An 84-year-old man comes to the physician with persistent dyspnea despite being treated with optimal medical therapy for congestive heart failure with low left ventricular ejection fraction. A recently published randomized clinical trial compared an angiotensin-neprilysin inhibitor (ANi) to an angiotensin-converting enzyme inhibitor (ACEi) in patients who have heart failure with a reduced ejection fraction. The following results were reported: The investigators also reported the following results for patients in the angiotensin-neprilysin inhibitor (ANi) and angiotensin-converting enzyme inhibitor (ACEi) groups:
Which of the following is the best interpretation of these results

Question

An 84-year-old man comes to the physician with persistent dyspnea despite being treated with optimal medical therapy for congestive heart failure with low left ventricular ejection fraction.  A recently published randomized clinical trial compared an angiotensin-neprilysin inhibitor (ANi) to an angiotensin-converting enzyme inhibitor (ACEi) in patients who have heart failure with a reduced ejection fraction.  The following results were reported:  The investigators also reported the following results for patients in the angiotensin-neprilysin inhibitor (ANi) and angiotensin-converting enzyme inhibitor (ACEi) groups:
 Which of the following is the best interpretation of these results

Quizplus · Accepted Answer

Explanation: Neprilysin degrades bradykinin, which plays a role in angioedema pathways. There were 19 cases (11 + 5 + 3 + 0) of angioedema in the angiotensin-neprilysin inhibitor (ANi) group and 11 cases (5 + 4 + 2 + 0) in the angiotensin-converting enzyme inhibitor (ACEi) group. Drug-induced angioedema is a rare but serious adverse effect. Therefore, even though the P-values were not statistically significant, it is important to monitor angioedema events if the drug becomes available to a large number of patients with heart failure. It is possible that, when more patients are exposed to this drug, more cases of angioedema will be detected and, with the larger sample size, a statistically significant difference may be detected between the ANi and the ACEi groups. Postmarketing surveillance is the monitoring of the safety of medications or devices after they have been released on the market. The true safety profile of any medication is really understood only after the medication has been on the market for a period of time and has been used by a large number of patients. (Choice A) This was a randomized control trial comparing 2 active treatments; there is no placebo effect. (Choice B) Drug-induced angioedema is generally rare and there were no cases of angioedema with airway compromise recorded in this study. However, these results do not establish whether or not this complication can be definitively ruled out. For example, despite the fact that no such events were reported in this study, drug-induced angioedema with airway compromise is seen with ACEi. (Choice C) Randomized clinical trials are efficacy trials by design and are not powered to assess adverse effects, especially rare adverse effects. In addition to having potentially too few participants, follow-up times are often short, and in some populations, comorbidities and additional drug interactions may not be adequately represented in earlier phases of clinical testing. (Choice E) There were more angioedema events with the new drug; however, none of the P-values were statistically significant. Educational objective: Postmarketing surveillance is the monitoring of the safety of medications or devices after they have been released on the market. The true safety profile of any medication is really understood only after the medication has been on the market for a period of time and has been used by a large number of patients.

An 84-Year-Old Man Comes to the Physician with Persistent Dyspnea