What is the optimal management plan for a patient with heart failure, similar to those enrolled in the Surmount trial, with consideration of their clinical profile and medical history?

The SURMOUNT Trial: Not a Heart Failure Study

The SURMOUNT trial is not related to heart failure management—it is a weight loss trial investigating tirzepatide (a GLP-1/GIP receptor agonist) for obesity treatment. There appears to be confusion between SURMOUNT and the SHIFT trial (Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial), which is a landmark heart failure study.

The SHIFT Trial: Key Heart Failure Evidence

The SHIFT trial demonstrated that ivabradine reduces the risk of hospitalization for worsening heart failure in patients with HFrEF, elevated heart rate, and symptomatic disease despite optimal medical therapy. 1

Trial Design and Population

• Enrolled 6,558 adult patients with stable NYHA class II-IV heart failure, LVEF ≤35%, and resting heart rate ≥70 bpm 1
• 68% had coronary artery disease as the underlying cause of heart failure 1
• Baseline characteristics: 49% NYHA class II, 50% NYHA class III, 2% NYHA class IV, with mean LVEF of 29% 1
• All patients required clinical stability for at least 4 weeks on optimized medical therapy and prior hospitalization for heart failure within 12 months 1

Background Medical Therapy

• 89% were taking beta-blockers, but only 26% were on guideline-defined target daily doses 1
• Main reasons for suboptimal beta-blocker dosing: hypotension (45%), fatigue (32%), dyspnea (14%), dizziness (12%), history of cardiac decompensation (9%), and bradycardia (6%) 1
• 91% were on ACE inhibitors/ARBs, 83% on diuretics, and 60% on anti-aldosterone agents 1
• Device therapy was uncommon: only 3.2% had ICDs and 1.1% had CRT devices 1

Primary Results

Ivabradine reduced the composite endpoint of hospitalization for worsening heart failure or cardiovascular death (HR 0.82,95% CI 0.75-0.90, p<0.0001) over a median follow-up of 22.9 months. 1

• The benefit was driven entirely by reduction in heart failure hospitalizations (HR 0.74,95% CI 0.66-0.83) 1
• No favorable effect on cardiovascular mortality was observed (HR 0.91,95% CI 0.80-1.03) 1
• Hospitalization for worsening heart failure occurred in 15.6% of ivabradine patients versus 20.2% of placebo patients 1

Dosing Strategy

• Patients initiated on 5 mg twice daily, then titrated to 7.5 mg twice daily or decreased to 2.5 mg twice daily to maintain resting heart rate between 50-60 bpm 1
• At 1 month: 63% were taking 7.5 mg BID, 26% were on 5 mg BID, 8% on 2.5 mg BID, and 3% had withdrawn (primarily for bradycardia) 1

Current Guideline Integration

2022 AHA/ACC/HFSA Guidelines Position

Current guidelines recommend ivabradine for patients with HFrEF who remain symptomatic despite optimal GDMT, particularly when beta-blocker up-titration is limited by side effects rather than heart rate control. 2

• Ivabradine should be added when target heart rate (<70 bpm) is not achieved and increasing beta-blocker dose is not feasible in patients with sinus rhythm 2
• SGLT2 inhibitors are now prioritized as part of the four-pillar foundational therapy (ACE inhibitors/ARBs/ARNI, beta-blockers, MRAs, SGLT2 inhibitors) 3

Optimal Management Algorithm for SHIFT-Like Patients

For patients with HFrEF, LVEF ≤35%, NYHA class II-IV, and heart rate ≥70 bpm despite beta-blocker therapy:

1. First, maximize beta-blocker dosing to target doses (carvedilol 25 mg BID, metoprolol succinate 200 mg daily, or bisoprolol 10 mg daily) unless contraindicated 2, 3

2. If beta-blocker up-titration is limited by hypotension, fatigue, or other side effects (not bradycardia), and heart rate remains ≥70 bpm in sinus rhythm, add ivabradine 5 mg BID 2, 1

3. Ensure all four foundational therapies are initiated rapidly (within 3 months of diagnosis): ACE inhibitor/ARB/ARNI, beta-blocker, MRA, and SGLT2 inhibitor 3

4. For patients with atrial fibrillation, consider digoxin instead of ivabradine for rate control 2

5. Monitor closely for bradycardia (target heart rate 50-60 bpm) and adjust ivabradine dose accordingly 1

Critical Pitfalls to Avoid

• Do not use ivabradine as a substitute for beta-blockers—it should only be added when beta-blocker optimization is not possible 2
• Ivabradine is contraindicated in patients with severe hepatic impairment (Child-Pugh C) and should be used cautiously with CYP3A4 inhibitors 1
• The SHIFT trial population had very low device therapy rates (3.2% ICDs, 1.1% CRT), which does not reflect current practice where device therapy should be considered per 2022 guidelines 2, 1
• Patients not on beta-blockers due to COPD, asthma, or hypotension may benefit from ivabradine, but this represents off-label use beyond SHIFT trial evidence 1

Contemporary Context

The SHIFT trial was conducted before SGLT2 inhibitors became standard therapy, and most patients had suboptimal beta-blocker dosing and minimal device therapy. 1 Current management would emphasize:

• Earlier and more aggressive beta-blocker titration 3
• Universal SGLT2 inhibitor use across the ejection fraction spectrum 3
• More liberal ICD use for primary prevention in patients with LVEF ≤30-35% on optimal medical therapy ≥3 months 2
• CRT consideration for patients with LVEF ≤35%, sinus rhythm, NYHA class II-IV, and QRS ≥150 ms with LBBB 2