Besides bisoprolol, carvedilol seems interesting, although it has a shorter half-life (6h) and therefore needs to be taken twice a day (vs once daily for bisoprolol). But it has interesting additional properties:
An Updated Prioritization of Geroscience- Guided FDA-Approved Drugs Repurposed to Target Aging 2024
One study found that the beta blocker carvedilol reduced oxidative stress-induced apoptosis in cardiomyocytes (see Supplement 1).
One meta-analysis of interventional trials reported carvedilol, a non-selective beta-blocker, to decrease mortality significantly more than beta-1 selective beta blockers in patients with either heart failure or myocardial infarction.
From “contraindicated” to “first line” – Current mechanistic insights beyond canonical β-receptor signaling 2024
Today, four β-blockers are recommended for the treatment of HF (bisoprolol, carvedilol, metoprolol succinate (CR/XL) and nebivolol) in the European Guidelines.
Carvedilol-induced β1AR-Gi signaling also addresses the PI3K/Akt pathway and induces NOS3 activation, thereby promoting cardiomyocyte survival.
Carvedilol induces vasodilation via antagonism at peripheral α1AR inducing arterial vasodilation while concurrently suppressing reflex tachycardia via cardiac β1AR-blockade.
Carvedilol and its metabolites have anti-oxidative properties that manifest as antioxidation (e.g. reduced lipid peroxidation) and anti-inflammation. These capabilities are attributed to the chemical structure of carvedilol and its metabolites, which have a tricyclic carbazole structure.
Carvedilol – via the PKA/PGC1α pathway – leads to improved mitochondrial function in endothelial cells, resulting in protective/beneficial effects within the context of atherosclerosis.
Additionally, carvedilol - likely via modulation of potassium channels - stabilizes glucose homeostasis and attenuates hepatic glucose production, while enhancing muscular insulin signaling. Consistent with these observations, carvedilol has shown favorable in the context of metabolic disturbances in patients.
In Association of cardiovascular disease management drugs with Lewy body dementia: a case–control study 2023, the HR of carvedilol use with LBD was 0.67 [0.65-0.69], the best-performing beta-blocker and as good as telmisartan (but it’s an association study, not an RCT).
On the other hand, in the EPITERNA preprint, carvedilol was associated with a significantly shorter lifespan and was the worst-performing beta-blocker (again, association study).
In animal and computational models, it seems neuroprotective:
And there are three ongoing studies of carvedilol in NDDs:
Carvedilol is better than metoprolol for arrhythmias: Effect of Carvedilol vs Metoprolol on Atrial and Ventricular Arrhythmias Among Implantable Cardioverter-Defibrillator Recipients 2023
It also works well in atrial fibrillation:
So, if someone needs a BB (for instance to lower HR), then carvedilol might be the best option. What do you think @Davin8r?
However here carvedilol, although the best performing beta-blocker, ranks below placebo (not sure it’s a great paper though): EFFECT OF ANTIHYPERTENSIVE AGENTS ON RISK OF NEW-ONSET AND RECURRENT ATRIAL FIBRILLATION: A NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS 2024
Ramipril + HCTZ is the best combination to reduce the risk of new-onset and recurrent AF among patients with hypertension, diabetes, or AF. However, not all combinations were tested (due to a lack of trials). Telmisartan was the best-performing single agent. As ramipril + HCTZ = 0.95 vs 0.66 for ramipril and perindopril + indapamide = 0.51 vs 0.34 for perindopril, I can imagine that telmisartan + indapamide would be even better than ramipril + HCTZ.