Risk for sudden arrhythmic death with QT-prolonging medications may be overestimated
QT-prolonging medications are associated with an increased risk for sudden cardiac death, but research published in JAMA Internal Medicine showed that this risk was specifically linked to nonarrhythmic causes.
“Studies using consensus sudden cardiac death criteria that presume arrhythmic cause may overestimate the effects of QT-prolonging medications (QTPMs) on risk of sudden arrhythmic death,” Zian H. Tseng, MD, MAS, FHRS, professor of medicine in residence at the University of California, San Francisco, told Healio Primary Care.
“These definitions include the [American College of Cardiology/American Heart Association/Heart Rhythm Society], WHO, or Hinkle-Thaler definitions all widely used in all cohort studies and clinical trials, none of which require autopsy confirmation of arrhythmic cause — therefore, [sudden cardiac deaths] defined by these criteria should be considered presumed [sudden cardiac deaths],” he continued.
Tseng and colleagues explained that sudden cardiac death is responsible for 5% to 15% of deaths in the United States, and that WHO defines the condition as “sudden unexpected death within 1 hour of symptom onset or within 24 hours of having been observed alive and symptom free.”
The researchers evaluated data from a prospective autopsy study of presumed cases of WHO-defined sudden cardiac death in San Francisco County between Feb. 1, 2011 and March 1, 2014. They assessed 525 cases of presumed sudden cardiac death and a control group of 104 traumatic death cases.
Compared with controls, those with presumed sudden cardiac death were found to have higher exposure to QTPMs and were more likely to be taking QTPM (55.4% vs. 26.9%; P < .001).
The researchers identified an increased risk for sudden cardiac death among those with low exposure to QTPM (OR = 2.25; 95% CI, 1.03-4.96) and in those with high exposure (OR = 6.7; 95% CI, 1.47-30.67).
For autopsy-defined cases, researchers found that QTPM use was associated with increased risks for non-sudden arrhythmic death with low (adjusted OR = 2.88; 95% CI, 1.18-6.99), moderate (aOR = 2.62; 95% CI, 1.2-5.73) and high (aOR = 14.22; 95% CI, 2.91-69.3) exposure to these medications. However, exposure to QTPMs was not associated with sudden arrhythmic death at any level.
Tseng and colleagues explained that physicians should use caution when monitoring patients exposed to QTPMs because increased exposure to these medications was associated with a greater risk for sudden death.
“Clinicians should be aware that interventions focused solely on prevention of arrhythmic death are unlikely to entirely address the risk of sudden mortality in patients prescribed QTPMs,” Tseng said. “QTPMs were often prescribed for an indication associated with the autopsy-defined cause of death, for example psychiatric QTPM and illicit drug overdose. Thus, our results suggest efforts focused on reducing risks of comorbid conditions, including close monitoring for illicit drug use and sequelae of diabetes, psychiatric diseases, and renal failure, are important to reduce overall risk of sudden mortality in patients prescribed QTPMs.”
Tseng added that clinicians should also continue QT monitoring in patients prescribed QTPMs because the findings do not exclude an increased risk of sudden arrhythmic death with these medications. – by Erin Michael
Disclosures: Tseng reports receiving grants from the NIH/NHLBI and CDC during the conduct of the study outside the submitted work. Please see study for all other authors’ relevant financial disclosures.