so you feel confident and prepared if an episode occurs.

Your doctor or pharmacist will advise you on how many doses of GTN to use and when to stop and call an ambulance. Make sure you know this before you need it.

As a general principle, chest pain that is not relieved by GTN, is more severe than your usual angina, or is accompanied by breathlessness, sweating, or pain spreading to your arm or jaw should be treated as a potential heart attack. Call an ambulance immediately, do not drive yourself to hospital.

Australia: 000 · UK: 999 · USA/Canada: 911 · Europe: 112

Transdermal nitrate patches

Glyceryl trinitrate patches are adhesive patches applied to the skin, typically the chest, upper arm, or back, that release a steady, controlled amount of GTN through the skin over the course of the day. They are changed once daily and provide sustained protection against angina episodes throughout the wearing period.

Patches are useful for patients with frequent angina who need consistent background coverage rather than relying solely on on-demand treatment. They are applied in the morning and removed after a set number of hours, usually 12 to 14 hours, to allow a nitrate-free period overnight. This nitrate-free period is important to prevent tolerance developing.

Whether you wear your patch during the day or overnight depends on the pattern of your symptoms, your doctor is best placed to advise which timing works for you.

The site of application should be rotated daily to reduce the chance of skin irritation. Common sites include the chest wall, upper arm, shoulder, or back. Avoid areas of broken or irritated skin.

Long-acting oral nitrates

Isosorbide mononitrate and isosorbide dinitrate are oral tablets taken once or twice daily to provide longer-lasting angina protection. They are available in standard and modified-release formulations.

Isosorbide mononitrate, the more commonly prescribed of the two, is typically taken as a once-daily modified-release tablet in the morning. The modified-release formulation delivers the medication gradually throughout the day while allowing drug levels to fall overnight, preserving the nitrate-free period that prevents tolerance.

These oral nitrates are used for patients with more frequent or predictable angina where regular prevention is preferable to on-demand treatment alone. They are often prescribed alongside other angina medicines such as beta-blockers or calcium channel blockers.

Type	Form	Onset	Duration	Used for
GTN spray / tablet	Under the tongue	1–3 minutes	20–30 minutes	Immediate relief or pre-activity prevention
GTN patch	Skin patch	30–60 minutes	12–14 hours	All-day background protection
Isosorbide mononitrate	Oral tablet	30–60 minutes	Up to 24 hours (MR)	Regular daily prevention
Isosorbide dinitrate	Oral tablet	20–45 minutes	4–6 hours	Regular prevention, often twice daily

Side effects, what to expect

The most common side effects of nitrates are a direct consequence of how they work, by dilating blood vessels and lowering blood pressure. They are very common, particularly when you first start taking nitrates, and they usually ease as your body adjusts.

Headache is the most frequently reported side effect, particularly with the first few doses. The same vasodilation that relieves angina also widens the blood vessels in the scalp, causing a throbbing headache. For most patients this improves significantly within a few days as the body adapts. Paracetamol can be taken to manage the headache in the meantime. If headaches are severe or persistent, speak to your doctor, adjusting the dose or switching formulation often helps.

Flushing and warmth a feeling of heat or redness in the face, is also common and has the same vascular mechanism as the headache. It is temporary and harmless.

Dizziness and light-headedness occur because nitrates lower blood pressure. Sitting or lying down when using GTN spray significantly reduces this risk. Standing up quickly after taking a nitrate, particularly after exercise or in warm weather, can cause a more pronounced drop in blood pressure.

Tolerance the gradual reduction in effectiveness with regular use, is specific to long-acting nitrates and patches. It does not occur with occasional use of GTN spray. To prevent tolerance, long-acting nitrates are prescribed with a structured nitrate-free period each day, usually overnight, during which the body resets its sensitivity to the medication. Your doctor will advise on the specific timing for your prescription.

Headache with the first dose of GTN is very common, for most patients it improves significantly within days as the body adjusts
British Heart Foundation, Nitrate medicines guidance

The critical interaction with erectile dysfunction medicines

This is the most important safety message associated with nitrate medicines, and one that every patient taking nitrates needs to know clearly.

Nitrates must never be taken within 24 to 48 hours of erectile dysfunction medicines including sildenafil (Viagra, Revatio), tadalafil (Cialis), vardenafil (Levitra), and avanafil (Spedra). These medicines belong to a class called PDE5 inhibitors and they work by a related mechanism to nitrates. When taken together, the two drugs cause an additive and potentially catastrophic drop in blood pressure, severe hypotension that can cause fainting, heart attack, stroke, or death.

This interaction applies regardless of the dose of either medication and regardless of the time gap, the window of risk with tadalafil (Cialis) extends to 48 hours due to its longer duration of action.

This is not a reason to avoid discussing sexual health with your cardiologist. Erectile dysfunction is common in men with cardiovascular disease and is itself an important cardiovascular risk marker. There are approaches to managing both conditions safely, but the conversation needs to happen with your doctor, not by managing it yourself. If you are taking nitrates and have questions about sexual activity or erectile dysfunction, please raise it at your next appointment.

Other important cautions

Low blood pressure. Nitrates should be used with caution if your blood pressure is already low. If you feel very dizzy or faint after taking GTN, sit or lie down immediately and inform your doctor.

Aortic stenosis. Patients with significant narrowing of the aortic valve, aortic stenosis, may not tolerate nitrates well, as their heart depends on maintaining adequate filling pressure. Your cardiologist will advise you specifically if this applies to your situation.

Hypertrophic cardiomyopathy. Similarly, nitrates may worsen symptoms in some patients with hypertrophic cardiomyopathy, a condition where the heart muscle is thickened. Always confirm with your specialist whether nitrates are appropriate for you.

Alcohol. Alcohol enhances the blood pressure-lowering effect of nitrates and increases the risk of dizziness and faintness. Take care with alcohol consumption while on nitrate medicines.

Other blood pressure medicines. Nitrates add to the blood pressure-lowering effects of other antihypertensives, including ACE inhibitors, ARBs, beta-blockers, and calcium channel blockers. This combination is often intentional and beneficial, but worth being aware of in terms of dizziness risk, particularly on standing.

Practical tips for taking nitrates

Keep your GTN spray with you at all times. It is of no use at home if you need it while out. Many patients keep one spray in their pocket or bag and a second at home.

Check the expiry date. GTN spray and tablets have a limited shelf life and lose potency over time. Check the expiry date regularly and replace as needed.

Store correctly. GTN is sensitive to light and heat. Keep it in its original container, away from direct sunlight and warm environments. Do not store in a car glovebox in warm climates.

Know when to use it preventively. If you know that a particular activity tends to trigger your angina, climbing stairs, walking to the car in cold weather, using a dose of GTN two to three minutes before that activity can prevent the episode rather than treat it.

Tell all your doctors and pharmacists. Always inform any healthcare professional prescribing a new medicine that you are taking nitrates, so that interactions, particularly with blood pressure medicines, can be checked.

Heart Matters Resource

If your GTN is not working

If your chest pain is not relieved by GTN, is more severe than usual, or is accompanied by breathlessness or pain spreading to your arm or jaw, call an ambulance immediately. Do not drive yourself to hospital.

Read: Chest Pain, Causes and When to Seek Help →

Conclusion

Nitrates are a remarkably effective class of medicine, fast-acting, well-understood, and with a track record measured in decades. Knowing how to use your GTN spray correctly, understanding the difference between on-demand and preventive use, and being aware of the critical interaction with erectile dysfunction medicines will allow you to use these medicines safely and confidently.

If your angina symptoms are changing, becoming more frequent, occurring at rest, or requiring more GTN than usual, that is a signal to speak with your cardiologist rather than simply increasing your nitrate use. Changing symptom patterns deserve reassessment, not just more medication.

Used well, nitrates give you genuine control over a condition that can otherwise feel unpredictable. That is worth understanding clearly.

Statins: What Patients Ask Me Most

April 17, 2026April 15, 2026

Key Points

Statins are among the most prescribed medications in the world, and among the most stopped without anyone being told.
Most of what circulates online about statins is negative. The clinical evidence tells a more balanced story.
Statins do more than lower cholesterol, in people at genuine cardiac risk, research shows they stabilise vulnerable plaques and reduce the inflammatory process that triggers heart attacks.
Side effects are real and should never be dismissed. Muscle aches, fatigue, and memory concerns deserve a proper conversation with your doctor, and there are options.
Not everyone needs a statin. For those prescribed one after a cardiac event or because of genuinely high risk, the evidence for staying on it is strong.

I hear some version of this almost every week in clinic. A patient sits down, and somewhere in the conversation they mention, sometimes apologetically, that they have stopped their statin. Or they are thinking about stopping it. Or they started it and felt different, and nobody ever explained why they were on it in the first place.

I understand this completely. The conversation around statins in the lay media and on social media is overwhelmingly negative. Muscle pain, memory loss, fatigue, “I haven’t felt like myself since I started.” These are real experiences, and they deserve to be taken seriously, not brushed aside with a blanket reassurance that statins are safe.

What I want to do here is share the conversation I try to have in clinic: honest, balanced, and grounded in what the evidence actually shows.

What a Statin Actually Does

Most patients are told their statin lowers cholesterol. That is true, but it is a bit like saying a seatbelt stops you moving forward. Technically accurate, but it misses what matters.

The more important action of a statin, particularly for someone who has already had a heart attack or has significant coronary artery disease, is what it does to the plaques inside the artery wall.

Let me explain what I mean by that.

The Plaque Story, What Is Actually Happening Inside

Cross-section illustration of a coronary artery showing a lipid-rich plaque with inflammatory cells, alongside an actual OCT image from Prof. Peter Barlis's PhD thesis showing the view from inside a coronary artery

Left: an illustration of a coronary artery cross-section showing a lipid-rich plaque with inflammatory cells at the fibrous cap. Right: an actual OCT image from my PhD thesis, the view from inside a coronary artery, with the dark region indicating a lipid pool beneath the vessel wall.

I often show patients this image in clinic. On the left is an illustration of what a vulnerable plaque looks like in cross-section, the open vessel with blood flowing through it, and beneath the surface, a pool of soft, lipid-rich material. You can see the grey star-shaped cells sitting right at the boundary between the plaque and the vessel lining. Those are macrophages, inflammatory cells that have migrated into the plaque and are, in a sense, destabilising it from within.

On the right is a real image, from my own PhD research using a technology called optical coherence tomography, or OCT, which involves threading a tiny light-based probe inside a living coronary artery. The bright golden ring is the artery wall. The dark shadow at the bottom is exactly what it looks like on the illustration: a lipid pool sitting just beneath the surface, visible in extraordinary detail from inside the vessel itself.

The thin layer of tissue covering that lipid pool is called the fibrous cap. In a vulnerable plaque, this cap is thin and fragile, and those inflammatory cells are actively weakening it further. When the cap ruptures, the lipid-rich contents spill into the bloodstream. A clot forms almost instantly. Depending on how large that clot is, and which artery is involved, the result is either a smaller heart attack, what we call an NSTEMI, or a complete blockage and a larger event, an STEMI.

This is what most heart attacks actually are. Not a gradual narrowing that finally closes off. A rupture. A sudden event triggered by a plaque that may not have been causing any symptoms at all.

Where Statins Come In

Here is what changes the conversation for me, and what I explain to every patient who asks why they need to stay on their statin.

Statins stabilise vulnerable plaques. They reduce the inflammatory cells infiltrating the cap, those macrophages that are weakening it from within. Over time, research shows they can thicken the fibrous cap itself, making it more resistant to rupture. They change the biology of the plaque, not just the number on a blood test.

This is why, in patients who have already had a heart attack or who have established coronary disease, the evidence for statins is so compelling. It is not primarily about the LDL number. It is about reducing the likelihood that a vulnerable plaque will rupture and cause another event. This is also the reason the relationship between statins and your calcium score is more nuanced than it first appears.

~25%
Reduction in major cardiovascular events with high-intensity statin therapy in high-risk patients, regardless of starting cholesterol level
Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analyses

Who Actually Needs a Statin?

This is where I want to be direct: not everyone does.

There is a legitimate conversation to be had about patients who have been started on a statin primarily because a cholesterol number crossed a threshold, without a proper discussion of their individual cardiovascular risk, their age, their other risk factors, and what the medication is actually expected to achieve for them personally.

If you were prescribed a statin and never had a proper conversation about why, that is worth revisiting with your GP or cardiologist. Cardiovascular risk calculators, used by doctors worldwide, look at the full picture: age, blood pressure, smoking status, family history, and cholesterol together. The number on its own tells only part of the story. Emerging tools like the hs-CRP test and imaging such as the coronary calcium score can add further context in the right patient.

Where the evidence is clearest and most compelling is in people who have already had a cardiac event, those with established coronary artery disease, and those at genuinely high cardiovascular risk. For these patients, the benefit of staying on a statin is well established and significant.

Questions Patients Ask Me Most

These are the questions I hear most often in clinic, answered as honestly as I can. As always, these are for general information, and any decision about your own medication should be made in conversation with your doctor.

Will statins damage my muscles?

Mostly reassuring

Muscle discomfort affects around 5–10% of people on statins. Serious muscle damage is genuinely rare. Significant pain, weakness, or dark urine should prompt a call to your doctor, but general aching is often manageable with a dose change or switch to a different statin, which your doctor can discuss with you.

Can statins affect my memory?

Mostly reassuring

The overall evidence does not support a link between statins and dementia or significant cognitive decline. Some people notice a change in mental clarity, an experience that deserves investigation, not dismissal. This is worth raising with your doctor rather than simply stopping the medication.

Do I really need one if I feel fine?

Worth discussing

Not everyone does. If a statin was started purely because a number crossed a threshold, with no discussion of individual risk, that conversation is worth revisiting with your GP. For people who have had a cardiac event or have established coronary disease, the evidence is strong regardless of how they feel.

Can I take a break from my statin?

Please discuss first

This is a conversation to have with your doctor before making any change. Many people quietly stop and never mention it, but in those with coronary artery disease or a prior heart attack, statins are doing something important beyond lowering a number. There are almost always options if the current medication is not suiting you.

Are there alternatives if I can’t tolerate statins?

Yes, options exist

Every-other-day dosing works well for many people who experience daily side effects. Switching to a different statin often resolves muscle symptoms. Ezetimibe is a well-tolerated tablet that lowers cholesterol through a different mechanism and is often used alongside or instead of a statin. For high-risk patients who cannot tolerate statins at all, PCSK9 inhibitors are a highly effective option. All of these alternatives are best discussed with your doctor before making any changes.

Does it matter which statin I’m on?

Yes, they differ

Statins vary in potency and side effect profile. Rosuvastatin (Crestor) and atorvastatin (Lipitor) are the most potent. Some people tolerate one significantly better than another. If side effects are an issue, the answer is often a switch or dose adjustment, a discussion worth having with your doctor before considering stopping altogether.

Should I take my statin in the morning or at night?

It depends on the statin

There are some differences between statins, and timing can play a small role, but the most important factor is consistency. Taking it at the same time each day matters more than which hour is chosen. For a fuller explanation of the pharmacology behind this, see our article on the timing of cholesterol-lowering medications. Your doctor is best placed to advise on what suits your particular medication and routine.

Can I lower my cholesterol naturally?

Worth discussing

Many products claim to lower cholesterol naturally, most have not been tested in proper clinical trials, and caution is warranted. Two approaches with reasonable evidence behind them are plant sterols and a generous fibre intake. A Mediterranean-style diet remains the most well-studied dietary pattern for cardiovascular risk. None of these replace a statin when one is clinically indicated, but they can be meaningful complements. Any supplement addition is worth discussing with your doctor first.

The Side Effects, Taking Them Seriously

Muscle aches and pains are the most commonly reported side effect, and they are real. Roughly 5–10% of people on statins experience some degree of muscle discomfort, though true muscle damage (myopathy) is considerably rarer.

What is also real is the nocebo effect, the phenomenon where knowing a medication might cause symptoms makes those symptoms more likely to be noticed and attributed to it. Large blinded trials have shown that many people who report muscle symptoms on statins experience the same symptoms on placebo. That does not mean the symptoms are not real, it means the relationship between statins and those symptoms is more complex than it first appears.

Memory and cognitive concerns are raised frequently, and understandably, given how much has been written about them. The overall evidence does not support a causal link between statins and dementia or significant cognitive decline. Some people do notice a change in mental clarity when starting a statin, and this deserves investigation rather than dismissal.

My strong view is this: side effects should never simply be accepted. There are several different statins, they vary in their potency and their side effect profiles, and some people tolerate one far better than another. Dose adjustments matter. Every-other-day dosing works well for some patients. And if a statin genuinely cannot be tolerated, there are alternative lipid-lowering options, including ezetimibe and PCSK9 inhibitors, that achieve excellent results. All of this is a conversation to have with your doctor.

If you are experiencing side effects on your statin, the conversation with your doctor is always worth having before stopping. There is almost always something that can be tried.

What I Tell My Patients

When a patient comes to me having stopped their statin because of something they read online, I don’t argue with them. I show them the image above, the plaque, the cap, the inflammatory cells, and I explain what the evidence shows about what these medications actually do inside the artery wall. Most of the time, that conversation changes things.

Conclusion

Statins are not perfect medications, and the decision to take one, or stay on one, deserves a proper, individual conversation. Not every person with a mildly elevated cholesterol needs a statin, and side effects should never be dismissed or simply tolerated.

But for those with established heart disease or genuinely high risk, the evidence is clear: statins do something that no other medication currently does as well. They get inside the artery wall and stabilise the plaques that cause heart attacks. That is worth understanding, and worth a conversation before making a decision either way.

If you have questions about your statin, or you have stopped taking it and haven’t told your doctor, please bring it up at your next appointment. There are options, and the conversation is always worth having.

This article provides general information only and is not medical advice. Any decisions about your medications should be made in conversation with your cardiologist, GP, or pharmacist.

Iron Deficiency and the Heart

April 14, 2026

Key Points

Iron deficiency is extremely common in cardiac patients, particularly those with heart failure, chronic kidney disease, or those taking blood-thinning medications long-term.
You do not need to be anaemic to be iron deficient. Many patients have low iron stores with a normal haemoglobin, and still experience significant fatigue and reduced exercise capacity.
Medications including aspirin, dual antiplatelet therapy, and anticoagulants (blood thinners) can cause low-grade, ongoing gastrointestinal blood loss that slowly depletes iron stores over months to years.
In heart failure, correcting iron deficiency, even without anaemia, significantly improves symptoms, exercise capacity, and quality of life, and reduces hospital admissions.
When oral iron supplements are poorly tolerated or inadequately absorbed, intravenous iron infusion is safe, effective, and increasingly available.
Iron levels are straightforward to check with a blood test. If you are experiencing unexplained fatigue and are on cardiac medications, asking your doctor about iron studies is worthwhile.

Iron deficiency and the heart have a closer connection than most people realise. It sits in the background of the cardiovascular conversation, overshadowed by cholesterol, blood pressure, and rhythm, and yet it is one of the most prevalent and most correctable problems in cardiac patients.

In cardiology and haematology clinics, iron deficiency turns up regularly. In patients on long-term blood thinners, in those managing heart failure, in people with chronic kidney disease. Recognising it, testing for it, and treating it effectively can make a profound difference to how a patient feels and functions day to day.

Iron Deficiency and the Heart, Why Are Cardiac Patients at Risk?

Several factors make cardiac patients particularly vulnerable to iron depletion. Understanding them helps explain why this problem is so common in this specific group.

Blood-Thinning Medications and Slow Blood Loss

Many cardiac patients take medications that reduce the blood’s ability to clot, aspirin, dual antiplatelet therapy (aspirin combined with clopidogrel or ticagrelor), or anticoagulants such as warfarin or DOACs (direct oral anticoagulants). These medications are essential and life-saving in the right context.

But they carry a side effect that is easy to overlook: low-grade, ongoing blood loss from the gastrointestinal tract. The gut lining is naturally prone to minor bleeding, small erosions and microscopic leaks that the body usually handles without consequence.

When platelet function is reduced or clotting is impaired, these tiny bleeds become slightly larger and slightly more persistent. Over months and years, the cumulative blood loss is enough to steadily deplete iron stores, even without any obvious sign of bleeding.

I see this regularly, a patient on long-term blood thinners who has been increasingly fatigued for months. Their haemoglobin is normal, so anaemia has been excluded. But their ferritin is very low and their iron stores are essentially empty. Correcting it changes everything.

— A/Prof. Ali Bazargan, Haematologist

Medication	How It Can Deplete Iron	Risk Level
Aspirin	Reduces the blood’s clotting ability and can irritate the stomach lining, leading to minor ongoing blood loss	Moderate, increases with dose and duration
Dual antiplatelet therapy	Two clot-preventing medicines combined, greater stomach and gut bleeding risk than aspirin alone	Higher, particularly in first 12 months
Warfarin	Reduces the blood’s ability to clot, any gut bleed is larger and slower to stop	Moderate to high, especially when the blood-thinning effect is stronger than intended
DOACs (apixaban, rivaroxaban, dabigatran)	Direct blood thinners, gut bleeding risk varies by medication and dose	Moderate, rivaroxaban carries slightly higher gut bleeding risk than apixaban

Heart Failure

Iron deficiency is extraordinarily common in heart failure, affecting up to 50% of patients with the condition. The reasons are multiple: reduced appetite, gut wall swelling that impairs iron absorption, and chronic low-grade inflammation that prevents iron from being properly used.

In some patients, underlying kidney disease compounds the problem further.

What makes this particularly important is that iron deficiency worsens heart failure outcomes independently of whether anaemia is present. The heart muscle itself requires iron for energy production. Iron-deficient cardiac muscle functions less efficiently, contributing directly to the breathlessness, fatigue, and exercise intolerance that define heart failure symptoms.

50%
of patients with heart failure have iron deficiency, one of the most common and most treatable problems in this group, with or without anaemia
European Heart Journal

Chronic Kidney Disease

The kidneys play a central role in iron metabolism. They produce a hormone called erythropoietin, a chemical signal that tells the bone marrow to produce red blood cells, a process that requires iron. In chronic kidney disease, this signalling is impaired and iron utilisation breaks down.

Patients with chronic kidney disease are therefore at high risk of iron deficiency through multiple mechanisms simultaneously, reduced production, impaired utilisation, and often dietary restrictions or gut absorption problems on top.

Iron deficiency in this setting is a major driver of fatigue and anaemia, and managing it is an important part of comprehensive kidney and cardiac care.

Iron Deficiency Without Anaemia, Why This Matters

One of the most important things to understand is that iron deficiency and anaemia are not the same thing. Anaemia, a low haemoglobin or red cell count, is the late consequence of prolonged iron depletion.

Long before haemoglobin falls, iron stores in the body become exhausted. A patient with depleted iron stores but a normal haemoglobin has no anaemia, but they may have profound fatigue, reduced exercise capacity, impaired concentration, and poor quality of life.

The body is compensating, but at a cost. In heart failure particularly, this state of iron deficiency without anaemia is clinically significant and responds well to treatment.

Blood Test	What It Measures	What Low Levels Mean
Ferritin	Iron storage protein, reflects total body iron stores	Low ferritin is the earliest marker of iron depletion, even with normal haemoglobin
Transferrin saturation (TSAT)	Percentage of iron-carrying protein that is actually carrying iron	Below 20% suggests iron is not being delivered to tissues adequately
Haemoglobin (Red blood cell)	Iron is attached to red blood cells. Oxygen requires attachment to the iron on red cells in order to be carried in circulation	Falls late in iron deficiency, a normal result does not exclude iron depletion
Serum iron	Iron circulating in the blood at the time of the test	Variable day-to-day, less reliable than ferritin or TSAT alone

The Evidence for Treating Iron Deficiency in Heart Failure

The clinical trial evidence for intravenous iron in heart failure is now substantial. A large clinical trial (AFFIRM-AHF) showed that intravenous iron, given to iron-deficient patients hospitalised with acute heart failure, significantly reduced the risk of repeat heart failure admissions in the following year.

Patients also reported meaningful improvements in quality of life and their ability to be physically active.

A further large clinical trial (IRONMAN) added weight, showing that regular intravenous iron therapy reduced combined cardiovascular events and hospitalisations over a longer follow-up period. These trials have established correcting iron deficiency as a standard part of heart failure management, not an optional extra.

The AFFIRM-AHF data was genuinely practice-changing. We now routinely check iron studies in every heart failure patient, and treat deficiency proactively, not just when anaemia develops.

— Prof. Peter Barlis, Interventional Cardiologist

How Is Iron Deficiency Treated?

Treatment depends on the severity of deficiency, the underlying cause, and how well the gut can absorb oral iron.

Oral Iron Supplements

For mild iron deficiency without significant gut absorption problems, oral iron supplements, ferrous sulfate, ferrous fumarate, or ferrous gluconate, are a straightforward starting point. They are inexpensive and widely available.

The challenge is tolerability. Oral iron frequently causes nausea, constipation, and abdominal discomfort, particularly in older patients or those on multiple medications. Taking iron with food reduces side effects but also reduces absorption.

Alternate-day dosing has been shown to improve both absorption and tolerability compared to daily dosing, and is now commonly recommended. In patients with heart failure or chronic kidney disease, gut absorption is often impaired enough that oral iron cannot replenish stores adequately, even when tolerated. In these patients, intravenous iron is the more effective route.

Intravenous Iron Infusion

Intravenous iron bypasses the gut entirely, delivering iron directly into the bloodstream where it is immediately available for use. Modern iron preparations specifically designed for infusion, including Ferinject and Monofer, can deliver a large dose in a single session lasting around 15 minutes, making the treatment practical and efficient.

A cannula is placed in a vein in the arm, the infusion runs over the agreed time, and the patient goes home the same day. A small proportion of patients experience mild flushing, fever, hives, muscle ache, joint ache, or a temporary drop in phosphate levels, your team will advise on monitoring if needed. Very rarely, extravasation of iron under the skin can lead to marked discolouration. Serious reactions are rare with modern preparations.

For cardiac patients with significant heart failure and impaired gut absorption, intravenous iron is increasingly the first-line treatment of choice.

What to Expect, Iron Infusion

Preparation

Fasting is not usually required. A cannula is typically placed in the arm on arrival. The infusion generally takes around 15 minutes depending on the preparation used, your team will confirm the details beforehand.

During

Patients are typically monitored throughout. Mild flushing or warmth is common and usually passes quickly. Most people are able to read, use their phone, or rest comfortably during the infusion.

Afterwards

Most patients go home the same day. Many notice an improvement in energy and exercise capacity in the weeks that follow as iron stores are replenished, though timing varies from person to person.

Follow-up

Iron levels are typically rechecked after the infusion, your doctor will advise on timing. In some conditions such as heart failure or chronic kidney disease, repeat infusions may be needed over time.

Should You Ask About Your Iron Levels?

If you are a cardiac patient experiencing unexplained or worsening fatigue, and particularly if you are on long-term aspirin, dual antiplatelet therapy, or anticoagulation, asking your doctor to check a full iron study panel is entirely reasonable.

The test is simple, inexpensive, and the result is directly actionable. Iron studies include ferritin and transferrin saturation (TSAT), both are needed, as ferritin alone can be falsely elevated by inflammation and may miss cases where iron stores appear normal but iron is not actually reaching the body’s tissues properly.

As a general guide, a ferritin below 100 micrograms per litre, or a transferrin saturation below 20%, may suggest iron deficiency is present, though your doctor will interpret these results in the context of your full clinical picture. You do not need to wait until you are anaemic. By that point, iron stores have been empty for some time, and earlier identification tends to lead to better outcomes.

Heart Matters Resource

When in Doubt, Get Checked Out

If you have heart failure, chronic kidney disease, or are on long-term blood-thinning medications and are experiencing significant fatigue, ask your doctor to check your iron studies. It is a simple test and a treatable problem.

Visit our When in Doubt page →

Conclusion

Iron deficiency is common, underdiagnosed, and highly treatable in cardiac patients. Whether it arises from slow blood loss on blood-thinning therapy, from the metabolic demands of heart failure, or from the complex iron handling problems of chronic kidney disease, the end result is the same: depleted stores, profound fatigue, and a quality of life that does not have to be accepted as inevitable.

The evidence that treating iron deficiency in heart failure improves outcomes is now robust. The tools to do it, including intravenous iron infusion, are safe, practical, and increasingly accessible. What is needed is recognition that the problem exists in the first place.

If fatigue is limiting your life and you have not had your iron levels checked recently, that conversation with your doctor is worth having. It may be the most straightforward answer to a problem that has been hiding in plain sight.

Prof. Peter Barlis

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