A randomized controlled trial is conducted to evaluate the safety and efficacy of high-dose protovastatin compared with low-dose protovastatin in patients with stable coronary artery disease (CAD) in the prevention of CAD-related complications. A total of 12,780 patients with stable CAD who achieved low-density lipoprotein cholesterol (LDL-C)

Question

A randomized controlled trial is conducted to evaluate the safety and efficacy of high-dose protovastatin compared with low-dose protovastatin in patients with stable coronary artery disease (CAD) in the prevention of CAD-related complications.  A total of 12,780 patients with stable CAD who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (protovastatin 1 mg/d) are randomized (1:1) to high-dose (protovastatin 4 mg/d; n = 6,392) or low-dose (protovastatin 1 mg/d; n = 6,388) statin therapy.  The primary endpoint is a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization.  With a median follow-up of 4 years, the risk of the primary endpoint is 4.3% in the high-dose group and 5.4% in the low-dose group.  The difference in the risk of the primary endpoint is statistically significant.  Which of the following is the most accurate interpretation of these results?
A)Number needed to treat with high-dose protovastatin is 9
B)Number needed to treat with high-dose protovastatin is 91
C)Relative risk reduction for high-dose protovastatin is 1%
D)Relative risk reduction for high-dose protovastatin is 80%

Quizplus · Accepted Answer

Explanation: 11ec2b69_c0f4_9e90_8f63_0f0b437373cf_MD0005_00 The number needed to treat (NNT) is the number of patients who need to be treated with a specific drug (eg, high-dose protovastatin) to prevent 1 additional negative event (eg, 1 fewer event included in the composite outcome: cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization) when compared with a control group (eg, low-dose protovastatin). NNT is the inverse of the absolute risk reduction (ARR): NNT = 1 / ARR The ARR describes the difference in risk (or rate) of an unfavorable event (eg, composite event) between the treatment group (eg, high-dose protovastatin) and the control group (eg, low-dose protovastatin): ARR = (Risk_control − Risk_treatment) _control _treatment In this question, the risk of the primary endpoint is 5.4% (or 0.054) in the low-dose protovastatin group Risk_control and 4.3% (or 0.043) in the high-dose protovastatin group Risk_treatment. Therefore, the ARR for the composite event in the treatment group is: _control _treatment ARR = (Risk_control − Risk_treatment) = (0.054 − 0.043) = 0.011 _control _treatment and the NNT is: NNT = 1 / ARR = 1 / 0.011 = 90.9 ≈ 91 NNTs are always rounded up, so approximately 91 patients need to be treated with high-dose protovastatin to prevent 1 additional composite outcome (Choice A). Alternatively, this indicates that for every 91 patients treated with high-dose instead of low-dose protovastatin, 1 additional composite outcome is prevented. The lower the NNT, the more effective the treatment. (Choices C and D) The relative risk reduction (RRR) describes the relative decrease in the risk of an adverse event in the treatment group compared to a control group. It is calculated as: RRR = [(Risk_control − Risk_treatment) / Risk_control] = (0.054 − 0.043) / 0.054 = 0.20 (or 20%) _control _treatment _control Educational objective: The number needed to treat (NNT) is the number of patients who need to receive a treatment to prevent 1 additional negative event. NNT is the inverse of the absolute risk reduction. The lower the NNT, the more effective the treatment because fewer patients need be treated to prevent 1 additional negative event.

A Randomized Controlled Trial Is Conducted to Evaluate the Safety