QTc INTERVAL AND RISK AJC 1993; 72:21B
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Transcript of QTc INTERVAL AND RISK AJC 1993; 72:21B
QTc INTERVAL AND RISK AJC 1993; 72:21B
Relative Risk of Arrhythmias = 1.052x
where x = msec increase/10 above QTc 440msec
QTc = 440msec Risk = 1.0520 = 1.0
QTc = 500msec Risk = 1.0526 = 1.4
QTc = 640msec Risk = 1.05220= 2.8
DRUGS AND QTc: ISSUES
1. QTc prolongation and risk: exponential 2. Magnitude of the QTc signal: mean QTc; range & outliers3. Drug effect on QTc: a. direct: e.g., sotalol, cisapride b. indirect (interaction): i) drug-drug: terfenadine + ketoconazole ii) drug-gene: LQTS mutation/polymorphism
DRUGS AND QTc: Questions
1. Do the pre-clinical studies indicate an effect on ventricular repolarization?
2. Do clinical studies indicate a QTc signal?
3. What is the magnitude of the QTc signal?
4. Are there potential drug interactions?
5. Does the drug have unique characteristics?