Multiple Neurohumoral Modulating Agents in Systolic Dysfunction Heart Failure: Are We Lowering Blood Pressure Too Much?

Mak, George; Murphy, Niamh; Ali, Akbar Shoukat; Walsh, Alison; O’Loughlin, C.; Conlon, C.; McCaffrey, D.; Ledwidge, Mark; McDonald, Kenneth

doi:10.1016/j.cardfail.2008.03.003

Cited by 18 publications

(11 citation statements)

References 27 publications

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“…were smaller than observed in patients receiving spironolactone, which could be an additional benefit for patients with HFrEF whose blood pressure is already well controlled by baseline medications (e.g. angiotensin-converting enzyme inhibitors, beta-blockers, diuretics) 10,11 or whose blood pressure is low due to worsening HF. 4 In other populations, such as those with resistant hypertension, the greater blood pressure-lowering effect of spironolactone would be an advantage.…”

Section: Discussionmentioning

confidence: 75%

Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial

Pitt

Køber

Ponikowski³

et al. 2013

European Heart Journal

445

372

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AimsMineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non-steroidal MRA. We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease (CKD).Methods and resultsThis randomized, controlled, phase II trial consisted of two parts. In part A, the safety and tolerability of oral BAY 94-8862 [2.5, 5, or 10 mg once daily (q.d.)] was assessed in 65 patients with HFrEF and mild CKD. In part B, BAY 94-8862 (2.5, 5, or 10 mg q.d., or 5 mg twice daily) was compared with placebo and open-label spironolactone (25 or 50 mg/day) in 392 patients with HFrEF and moderate CKD. BAY 94-8862 was associated with significantly smaller mean increases in serum potassium concentration than spironolactone (0.04–0.30 and 0.45 mmol/L, respectively, P < 0.0001–0.0107) and lower incidences of hyperkalaemia (5.3 and 12.7%, respectively, P = 0.048) and WRF. BAY 94-8862 decreased the levels of B-type natriuretic peptide (BNP), amino-terminal proBNP, and albuminuria at least as much as spironolactone. Adverse events related to BAY 94-8862 were infrequent and mostly mild.ConclusionIn patients with HFrEF and moderate CKD, BAY 94-8862 5–10 mg/day was at least as effective as spironolactone 25 or 50 mg/day in decreasing biomarkers of haemodynamic stress, but it was associated with lower incidences of hyperkalaemia and WRF.

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Section: Discussionmentioning

confidence: 75%

Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial

Pitt

Køber

Ponikowski³

et al. 2013

European Heart Journal

445

372

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“…In a small prospective study, the step-wise addition of neurohormonal agents contributed to significant daytime and especially nocturnal hypotensive episodes, which were associated with an increase in cardiovascular events, despite stable pre-and post-treatment in-clinic blood pressure measurements. 10 Patients on angiotensin-converting enzyme inhibitors (ACEi) or ARBs are at increased risk of nocturnal hypotension because angiotensin-II is an important factor in maintaining systemic blood pressure. Recent data from Heart Failure Endpoint Evaluation of Angiotensin II Antagonist Losartan (HEAAL) revealed that visit-to-visit variability in blood pressure measurements were common in ambulatory patients with HFrEF and were associated with increased death or HF hospitalization.…”

Section: Risks Of Hypotensionmentioning

confidence: 99%

“…Hypotension may manifest by 2 potential mechanisms: (1) direct therapy-related vasodilatation or (2) volume depletion with improvement in myocardial function and reduction in diuretic requirement over time. Mak et al 10 have demonstrated that patients who experience hypotensive episodes after addition of ACEi, ARB, or β-blockers are at higher risk for subsequent HF readmissions and composite all-cause mortality and readmissions. Thus, therapyrelated hemodynamic perturbations may have contributed to the inverse-J relationship between intensity of neurohormonal modulation and event rates (Figure).…”

Section: Hypotension-a Major Clinical Trial Roadblockmentioning

confidence: 99%

Contemporary Drug Development in Heart Failure

Vaduganathan

Butler

Pitt

et al. 2015

Circ: Heart Failure

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“…Available evidence indicates that patients with lower resting BP (28), or who experience episodes of symptomatic hypotension also suffer greater morbidity and mortality when compared to those with normal BP (29,30). This is also true during acute heart failure (31).…”

Section: Renal and Electrolyte Consequences Of Diuretic Therapymentioning

confidence: 99%

The Canadian Cardiovascular Society Heart Failure Companion: Bridging Guidelines to Your Practice

Howlett

Chan

Ezekowitz

et al. 2016

Canadian Journal of Cardiology

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The Canadian Cardiovascular Society Heart Failure (HF) Guidelines Program has generated annual HF updates, including formal recommendations and supporting Practical Tips since 2006. Many clinicians indicate they routinely use the Canadian Cardiovascular Society HF Guidelines in their daily practice. However, many questions surrounding the actual implementation of the Guidelines into their daily practice remain. A consensus-based approach was used, including feedback from the Primary and Secondary HF Panels. This companion is intended to answer several key questions brought forth by HF practitioners such as appropriate timelines for initial assessments and subsequent reassessments of patients, the order in which medications should be added, how newer medications should be included in treatment algorithms, and when left ventricular function should be reassessed. A new treatment algorithm for HF with reduced ejection fraction is included. Several other practical issues are addressed such as an approach to management of hyperkalemia/hypokalemia, treatment of gout, when medications can be stopped, and whether a target blood pressure or heart rate is suggested. Finally, elements and teaching of self-care are described. This tool will hopefully function to allow better integration of the HF Guidelines into clinical practice.

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Multiple Neurohumoral Modulating Agents in Systolic Dysfunction Heart Failure: Are We Lowering Blood Pressure Too Much?

Cited by 18 publications

References 27 publications

Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial

Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial

Contemporary Drug Development in Heart Failure

The Canadian Cardiovascular Society Heart Failure Companion: Bridging Guidelines to Your Practice

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