The influence of heart failure on the pharmacokinetics of cardiovascular and non‐cardiovascular drugs: a critical appraisal of the evidence

Abstract

Prescribing in heart failure (HF), a common disease state that predominantly affects the older population, is often a challenging task because of the dynamic nature of the condition, requiring frequent monitoring and medication review, the presence of various comorbidities, and the frailty phenotype of many patients. The significant alterations in various organs and tissues occurring in HF, particularly the reduced cardiac output with peripheral hypoperfusion and the structural and functional changes of the gastrointestinal tract, liver and kidney, might affect the pharmacokinetics of several drugs. This review critically appraises the results of published studies investigating the pharmacokinetics of currently marketed cardiovascular and selected non-cardiovascular drugs in HF patients and control groups, identifies gaps in the current knowledge, and suggests avenues for future research in this complex patient population.

Plasma Concentration and Pharmacodynamics of Edoxaban in Patients with Nonvalvular Atrial Fibrillation and Acute Heart Failure

“…It has been reported that this may be due to reduced drug clearance and reduced volume of distribution in patients with heart failure [33]. Of potentially major clinical relevance, there are also reports of patients with heart failure with a significantly prolonged elimination half-life (t ½ ) for oral furosemide (+ 70%); significantly reduced clearance (− 50%) after intravenous furosemide administration, although volume of distribution and t ½ were similar to values in controls; significantly shorter t ½ (− 44%) for carvedilol; and increased values for time to reach peak plasma concentration (+ 67%) and t ½ (+ 130%), and reduced clearance (− 75%), after oral enalapril administration in patients with heart failure [32]. Although the prothrombin time-international normalized ratio is known to be unstable when warfarin is used in patients with heart failure [14], the results from our study show that edoxaban pharmacokinetics and pharmacodynamics are not affected by acute heart failure.…”

“…Although data for DOACs have been limited, there have been multiple reports showing irregular pharmacokinetics of other drugs in patients with acute heart failure [32]. For example, the peak plasma tolvaptan concentration after administration of 15 mg in patients with heart failure was 1.9 times higher than that in healthy people, and the area under the plasma concentration-time curve was 3.4 times higher.…”

Interindividual Variability of Apixaban Plasma Concentrations: Influence of Clinical and Genetic Factors in a Real-Life Cohort of Atrial Fibrillation Patients

“…Apixaban has low hydrosolubility [40,41], and therefore, the systemic expansion of interstitial fluid that happens in periodic temporary decompensations of heart failure cannot explain the reduced plasma values. Other possible causes could be the systemic arterial hypoperfusion status, venous congestion, and neurohormonal activation, which negatively influences the integrity and function of the key organs, in particular the gastrointestinal tract, liver, and kidneys [42].…”

Novel use of cangrelor in pediatrics: A pilot cohort study demonstrating use in ventricular assist devices

“…While many of these variables are not modifiable, the clinician must develop strategies to mitigate the risks. Pharmacodynamics and pharmacokinetics of commonly used medications are altered in end‐stage heart failure 25,34,35 and 20%‐40% of the population have an inadequate platelet response to clopidogrel, 24,36‐38 thus a novel approach to long term antiplatelet therapy is necessary. Cangrelor is an intravenous, short‐acting, reversible P2Y 12 antagonist that does not require hepatic activation making it an ideal agent in selected patients.…”