Archives

  • 2018-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • br Implementation of sacubitril valsartan into clinical prac

    2023-01-16


    Implementation of sacubitril/valsartan into clinical practice Following on from the results of PARADIGM-HF, sacubitril/valsartan was given regulatory approval for use in patients who conform to the main inclusion criteria of the trial; NYHA functional class II–IV, reduced left ventricular ejection fraction (<40%), receiving guideline recommended treatment with a beta-blocker and MRA, a systolic blood pressure of ≥100 mm Hg, estimated glomerular OPP rate (eGFR) ≥30 mL/min/1.73 m2 and potassium ≤5.2 mmol/L [63,64]. The requirement for elevated NP levels for trial inclusion was omitted from the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) prescribing information, reflecting that the majority of patients with HFrEF have elevated NP levels and furthermore, no interaction with treatment effect and baseline NP levels was reported [20]. The European Society of Cardiology (ESC) and American College of Cardiology (ACC) guideline committees have both awarded a Class 1B recommendation for sacubitril/valsartan to reduce the risk of HF hospitalisation and death in HFrEF patients who remain symptomatic despite treatment with an ACE inhibitor or ARB, beta-blocker and MRA [67,68]. ESC guidelines maintain that patients should be established on an ACE inhibitor or ARB for a minimum of one-month prior to switching to sacubitril/valsartan however ACC guidance is less strict regarding this, permitting initiation in ACE inhibitor/ARB naïve patients [64,67,68]. This more liberal approach has some support from the results of the TITRATION study examining two initiation and up-titration regimens for sacubitril/valsartan; 7% of patients were ACE inhibitor/ARB naïve, reporting equivalent rates of adverse events to the total population [69]. A small proportion of this cohort were hospitalised patients (11%) and further information regarding the safety of initiation of sacubitril/valsartan in this group will be provided by two on-going trials in patients stabilised following an acute decompensation of HFrEF (PIONEER-HF; ClinicalTrials.gov ID NCT02554890 and TRANSITION; NCT02661217). The observation in PARADIGM-HF that sacubitril/valsartan was associated with lower rates of renal dysfunction and hyperkalaemia (including in those prescribed an MRA at baseline or those who commenced an MRA during follow-up) may translate into a higher proportion of patients being able to achieve optimal RAAS inhibition (as well as the additional benefits associated with concomitant neprilysin inhibition) with initiation of an ARNI rather than an ACE inhibitor OPP or ARB [70].
    What next for sacubitril/valsartan? A wide-ranging portfolio of post-regulatory approval trials and observational studies are underway to further establish the role and safety of sacubitril/valsartan in clinical practice as well as helping to deepen our understanding into the mechanism of action of ARNIs. These are summarised in Table 1. The second, the Prospective ARNI vs ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI (PARADISE-MI; NCT02924727), will assess the effect of sacubitril/valsartan compared to ramipril in patients with left ventricular systolic dysfunction and/or pulmonary congestion following acute myocardial infarction. This population is at high risk of developing symptomatic HFrEF in the future, as evidenced by the high prevalence of prior myocardial infarction in the PARADIGM-HF cohort (43%) [20]. PARADISE-MI will provide evidence for the role of sacubitril/valsartan in the continuum of risk from acute myocardial infarction to symptomatic chronic HFrEF in a similar manner to previous trials has for ACE inhibitors and ARB [72–75].
    Summary
    Conflict of interest
    Introduction Although decades of epidemiological studies have firmly established the inverse relationship between HDL levels and cardiovascular events [1], recent studies emphasize HDL‘s functionality as a better predictor of cardiovascular disease (CVD) [2], [3]. Chronic kidney disease (CKD) impairs HDL functions including the capacity to accept cholesterol from lipid-loaded cells as well as the ability to lessen inflammation and oxidant stress, especially in patients with advanced CKD on maintenance hemodialysis (MHD) [4], [5], [6], [7]. The MHD population is also unique in its lack of benefit from standard lipid-lowering interventions that highlights an urgent need to develop additional therapeutic strategies.