A widely used blood pressure medicine may be linked to a higher risk of sudden cardiac arrest when taken at high doses, according to research using large European health databases.
The finding concerns nifedipine, a drug that has been prescribed for decades to treat high blood pressure and chest pain.
Sudden cardiac arrest happens when the heart suddenly loses its ability to pump blood effectively. A person usually collapses, becomes unresponsive and stops breathing normally, and treatment with CPR and a defibrillator may be needed within minutes to save their life.
Cardiac arrest is different from a heart attack. A heart attack usually happens when blood flow to part of the heart is blocked, while cardiac arrest is mainly an electrical problem that causes the heart’s normal rhythm to fail.
However, a heart attack can sometimes trigger cardiac arrest. Because cardiac arrest often occurs without much warning, researchers have found it difficult to identify all of the factors that may increase a person’s risk.
The study examined two medicines called nifedipine and amlodipine. Both belong to a group of drugs known as calcium channel blockers and are commonly used to lower blood pressure and treat angina, the chest discomfort caused by reduced blood flow to the heart.
These medicines work by reducing the movement of calcium into certain muscle cells. This helps blood vessels relax and widen, lowering blood pressure and reducing the amount of work the heart has to do.
Researchers first used information from the Amsterdam Resuscitation Studies, known as the ARREST registry, in the Netherlands. This database collects detailed information about people who experience cardiac arrest outside hospitals.
The analysis included more than 2,500 people who had experienced sudden cardiac arrest. Researchers compared their medication use with information from more than 10,000 people who had not experienced cardiac arrest.
The strongest concern involved people taking a high dose of nifedipine, defined in the study as 60 milligrams per day. This group had a higher risk of sudden cardiac arrest than people who were not taking the medicine.
The same pattern was not seen with amlodipine. Although the two medicines are used for similar health problems, amlodipine was not associated with the same increase in cardiac arrest risk in the analysis.
To see whether the Dutch finding could be repeated, the researchers turned to a second large source of information. They examined the Danish Cardiac Arrest Registry, which included more than 8,000 cardiac arrest cases and around 40,000 comparison participants.
The Danish results supported the main finding. High-dose nifedipine was again associated with a greater risk of sudden cardiac arrest, strengthening the possibility that the link was not simply a chance result in one population.
Researchers also explored why nifedipine and amlodipine might have different effects. Laboratory experiments suggested that high concentrations of nifedipine may affect electrical activity in heart cells in a way that could make dangerous heart rhythms more likely.
This possible explanation is important because sudden cardiac arrest is often caused by a severe disturbance in the heart’s electrical rhythm. Still, laboratory findings cannot prove that the medicine caused cardiac arrests in the people included in the registries.
The research was observational, meaning the patients were not randomly assigned to receive nifedipine or another medicine. People taking high-dose nifedipine may have differed from other participants in ways that also affected their cardiac risk.
Even careful statistical analysis cannot remove every possible difference between groups. For that reason, the findings show an association rather than definite proof that high-dose nifedipine directly causes sudden cardiac arrest.
The results also do not mean that everyone taking nifedipine is in immediate danger. The concern was particularly associated with the higher dose studied, and the risks and benefits can differ greatly between individual patients.
Nifedipine has important medical benefits and can help control conditions that themselves raise the risk of serious heart problems. Stopping blood pressure or angina medicine suddenly without medical advice could therefore be dangerous.
Patients taking nifedipine should not change their dose or stop the drug because of this research alone. Anyone concerned about their treatment can discuss the dose, other risk factors and possible alternatives with their doctor or pharmacist.
The research was presented at the European Heart Rhythm Association’s annual congress and was based on data from the Dutch ARREST registry and the Danish Cardiac Arrest Registry. The findings highlight why researchers continue monitoring the safety of medicines even after they have been used for many years.
The study is notable because the association appeared in two separate national datasets and because researchers found a possible biological explanation. However, its observational design means further research is needed before firm conclusions can be made about cause and effect.
For now, the findings provide a reason for doctors to be aware of a possible risk when considering high-dose nifedipine. They also reinforce a broader lesson in medicine: even familiar drugs should continue to be studied as larger and better health databases make uncommon safety problems easier to detect.
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