Cardiology Update, 9/17/25
Highlights from the European Society of Cardiology 2025 meeting
Extra-high potassium was even better for patients with ICDs
Among 1,200 patients with implantable cardio converter–defibrillators and baseline plasma levels 4.3 mmol/L or lower, those who were randomized to potassium supplementation (and/or spironolactone) to achieve a high normal level of 4.5 to 5.0 mmol/L experienced significantly lower rates of ventricular tachycardia (15% vs 20%) and unplanned hospitalization due to arryhtmias (7% vs 11%) over three years of follow up. Mortality was similar in the treated group (5.7%) and standard care (6.7%).
Potassium-supplemented patients had numerically more instances of severe hyperkalemia than patients assigned to usual care, but this occurred rarely and was not statistically significant.
Digitoxin (which is not digoxin) improved outcomes in heart failure
Digitoxin is a cardiac glycoside like digoxin, but more lipophilic and more easily bound to serum proteins. This makes digitoxin more excretable in the gut (assuming normal liver function) and less prone to reach toxic levels when renal function is impaired, compared to digoxin.
Among 1,240 patients with heart failure with reduced ejection fraction who were randomized to receive either digitoxin or placebo as add-on therapy, an absolute 4.6% fewer (39.5% vs 44.1%) experienced a first hospital admission for worsening heart failure. They had numerically lower mortality (27% vs 29.5%), although this did not reach significance. They also had more serious adverse events (4.7% vs 2.8%), which were usually cardiac disorders.
The improvement was impressive because patients were already taking three or four medications for heart failure.
Because digitoxin has a longer half-life than digoxin, it has its own potential for toxicity, especially if the dose is titrated too rapidly or if liver disease is present.
Digitoxin is not available in the U.S. currently.
—Bavendiek et al, “Digitoxin in Patients with Heart Failure and Reduced Ejection Fraction”, NEJM 2025
Aspirin’s role after MI may be more nuanced than we thought
For patients taking anticoagulants who experience acute coronary syndromes, major cardiology society guidelines have advised dual antiplatelet therapy after acute coronary syndromes, with the aspirin discontinued in the first month to reduce bleeding risk.
A recently published trial suggests the risks to patients from this recommendation may be larger than realized.
Aspirin plus anticoagulants = more deadly bleeding (AQUATIC trial)
Among 872 patients at multiple centers in France who were taking oral anticoagulants and had recent coronary stents in place, more people randomized to take aspirin had died at 2 years (13% vs. 8% taking placebo), and had three times the rate of major bleeding (10% vs 3%).
Nor was the aspirin preventive, as they also experienced more events in the composite outcome (17% vs. 12%) of cardiovascular death, MI, stroke, coronary revascularization, or acute limb ischemia.
These were patients at high risk for cardiovascular events, who should have benefited from antiplatelet monotherapy, yet they experienced net harm from aspirin.
The trial is bound to cause consternation and could pave the way for a larger trial testing antiplatelet monotherapy (e.g., clopidogrel) vs placebo in patients who are also taking oral anticoagulation.
Aspirin didn’t help after low-risk MI (TARGET-FIRST trial)
Another, even larger trial muddied the waters as to the strength of aspirin’s benefit in low-risk patients.
In the TARGET-FIRST trial (n=2,246) in Europe, patients with low-risk MI (completely revascularized within 7 days, not taking oral anticoagulants) whose aspirin was discontinued after one month (and continued antiplatelet monotherapy) had similar outcomes to those taking dual antiplatelet therapy after one year (2.2% vs 2.1%) for the composite outcome of death from any cause, myocardial infarction, stent thrombosis, stroke, or major bleeding). Unfortunately, they combined bleeding risk along with cardiovascular risk (apples and oranges).
Patients whose aspirin was stopped experienced less bleeding (2.6% vs 5.6%), mostly driven by “BARC 2” severity (requiring medical attention but not life-threatening).
There was no increase in MIs in the group from whom aspirin was withdrawn. Stent thrombosis occurred in one patient in the single antiplatelet group (0.1% vs. 0).
Aspirin’s overall benefits post-MI redemonstrated (NEO-MINDSET)
Today, aspirin continues to be recommended as part of DAPT in patients with MI, and its known benefits among “all comers” after MI were redemonstrated in the NEO-MINDSET trial.
Among patients not taking anticoagulation, randomization to early withdrawal of aspirin (while continuing to take a potent single P2Y12 inhibitor as monotherapy, either prasugrel or ticagrelor) led to more cardiovascular events at 12 months, compared to patients randomized to dual antiplatelet therapy. Those whose aspirin was withdrawn did experience significantly less bleeding events than those on DAPT.
—Guimarães et al, “Early Withdrawal of Aspirin after PCI in Acute Coronary Syndromes”, NEJM 2025
Beta-blockers after MI with normal EF: any benefit?
Cardiology society guidelines advise that beta-blockers be started in all patients after myocardial infarction who have no contraindication.
That includes those with preserved left ventricular ejection fraction, but the evidence for any benefit is lower than for patients with low EF. Patients with HFpEF have been advised to stop the beta blocker in the year following the MI, while those with low EF are advised to take beta blockers long-term.
At the European Society of Cardiology, two massive trials enrolling patients with ejection fraction ≥40% had somewhat conflicting results:
REBOOT-CNIC found beta blockers had zero benefit on any measure (death, reinfarction, hospitalization for heart failure, or the composite of these), over a median follow-up of almost four years, among >8,400 patients in Spain and Italy.
BETAMI-DANBLOC found a lower risk of the composite of death or major adverse cardiovascular event, a finding driven primarily by fewer new MIs in the beta-blocked group among the ~5,600 Scandinavian patients.
In subgroup analyses, any potential benefit in BETAMI-DANBLOC appeared to be concentrated in the patients with mildly depressed ejection fraction (41-49%), bringing both trials more closely in alignment for patients with normal EF (≥50%), who seem to experience very little or no benefit from beta-blockers after MI.
Physiology Flashback!
ICU Physiology in 1000 Words: Venous Excess & the Myth of Venous Return
Jon-Emile S. Kenny MD [@heart_lung]
