A study is conducted to assess the role of different treatment regimens on cardiovascular outcomes. Two treatment arms are evaluated: high-dose hydrochlorothiazide (100 mg/day) and low-dose hydrochlorothiazide (25 mg/day). After a defined follow-up period, the mean systolic blood pressure (BP) in the high-dose group is 139 mm Hg, with a mean diastolic BP of 88 mm Hg. In the low-dose group, the mean values are 143 mm Hg and 92 mm Hg, respectively. A 2-sample t-test gives p-values of 0.03 for the systolic BP and 0.04 for the diastolic BP differences between the high-dose and low-dose groups. The relative risk of sudden cardiac death in the low-dose as compared to the high-dose group is 0.4 (95% confidence interval 0.25-0.55).
Which of the following is the best statement concerning the results of the study with this patient sample?
A)High-dose hydrochlorothiazide doubled the risk of sudden cardiac death in the sample.
B)High-dose hydrochlorothiazide has no statistical benefit in lowering blood pressure as compared to low-dose hydrochlorothiazide.
C)Hydrochlorothiazide dose is not significantly related to the risk of sudden cardiac death.
D)Low-dose hydrochlorothiazide reduced the risk of sudden cardiac death in the sample by 40%.
E)The risk of sudden cardiac death in the low-dose group is 40% of the risk in the high-dose group.

Question

A study is conducted to assess the role of different treatment regimens on cardiovascular outcomes.  Two treatment arms are evaluated:  high-dose hydrochlorothiazide (100 mg/day) and low-dose hydrochlorothiazide (25 mg/day).  After a defined follow-up period, the mean systolic blood pressure (BP) in the high-dose group is 139 mm Hg, with a mean diastolic BP of 88 mm Hg.  In the low-dose group, the mean values are 143 mm Hg and 92 mm Hg, respectively.  A 2-sample t-test gives p-values of 0.03 for the systolic BP and 0.04 for the diastolic BP differences between the high-dose and low-dose groups.  The relative risk of sudden cardiac death in the low-dose as compared to the high-dose group is 0.4 (95% confidence interval 0.25-0.55). 
Which of the following is the best statement concerning the results of the study with this patient sample?
A)High-dose hydrochlorothiazide doubled the risk of sudden cardiac death in the sample.
B)High-dose hydrochlorothiazide has no statistical benefit in lowering blood pressure as compared to low-dose hydrochlorothiazide.
C)Hydrochlorothiazide dose is not significantly related to the risk of sudden cardiac death.
D)Low-dose hydrochlorothiazide reduced the risk of sudden cardiac death in the sample by 40%.
E)The risk of sudden cardiac death in the low-dose group is 40% of the risk in the high-dose group.

Quizplus · Accepted Answer

Explanation: Relative risk (RR) is a measure of effect that can be calculated in follow-up studies. It is a ratio of 2 risks: Risk of a certain outcome (eg, sudden cardiac death [SCD]) in a given group (eg, low-dose hydrochlorothiazide [HCTZ]) divided by Risk of that same outcome in another group (eg, high-dose HCTZ). RR >1 indicates increased risk in the group in the numerator; RR <1 indicates decreased risk in the group in the numerator. RR = 1 (null value) indicates no difference in risk between the groups. A confidence interval that does not include the null value reflects statistically significant results. Interpretation of RR depends on which group is used as reference (ie, the denominator). The numerator in the RR often represents the exposed group (eg, group receiving medication), with the denominator representing the unexposed group (eg, placebo). However, in this scenario, the high-dose HCTZ group is set as a reference group. Therefore, RR = 0.4 for low-dose compared to high-dose HCTZ treatment indicates a protective effect (decreased risk of SCD) of a lower dose of the drug. The RR is statistically significant, as the confidence interval (0.25-0.55) does not include the null value. Mathematically, RR = 0.4 means that the SCD risk of the group in the numerator is 40% that of the group in the denominator. Assume that the risk of SCD in the low-dose group was 1.0% and the risk in the high-dose group was 2.5% (these values are hypothetical). The RR of SCD in the low-dose group compared to the high-dose group would be 1.0/2.5 = 0.4. Therefore, the low-dose group has a risk of SCD that is 40% that of the high-dose group. (Choices A and D) No information is provided regarding the baseline risk of SCD in the overall sample; therefore, no conclusions about risk reduction (or increase) compared to baseline (ie, no treatment) would be valid. (Choice B) High-dose HCTZ treatment seems to be statistically more effective in reducing blood pressure than low-dose HCTZ treatment as the p-values for the 2-sample t-tests are both <0.05. (Choice C) The association between SCD and HCTZ is statistically significant because the confidence interval (0.25-0.55) does not include the null value. Educational objective: When assessing measures of effect, it is important to recognize which groups are being compared as the interpretation of the measures can differ.

A Study Is Conducted to Assess the Role of Different