The Top Heart Failure Medications: Risks Vs. Benefits

Last updated:February 4, 2024

What are the risks and benefits of heart failure medications? The side effects of these drugs can compromise your quality of life. Here’s how to avoid them.

Prescription heart failure medications are so common — millions of Americans currently take at least one to treat everything from high blood pressure and high cholesterol to heart failure and stroke — that it’s easy to assume that they are easy on your system, that the side effects must be minor because so many people take them.

Browse This Article

See below for:

Not so. One of the two top reasons patients give for not taking heart failure medications as prescribed is “fear of side effects.” The other major reason, the American Heart Association (AHA) Report noted, is: “difficulty understanding the benefits and adverse effects of complex drug therapies.” So pay close attention to your doctor’s warnings and directions.

Side effects and adverse reactions are frightening stuff, to be sure, but because these meds are intended to keep your heart pumping, simply stopping them isn’t the right path to take. According to an AHA report, patients who don’t take their meds as prescribed “are more likely to have adverse health events.”

Important Note: any side effect warrants a call to your doctor. In most cases, the adverse effect can be treated by changing doses or switching to a different medicine, according to Ana Barac, MD, PhD., a cardiologist and faculty member at MedStar Washington Hospital Center and medical director of cardiac rehabilitation at Medstar Heart & Vascular Institute in Washington, DC.

So how to solve the problem? It starts with understanding heart failure medications you take, both their benefits and risks. “Studies show that patient compliance in their treatment program is increased when they understand why they’re being prescribed a drug and when there is a plan in place for how to take the drug and what to do if a side effect is experienced,” says Dr. Barac.

Live longer or better? Side effects of heart failure medications can make you think twice

It’s also important for you to understand how your drug regimen may affect your life in addition to keeping your heart pumping, particularly if you take multiple heart failure medications. All drugs have side effects and many are minor or go away after your body adjusts to the medicine. However, some are more severe and impactful.

One study revealed that seniors taking multiple medications for heart health lived longer. But those who took fewer meds were able to stay more active. The study was published in Circulation: Cardiovascular Quality and Outcomes.

Researchers examined claims data from nearly 4,800 nursing home residents, most of whom were white women with an average age of 84. The study looked at deaths, hospitalizations and decreased ability to manage daily activities after the residents were prescribed one of four kinds of medications after leaving the hospital following a heart attack. Those heart failure medications were beta-blockers, blood thinners, blood pressure drugs and statins.

Results showed that residents prescribed three or four medications after hospital discharge were less likely to die within 90 days compared with those prescribed just one medication. The death risk between those taking one or two medications did not differ.

Additional analysis found that, with the exception of blood thinners, greater medication use was associated with a 30% increase in functional decline.

“Since using more medications may interfere with older adults’ ability to do their daily activities, more medications should not be taken by older adults who wish to maintain their independence and daily functioning rather than live longer,” lead author Andrew R. Zullo, PharmD, PhD, an assistant professor at the Brown University School of Public Health, said in a statement. “Using more medications after a heart attack does not simply improve all health outcomes.”

Depression, bipolar linked to beta-blockers and calcium channel blockers

According to a study in the journal Hypertension, people who take certain blood pressure-lowering medications may be at an elevated risk of developing mood disorders, including depression and bipolar disorder. Researchers examined data on more than 144,000 adults with an average age of 56. Just over 32,000 of them were taking one of four types of drugs to treat their hypertension: angiotensin agonists (ACE inhibitors and angiotensin receptor blockers), beta-blockers, calcium channel blockers and thiazide diuretics.

Over a 5-year period, those on a beta-blocker or calcium channel blocker were twice as likely to have been hospitalized for mental illness (mostly depression) compared to those on an angiotensin agonist. People on an angiotensin agonist were also 50% less likely to be hospitalized with a mood disorder compared to those who weren’t on any hypertension drug. And those taking a thiazide diuretic had no impact on risk for hospitalization. Although the researchers weren’t sure exactly what led to the increase in mood disorders with some of these drugs, the results may indicate that patients with high blood pressure that are at risk for mood disorders could be better off with an angiotensin agonist. If changing doses or switching heart failure medications does not help, your doctor may add medicine that directly targets the adverse effect.

Side effects of heart failure medications may be temporary

Certain side effects may also go away relatively soon after you start taking a new drug, as your body adjusts to the medication. In addition, remember to tell your doctor and/or pharmacist about any other prescriptions, vitamins, supplements, and over-the-counter medications you take on a regular basis, in order to prevent dangerous drug interactions. (See MedShadow’s Heart Drugs Can Interact with Common Meds)

Many heart failure medications are prescribed after a life-threatening cardiovascular event, or to prevent a life-threatening event, so do not stop taking a prescribed heart medication without guidance from your doctor. This includes temporarily stopping a medication for elective surgeries (knee replacement, for example) or dental appointments.

These are all important points to discuss with your doctor. Whether you’ve recently been prescribed a heart failure medications or have been taking one (or more) for years, use this helpful guide to the benefits and risks as a good conversation starter at your next doctor visit.

ANGIOTENSIN AGONISTS, ACE Inhibitors

(angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers)

Common ACE inhibitors: Prinivil (lisinopril), Accupril (quinapril), fosinopril, captopril, Vasotec (enalapril), perindopril, Altace (ramipril), trandolapril

How they help: These medicines block the production of a hormone called angiotensin II, which triggers the muscles surrounding blood vessels to contract, causing arteries to constrict. They were originally introduced to lower blood pressure (BP); used alone they promote a moderate BP reduction (if you need a more significant reduction, you might take one along with a diuretic). ACE inhibitors are also commonly prescribed after a heart attack or congestive heart failure to prevent further heart damage. In some cases, they’re also given to those who are at high risk of heart failure.

Possible risks: These drugs are generally considered to be safe and well-tolerated, but a too-steep drop in blood pressure, which can cause dizziness and fainting, has been noted. Other side effects to look for include hives or other allergic reactions and dry cough.

Most worrisome side effects: Reduced kidney function and increased potassium levels (which can lead to abnormal heart rhythms); swelling of the face and throat, which could signal angioedema, a condition that can lead to obstructed airways. A study reported in the BMJ found that the use of ACE inhibitors may slightly increase the risk of developing lung cancer. Researchers looked at nearly one million people that were prescribed blood pressure-lowering drugs in the United Kingdom. Once prescribed, they were followed for an average of 6.4 years. Some people received an ACE inhibitor, some received an angiotensin receptor blockers (ARB), and others received both groups of drugs. The patients taking an ACE inhibitor had a 14% increased risk of lung cancer compared to those on an ARB. The risk also increased the longer a patient was on an ACE inhibitor. After 10 years, the increased risk rose to 31% compared to ARBs. (See MedShadow’s ACE Inhibitors.)

ANGIOTENSIN RECEPTOR BLOCKERS / ARB

Common ARBs: Edarbi (azilsartan), Atacand (candesartan), eprosartan, Avapro (irbesartan), Cozaar (losartan), Benicar (olmesartan), Micardis (telmisartan), Diovan (valsartan)

How they help: The effects of ARBs and ACE inhibitors are similar, but they work in different ways to prevent angiotensin from causing blood vessel constriction. ARBs interfere with angiotensin by blocking its receptors on the muscles surrounding blood vessels, which prevents the muscles from contracting. As a result, blood vessels relax and blood pressure is lowered. ARBs are commonly prescribed to reduce high blood pressure, treat heart failure, or help prevent kidney failure in people with diabetes. ARBs are often given to people who have trouble tolerating ACE inhibitors due to dry cough.

Possible risks: Most people tolerate ARBs well, but some experience dizziness, low blood pressure, or diarrhea.

Most worrisome side effects: Hyperkalemia, or high potassium levels, which can lead to abnormal heart rhythms, and angioedema, swelling that can lead to airway blockage.

In 2018 some generic versions of the ARBs valsartan, losartan and irbesartan were reported to contain a potentially dangerous component, N-nitrosodimethylamine (NDMA), which laboratory studies have shown can cause cancer or liver damage in patients. Since then some of these ARBs (but not all valsartan, losartan and irbesartan) and medications that combine them with other drugs have been recalled by the Food and Drug Administration (FDA). The FDA keeps a list of the drugs that have been recalled, so you can check to see if yours is among them. The FDA has warned that due to ongoing manufacturing issues in which these ARBs are being contaminated, there may be a shortage of these commonly prescribed blood pressure drugs.

“Valsartan products are in shortage, and we know that other types of products may fall into shortage soon,” former FDA Commissioner Scott Gottlieb said in a statement.

To prevent dangerous cardiovascular events that can occur if blood pressure medications are stopped abruptly, including stroke, the FDA urges people taking any of the recalled drugs to continue taking them until a doctor or pharmacist can replace them.

“We remind patients taking these medications or any recalled ARB to continue taking their current medicine until their pharmacist provides a replacement or their doctor provides an alternative treatment option,” he added.

Going forward, the FDA’s focus “is to balance the risk of patients ingesting low levels of the impurities (below the interim acceptable levels) for a short period of time with the risk that there is a shortage.”

BETA BLOCKERS

(Beta-Adrenergic Blocking Agents)

Common beta blockers: Toprol-XL (metoprolol), Coreg (carvedilol) and Brevibloc (esmolol), bisoprolol

How they help: Beta blockers interfere with the action of adrenaline (also known as the hormone epinephrine) in the body, by blocking beta receptors on the heart, lungs and other organs. By blocking adrenaline, beta blockers slow the heart rate and decrease the strength of heart-muscle contractions, minimizing how hard your heart works. Beta blockers work to lower the activity of the heart as well as lower blood pressure. They are required after a heart attack when the event is accompanied by heart failure, where the heart is permanently damaged.

Many heart attacks do not involve this failure, yet many of those patients are still prescribed beta blockers. A study in the Journal of the American College of Cardiology indicates that the drugs do not help them live any longer than those not on the medications.

Researchers focused on data regarding 179,000 patients who suffered a heart attack without heart failure. After a year following the heart attack, there was no difference in the death rates between those prescribed a beta blocker and those who were not.

Beta blockers are associated with a host of side effects, including more serious ones such as shortness of breath, dizziness, trouble sleeping and depression. The study questions whether beta-blockers should be prescribed at all to those who have had a heart attack but did not suffer heart failure.

“This study suggests that there may be no mortality advantage associated with the prescription of beta blockers for patients with a heart attack and no heart failure,” Chris Gale, MD, a cardiologist at the University of Leeds (UK), who worked on the study, said in a statement.

Beta blockers are also used to prevent ventricular arrhythmia. And they were once considered a “first choice” drug to treat high blood pressure, but no more, especially for patients who have no other diagnosed heart condition.

Possible risks: Cold hands and feet, fatigue, dizziness, weight gain and nausea are commonly reported side effects. Less common risks are headache and the onset of depression.

Most worrisome side effects: They can slow the heart rate down too much, resulting in dizziness or fainting. Beta blockers constrict airways, which can lead to shortness of breath. People with chronic lung diseases or asthma should only use cardioselective beta blockers, those that primarily block beta receptors on the heart. Also look for any signs of an allergic reaction, such as rash, swelling or difficulty breathing. (See MedShadow’s Should You worry About Beta Blockers?)

DIURETICS

(also known as water pills)

Common diuretics: Lasix (furosemide), Bumex (bumetanide), Demadex (torsemide), Diuril (chlorothiazide), Midamor (amiloride), chlorthalidone, hydrochlorothiazide,, indapamide, Zaroxolyn (metolazone), Dyrenium (triamterene)

How they help: Diuretics help to ease the heart’s workload by reducing fluid and sodium buildup in the lungs and other parts of the body. In turn, there is less pressure on the walls of your arteries. Each diuretic works a bit differently in your kidneys and removes fluid at varied rates. Most of them help the kidneys release sodium into your urine. Sodium removes water from the blood, which decreases the volume of fluid flowing through blood vessels, and in turn lowers blood pressure. Diuretics are often the first line of defense when treating high blood pressure and heart problems related to high blood pressure. Diuretics are also often given to improve heart failure symptoms.

Possible risks: Diuretics are generally considered safe and well-tolerated. The most common side effect of these heart failure medications is increased urination (that’s why patients are often told not to take these drugs at night). Other risks include: allergic reactions; too low blood pressure (causing dizziness); headaches; increased thirst; muscle cramps; the development of gout (rare); menstrual changes; and impotence. People who take diuretics or ACE inhibitors face a higher risk of heat-related illnesses and dehydration that may require a trip to the hospital. Australian researchers conducted an analysis, published in the Journal of Clinical Pharmacy and Therapeutics, of the prescription drug intake of 6,700 veterans who were admitted to a hospital for heat-related illness or dehydration.

Among heart failure medications classes with a higher than normal risk of hospital admission for dehydration or heat-related illness, the highest risk — 2.79 — was seen in veterans who had initiated treatment with an ACE inhibitor and diuretics. Patients who had started SSRIs (selective serotonin reuptake inhibitors), a common type of antidepressant, had the lowest additional risk with 1.17. There was no additional risk for hospital admission for dehydration or heat-related illness associated with anticonvulsants, Parkinson’s disease drugs, hypnotics, anti-anxiety drugs or antihistamines.

“Prescribers and patients should be aware of the potential for medicines to be associated with increased risk of dehydration and heat-related illness,” the researchers conclude.

Most worrisome side effects: If too much fluid is removed, you could have reduced kidney function; low or high potassium, magnesium and/or calcium levels, all of which come with their own set of serious side effects, such as heart problems, vomiting, diarrhea, and more.

Diuretics can also increase your risk of developing gout, a painful, inflammatory type of arthritis caused by a buildup of uric acid crystals in the joints, usually starting in the big toe. Since diuretics reduce the amount of fluid in the body, the fluid that remains is more concentrated, and the amount of uric acid that is passed out of the body in urine is reduced. People who have high levels of uric acid in their blood (their body makes too much, or they have excessive amounts of high-purine foods in their diet, such as organ meats, or high alcohol intake) form crystals from uric acid. A gout attack occurs when these crystals lodge in or around joints. (See MedShadow’s 6 Medications That Can Harm the Kidneys.)

CALCIUM CHANNEL BLOCKERS

Common calcium channel blockers: Norvasc (amlodipine), Cardizem (diltiazem), nicardipine, Procardia (nifedipine), nisoldipine, Calan SR (verapamil),

How they help: As the name implies, these medications prevent calcium from getting into cells of the heart and blood vessel walls. Calcium is necessary for the conduction of electrical signals that trigger heart cells to contract. Calcium channel blockers interfere with this process, allowing the blood vessels to relax and widen so that the heart is able to pump more easily. Some can also slow the heart rate. They’re prescribed to control high blood pressure, irregular heartbeat (arrhythmia) and relieve angina (chest pain). Studies show that African Americans with hypertension do well controlling their BP with calcium channel blockers or diuretics, but not ACE inhibitors or ARBs.

Possible risks: Along with allergic reactions, side effects associated with calcium channel blockers include constipation or diarrhea; dizziness or lightheadedness; flushing or feeling warm; nausea; headaches; fatigue; and swelling in the feet and lower legs.

Most worrisome side effects: Certain calcium channel blockers can cause yellowing of the skin or eyes (jaundice), fainting, rapid heartbeat, or an increase in severity or frequency of angina.

ANTICOAGULANTS AS HEART FAILURE MEDICATIONS

(blood thinners)

Common anticoagulants: Coumadin (warfarin), Pradaxa (dabigatran), Xarelto (rivaroxaban), Eliquis (apixaban), Savaysa (edoxaban)

How they help: For heart failure patients who also have atrial fibrillation (a common type of arrhythmia), blood thinners are used to treat and prevent the formation of blood clots. Warfarin blocks vitamin K, a nutrient that the liver uses to produce clotting proteins. Newer anticoagulants, known as direct-acting oral anticoagulants (DOAC), act against clotting factors, such as thrombin. Unlike warfarin, these drugs (dabigatran, rivaroxaban, apixaban and edoxaban) do not require regular blood monitoring or regulation of vitamin K in the diet. (See MedShadow’s Next-Gen Blood Thinners: What’s Right For You?)

Possible risks: Because warfarin blocks vitamin K, which is found in leafy, green vegetables, some people stop eating them to avoid counteracting the drug. But spinach lovers (and kale, broccoli and more) don’t necessarily need to give up a favorite food, you just need to take in about the same amount of vitamin K every day. Your doctor or a nutritionist may need to review your food choices to make appropriate, safe recommendations. Consistency is important, changes in your eating patterns can lead to too much or too little blood thinning.

Blood thinners also are sensitive to many other heart failure medications that either decrease or increase its anticoagulant effects. Some research suggests that DOACs may cause less risk of bleeding and other problems compared to warfarin.

Most worrisome side effects: Too much or too little blood thinning can pose serious challenges. Your doctor will likely monitor the drug’s effects with frequent blood tests if you’re taking warfarin. Though there is a risk for bleeding with DOACs, they appear to have fewer food and drug interactions than warfarin.

ANTIPLATELETS

Common antiplatelets: Plavix clopidogrel), Brilinta (ticagrelor), aspirin

How they help: Also known as blood thinners, antiplatelets are used to prevent blood clots from forming in the heart or brain in patients with heart disease. Plavix is more potent than aspirin and is often prescribed in combination with aspirin. Brilinta, also taken with aspirin, may be even more potent than Plavix but is associated with more shortness of breath and major bleeding than Plavix.

Antiplatelet drugs work by interfering with normal platelet functions, chiefly stopping prostaglandins, which are naturally occurring substances that help blood platelets clump together. They’re often prescribed after a patient has had a heart attack or stroke.

Possible risks: It’s widely known that aspirin carries an increased risk of internal bleeding. Some of this is fairly minor, such as a nosebleed. When stomach bleeding occurs, patients and their doctors must carefully weigh the pros and cons of being on aspirin or another antiplatelet regimen. (About 3% of Plavix patients experience moderate or severe bleeding problems.) Some patients who deem their heart attack risk greater than dealing with stomach bleeding often take a proton pump inhibitor to protect the stomach lining. Other allergic reactions can occur.

Most worrisome side effects: Bleeding into the brain is extremely dangerous and life-threatening. Signs this might be happening include a sudden severe headache, seizures, changes in vision, weakness on one side of the body, a sense of numbness, and/or difficulty speaking. Some people have a condition known as clopidogrel resistance in which their body is unable to convert clopidogrel (Plavix) into its active form. An enzyme found in liver cells is needed for processing clopidogrel. In people with clopidogrel resistance, the gene that provides instructions for the manufacture of this enzyme is flawed. As a result, the enzyme does not work to convert clopidogrel to its active form. People who are given clopidogrel and are resistant to it are at risk for heart attacks, strokes, and blood clots. There are tests available to identify clopidogrel resistance.

Low-dose aspirin no longer used for prevention: Low-dose aspirin may be prescribed for people who have had a heart attack or stroke to prevent another event. But aspirin’s use in preventing a heart attack or stroke — which was common for years — is discouraged. A 2019 study in JAMA supported earlier research and determined that people without cardiovascular disease should not take a daily low-dose aspirin, as the benefit in reducing heart attack and stroke is relatively modest but is associated with an increased risk for serious internal bleeding.

Researchers conducted a meta-analysis of 13 trials involving more than 164,000 patients that examined aspirin use to prevent heart attack or stroke in those with and without cardiovascular disease. While aspirin use was associated with a lower risk of cardiovascular events, it was also associated with an increased risk of major bleeding.

“We found that for every 265 patients treated with aspirin for five years, one heart attack, stroke or death from cardiovascular disease would be prevented,” Sean Zheng, MA, Imperial College London, said in a statement. “On the other hand, for every 210 patients treated with aspirin over the same period, one would have a serious bleeding event.”

The researchers say the guidelines recommending using aspirin to prevent cardiovascular events in those deemed at high risk, or those with diabetes may need to be reconsidered.

“Our study shows that in [high-risk] groups, cardiovascular benefit and bleeding risks were matched with no clear evidence of a net benefit,” Zheng said. “This suggests the use of aspirin in patients without cardiovascular disease should not be routinely recommended.”

A study published in the European Heart Journal also found that in people without cardiovascular disease, taking a low-dose aspirin didn’t provide any benefits but did increase bleeding risk.

Researchers examined 11 clinical trials comparing low-dose aspirin to placebo in more than 157,000 adults without atherosclerosis, a condition in which fatty deposits accumulate in the arteries, causing the blood vessels to thicken.

Results showed that compared to those taking a placebo, the rates of heart attack, stroke and death weren’t any lower. Also, those on aspirin were nearly 50% more likely to have major bleeding compared to those on placebo.

“Many professionals have a hard time believing that aspirin may not be so beneficial because there has been such a widespread and favorable view of this medication,” co-author Anthony A. Bavry, MD, cardiologist and professor at the University of Florida School of Medicine, said in a statement. “This certainly does not settle the debate, but it does call for a reappraisal of society’s overwhelmingly positive view of aspirin therapy.”

More proof that if you are healthy, taking a daily low-dose aspirin to prevent cardiovascular events may not only not help you, it can potentially be harmful: Researchers enrolled more than 19,000 older people in a double-blind, placebo-controlled trial. The participants did not have heart problems, dementia or any kind of physical disability. Half were given 100 mg of aspirin daily, while the other half received a placebo. After about five years, there was no difference in “disability-free” survival between the two groups, researchers reported in the New England Journal of Medicine.

A related analysis found that there was a significantly increased risk of bleeding – primarily in the gastrointestinal tract and brain – in those that were taking aspirin. Bleeding that required a transfusion or hospitalization occurred in 3.8% of the aspirin group compared to 2.7% of the placebo group.

Yet another study found that people at moderate risk of developing cardiovascular disease who take a low-dose aspirin daily don’t have fewer heart problems compared to those that don’t take anything.

Researchers enrolled more than 12,500 people aged 55 and older (men) or 60 and older (women) considered to be at moderate risk of cardiovascular disease because of high cholesterol, high blood pressure or smoking. Half were given a low dose (100 mg) of aspirin daily, while the others were given a placebo. Patients were followed for an average of five years. The study was sponsored by Bayer, which manufactures brand-name aspirin.

Results, published in the Lancet, showed aspirin did not help to prevent a first heart attack or stroke any more than a placebo.

About 4% in each group suffered a heart issue after five years. Study author J. Michael Gaziano, MD, of Brigham and Women’s Hospital in Boston, said one reason the rate of cardiovascular events was so low is that many of the patients were taking cholesterol and hypertension drugs that may have already been helping to cut cardiovascular risk.

Results also showed gastrointestinal bleeding events were higher in the aspirin group. Dr. Jane Armitage, University of Oxford, worked on the study and told the Associated Press that if you are healthy, it’s not worth taking a daily aspirin. Low-dose aspirin is still recommended for people who have had a heart attack or other cardiovascular event, as studies have shown it is effective in preventing another one from happening.

The bottom line: If you have not had a cardio event, taking a low-dose aspirin doesn’t help to reduce your risk of a heart attack or death – but it can increase your risk for major bleeding.

(See MedShadow’s Pros and Cons of Aspirin)

STATINS

(Cholesterol-lowering drugs)

Common statins: Zocor (simvastatin), Lipitor (atorvastatin), Crestor (rosuvastatin), Lescol XL (fluvastatin), Altoprev (lovastatin), Livalo (pitavastatin), Pravachol (pravastatin)

How Mindfulness Meditation Can Help Reduce Meds

Meghan Rabbitt

How they help: Statins are considered a must for those that have experienced a heart attack or stroke, as clinical evidence is strong that they can prevent another one from occurring.

Statins are prescribed to many people who have not had a heart attack or stroke. Statins are among the most popular drugs prescribed to American adults. Nearly three-quarters of people with cardiovascular disease take a statin. These drugs have been shown to lower LDL (often referred to as “bad”) cholesterol by 20% to 50%. Although about half using statins in a study didn’t reach the goal of lowering LDL by 40%. They prompt the liver to remove more cholesterol from the blood than it does naturally. They’re commonly prescribed for individuals with high cholesterol, as well as those who’ve had a heart attack. They are also prescribed to patients who have clogged arteries, a condition known as atherosclerosis, or those at risk for it.

Possible risks: It’s prudent to avoid grapefruit juice as it increases the effects of atorvastatin, simvastatin and lovastatin. Grapefruit is fine to drink if you’re on pravastatin or rosuvastatin. The most common side effect is mild muscle discomfort (myopathy). This pain is often dosage-related and lowering the dose can lessen or remove the pain. Statin-takers sometimes complain about cognitive declines – forgetfulness and fuzzy thinking. CoQ-10 taken with statins has been shown to decrease mild to moderate muscle pain in about a third of users with symptom improvement in 75% of users. Research has linked statins to a very low risk of serious liver injury, but the potential cardiovascular benefits of statins are thought to outweigh any risk to the liver. As with any medication, allergic reactions are possible.

Statin controversy on need and side effects: Current US guidelines recommend that adults between 40 and 75 years of age should be put on a low-to-moderate dose of a statin if they have one or more risk factors for the disease and a 10% or greater risk of a heart attack or stroke within the next 10 years as a result. These risk factors include high cholesterol, high blood pressure, smoking and diabetes.

With those guidelines, as many as 40% of older Americans should take a statin to curtail their risk of developing heart disease or having a cardiovascular event. Many doctors argue that’s too many people.

The side effects of statins can be troubling for those taking them – muscle aches, cognitive decline and more. But there is a debate on how widespread or serious these side effects are. Studies indicate only a small portion of statin-takers experience side effects, others say they can be minimized by lowering the dose or switching to another statin, the AHA says people are ascribing side effects to statins that actually come from somewhere else and some doctors find the side effects are common and disturbing. Read on for more on the debate.

Statins overprescribed? Another study, published in the Annals of Internal Medicine, argues that statins may be overprescribed since in many people, the risks of the cholesterol-lowering drugs outweigh their benefits. Researchers looked at data from more than 40 studies on four commonly prescribed statins: atorvastatin), simvastatin, pravastatin and rosuvastatin. They used a computer model to analyze the benefits and risks of statins. Results found that the harms of the drug outweigh the benefits until a patient’s risk is much higher than the 10% threshold cited in the US guidelines.

Responding to that study, the American Heart Association says the benefits of statin medications outweigh their risks. The AHA said that about 10% of Americans on a statin stop taking it because of side effects that they believe are caused by the drug, but may not be. If you think you are experiencing side effects from a statin, you should not stop taking it, Mark Creager, MD, director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center, said in a statement. Instead, talk to your doctor. Creager noted that stopping a statin can increase the risk of a heart attack or stroke.

However, if your urine suddenly turns dark, you should stop taking a statin immediately as this can be a sign of a rare condition called rhabdomyolysis. However, the AHA said, based on a review of research, this was observed in less than 0.1% of people on a statin.

One common side effect reported with statins is muscle aches or pain. The AHA said based on their analysis of studies, “no more than 1% of patients develop muscle symptoms that are likely caused by statin drugs.” The group also said that muscle aches and pain can have many causes, such as low vitamin D levels, and are common in middle-aged and older adults.

The AHA also said that some complaints of muscle pain while on a statin are a result of the so-called “nocebo effect.” This is the idea that if a person is told of the potential side effects of a medicine, they are more likely to experience them. The AHA argued that reports in the media of statins causing muscle pain, doctors warning about muscle aches and drug package inserts advising of the possibility support this idea.

The AHA analysis found that statins may slightly raise the risk for diabetes, but only in those who already have risk factors for it, such as obesity. In addition, there was no evidence of a relationship between statins and conditions such as cancer, cataracts, cognitive dysfunction, peripheral neuropathy, erectile dysfunction and tendonitis.

Statins underused? An analysis in The Lancet also suggests that statins get a bad rap and that their benefits greatly outweigh any risks associated with them, as side-effect rates have been greatly exaggerated. The review does concede that serious side effects, including muscle pain and weakness, diabetes and hemorrhagic stroke, can be caused by long-term statin use. However, the authors note that the number of people potentially impacted by these effects is quite small. For example, statin use may cause muscle pain or weakness in only 50 to 100 patients per 10,000 treated for five years. The researchers also noted that the negative stories on statins in recent years may have led to avoidable deaths in people who stopped taking statins as a result of negative press.

“It is, therefore, of concern that exaggerated claims about side-effect rates with statin therapy may be responsible for its under-use among individuals at increased risk of cardiovascular events,” the article states. “For, whereas the rare cases of myopathy and any muscle-related symptoms that are attributed to statin therapy generally resolve rapidly when treatment is stopped, the heart attacks or strokes that may occur if statin therapy is stopped unnecessarily can be devastating.” There was no indication in the analysis that statins cause side effects reported in some observational studies, such as aggression, kidney injury, liver disease, memory loss and sleep problems.

However, some experts don’t agree. “Although reported rates of adverse events in clinical trials are low, this does not reflect the experience of clinicians who see patients who are taking statins,” Rita Redberg, MD, a cardiologist at the University of California San Francisco Medical Center, and Mitchell Katz, MD, director of the Los Angeles County Health Agency wrote in JAMA. Statins have been associated with a host of side effects. Based on observational studies, as much as 15% of those taking the heart failure medications experience muscle aches and pains. And, again, there is also some evidence statins may boost the risk of developing diabetes.

Redberg and Katz also expressed concern that broadening the scope of people recommended for statins might give them a false sense of security when it comes to protecting against CVD.

“For example, people taking statins are more likely to become obese and more sedentary over time than nonstatin users, likely because these people mistakenly think they do not need to eat a healthy diet and exercise as they can just take a pill to give them the same benefit.”

(See MedShadow’s So, Your Doctor Wants You to Take a Statin. What Are the Risks?)

Statins for seniors: Evidence indicates that doctors may want to think twice before prescribing a statin to seniors with no history of heart disease for prevention of heart attack. A study published in JAMA Internal Medicine found that statins do not appear to reduce that risk, and the mortality rate was higher in those taking a statin compared to those not on one.

Researchers analyzed data from 2,867 adults aged 65 and older with high blood pressure but without plaque build-up in the arteries that took part in the Lipid-Lowering Trial component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, which was conducted from 1994 to 2002. Of that total, 1,467 took pravastatin daily and the other 1,400 received usual care from their doctor to lower cholesterol.

There was no difference in cardiovascular events between the two groups. Stroke, heart failure and cancer rates were similar in the two groups. Side effects such as muscle pain and fatigue have been reported with statins, and those may have a larger impact on seniors, according to lead author Benjamin Han, MD, of the New York University School of Medicine.

“Anything that can affect their physical function, anything that can affect their ability to do activities on a daily basis, puts them at a higher risk for the further decline and a higher risk for mortality,” Han told HealthDay news in an interview.

In an accompanying editor’s note, Gregory Curfman, MD, former editor-in-chief of Harvard Health Publications, noted that statins have been associated with musculoskeletal disorders and cognitive dysfunction, which can boost the risk for falls. Because these issues can have a large impact on older adults, Curfman suggests physicians carefully consider the risk before prescribing or continuing statins in this population. (See MedShadow’s Do Statin Drugs Need a Re-Think?)

Most worrisome side effects: Recent research has suggested that statins increase the risk for type 2 diabetes by 9% on average with women at a slightly higher risk. Rare cases of severe muscle damage (rhabdomyolysis) requiring hospitalization have been noted. Alert your doctor if you have extreme muscle pain, especially if your urine has a tea-colored hue. (See MedShadow’s Statins: How Safe Are These Life-Savers?)

Risk when stopping a statin: Although statins are considered effective, many patients have reported that they stopped taking the drugs within six months to a year because of side effects. One study analyzed whether people who continued taking statins ended up with better outcomes compared to those who abruptly stopped taking the drugs. Data were drawn from two Boston hospitals between 2000 and 2011 and reported in a study in the Annals of Internal Medicine.

Of the more than 200,000 adults whose data was studied, nearly 45,000 reported a side effect they thought might be related to the medication (usually muscle aches or stomach pain). Of those 45,000, researchers focused on 28,266 from that group. The majority — 19,989 individuals — kept taking statins anyway. Approximately four years after the side effects were reported, 3,677 patients had died or suffered a heart attack or stroke. Among those who continued taking statins, 12.2% fell into that group, compared to 13.9% of those who stopped statins after a possible side effect.

Drug interactions: Also, doctors and patients need to be aware of drug-drug interactions between statins and other heart failure medications used to treat heart disease, according to recommendations from the American Heart Association (AHA). In many cases, people taking statins are also taking other heart failure medications.

The AHA published a list of drugs often given to heart patients that can interact with statins. These include:

Calcium channel blockers, including Norvasc (amlodipine), Cardizem (diltiazem) and Calan (verapamil).
Drugs to treat irregular heartbeat, such as Multaq (dronedarone), Cordarone (amiodarone) and Digox (digoxin)
Heart failure medications, including Entresto (sacubitril/valsartan) and Corlanor (ivabradine)
Drugs known as fibrates which are used to lower triglycerides, another type of lipid (fat) in the blood, such as Lopid (gemfibrozil)
Blood thinners, such as Coumadin (warfarin) and Brilinta (ticagrelor)

The most common interaction when taking these heart failure medications in combination with a statin is that it can increase the level of the statin in the blood, which can lead to muscle weakness or pain. However, the benefits of taking the medications outweigh the risks, which are relatively minor, the recommendations state. To minimize the risks, a doctor should adjust the dose of the statin.

But there are some drug combinations that should be avoided. For example, Lopid should never be taken with the statins lovastatin, pravastatin, and simvastatin).

In other instances, the AHA recommends limiting the dose of a statin when taken together with another heart failure medications. People who take Norvasc should be limited to 20 mg a day or less of lovastatin or simvastatin. Patients on amiodarone should take, at most, 20 mg a day of simvastatin or 40 mg a day of lovastatin. Simvastatin should also be limited to 10 mg a day when given in combination with dronedarone.

Lovastatin and simvastatin should be avoided if you’re taking Pradaxa (dabigatran), a blood thinner often prescribed to patients with a type of irregular heartbeat known as atrial fibrillation to help prevent blood clots and strokes. The combination may significantly increase the risk of internal bleeding.

Canadian researchers conducted a pair of studies on almost 46,000 people over 65 who began taking Pradaxa between 2012 and 2016. The bleeding risk was more than 40% higher in those who were also taking lovastatin and simvastatin, the researchers reported in the Canadian Medical Association Journal.

“We found no difference in the risk of stroke in patients receiving dabigatran who were prescribed lovastatin or simvastatin versus other statins,” said Tony Antoniou, PharmD, one of the researchers said. “However, an increase in the risk of bleeding requiring hospital admission or emergency department visits was seen with lovastatin and simvastatin compared with the other statins.”

NEXLETOL AND NEXLIZET

Cholesterol lowering drug Nexletol (bempedoic acid) was approved by the FDA in early 2020 as the first in its class of heart failure medications. It’s a once daily pill that lowers LDL (low-density lipoprotein) cholesterol and is to be used as an adjunct to statins. The FDA required the following to be on the Nexletol label: “It is not known if NEXLETOL can decrease problems from high cholesterol, such as heart attacks, stroke, death, or other heart problems.”

Combination drug Nexlizet brings together Nexletol and exetimibe and will be marketed in the US starting in July 2020. It is indicated for use on top of maximally tolerated statins with specific heart disease diagnoses who haven’t met their LDL-C targets. Exetimibe inhibits cholesterol absorption in the gut. More info in this MedPage article.

VASODILATORS AS HEART FAILURE MEDICATIONS

Common vasodilators: nitroglycerin, minoxidil, Isordil (isosorbide), hydralazine,

How they help: These drugs work directly on the muscles in the walls of arteries to dilate blood vessels so blood flows more easily and your heart doesn’t have to work as hard. They are most often prescribed after heart failure to improve symptoms and prolong your survival. Doctors may also prescribe one for pulmonary hypertension (blood pressure that affects the arteries in your lungs); for high blood pressure during pregnancy or childbirth; and less often to treat high blood pressure (generally as a last resort medicine when other blood pressure medications haven’t worked).

Possible risks: Vasodilators are powerful heart failure medications with a number of associated side effects, including headaches, dizziness, flushing, varying degrees of sodium and water retention (edema), facial changes, excessive hair growth, allergic reactions, and increased risk of developing lupus (although this is very rare).

Most worrisome side effects of these heart failure medications: Chest pain, rapid heartbeat, heart palpitations, and a severe headache that doesn’t go away should be immediately reported. Taking a vasodilator together with an erection-enhancing drug, such as Viagra (sildenafil), Levitra (vardenafil) or Cialis (tadalafil), can lead to very low blood pressure, loss of consciousness and even death.