Transthyretin Cardiac Amyloidosis (ATTR-CM) Treatment: Medication, Lifestyle Changes, and More
Treatment options for transthyretin cardiac amyloidosis (ATTR-CM), also known as transthyretin amyloid cardiomyopathy, have grown considerably in recent years. This condition is caused by an irregular protein, called transthyretin (TTR), that’s produced in the liver and builds up in the heart. This buildup causes the heart walls to stiffen, making it harder for the heart to pump blood, eventually leading to heart failure and frequently to early death.
Until recently, there was no medication to treat ATTR-CM directly. There is still no cure, but recent treatment advances have made it possible to slow the disease’s progression or stop it from getting worse. Treatment for the condition also aims to manage heart failure and other symptoms or complications stemming from ATTR-CM.
Disease-modifying drugs have become a cornerstone of ATTR-CM treatment in recent years. These new advanced medications can slow or stop the buildup of new TTR proteins in the heart.
A decade ago, “management was primarily focused on treating heart failure symptoms,” says Ajay Vallakati, MBBS, an advanced heart failure and transplant cardiologist at the Ohio State University Wexner Medical Center in Dublin, Ohio. “Now we have TTR stabilizers and TTR gene silencers,” which can help stop ATTR-CM from getting worse.
There isn't much existing research that directly compares the efficacy of stabilizers versus silencers, so it’s important to have a conversation with your doctor to decide which option may be right for you, or if it makes sense for you to take both of them.
Regardless of what you decide, you’ll reap the most protection by starting treatment as soon as possible. “Early diagnosis and initiation of treatment are crucial, as they offer the greatest potential benefit,” Dr. Vallakati says.
TTR Stabilizers
Stabilizers are oral medications that stop TTR proteins from clumping inside the heart.
With ATTR-CM, “the TTR protein that is secreted from the liver breaks loose and gets stuck inside the heart muscle, and stabilizers prevent it from breaking loose,” explains Ashesh Parikh, DO, a cardiologist with Texas Health Presbyterian Hospital Plano and with Texas Health Physicians Group.
As a result, stabilizing medications have been shown to greatly slow ATTR-CM’s progression and help people live longer, healthier lives.
Medications in this class include:
Acoramidis (Attruby)
Tafamidis (Vyndagel, Vyndamax)
Side effects of stabilizers for ATTR can include headaches, urinary tract infections, swelling, gas or diarrhea, muscle pain, upper respiratory infections, shortness of breath, constipation, vaginal infections, eye disorders (such as punctate keratitis), bleeding, sudden heart failure, atrial fibrillation, and kidney impairment.
TTR Silencers
Silencers work differently than stabilizers, but they still protect the body from the effects of TTR to slow or stop the progression of ATTR-CM. These injectable medications “create a barrier or a halo around the proteins [that are released by the liver], preventing the proteins from settling in the heart,” Dr. Parikh explains.
There is one medication in the class approved for the direct treatment of ATTR-CM and its underlying cause:
Vutrisiran (Amvuttra)
There are also two TTR silencers that have been approved for the treatment of polyneuropathy due to ATTR-CM, a type of nerve damage that can cause a variety of symptoms, including numbness or pain, loss of balance, and gastrointestinal issues.
Inotersen (Tegsedi)
Patisiran (Onpattro)
Side effects of TTR silencers can include changes in vision, chest tightness or pain, muscle pain or stiffness, muscle or joint pain, trouble breathing, dizziness or fainting, slowed heartbeat, or unusual tiredness or weakness.
Off-Label Treatments
Diflunisal (Dolobid) is an oral nonsteroidal anti-inflammatory drug (NSAID) that can work as a stabilizer and has shown the ability to reduce the risk of early death. But it’s not FDA-approved to treat ATTR-CM, so it may be prescribed off-label. It does have significant side effects, including stomach discomfort, kidney dysfunction, bleeding, and swelling, which cause about a quarter of users to discontinue the drug.
ATTR-CM can cause long-term complications including heart failure and atrial fibrillation or afib, especially if diagnosis and treatment with a stabilizer or silencer isn’t started early. That can lead to symptoms like leg swelling, shortness of breath, heart palpitations, and fatigue.
“These things need to be treated separately from a person’s ATTR-CM,” Parikh says.
Diuretics
Diuretics, sometimes called water pills, are medications that make your body excrete more urine to maintain normal fluid balance. That can help manage symptoms of swelling, but not all diuretics are appropriate for people with ATTR-CM.
Medication in this class include:
Torsemide (Demadex, Soaanz)
Bumetanide (Bumex)
Side effects can include gastrointestinal upset, loss of appetite, hair loss, headache, fatigue, muscle cramps, gout, and unbalanced electrolytes.
Aldosterone Agonists
Also called aldosterone receptor agonists, these oral medications keep the body from producing aldosterone, a hormone that raises blood pressure. That’s helpful for some people with ATTR-CM, since heart failure and fluid retention can cause a person’s blood pressure to go up.
Aldosterone agonists are often used alongside loop diuretics to manage heart failure symptoms in ATTR-CM.
Medications in this class include:
Spironolactone (Aldactone and CaroSpir)
Eplerenone (Inspra)
Finerenone (Kerendia)
Common side effects can include cough, dizziness, headache, diarrhea, or high potassium levels. Spironolactone may also cause enlarged breasts (regardless of sex), erection problems, or vaginal bleeding after menopause.
Antiarrhythmics
Heart rhythm–supporting medications can help manage heart palpitations caused by afib. Not all types of antiarrhythmics are appropriate for people with ATTR-CM. Doctors typically rely on amiodarone (Nexterone, Pacerone). Side effects of amiodarone can include coughing, dizziness or lightheadedness, fever, sensitivity to sunlight, and shaking, numbness, or weakness in your hands or feet.
Anticoagulants
Anticoagulants, also known as blood thinners, reduce the risk of blood clots, which is higher when a person with ATTR-CM has afib.
Medications in this class include:
Warfarin (Jantoven, Coumadin)
Dabigatran (Pradaxa)
Apixaban (Eliquis)
Edoxaban (Lixiana, Savaysa)
Heparin
The most common side effect of anticoagulants is bleeding. You may experience other side effects depending on the medication your doctor prescribes, such as indigestion, gastrointestinal bleeding, or low platelet counts.
In the past, people with ATTR-CM often underwent organ transplantation. These procedures have become less common with the advent of stabilizers and silencers. But certain patients may still be candidates for transplants.
Liver Transplant
Because TTR proteins are produced in the liver, liver transplantation was once used to slow the progression of ATTR-CM. The procedure wasn’t considered a cure, however, since TTR protein production could continue even with a new liver.
“With the development of gene silencers, medications are now available that decrease the production of TTR in the liver,” says Vallakati. “As a result, liver transplantation is no longer necessary for most patients.”
Heart Transplant
Patients who develop advanced heart failure from ATTR-CM may require a heart transplant.
“These patients often experience shortness of breath at rest,” Vallakati says. “Heart transplantation improves their symptoms and increases survival.”
This procedure can help people with severe ATTR-CM live longer, too: Research shows that the five-year survival rate for ATTR-CM patients who undergo heart transplantation is up to 90 percent.
But heart transplantation won’t cure ATTR-CM. “After heart transplantation, we continue treatment with stabilizers, silencers, or both to prevent new deposition of TTR protein in the transplanted heart,” says Vallakati.
Kidney Transplant
In rare instances, a person who develops kidney failure due to heart failure caused by ATTR-CM may need a kidney transplant. These procedures may be performed in conjunction with a heart transplant.
Healthy habits and self-care can support your prescribed ATTR-CM treatment plan and help you feel your best.
Limit Salt Intake
Parikh says you may need to cut back on salt if your ATTR-CM has led to heart failure, since too much salt can make heart failure symptoms like fluid buildup and swelling worse. Your sodium limit depends on individual health factors, so find out from your doctor how much salt is safe for you to have.
Eat a Heart-Healthy Diet
It’s always a wise choice to eat heart-healthy foods, whether you have ATTR-CM or not. Try to stick with whole, minimally processed foods like fruits and vegetables, whole grains, plant-based proteins like beans, tofu, and nuts, lean animal proteins like fish and skinless poultry, and low-fat dairy. Limit alcohol, added sugar, and foods that are high in saturated fat, like red meat and full-fat dairy.
Stay Active
It’s not always easy to get regular exercise, especially if you have symptoms like shortness of breath or fatigue. But any activity that you can do will improve your endurance, even if it’s just short walks around the block. Your doctor can help you decide on an exercise plan that’s safe for you. They may also recommend physical therapy or cardiac rehabilitation, which can help you work up to being more active.
A handful of small studies suggest that epigallocatechin-3-gallate (EGCG), an antioxidant compound found in green tea, may help prevent the production of TTR proteins. But other research looking at ATTR-CM patients who took EGCG supplements showed no benefit.
EGCG is unlikely to pose safety concerns for most people, but always ask your doctor before trying a new complementary or integrative approach.
When you have ATTR-CM, TTR proteins can build up in other parts of the body and lead to problems like carpal tunnel syndrome, spinal stenosis, or peripheral neuropathy. Pain caused by these conditions can be managed with medications like gabapentin, which can calm overactive nerves, Vallakati says. In some cases, surgery can also treat carpal tunnel syndrome and spinal stenosis.
Life with any chronic disease, including ATTR-CM, can come with emotional challenges and uncertainties. Coping isn’t always easy, but you don’t have to do it alone. Let your doctor know if you’re struggling with feelings of depression or anxiety. They can recommend resources like a support group or a mental health professional.
Treatment options for ATTR-CM, a cardiac condition caused by abnormal proteins accumulating in the heart, have expanded considerably in recent years.
Therapeutic approaches now include disease-modifying medications — TTR stabilizers and silencers — that can slow or stop disease progression by treating its root cause.
Many people with ATTR-CM will require other drugs and therapies to help manage the symptoms and complications of the disease.
Early diagnosis and treatment provide the greatest benefits, and ongoing care may involve mental health support and conversations with your doctor about long-term management.
