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https://www.nejm.org/doi/full/10.1056/NEJMoa2405923?query=clinical-medicine

Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain.

Recent attempts to improve outcomes with intensified renin–angiotensin–aldosterone inhibition have not shown improvements in outcomes.7,8 A trial of routine aldosterone antagonism with spironolactone in addition to standard therapy among 1603 patients after myocardial infarction without heart failure showed no improvement in outcomes.9 

https://pubmed.ncbi.nlm.nih.gov/27102506/   “ In a non-pre-specified exploratory analysis, the odds of death were reduced in the treatment group (3 [0.5%] vs. 15 [2.4%]; HR: 0.20; 95% CI: 0.06 to 0.70) in the subgroup of ST-segment elevation MI (n = 1,229), but not in non-ST-segment elevation MI (p for interaction = 0.01).”’

However, there was a significant reduction in mortality in the subgroup of 1229 patients with ST-segment elevation myocardial infarction (STEMI), a finding that highlights the need for a large trial.

 We conducted the CLEAR trial to evaluate whether routine use of spironolactone is beneficial in patients after myocardial infarction.

Couturaud F et al. Extended treatment of venous thromboembolism with reduced-dose versus full-dose direct oral anticoagulants in patients at high risk of recurrence: A non-inferiority, multicentre, randomised, open-label, blinded endpoint trial. Lancet 2025 Mar 1; 405:725. (https://doi.org/10.1016/S0140-6736(24)02842-3)

https://www.nejm.org/doi/full/10.1056/NEJMoa2405404

NNT of 4! systemic metronid and topical clinda bid for one week

What Was Studied?

The EMPA-KIDNEY trial followed 6,609 CKD patients at risk of disease progression. Participants were randomly assigned to receive empagliflozin (10 mg daily) or a placebo for a median of 2 years. After this ‘active’ phase, 4,891 patients entered a 2-year post-trial observational period where neither group received the trial drug, but doctors could prescribe open-label SGLT2 inhibitors. The goal? To see if empagliflozin’s benefits persisted after stopping treatment.

Key Findings

Limitations

Should This Change Practice?

Yes. Here’s why:

For clinicians, this reinforces SGLT2 inhibitors as a first-line therapy for CKD, regardless of diabetes status. The modest NNT (24 over 4 years) highlights its clinical meaningfulness in a high-risk population.

Metformin while not necessarily first line therapy for diabetes depending on the patients co-morbid conditions it is certainly highly ranked on the list of medications!

I know often metformin is stopped while coming into the hospital for fear of potentially lactic acidosis or an increase in AKI with contrast studies however this ‘belief’ is largely based on myth and misconception. Metformin's contraindications should be contraindicated - PMC

I also know that often metformin is held at discharge if the patients GFR is near or around 30

However, two new studies.

Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation Study - ClinicalKey

4,278 Scottish residents with a diagnosis of type 2 diabetes were identified as prevalent metformin users with incident CKD stage 4. (it was stopped when they reached CKD 5)

Results:

Compared with continuing metformin, stopping metformin was associated with a lower 3-year survival (63.7% [95% CI, 60.9-66.6] vs 70.5% [95% CI, 68.0-73.0]; HR, 1.26 [95% CI, 1.10-1.44])    (THAT WOULD BE ROUGHLY A NNT OF 14)

Interestingly the thing we think metformin prevents (MACE) was the same in both groups  (HR, 1.05 [95% CI, 0.88-1.26]).

Could it be possible that metformin saves your life on some other mechanism that we don’t totally understand??

Discontinuing metformin was associated with a higher risk of death from respiratory diseases (HR, 1.51 [95% CI, 1.06-2.12]) MAYBE THAT IS THE SECRET!?

Trial 2

Clinical outcomes following discontinuation of metformin in patients with type 2 diabetes and advanced chronic kidney disease in Hong Kong: a territory-wide, retrospective cohort and target trial emulation study - ScienceDirect

33,586 metformin users with new-onset eGFR < 30 ml/min/1.73 m2 were included in the study and 7500 (22.3%) of whom discontinued metformin within 6 months whereas 26,086 (77.7%) continued use of metformin. They were followed for a median duration of 3.8 (IQR: 2.2–6.1) years,

This time, those in which metformin was discontinued had higher risk of MACE (weighted and adjusted HR = 1.40, 95% CI: 1.29–1.52),

AND once again if you stopped the metformin you had a higher incidence of death  (HR = 1.22, 1.18–1.27). 

BUT get this, if you stopped the metformin you had higher rates of progression to END STAGE KIDNEY DISEASE (HR = 1.52, 1.42–1.62)!!!

Yes, stopping metformin was associated with all the badness of the heart and kidneys

PS- no association observed for the risk of lactic acidosis (still)

Obviously, these are both observational studies so there could be unaccounted for confounders that can only truly be ruled out with an RCT. Now that metformin is $4 a month at Walmart and the new fancy diabetic drugs are $20-$40 per day it is very unlikely we will see the proper drug company run trial anytime in the near future. However it does seem possible and even reasonable we continue metformin even at smaller doses (500mg daily or 500mg BID) may actually decrease the one thing we are all trying to fight against…..death

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2825813


Conclusions and Relevance  In this randomized clinical trial assessing simultaneous vs sequential administration of mRNA COVID-19 and IIV4 vaccines, reactogenicity was comparable in both groups. These findings support the option of simultaneous administration of these vaccines.

https://www.bmj.com/content/388/bmj-2024-081164


systematic review and meta-analysis on prehabilitation before surgery, published in the BMJ in February 2025.Prehabilitation aims to prepare patients for surgery through interventions like exercise, nutrition, and psychological support. This study looked at which prehabilitation components are most effective for improving key outcomes after surgery.The researchers analyzed 186 randomized trials with over 15,000 participants. They used advanced statistical methods to compare different prehabilitation approaches.The key findings were:

When looking at individual components, exercise and nutrition consistently showed the most benefit across all outcomes.However, there are important limitations to consider. The overall certainty of evidence was low to very low for most comparisons. This was mainly due to potential bias in the original trials and imprecision in the results.So what does this mean for clinical practice? While not definitive, this study suggests that exercise and nutritional prehabilitation, either alone or as part of multicomponent programs, likely benefit surgical patients. Clinicians should consider incorporating these approaches when preparing patients for surgery.However, we still need large, high-quality trials to confirm these findings before making strong recommendations. Future research should focus on well-designed studies looking at the outcomes that matter most to patients and healthcare systems.In summary, this study provides promising evidence for prehabilitation, particularly exercise and nutrition-based approaches. 

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