Optimal Pharmacologic Treatment of Heart Failure With Preserved and Mildly Reduced Ejection Fraction

Xiang, Boyang; Zhang, Ruiqi; Wu, Xiaoguang; Zhou, Xiang

doi:10.1001/jamanetworkopen.2022.31963

Cited by 19 publications

(20 citation statements)

References 28 publications

(63 reference statements)

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“…Also, a meta-analysis showed no benefit in the risk of all-cause mortality or cardiovascular death for six therapeutic drugs, including SGLT2i, ARNI and mineralcorticoid receptor antagonist (MRA). Compared with placebo, SGLT2i, ARNI and MRA were related to the significant reduction of HF hospitalization risk, among which SGLT2i had the most significant effect (Xiang et al, 2022). Moreover, the results of the DELIVER study demonstrated that dagliflozin reduces the risk of cardiovascular death or worsening heart failure in HFpEF patients independent of baseline renal function (Solomon et al, 2022), our study also included patients with eGFR< 30 ml/min/1.73 m 2 , and confirmed the consistency of the efficacy of spironolactone in this population, further demonstrating the benefit of spironolactone in patients with HFpEF and CKD.…”

Section: Discussionmentioning

confidence: 90%

Association between dosing of spironolactone and outcomes in heart failure with preserved ejection fraction patients combined with chronic kidney disease------Balance of efficacy and risk

Qu²,

Gao³

et al. 2023

Front. Pharmacol.

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Aims: Few studies have compared the association between dosing of spironolactone and outcomes in patients with heart failure with preserved ejection fraction (HFpEF), and whether spironolactone dose could significantly affect the prognosis of HFpEF patients combined with chronic kidney disease (CKD) remains unclear. Our aim was to directly compare ‘high vs. low’ doses of spironolactone in an attempt to find a benefit-risk-balanced point, and infer an adequate dose for HFpEF with CKD patients.Methods: Overall, 4,321 symptomatic heart failure inpatients were initially screened from January 2013 to December 2019, and all enrolled patients were followed-up for 36 months; After including patients who meet the diagnostic criteria of HFpEF and CKD with ejection fraction > 45% and estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, a total of 387 patients was selected. Primary outcome was a composite of all-cause death, heart failure (HF) hospitalization and non-fatal stroke. The key safety outcome was hyperkalemia rates during the follow-up period.Results: The primary outcome event rates in patients with or without spironolactone were 12.74 and 21.45 per 100 person-years, respectively. Compared with patients not taking spironolactone, the adjusted hazard ratio (HR) [95% confidence interval (CI)] was 0.55 (0.38–0.79) with spironolactone group for primary outcomes. After grouped by the daily dose of spironolactone, low-dose group (≤ 40 mg) was associated with lower relative risk for the primary efficacy outcome [adjusted HR (95% CI) was 0.43 (0.23–0.81), 0.50 (0.33–0.76) and 0.74 (0.36–2.79) with < 40 mg, 40 mg and >40 mg, respectively]. During 3-year follow-up, the risk for hyperkalemia was amplified in the higher dose group (>40 mg) while showed no significant difference compared with low dose group (p = 0.425).Conclusion: HFpEF with CKD patients using spironolactone had lower risk of adverse cardiovascular outcomes. And the use of low-dose spironolactone (≤ 40 mg) showed the best efficacy and safety, therefore we may recommend ≤ 40 mg as the optimal initial dose for these patients. However, this was a relatively small sample size, retrospective study, and further adequately powered randomized trials are needed to verify these results.

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Section: Discussionmentioning

confidence: 90%

Association between dosing of spironolactone and outcomes in heart failure with preserved ejection fraction patients combined with chronic kidney disease------Balance of efficacy and risk

Qu²,

Gao³

et al. 2023

Front. Pharmacol.

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“…SGLT2 inhibitors are therefore recommended for all patients with HFmrEF. A recent meta-analysis of studies on the management of HF with mildly reduced or preserved ejection fraction (EF>40%) confirmed that SGLT2 inhibitors are currently the optimal drug class for these patients [ 132 ]. Overall evidence suggests a potential accumulative improvement in HF hospitalization rather than all-cause death with the combination of SGLT2 inhibitors with an ACEi/ARB/ARNI, an MRA or a beta blocker [ 132 , 133 ].…”

Section: Chronic Heart Failurementioning

confidence: 99%

“…A recent meta-analysis of studies on the management of HF with mildly reduced or preserved ejection fraction (EF>40%) confirmed that SGLT2 inhibitors are currently the optimal drug class for these patients [ 132 ]. Overall evidence suggests a potential accumulative improvement in HF hospitalization rather than all-cause death with the combination of SGLT2 inhibitors with an ACEi/ARB/ARNI, an MRA or a beta blocker [ 132 , 133 ]. However, RAASi through ACEi, ARB or ARNI has not yet been specifically investigated among patients with HFmrEF in a RCT and current evidence for their use remains limited.…”

Section: Chronic Heart Failurementioning

confidence: 99%

“…Other therapeutic options may be considered, although none of the large RCTs conducted in HFpEF were able to meet their primary endpoints (PEP-CHF trial of perindopril [ 136 ], CHARM-Preserved trial of candesartan [ 137 ], I-PRESERVE trial of irbesartan [ 138 ], TOPCAT trial of spironolactone [ 139 ], DIG-Preserved trial of digoxin [ 140 ], and PARAGON-HF of sacubitril/valsartan [ 141 ]. However, available evidence suggests a potential benefit on the level of HF hospitalization with the combination of SGLT2 inhibitors with other drugs such as ACEi, ARBs, ARNI, MRA and β-blockers [ 132 ]. The improvement of mortality with the use of these drugs is less established among patients with HFpEF [ 132 ].…”

Section: Chronic Heart Failurementioning

confidence: 99%

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NHC/ SHA 2023 Focused update of the 2019 guidelines for the management of heart failure

Al Habeeb,

Tash,

Elasfar

et al. 2023

Journal of the Saudi Heart Association

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Background The burden of cardiovascular diseases is undeniable in local populations, who have high mortality rates and a young age of disease onset. A systematic review of emerging evidence and update of the Saudi Heart Association (SHA) 2019 heart failure (HF) guidelines was therefore undertaken. Methodology A panel of expert cardiologists reviewed recommendations of the 2019 guidelines following the Saudi Heart Association methodology for guideline recommendations. When needed, the panel provided updated and new recommendations endorsed by the national heart council that are appropriate for clinical practice and local resources in Saudi Arabia. Recommendations and conclusion The focused update describes the appropriate use of clinical assessment as well as invasive and non-invasive modalities for the classification and diagnosis of HF. The prevention of HF was emphasized by expanding on both primary and secondary prevention approaches. Pharmacological treatment of HF was supplemented with recommendations on newer therapies, such as SGLT-2 inhibitors. Recommendations were also provided on the management of patients with cardiovascular and non-cardiovascular co-morbidities, with a focus on cardio-oncology and pregnancy. Updated clinical algorithms were included in support of HF management in both the acute and chronic settings. The implementation of this focused update on HF management in clinical practice is expected to lead to improved patient outcomes by providing evidence-based comprehensive guidance for practitioners in Saudi Arabia.

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“…3 In addition, a recent meta-analysis found that sacubitril/valsartan was associated with a significant reduction in the risk of HF hospitalization in patients with HFpEF when compared to placebo. 4 Therefore, the AHA/ACC/HFSA Guideline will be updated in 2022 to recommend sacubitril/valsartan treatment for patients with HFpEF as a class IIb indication. 5 Sacubitril/valsartan is started at a low dose and up-titrated to the target dose with consideration of safety and tolerability.…”

Section: Introductionmentioning

confidence: 99%

Up-Titration of Sacubitril/Valsartan Among Patients With Heart Failure and Preserved Ejection Fraction

Matsumura

Ijichi

Morimoto³

et al. 2023

J Cardiovasc Pharmacol Ther

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Aims: In recent large trials, sacubitril/valsartan demonstrated favorable effects in patients with HF. However, many patients do not achieve the target dose of treatment. This study investigated the factors linked to up-titration of sacubitril/valsartan in patients with heart failure and preserved ejection fraction (HFpEF). Methods: Using a multicenter retrospective database, 204 consecutive patients with HFpEF (left ventricular ejection fraction ≥ 40%) who were treated with sacubitril/valsartan between October 2020 and March 2022 were analyzed. Up-titration was defined as an increase in dosage above 24/26 mg BID beyond 12 weeks after the initiation of sacubitril/valsartan. Results: Among the patients, 55% underwent up-titration, and 8% discontinued the drug. The baseline systolic blood pressure (SBP) was higher in patients with up-titration than in those with no up-titration; SBP values similar to that at baseline were observed between the 2 groups at 2 to 4 weeks and at 12 weeks after the commencement of sacubitril/valsartan treatment. The majority of those who discontinued sacubitril/valsartan did so because of hypotension. The multivariable logistic regression model showed that a history of hypertension, history of atrial fibrillation, baseline SBP, and baseline estimated glomerular filtration rate <60 mL/min/1.73 m2 were associated with sacubitril/valsartan up-titration. Conclusion: Approximately half of all patients did not undergo up-titration, and 8% of those with HFpEF discontinued the sacubitril/valsartan therapy. For aggressive up-titration and continuation of sacubitril/valsartan, patients with lower baseline SBP, renal dysfunction, absence of a history of hypertension, and presence of atrial fibrillation may require more careful monitoring.

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Optimal Pharmacologic Treatment of Heart Failure With Preserved and Mildly Reduced Ejection Fraction

Cited by 19 publications

References 28 publications

Association between dosing of spironolactone and outcomes in heart failure with preserved ejection fraction patients combined with chronic kidney disease------Balance of efficacy and risk

Association between dosing of spironolactone and outcomes in heart failure with preserved ejection fraction patients combined with chronic kidney disease------Balance of efficacy and risk

NHC/ SHA 2023 Focused update of the 2019 guidelines for the management of heart failure

Up-Titration of Sacubitril/Valsartan Among Patients With Heart Failure and Preserved Ejection Fraction

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