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

Abstract

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.

Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study

“…We observed that ACEI/ARB‐naïve patients were similar to patients on an ACEI or ARB able to initiate, up‐titrate and maintain sacubitril/valsartan. These findings address a key question that had remained unanswered in the PARADIGM‐HF study …”

“…These findings address a key question that had remained unanswered in the PARADIGM-HF study. 23 Tolerability to sacubitril/valsartan in TRANSITION appears comparable to that reported for beta-blockers and ACEIs/ARBs under real-life conditions. 2 During the sacubitril/valsartan initiation and up-titration phase in the PARADIGM-HF run-in (median drug exposure 29 days), 5.8% of patients discontinued permanently because of an AE, 5 which is comparable to the 6.4% overall discontinuation due to AEs in TRANSITION, considering the challenging scenario of a recent ADHF episode.…”

Novel doses of sacubitril/valsartan in patients unable to tolerate traditional therapy: Effects on N‐terminal pro B‐type natriuretic peptide levels

“…Subsequent “real world” studies also show a significant increase in hypotensive episodes with S/V as compared with ACEI 16 . Thus, despite estimates of profound benefit to HF patients, in current clinical practice, many patients cannot tolerate high doses of S/V, or even the smallest approved dose of 24/26 mg twice daily due to several factors including hypotension 10,17,18 . This remains even more so in older patients 14 .…”

Miejsce diuretyków pętlowych w leczeniu ostrej niewydolności serca

“…The NKCC1 isoform is also expressed in the hearing organ, and this local action of diuretics within the ear likely explains their ototoxicity [10]. Other adverse effects of diuretics include electrolyte disturbances such as hypokalaemia, hypomagnesaemia, hypocalcaemia, hyponatraemia, along with hyperuricaemia and dysglycaemia [5,11].…”