QT Interval Not the Only CV Culprit
It’s no secret that unwanted cardiovascular toxicology is a leading cause of product withdrawals and update labeling. Over the years QT interval prolongation and proarrhythmia have become the likely culprits.
While these saboteurs are problematic, as researchers, they aren’t the only ones we should be investigating.
At CorDynamics, we had a hunch that if we took a data set of compounds accused of having some sort of positive cardiovascular finding we would find that changing cardiac pump function, QRS duration lengthening and PR interval prolongation are just as problematic to drug development programs. We were right as the graph below illustrates.
Recently a JAMA study backed up our findings and proved that PR interval prolongation, commonly known as first-degree atrioventricular block, is associated with significantly increased risks of atrial fibrillation, pacemaker implantation and, most importantly, all-cause mortality. Looking at our internal dataset above, almost 50% of novel test articles we work with in certain models have the propensity to delay atrioventricular conduction—the biomarker for which is long PR interval. As the JAMA article demonstrates, these unanticipated properties can be just as deadly.
It’s pretty simple. If you are developing a compound, you want to know of these potential effects. Don’t be afraid of the data—better to deal with these issues earlier, rather than in the clinic.
What’s the solution?
Interrogating cardiovascular effects early can greatly reduce late-stage compound attrition. I’ve always believed a robust testing funnel constructed to de-risk compounds early —using an integrative approach combining ion channel, isolated heart, and in vivo assessments —is the industry gold standard. Such an approach is not just good science, it’s good business too.
Regards,
Dr. Michael Gralinski, CorDynamics CEO
Related Posts via Categories
- Tags:
- QT Interval
