A randomized controlled trial assigned patients with diabetes to a new combination antihypertensive pill or placebo group for blood pressure control. Routine administration of the combination pill was associated with a reduction in the risk for some macrovascular or microvascular events at the end of the trial. The investigators decided to follow-up with patients after the end of the study to see if the benefits of therapy were sustained. They report the following hazard ratio curves comparing the combination pill to placebo from the end of the trial (T1) to 6 years afterward. Administration of the combination pill resulted in a statistically significant sustained reduction in events for which of the following outcomes (setting α = 0.05)?
A)Cardiovascular mortality and all-cause mortality
B)Cardiovascular mortality and stroke
C)Major clinical microvascular events and myocardial infarction
D)Major clinical microvascular events and stroke
E)Major macrovascular events and myocardial infarction

Question

A randomized controlled trial assigned patients with diabetes to a new combination antihypertensive pill or placebo group for blood pressure control.  Routine administration of the combination pill was associated with a reduction in the risk for some macrovascular or microvascular events at the end of the trial.  The investigators decided to follow-up with patients after the end of the study to see if the benefits of therapy were sustained.  They report the following hazard ratio curves comparing the combination pill to placebo from the end of the trial (T1) to 6 years afterward.  Administration of the combination pill resulted in a statistically significant sustained reduction in events for which of the following outcomes (setting α = 0.05)?
A)Cardiovascular mortality and all-cause mortality 
B)Cardiovascular mortality and stroke 
C)Major clinical microvascular events and myocardial infarction 
D)Major clinical microvascular events and stroke 
E)Major macrovascular events and myocardial infarction

Quizplus · Accepted Answer

Explanation: The hazard ratio (HR) is a measure of risk that describes the chance of events occurring in one study arm compared to another (eg, treatment versus control group). HRs differ from relative risks in that they can be calculated at multiple time intervals throughout a study period. HRs are used frequently in drug trials to analyze survival or time-to-event data. An HR >1 indicates increased risk, HR <1 indicates decreased risk, and HR = 1 indicates no change in risk. For all the events listed (except for major clinical microvascular events), the HRs were <1 (below the dotted horizontal line), reflecting decreased risk. However, only 2 outcomes achieved statistical significance (p <0.05) at T1 and at the 6-year mark: all-cause mortality and cardiovascular mortality (both with p = 0.04 at the 6-year mark). Setting statistical significance at α = 0.05 means that researchers are willing to accept a 5% chance (but no more) that the observed differences will be considered significant when no difference actually exists (simplified explanation). The actual number of events is sometimes reported for each study arm, allowing for a more complete interpretation of the HR. (Choice B) Although there appears to be a reduction in the likelihood of stroke (HR <1), this difference was not statistically significant (p = 0.33). (Choices C and D) The reductions in myocardial infarction and stroke were not statistically significant. There also appears to be a nonsignificant increase in major clinical microvascular events (HR >1). (Choice E) The HRs for myocardial infarction and major macrovascular events did not achieve statistical significance, although the reduction for the latter came close (given p = 0.07). With increased power (increased sample size) or additional years of follow-up, this outcome could become significant. Educational objective: The hazard ratio (HR) is a measure of risk that describes the chance of events occurring in one study arm compared to another. HRs can be calculated at multiple time intervals throughout a study period and are used frequently in drug trials to analyze survival or time-to-event data.

A Randomized Controlled Trial Assigned Patients with Diabetes to a New