High-Impact Studies Review — March 2025

The 2025 update to the American College of Cardiology (ACC) and American Heart Association (AHA) guidelines for Acute Coronary Syndrome (ACS) introduces important changes based on the latest clinical evidence. The new recommendations focus on optimizing early risk stratification, refining antithrombotic therapy, and tailoring invasive management strategies to improve patient outcomes.

Key Updates and Findings

• Dual Antiplatelet Therapy (DAPT): Used to be: Clopidogrel was often an equivalent option. Now: Ticagrelor or prasugrel is now the preferred P2Y12 inhibitor over clopidogrel in all patients undergoing PCI unless contraindicated.
• ECG Timing and Risk Assessment: All patients with suspected ACS should have an ECG performed within 10 minutes of arrival to facilitate rapid classification and treatment initiation.
• Radial vs. Femoral PCI Access: Radial artery access is strongly recommended over femoral access due to lower bleeding risks, fewer vascular complications, and reduced mortality.
• Complete Revascularization Strategy: Routine PCI of non-culprit lesions in STEMI patients is not recommended during the initial procedure, except in cases of cardiogenic shock.
• High-Intensity Statins and Lipid Management: High-intensity statins should be initiated in all ACS patients. If LDL remains ≥70 mg/dL, additional lipid-lowering agents (ezetimibe or PCSK9 inhibitors) should be considered.
• Beta-Blocker Therapy: Used to be: For all, regardless of risk factors. Now: Early beta-blocker use is no longer required for all ACS patients. Therapy should be reserved for those with ongoing ischemia, hypertension, or left ventricular dysfunction.
• Anticoagulation Strategy: Selection of unfractionated heparin (UFH), enoxaparin, or bivalirudin should be individualized based on renal function, prior anticoagulation, and bleeding risk.
• Early Discharge for Low-Risk NSTEMI: Selected low-risk patients with negative troponins and normal ECG findings may be safely discharged within 24 hours with close outpatient follow-up.
• Cardiogenic Shock Management: Emergency PCI should target the culprit vessel only. Non-culprit PCI at the time of intervention is discouraged unless clinically indicated.

Clinical Implications

These updates emphasize a more individualized approach to ACS management, balancing ischemic protection with bleeding risk. The move toward radial PCI access, a shift in beta-blocker recommendations, and an intensified focus on lipid-lowering strategies mark significant changes in clinical practice.

Clinical Pharmacist's Perspective

Pharmacists play a key role in ensuring appropriate DAPT selection, optimizing statin therapy adherence, and managing anticoagulation. The inclusion of PCSK9 inhibitors highlights the need for careful assessment of cost-effectiveness in high-risk patients. Close monitoring of potential drug interactions is also essential to ensure safe therapy implementation.

This systematic review and meta-analysis of 12 randomized controlled trials (RCTs) involving 1,170 patients examined the effects of short-acting beta-blockers in septic shock. The findings suggest potential benefits in mortality reduction and heart rate control, but also raise concerns about prolonged vasopressor use.

• Reduction in 28-Day Mortality: Short-acting beta-blockers were associated with a 24% relative reduction in 28-day mortality (RR 0.76, 95% CI 0.62–0.93).
• New-Onset Tachyarrhythmia Prevention: Significant reduction in tachyarrhythmias (RR 0.37, 95% CI 0.18–0.78), suggesting improved heart rate control.
• Impact on Hemodynamics: Beta-blockers stabilized heart rate but prolonged vasopressor requirements by an average of 1.04 days (95% CI 0.37–1.72).
• No Clear Benefit on Long-Term Outcomes: No significant impact was observed on 90-day mortality, ICU length of stay, or mechanical ventilation duration.

Beta-blockers such as esmolol and landiolol counteract excessive catecholamine stimulation, which can cause myocardial stress, endothelial injury, and metabolic dysfunction in septic shock. By reducing sympathetic overdrive, they may improve cardiac efficiency and tissue oxygenation while preventing secondary organ dysfunction.

The potential mortality benefit makes beta-blockers a promising adjunctive therapy in septic shock, particularly for patients with persistent tachycardia despite adequate fluid resuscitation and vasopressor therapy. However, the prolonged vasopressor requirements suggest that beta-blockers should be used selectively and with careful monitoring.

The use of beta-blockers in septic shock remains controversial and should be limited to patients who demonstrate clear benefit. Pharmacists should focus on:

• Dosing and titration: Adjust doses carefully to prevent excessive bradycardia and hypotension.
• Monitoring interactions: Watch for interactions with vasopressors and inotropes that could impact hemodynamics.
• Assessing patient eligibility: Ensure beta-blockers are used in clinically stable individuals with controlled shock parameters.

As further studies emerge, pharmacists can help refine treatment protocols to integrate beta-blockers safely in select patients.

In a randomized, double-blind trial of 150 adults, both nebulized (0.75 mg/kg) and IV (0.3 mg/kg) ketamine provided substantial pain relief at 30 minutes with comparable safety profiles.

• Both regimens significantly reduced pain scores.
• No clinically significant differences in adverse effects.
• Noninvasive nebulized administration may benefit patients without IV access.

This pilot trial evaluated dexmedetomidine (1 µg/kg/hr) for enhancing vasopressor sensitivity in refractory septic shock. The trial was halted early due to a lower phenylephrine response and higher early mortality in the dexmedetomidine group.

• Significantly lower MAP response to phenylephrine in the dexmedetomidine group.
• Higher early mortality noted, raising safety concerns.
• No significant improvements in vasopressor dose requirements.

A multicenter retrospective study of 368 pediatric severe TBI patients found that TXA administration was not associated with a reduction in inhospital mortality or poor neurologic outcomes.

• Inhospital mortality: 14% overall with no significant difference between TXA and non-TXA groups.
• Poor neurologic outcomes were similar regardless of TXA use.
• Results do not support routine TXA administration for severe pediatric TBI.