From the Guidelines
For acute exacerbation of HFrEF with hypotension (BP 90/49), I recommend temporarily holding perindopril and dapagliflozin, and possibly reducing metoprolol to 12.5mg BID while initiating IV diuretics, as the most recent guidelines from 2022 suggest careful management of hypotension in HFrEF patients 1.
Treatment Approach
The patient is currently on apixaban 2.5mg BID, dapagliflozin 10mg/day, furosemide 40mg BID, metoprolol 25mg BID, and perindopril 2mg QD. Given the hypotensive state, it is crucial to balance the need for diuresis with the risk of further lowering blood pressure.
- Temporarily holding the ACE inhibitor (perindopril) and SGLT2 inhibitor (dapagliflozin) until blood pressure stabilizes above 100/60 mmHg is recommended, as these medications can contribute to hypotension.
- Consider reducing metoprolol to 12.5mg BID or temporarily holding it if bradycardia is present, as beta-blockers can also lower blood pressure, but their use is supported in HFrEF for reducing mortality, as shown in the 2022 guidelines 1.
- Continue apixaban at the current dose to prevent thromboembolism, as anticoagulation is crucial in patients with HFrEF, especially if they have a history of atrial fibrillation or venous thromboembolism.
- Initiate IV furosemide at 40-80mg bolus followed by continuous infusion at 5-10mg/hour, titrated to response, as IV diuretics are more effective than oral formulations in acute exacerbations, and their use is recommended in the 2016 ESC guidelines for acute heart failure management 1.
- Monitor fluid status, renal function, electrolytes (especially potassium, sodium, and magnesium), and daily weights closely, as diuretic therapy can lead to electrolyte imbalances and renal dysfunction.
- If the patient shows signs of end-organ hypoperfusion despite diuresis, consider adding IV inotropic support with dobutamine (starting at 2.5 mcg/kg/min), as inotropic agents may be necessary in cases of severe hypotension or hypoperfusion, according to the 2016 ESC guidelines 1.
Rationale
The approach outlined above prioritizes the management of acute volume overload while minimizing the risk of further hypotension, which could compromise organ perfusion. The temporary reduction in neurohormonal blockade (by holding ACE inhibitors and possibly reducing beta-blockers) allows for hemodynamic recovery, while IV diuretics address congestion more effectively than oral formulations during acute exacerbation. This strategy is supported by the most recent guidelines and evidence, emphasizing the importance of careful blood pressure management and the role of diuretics and inotropes in acute heart failure 1.
From the FDA Drug Label
The efficacy and safety of dapagliflozin 10 mg were assessed independently in two Phase 3 trials in adult patients with heart failure Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF, NCT03036124) was an international, multicenter, randomized, double-blind, placebo-controlled trial in patients with heart failure [New York Heart Association (NYHA) functional class II-IV] with reduced ejection fraction [left ventricular ejection fraction (LVEF) 40% or less] to determine whether dapagliflozin reduces the risk of cardiovascular death and hospitalization for heart failure.
In DAPA-HF, at baseline, 94% of patients were treated with ACEi, ARB or angiotensin receptor-neprilysin inhibitor (ARNI, including sacubitril/valsartan 11%), 96% with beta-blocker, 71% with mineralocorticoid receptor antagonist (MRA), 93% with diuretic, and 26% had an implantable device (with defibrillator function)
Table 17: Treatment Effect for the Primary Composite Endpointand, its Components in the DAPA-HF and DELIVER Trials
- Full analysis set. † Two-sided p-values. ‡ In DAPA-HF, the CV death component of the primary endpoint included death of undetermined cause. In DELIVER, the CV death component of the primary endpoint excluded death of undetermined cause DAPA-HF Trial Patients with events(event rate) Hazard ratio(95% CI) p-value† Dapagliflozin 10 mgN=2373 PlaceboN=2371 Composite of Hospitalization for Heart Failure, CV Death‡ or Urgent Heart Failure Visit 386(11.6) 502(15.6) 0.74(0.65,0. 85) <0.0001
The patient's current treatment regimen includes dapagliflozin 10mg/day, which has been shown to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF), as demonstrated in the DAPA-HF trial 2.
- The patient is also taking furosemide 40mg BID, which is a common treatment for acute exacerbation of heart failure.
- However, the patient's low blood pressure (90/49) may require careful consideration when initiating or adjusting treatment for acute exacerbation of heart failure.
- The use of dapagliflozin in this patient may be beneficial in reducing the risk of worsening heart failure, but the patient's low blood pressure and current medication regimen should be carefully monitored and adjusted as needed.
- Key considerations for treatment include:
- Monitoring the patient's blood pressure and renal function closely
- Adjusting the patient's diuretic regimen as needed to manage volume overload and blood pressure
- Considering the use of vasopressors or other blood pressure-supporting medications if necessary to maintain adequate blood pressure.
From the Research
Treatment Approach
The patient presents with acute exacerbation of heart failure with reduced ejection fraction (HFrEF) and hypotension (BP 90/49). The current medication regimen includes apixaban, dapagliflozin, furosemide, metoprolol, and perindopril.
Management of Hypotension
- In patients with signs of shock and/or severe congestion, hospitalization is advised 3.
- For non-severe and asymptomatic hypotension, European and US guidelines recommend maintaining the same drug dosage 3.
- In cases of symptomatic or severe persistent hypotension (systolic blood pressure < 90 mmHg), it is recommended to first decrease blood pressure reducing drugs not indicated in HFrEF as well as the loop diuretic dose in the absence of associated signs of congestion 3.
Renin-Angiotensin-Aldosterone System (RAAS) Inhibitors and Beta-Blockers
- Combination therapy with angiotensin-converting enzyme inhibitor (ACEI) and beta-blocker is recommended for the treatment of HFrEF 4.
- Angiotensin receptor blocker (ARB) is not superior to ACEI in improving mortality and is an alternative for patients who are intolerant to ACEI 4.
- The use of ACEi/ARB in patients hospitalized for heart failure is associated with lower 1-year mortality risk and lower 1-6-year mortality risk in those with heart failure preserved ejection fraction (HFpEF) 5.
Beta-Blocker Management
- Early blockade of the beta-adrenergic signaling pathway with beta-blocker therapy is recommended as the first-line medication for patients with HF and reduced ejection fraction (HFrEF) 6.
- In patients with severe acute HF, including those with resolved cardiogenic shock, beta-blocker initiation can be hazardous 6.