The edition · Clinical Pharmacology
Heart failure therapy was linked to lower mortality after 65 — frailty, not age, holds prescribing back
A meta-analysis of 92,916 older patients linked guideline therapy for reduced ejection fraction with 31% lower mortality, but frail patients were a third less likely to get it. Also: the ACC statement on DOAC dosing, CYP3A4 inhibitors and ruxolitinib toxicity, and a vancomycin premix recall.
The edition in brief
A meta-analysis of 34 studies with 92,916 patients aged 65 or over with reduced ejection fraction found guideline-directed medical therapy was associated with lower mortality (HR 0.69, 95% CI 0.64–0.74); frail patients were less likely to receive it (RR 0.63), beta-blockers raised bradycardia risk (RR 3.98), and hypotension, kidney injury and hypoglycaemia did not differ. The 2026 ACC scientific statement on direct oral anticoagulants highlights continued under-use and inappropriate dosing, particularly in kidney and liver disease, obesity, frailty, cancer and after bleeding, and covers interactions and periprocedural management. A Swiss real-world pharmacokinetic study of ruxolitinib in 77 patients found 45% between-patient variability in clearance; strong CYP3A4 or dual CYP2C9/CYP3A4 inhibitors cut clearance by 39% and nearly tripled trough levels, and higher exposure was associated with toxicity but not efficacy. Baxter's vancomycin 1 g in 200 mL dextrose GALAXY premix is subject to an ongoing FDA Class II recall for manufacturing (CGMP) deviations.
ACC statement: DOACs remain under-used and wrongly dosed in the patients who need them most
Audit DOAC doses against each drug's own criteria, because inappropriate under-dosing is the commonest error.
Class II recall of Baxter vancomycin premix bags for manufacturing deviations
Quarantine the affected vancomycin premix if you stock it and switch to another preparation; clinical use of vancomycin is unchanged.
CYP3A4 inhibitors nearly triple ruxolitinib trough levels, and higher exposure tracks with toxicity
Lower the ruxolitinib dose when a strong CYP3A4 or dual CYP2C9/CYP3A4 inhibitor is added, and monitor for toxicity.
When you stop a drug, record what happens next
Plan every deprescribing taper and report withdrawal reactions as adverse drug reactions.
Guideline heart failure therapy was linked to lower mortality after 65, but frail patients miss out
Start and titrate heart failure therapy in older and frail patients with reduced ejection fraction, watching heart rate, rather than withholding it.
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