Uptitration of Medications in HF: Start Low But Aim High and Stay High Treatment of HFrEF: What Have We Achieved?[1,2] In the CONSENSUS Trial, 1-year mortality was still 50% to 60% in the placebo group 2016 ESC HF Guidelines for Chronic HF Management[3] It is recommended to treat patients with the maximum tolerated doses of each drug ESC 2016 Guidelines for HF: Evidence Based Disease Modifying Therapies With Recommended Doses[3] Target doses are specific for the individual therapies and should be reached unless the patients have reasons to not uptitrate the drug There may be barriers to uptitration such as hypotension or bradycardia but every effort should be made to achieve target dose when possible Diuretic Use in HFrEF[3,4] Variation in Drug Titration Steps to Achieve Optimal Dosing[3,,5-7] HEAAL: Benefit of Achieving Target Dose With ARB Therapy[8] Those patients who had the higher end of the guideline-recommended therapy at target dosing did better in terms of cardiovascular hospitalizations and cardiovascular death in the combination outcomes Patients who tolerate the targeted doses are usually healthier Target Doses in HFrEF Yield Better Outcomes[9-10] Heart failure medications may not be beneficial if used in an inappropriate dose because drug efficacy is based on correct drug with correct uptitration There have also been observational data that have reflected better outcomes at target doses BIOSTAT-CHF: How Are We Doing With Uptitration?[10] ESC HF Long Term Registry: Use of Pharmacological Therapies[11] ESC HF Long Term Registry: Patients at Target Dose With Recommended Drug Therapies[11] HFrEF with AF: Decreased Benefit With BB[12,13] The goal may simply be a target heart rate rather than a target dose[12] There is concern for what is the lowest heart rate that should be achieved; a goal of a heart rate between 60 and 65 beats per minute (bpm) may be acceptable[13] There is also concern for side effects, especially in men CIBIS-ELD: Beta Blockade Use in the Elderly With HF[14] TITRATION Study: Uptitration of Sacubitril/Valsartan[15] Gap Between What is Achievable in Clinical Trials and the "Real World" Germany "Real Word Data": Sacubitril/Valsartan Use -- Results[16] Underdosing of NOACs in Anticoagulation for NVAF[17,18] Prescribing of lower doses of non-vitamin K antagonist oral anticoagulants (NOACs) is as high as 50% in some countries[18] Why Are Drugs Not Uptitrated in HFrEF? While the patient may think they are doing okay because their symptoms have improved, they may continue to have disease progression. Therefore the recommended therapies should be titrated to the maximum tolerated dose when possible Legitimate Reasons for Not Uptitrating Drug Doses Managing Renal Impairment and Hyperkalemia With Uptitration of RAS Inhibitors[5,19-21] When compared to enalapril, sacubitril/valsartan led to a slower rate of decrease in the estimated glomerular filtration rate (eGFR) and improved CV outcomes, even in patients with CKD, despite causing a modest increase in urinary albumin/creatinine ratio (UACR)[19] Two potassium binder agents are now available for eligible patients who are susceptible to hyperkalemia[5,20,21] Less Legitimate Reasons for Not Uptitrating Drug Doses in HFrEF BIOSTAT CHF: Reasons for Not Uptitrating Therapies[10] Solutions for Improving Drug Uptitrations Conclusions Thank you
