People with atrial fibrillation often need more than one medicine to protect their heart and reduce their risk of stroke.
But a large study suggests that one commonly used combination of medicines may increase the chance of serious bleeding in older adults.
Atrial fibrillation, often called AFib, is an irregular heartbeat in which the heart’s upper chambers do not beat in a normal rhythm. Blood can collect inside the heart and form clots, which may travel to the brain and cause a stroke. For this reason, many people with AFib take blood-thinning medicines.
Two widely used blood thinners are apixaban and rivaroxaban. These medicines reduce the body’s ability to form dangerous blood clots, but they can also make bleeding more likely. Doctors therefore have to carefully balance protection from stroke against the possibility of excessive bleeding.
Many patients also need medicine to slow a fast heart rate caused by AFib. Diltiazem and metoprolol are two common options. Although both can help control heart rate, they work differently in the body and may interact differently with other medicines.
Researchers examined Medicare data from more than 200,000 people aged 65 or older with atrial fibrillation. The patients had started taking apixaban or rivaroxaban and were also treated with either diltiazem or metoprolol. The study covered treatment beginning between 2012 and 2020.
The researchers found that people taking diltiazem had a greater risk of serious bleeding than those taking metoprolol. Overall, the risk of hospitalization or death related to bleeding was about 20% higher in the diltiazem group. The difference was especially noticeable among people taking higher doses of diltiazem.
There is a biological reason why this interaction may occur. The body uses certain proteins and enzymes to remove apixaban and rivaroxaban from the bloodstream. Diltiazem can interfere with some of these processes, potentially increasing the amount of the blood thinner circulating in the body.
If blood-thinner levels become higher, the medicine may have a stronger effect than intended. That can increase the chance of bleeding in places such as the digestive system or brain. Older adults can be particularly vulnerable because they are more likely to take several medicines and may process drugs differently.
Importantly, the study did not find a major difference between the two groups in the risk of ischemic stroke or other serious clot-related events. This suggests that the increased bleeding seen with diltiazem was not accompanied by a clear improvement in protection against these events.
The findings do not mean that everyone taking diltiazem with apixaban or rivaroxaban should stop their medication. Suddenly stopping a blood thinner can sharply increase stroke risk, while stopping heart medicines can create other problems. Patients concerned about their combination of medicines should speak with their doctor or pharmacist before making any changes.
The research may help doctors choose heart-rate medicines more carefully for people who already take certain blood thinners. Future work could also examine whether monitoring drug levels, adjusting doses, or considering individual differences in how medicines are processed could make treatment safer.
The study was published in JAMA and included researchers from several U.S. institutions. It highlights an important issue in modern medicine: a drug may be safe on its own, yet its effects can change when it is combined with another medicine.
For people with atrial fibrillation, the goal remains to prevent dangerous blood clots while keeping bleeding risk as low as possible. Carefully reviewing all medications, especially in older adults taking several drugs, can be an important part of achieving that balance.
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