HAMBURG, Germany – Use of some antibiotic and antipsychotic drugs increases the risk of sudden cardiac arrest (SCA) among people with type 2 diabetes who do not have a history of cardiovascular disease (CVD), shows the first such analysis of real-world, primary care data.

People with type 2 diabetes who do not have a history of CVD have almost three times the risk of SCA if they take antipsychotic medications and nearly double the risk if they take certain antibiotics that prolong the QT interval, notably, macrolides and fluoroquinolones.

"These data show that commonly prescribed drugs ― antipsychotic medications, used by about 3% of people with type 2 diabetes, and antibiotics, taken by 5% to 10%, convey an increased risk of sudden cardiac arrest in those without a history of cardiovascular disease," said Peter Harms, MSc, who presented the study at the European Association for the Study of Diabetes (EASD) 2023 Annual Meeting. Another drug associated with an increase in SCA among patients with diabetes was domperidone, an antinausea medication.

"Perhaps these drugs could be avoided in some cases, and GPs should be more aware of the possible consequences of their use," he added. "If the patient has type 2 diabetes, then maybe it's better to avoid some of these medications and try and cope without them, or at least find an alternative antibiotic."

Harms, an epidemiologist from Amsterdam University Medical Centers, the Netherlands, highlighted that their study was unique because the investigators drew upon primary care data. "These data are extensive, and we find a lot of associations which are very real."

SCA is associated with 50% of all cardiac deaths and accounts for 20% of all mortality in high-income countries. Of those people who experience SCA, 80% of cases prove fatal.

"As the name suggests, it is difficult to predict because it is sudden, especially in people without a cardiovascular disease history," Harms pointed out in an interview with Medscape Medical News. He highlighted that "around half of those who experience SCA, often between the ages of 40 and 60 years, have never seen a cardiologist, but many do have type 2 diabetes.

"We need to better understand how to recognize people at risk of SCA, know who to watch and how to prevent these events," he emphasized.

Vladimira Fejfarova, MD, co-moderated the session and commented on the study. "From the clinical point of view, it's necessary to evaluate risk factors that can contribute to sudden cardiac arrest."

Overall, the researchers found that among people with type 2 diabetes who do not have a history of CVD, hypoglycemia, severe hypertension, dyslipidemia, and use of QTc-prolonging medications are associated with SCA risk. Among people with type 2 diabetes and CVD, albuminuria and heart failure are associated with SCA risk.

Fejfarova added: "With type 2 diabetes and also type 1, we need to look more at adverse events, especially when treating infections with macrolides, but also mycotic infections, because antimycotic drugs are known to influence QT intervals that could contribute to sudden cardiac arrest.

"We need to be more cautious with prescribing certain antibiotics that have these side effects in our patients with diabetes," asserted Fejfarova, from the Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Type 2 Diabetes Double the Risk of SCA

The researcher decided to investigate the population of people with type 2 diabetes because their risk of SCD is around twice that of those without type 2 diabetes. Because these patients have relatively frequent checkups with general practitioners, Harms turned to primary care databases that contained comprehensive and relatively routine information on risk indicators.

Longitudinal associations between clinical characteristics of 3919 patients with type 2 diabetes ― both those with and those without a history of CVD ― and SCA (a total of 689 patients) were determined.

Cases were found in the AmsteRdam REsuscitation STtudies (ARREST) registry of out-of-hospital resuscitation attempts by emergency medical services in the Dutch region of Noord-Holland from 2010–2019. Case patients were matched with up to five control patients. The control group comprised people with type 2 diabetes who had not experienced an SCA. Control patients were sourced from the same primary care practices and who were of similar age and sex. Clinical measurements, including blood pressure and blood glucose readings, medication use, and medical history for the 5 years leading up to an SCA, were obtained from general practice records. A multivariable analysis was performed, and results were stratified for people with and for those without a history of CVD.

Of particular interest were drugs that interfere with cardiac function, including some prokinetic, antibiotic, and antipsychotic medications. All of the drugs are known to be associated with a change in QTc prolongation. Examples include domperidone (QTc-prolonging prokinetic), macrolides and fluoroquinolones (QTc-prolonging antibiotics), and haloperidol (a QTc-prolonging antipsychotic).

Antibiotic and Antipsychotic Use Might Contribute to SCA in T2D

Case patients and control patients were similar in age, A1c level, and other characteristics with the exception that more patients with SCA had a history of CVD (40.0% vs 29.4%).

"Looking at the associations in the overall population, insulin use was strongly associated with SCA risk [hazard ratio (HR), 2.38] and perhaps this was an indicator of severity of type 2 diabetes," remarked Harms. "Also, unsurprisingly, a history of arrhythmia [HR, 1.68] and, more surprisingly, prokinetic drug use [HR, 1.66; 95% CI, 1.20 – 2.31], specifically those known for QTc-prolongation, were associated with SCA."

Among people who had experienced an SCA and who did not have a history of CVD (337 case patients/2023 control patients), QTc-prolonging antipsychotic medication use was associated with SCA at an HR of 2.87, and antibiotic medication use was associated with SCA at an HR of 1.66. A low fasting glucose level (<4.5 mmol/mol) was associated with SCA at an HR of 2.5; severely high systolic blood pressure (>180 mm Hg) was associated with SCA at an HR of 2.21; low HDL cholesterol level, with an HR of 1.35; and high LDL cholesterol level (>2.6 mmol/L), with an HR of 1.64.

Among people with a history of CVD (352 case patients/1207 control patients), associations between albuminuria and SCA were moderate (HR, 1.54) and severe (HR 1.55); heart failure was associated with SCA at an HR of 1.85 (95% CI, 1.50 – 2.29).

Co-moderator Fejfarova added that in addition to the findings from Harms' study, other research presented in the same session highlighted the importance of checking patients for the presence of arrhythmias that could lead to the development of atrioventricular blocks, sinus node diseases, and SCA.

Harms and Fejfarova have disclosed no relevant financial relationships.

European Association for the Study of Diabetes (EASD) 2023 Annual Meeting: Abstract 172. Presented October 5, 2023.