How the Evidence Fits Together in Practice

Medications for Opioid Use Disorder in Practice
🔒 Full Review for Subscribers Practice Signal Addiction Medicine Confirmatory Grade: Moderate

All three FDA-approved medications for opioid use disorder are effective, but buprenorphine-naloxone offers a modest edge in overdose prevention, and treatment continuity plus harm reduction matter more than agent choice alone.

The 2026 Lipid Reset: Targets Are Back, the Stepladder Is Gone, and Eligibility Just Expanded
🔓 Free Sample Practice Signal Cardiology Practice-changing Grade: Moderate

The 2026 dyslipidemia guideline restores absolute LDL-C targets and permits non-sequential nonstatin selection while expanding statin eligibility to roughly 87.5 million US adults, so pharmacists should prepare for more shared decision-making, absolute-risk counseling, and earlier use of PCSK9 inhibitors, inclisiran, and bempedoic acid.

Anticoagulation Reversal & AF Stroke Prevention
🔒 Full Review for Subscribers Practice Signal Cardiology Practice-changing Grade: Moderate

In atrial fibrillation, the anticoagulation risk-benefit calculus now hinges on drug-specific reversal (idarucizumab for dabigatran, off-label four-factor prothrombin complex concentrate as the pragmatic default for factor Xa inhibitors after andexanet's withdrawal) and on left atrial appendage closure as a bleeding-sparing but not stroke-superior alternative in selected patients.

Factor XI Inhibitors: A New Frontier in Anticoagulation
🔒 Full Review for Subscribers Practice Signal Cardiology Practice-changing Grade: High

Factor XI/XIa inhibitors are moving from clinical trials to regulatory review, with asundexian now the first molecule in this class under FDA priority review for US market approval. OCEANIC-STROKE demonstrated a 26% reduction in recurrent ischemic stroke (HR 0.74, P<0.001) without increased major bleeding when added to antiplatelet therapy in 12,327 patients with noncardioembolic stroke or high-risk TIA. The class includes two oral FXIa inhibitors (asundexian, milvexian) and one subcutaneous anti-FXI monoclonal antibody (abelacimab), each pursuing different indications with different results. Asundexian failed in atrial fibrillation (OCEANIC-AF terminated early, HR 3.79 for stroke vs apixaban), while milvexian and abelacimab AF trials remain ongoing. For acute care pharmacists, the practical question is no longer whether FXIa inhibition works, but how to build formulary frameworks for a drug that looks like an anticoagulant, acts on the coagulation cascade, yet has a bleeding profile indistinguishable from placebo.

Model-Informed TDM and Precision Dosing
🔒 Full Review for Subscribers Practice Signal Clinical Pharmacokinetics Confirmatory Grade: Low

Across ICU vancomycin, pediatric vancomycin population pharmacokinetic (popPK) modeling, and pediatric tacrolimus, target attainment depends as much on monitoring infrastructure, model selection, and human-factor interventions as on the drug concentration itself.

Antipsychotics for ICU Delirium: A Decade of Negative Trials
🔒 Full Review for Subscribers Practice Signal Critical Care Practice-changing Grade: High

Antipsychotics do not resolve ICU delirium, shorten hospitalization, or improve survival. Five large randomized trials (MIND-USA, AID-ICU, REDUCE, MENDS2, DahLIA), two meta-analyses, and the 2025 PADIS guideline update converge on the same conclusion: haloperidol, ziprasidone, and atypical antipsychotics lack efficacy as delirium treatments in critically ill patients. Pharmacists should challenge reflexive antipsychotic orders for ICU delirium and instead champion the ABCDEF bundle, reserving antipsychotics only for brief management of severe agitation that threatens patient safety.

Fixed vs Weight-Based 4F-PCC Dosing for Bleeding Reversal
🔒 Full Review for Subscribers Practice Signal Emergency / Critical Care Hypothesis-generating Grade: Low

For extracranial warfarin and factor Xa inhibitor major bleeding, fixed-dose four-factor prothrombin complex concentrate (4F-PCC) is a reasonable, faster, and more resource-sparing default when paired with a repeat-dose pathway, while weight and international normalized ratio (INR) based dosing remains preferred for vitamin K antagonist associated intracranial hemorrhage.

GLP-1 Receptor Agonists Beyond Diabetes
🔒 Full Review for Subscribers Practice Signal Endocrinology / Obesity Practice-changing Grade: High

Across obesity, cardiovascular disease, heart failure with preserved ejection fraction, chronic kidney disease, metabolic dysfunction-associated steatohepatitis, and even alcohol use disorder, GLP-1 receptor agonist (GLP-1RA) benefit tracks the patient's comorbid disease profile more than any BMI threshold, and pharmacists should frame these agents as indefinite, disease-targeted chronic therapy.

Deprescribing Works on Paper. Does It Change Outcomes?
🔓 Free Sample Practice Signal Geriatrics / Polypharmacy Practice-changing Grade: Moderate

Pharmacist-led medication review and embedded decision-support algorithms reliably reduce inappropriate prescribing in older adults, and newer transition-of-care and N-of-1 approaches are beginning to link deprescribing to hard outcomes like readmission, but consistent downstream mortality or symptom benefit remains unproven.

GDMT for Heart Failure
🔓 Free Sample Practice Signal Heart Failure Practice-changing Grade: High

Full four-pillar guideline-directed medical therapy remains the foundation for heart failure with reduced ejection fraction, and finerenone now extends disease-modifying options into the mildly reduced and preserved ejection fraction range, but the persistent gap is implementation in the highest-risk patients rather than a lack of proven therapies.

Stewardship That Sticks: Dose Optimization and the Interventions That Actually Change Prescribing
🔓 Free Sample Practice Signal Infectious Disease / Antimicrobials Practice-changing Grade: Low

Antimicrobial stewardship that changes prescribing depends on active, patient-specific, pharmacist-delivered interventions (audit and feedback, time-outs, dose individualization) rather than passive alerts or education alone.

Nonsteroidal MRAs (Finerenone) in Cardiorenal Protection
🔒 Full Review for Subscribers Practice Signal Nephrology / Cardiorenal Practice-changing Grade: High

Finerenone now has randomized evidence for cardiorenal protection across type 2 diabetic and non-diabetic albuminuric chronic kidney disease (CKD), and should be considered as an add-on to maximally tolerated renin-angiotensin system (RAS) blockade with a structured potassium monitoring plan rather than reserved for advanced disease.

Continuous Levodopa and MS Infusions in Neurology
🔒 Full Review for Subscribers Practice Signal Neurology Confirmatory Grade: Low

Subcutaneous continuous drug delivery, whether foslevodopa/foscarbidopa for Parkinson OFF time or subcutaneous natalizumab for multiple sclerosis, offers durable disease control or major operational and experience gains, shifting the pharmacist's role toward infusion-site care, dose reconciliation, and patient selection.

Acute Ischemic Stroke Reperfusion: Extended-Window Thrombolytics
🔒 Full Review for Subscribers Practice Signal Neurology Practice-changing Grade: High

Imaging-based selection now extends intravenous thrombolysis to 9 hours and wake-up stroke, and tenecteplase has become an equal first-line agent to alteplase within 4.5 hours, but adding a late-window lytic on top of thrombectomy in perfusion-selected large-vessel occlusion has not improved functional outcomes.

Alzheimer's Blood Tests: What Pharmacists Need to Know
🔒 Full Review for Subscribers Practice Signal Neurology Practice-changing Grade: High

Plasma p-tau217 blood tests can identify Alzheimer's disease pathology with accuracy approaching PET and CSF, but they detect amyloid status, not cognitive decline. Current guidelines restrict their use to specialty settings with objective cognitive impairment, yet direct-to-consumer tests and primary care ordering are already outpacing the evidence. Pharmacists should be prepared to counsel patients on what these results do and do not mean, flag false-positive risk in patients with severe renal impairment (eGFR 30 or below), and understand that a positive result does not equal a dementia diagnosis.

KRAS Inhibitors in Pancreatic Cancer
🔓 Free Sample Practice Signal Oncology Practice-changing Grade: Moderate

In previously treated RAS-mutated metastatic pancreatic cancer, oral daraxonrasib doubled median overall survival versus chemotherapy (hazard ratio [HR] 0.40), making pan-RAS inhibition a likely new second-line standard once RAS status is confirmed.

KRAS Inhibitors in Pancreatic Cancer
🔒 Full Review for Subscribers Practice Signal Oncology Practice-changing Grade: Moderate

Pan-RAS and mutation-specific KRAS inhibitors are transforming PDAC treatment, from sotorasib and adagrasib (G12C) to daraxonrasib covering >90% of KRAS mutations.

Immune Checkpoint Inhibitors in GI and Liver Cancers
🔒 Full Review for Subscribers Practice Signal Oncology Pharmacy Practice-changing Grade: High

PD-1/PD-L1 checkpoint inhibitors have moved from metastatic salvage to validated first-line and adjuvant use across GI and liver cancers, but the strength of evidence and the role of the chemotherapy backbone differ sharply by tumor type and treatment setting.