Beta-Blocker Side Effects May Increase Risk of Limb Loss for Users With Severed Artery Disease

Lowest risks of limb loss for heart failure patients were linked to the use of SLGT2 drugs like Invokana or Jardiance.

The use of a popular class of blood pressure drugs known as beta-blocker drugs, which include Lopressor, Toprol-XL and others, may significantly raise the risk of amputations among heart failure patients, particularly those with severe peripheral artery disease.

However, according to preliminary findings presented at a recent annual meeting of the Society for Cardiovascular Angiography and Interventions, using mineralocorticoid receptor antagonists, like Inspra, rather than beta-blockers to treat heart failure, significantly reduced a person’s risk of needing major or minor limb amputations.

Beta-blockers are commonly used to treat patients with heart failure. The medication works to slow the heart rate, lower blood pressure, and reduce the overall workload of the heart, especially among patients with severe peripheral artery disease (PAD).

Severe peripheral artery disease is a condition where blood flow to the legs and feet is reduced. It can cause minor symptoms like tingling and numbness, or major issues like tissue damage. It can also lead to amputation.

Patients with heart failure and PAD are often given beta-blockers like Lopressor, Tenormin, Toprol-XL and Inderal. However, the findings of the new study indicate these medications can increase the risk of major amputations by over 80%, and minor amputations by at least 60%.

In this new study, researchers from the Yale School of Medicine, led by Dr. Patrick Kwaah, studied side effects of beta-blocker used among heart failure patients. They examined a database of de-identified electronic health records to compare heart drug use with the risk of limb amputations.

According to their findings, patients with chronic heart failure and the most severe form of PAD had different risks of major and minor amputations, depending on the drugs they used. The data indicates patients taking beta-blockers face the greatest risk of both major and minor amputations. The risk of needing a major amputation was 81%, while the risk of needing a minor amputation was 60%.

Patients taking mineralocorticoid receptor antagonists like Inspra had a 35% lower risk of major amputations and a 13% lower risk of minor amputations. Heart failure patients taking SGLT2 inhibitors like Farxiga, Jardiance, and Invokana had a 41% lower risk of amputation, but there was no higher or lower risk for minor amputations. Angiotensin receptor blockers like Diovan lowered patients’ risk of major amputations by 18%, but had no effect, positive or negative, on minor amputation rates, researchers determined.

Alternatively, patients who took angiotensin receptor-neprilysin inhibitors (ARNIs) like Entresto had no positive or negative decrease or increase in their risk of major or minor amputations. Similarly, taking angiotensin-converting enzyme inhibitors (ACE) like Lotensin and Vasotec neither increased nor decreased the risk of amputations among patients.

Researchers said the data indicates SGLT2 inhibitors, like Invokana and Farxiga, offer minimal risks, while beta-blockers pose the greatest risks. The link between beta-blockers and the risk of limb amputations may be because the drugs help people with heart failure live longer, so they have more time to develop the need for amputations, according to researchers.

However, they emphasized the results are from an observational study and should be followed up with a randomized trial. The findings are considered preliminary until peer reviewed.

Prior research has also warned about negative side effects of beta-blockers. A study published last year indicated beta-blockers may in fact increase a patient’s risk of stroke when taken before surgery, especially among Black and Latino patients.