Benefit–risk review of different drug classes used in chronic heart failure

ABSTRACT

Introduction: Heart failure (HF) is an important public health problem with an increasing prevalence across the globe. The mortality rates from this complex clinical problem have stabilized in the recent years with the use of pharmacotherapeutics which demonstrated survival benefits in patients with HF with reduced ejection fraction (HFrEF).

Areas covered: We reviewed the seven classes of medications which constitute the guideline-directed medical therapy (GDMT) in chronic HF patients. We discussed clinical trials which support or contradict their use, potential adverse events, and available real-world data on utilization and safety.

Expert opinion: Loop diuretics form a major component of baseline therapy in HF patients to maintain euvolemia. As diastolic HF is more volume sensitive then systolic HF, diuretic use should be judiciously monitored to prevent states of volume depletion and associated complications. Neurohormonal modulation with pharmacotherapies are efficacious in reducing morbidity and mortality in the chronic HFrEF population. However, registry data showed that treatment intolerance and adverse events result in lower prescription rates of GDMT. Sacubitril/valsartan represents a major therapeutic advance in the treatment of HFrEF patients and can be safely used in addition to other GDMTs. Therapies to improve outcomes in diastolic HF  patients are needed.

KEYWORDS:

• Heart failure
• HFpEF
• HFrEF
• sacubitril/valsartan
• risk-benefit evaluation

Article highlights

• For the last 2–3 decades angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, ß-adrenergic blockers, and the combination of isosorbide dinitrate and hydralazine, have been the standard of care to improve outcomes in patients with HF and reduced ejection fraction.

• Sacubitril/valsartan treatment in addition to guideline-directed medical treatment demonstrated a substantial benefit in reducing the primary composite of CV-related death or heart failure hospitalization compared to enalapril in the PARADIGM-HF trial.

• The SHIFT trial supports the importance of heart-rate reduction with ivabradine for improvement of clinical outcomes in heart failure with reduced ejection fraction and confirms the important role of heart rate in the pathophysiology of this disorder.

• The TOPCAT trial showed that treatment with spironolactone in patients with heart failure and a preserved ejection fraction did not significantly reduce the incidence of the primary composite outcome of death from CV causes, aborted cardiac arrest, or hospitalization for the management of heart failure.

• However, a post hoc analysis of the TOPCAT trial demonstrated a significantly positive reduction in the primary outcomes in a subgroup of patients enrolled from the Americas (27–32%) but not in those from Russia or Georgia (8%-9%).

• Available real-world registry data suggest either under-representiveness of the ambulatory chronic heart failure patients in randomized controlled trials or underutilization of guideline-directed medical treatment in appropriate patient populations in which it is indicated.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A peer reviewer on this manuscript declared that they are a consultant for Bayer, Sanofi, Astra Zeneca, Stealth Petides, Relypsa/vifor, KBP pharmaceuticals, Sarfez, Triicida, scPharmanceuticals stock options and involved in the following patent: site specific delivery of eplerenone to the myocardium. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.