A 62-year-old man with a history of dyslipidemia and type 2 diabetes mellitus comes to the emergency department due to severe substernal chest pain and diaphoresis that began 2 hours ago. His ECG shows ST- segment elevation in leads V1 to V4. He is taken to the cardiac catheterization lab and a complete occlusion of the mid-left anterior descending artery (LAD) is diagnosed. A drug-eluting stent is placed in the LAD with complete restoration of flow, and the patient is started on aspirin and clopidogrel. On the third day of hospitalization, the option of adding rivaroxaban is discussed with the patient. He asks about the benefits and risks of the added therapy. Based on the research abstract, which of the following measures would best reflect the net clinical benefit of rivoraxaban?
A)"Death from any cause/myocardial infarction/stroke" and "intracranial hemorrhage"
B)"Death from cardiovascular causes" and "fatal bleeding"
C)"Death from myocardial infarction" and "TIMI bleeding requiring medical attention"
D)"Intracranial hemorrhage" and "fatal bleeding"
E)"Primary efficacy endpoint" only

Question

A 62-year-old man with a history of dyslipidemia and type 2 diabetes mellitus comes to the emergency department due to severe substernal chest pain and diaphoresis that began 2 hours ago.  His ECG shows ST- segment elevation in leads V1 to V4.  He is taken to the cardiac catheterization lab and a complete occlusion of the mid-left anterior descending artery (LAD) is diagnosed.  A drug-eluting stent is placed in the LAD with complete restoration of flow, and the patient is started on aspirin and clopidogrel.  On the third day of hospitalization, the option of adding rivaroxaban is discussed with the patient.  He asks about the benefits and risks of the added therapy.  Based on the research abstract, which of the following measures would best reflect the net clinical benefit of rivoraxaban?
A)"Death from any cause/myocardial infarction/stroke" and "intracranial hemorrhage"
B)"Death from cardiovascular causes" and "fatal bleeding"
C)"Death from myocardial infarction" and "TIMI bleeding requiring medical attention"
D)"Intracranial hemorrhage" and "fatal bleeding"
E)"Primary efficacy endpoint" only

Quizplus · Accepted Answer

Explanation: This randomized clinical trial examined the benefits of twice-daily rivaroxaban at doses of 2.5 mg and 5 mg as an adjunctive therapy in patients with recent acute coronary syndrome. The study's primary efficacy endpoint was a composite of death from cardiovascular causes, myocardial infarction, or stroke. The primary safety endpoint was TIMI (thrombolysis in myocardial infarction) bleeding not related to coronary artery bypass grafting (CABG). The net clinical benefit (NCB) or clinical usefulness of a medication is a measure of its possible benefit minus its possible harm. NCB needs to be viewed in light of the specific clinical situation. For example, in patients with refractory or untreatable cancer, chemotherapy treatment leading to significant clinical improvement might result in a favorable NCB despite substantial toxicity of the medication. Furthermore, a new drug does not need a greater efficacy than the standard therapy for it to have a favorable NCB. For example, a new drug that avoids significant organ toxicity may have a favorable NCB even if it has less efficacy than the standard agent. From all the options listed, death from any cause/myocardial infarction/stroke and intracranial hemorrhage are the best reflection of the NCB of rivaroxaban, as they reflect both possible benefit (reduced risk of death from any cause/myocardial infarction/stroke) and harm (increased risk of intracranial bleeding). More specifically: Hazard ratio for death from any cause/myocardial infarction/stroke was 0.84 (95% confidence interval [CI], 0.74 to 0.95) in the rivaroxaban combined group compared to placebo, reflecting the statistically significant benefit of rivaroxaban in reducing death from all-cause as compared to placebo. Hazard ratio for intracranial bleeding was 3.28 (95% CI, 1.28 to 8.42), demonstrating the harm of rivaroxaban as reflected in a statistically significant increased risk of intracranial bleeding. (Choices B and C) Although the variables listed reflect both benefit (eg, reduced risk of death) and harm (eg, increased risk of bleeding), death from any cause is a better measure of NCB than death from specific causes. In addition, there was no statistically significant difference in fatal bleeding between the rivaroxaban groups and the placebo group as the CIs of the hazard ratios all included the null value (1.0 for hazard ratio). (Choice D) The intracranial and fatal bleeding risks are measures of harm only. (Choice E) The reduction in the combined primary efficacy endpoint is a measure of the benefits of rivaroxaban. The NCB of a medication is a measure of its possible benefit minus its possible harm. Educational objective: The net clinical benefit of a medication is a measure of its possible benefit minus its possible harm.

A 62-Year-Old Man with a History of Dyslipidemia and Type