PARADISE MI Trial: Is Sacubitril/valsartan (Entresto) useful in patients with acute MI?

The PARADISE MI trial is the first of the 10 new trials visual abstracts that we have added to the app. You can download the JPEG of the visual abstract from below. You can use it any way you like as long as you cite the visualmed app or the website along with the original article.

PARADISE MI Trial Entresto in acute MI

Use of Sacubitril/valsartan in Acute MI?

Sacubitril, a neprilysin inhibitor, has shown to be beneficial when combined with an ARB in patients with chronic heart failure. A similar hypothesis was generated that it might be useful in patients with acute ischemic HF or patients with acute MI who had reduced EF or clinical heart failure. To prove this hypothesis, the PARADISE MI trial was designed. The recruitment was intense and the authors were able to recruit more than 5,000 patients that suitably powered this prospective superiority trial.

Inclusion criteria included patients with reduced EF after the MI

The included population was diverse and consisted of 24% females. Only those acute MI patients were included whose Left ventricular ejection fraction (LVEF) was ‚ȧ40% with or without pulmonary congestion. This is important as neprilysin inhibition has been primarily found to be useful in heart failure patients. Also, recall that the PIONEER-HF trial showed significant improvement of NT-proBNP of patients with acute HF who were put on neprilysin inhibition.

PIONEER HF Trial entresto in acute heart failure

Sacubitril/valsartan failed to show superiority over ACEi Ramipril

The primary outcome of cardiovascular (CV) death, first HF hospitalization, or outpatient HF occurred in 11.9% sacubitril/valsartan patients vs. 13.2% in the ramipril group. (p = 0.17) The findings are significantly different from prior trials. One key difference is the use of Ramipril and acute MI population who had MI within the prior 7 days. In the prior studies, the comparison was made with enalapril such as seen in the PARADIGM-HF trial which was done for chronic heart failure patients.

PARADIGM HF Trial ARNI in heart failure

Incremental benefit and safety in acute MI

The authors of PARADISE-MI argued that there is an incremental benefit of ARNI in this specific patient group but is that enough to compel cardiologists to prescribe this drug? ACEi and ARBs are cheaper and easily accessible and with newer data physicians are leaning more towards prescribing these meds over ARNI especially in the vulnerable population who are unable to afford their meds.

How to keep yourself updated with the latest medical literature using the Visualmed app

Did you know that there are around 30,000 journals that are publishing more than 2 million articles each year? (source). The amount of data inflow is exponential and the most difficult task is to keep yourself up to date with all this information. If you’re a physician, the only time you’ll be able to read any scientific article is either during a journal club meeting or maybe on weekends if you don’t have any family. The truth is we are publishing way more than we can digest. If we talk about just cardiology, ~ 87 landmark, practice-changing trials were published in 2020 (source). Most of these trials get traction through medical media websites but some of the important ones are simply missed and get archived without getting much traction. Now the question remains, how do we keep ourselves up to date with all this knowledge?

In 2018, I was a medicine resident at the University of Connecticut Health Center in Farmington CT, USA. I was scheduled to rotate through the ICU during the latter half of the year. During that rotation, two important clinical trials were published, namely the SALT-ED and the SMART trial. These trials highlighted an important question in clinical medicine which is whether to use balanced crystalloids or just saline in hospitalized and critically ill patients respectively. As a senior ICU resident, it was difficult for me at that time to go through the complete study so I came up with an idea to summarize the key points of the trial as a visual infographic. The SALT-ED trial was the first study that I visualized. My colleagues loved the infographic summary and asked if I could summarize other important studies as well. This was how Visualmed started. The idea started with a website, where I compiled all the key trials but keeping up with even landmark studies was difficult. Eventually, I decided to focus on app format only as it was easier to manage compared to the website. Now, after 3 years of hard work, I have finally launched the free version of the app that contains ~1000 summaries of landmark clinical trials.

When designing the app, my idea was to keep it as simple as possible. This is the reason the landing page of Visualmed is simply a list of medical topics and subcategories with a search bar on top. The search function is dynamic. This means if you start typing a drug or a disease name, the trials on that particular topic will pop up in real-time provided that it’s available in the app. Unlike other apps in the same category, Visualmed contains a one-page summary only. This means that once you tap on a trial, it’ll pop up one verticle image that squeezes all the key information from that trial.

I try to focus on the primary outcome and 2 key secondary outcomes of the study. One important part that I’m trying to introduce is the key limitation of the trial. The plan is to update all the available infographics and add key limitations to each of those. The idea of Visualmed is to provide a key concept of the trial. This is in no way an alternative to reading and going through the full study. Nevertheless, we do need a platform or a search engine for practice-changing evidence-based medicine and Visualmed provides just that.

The app has now more than 30,000 physicians who used it on daily basis for quick reference of the studies. Each trial is linked to its original study and I believe this provides a unique source to encourage physicians to go through these studies and improve their own knowledge as well as practice evidence-based medicine. The app is currently in its initial stages. I have shortlisted more than 5,000 landmark studies that had been published in notable journals such as NEJM, JAMA, BMJ and the Lancet. The plan is to add all those studies to the app eventually. Right now, the app gets updated with 40 new trials every month and we are trying to increase that to at least 50-70 trials a month.

In conclusion, if you read through this article, I would like to encourage you to download the app. It’s totally free and there are no advertisements. The app is meant to be used by physicians and healthcare workers only. Here are the download links:

Visualmed for iPhone

Visualmed for Android