In May 2019 I attended the European Society of Cardiology Heart Failure Association Congress. There were plentiful updates on heart failure topics that are relevant to practitioners interested in heart failure medicines optimisation, experts in the field, and those who care for patients who have heart failure among other conditions.
Diabetes, cardiovascular disease and heart failure
Cardiometabolic management and the emerging benefits of sodium-glucose transport protein 2 (SGLT2) inhibitors in patients with diabetes and cardiovascular disease (CVD) featured strongly at the congress, as did the cardiorenal protection properties of SGLT2 inhibitors. It was reported that patients with diabetes and coronary artery disease have, on average, 12 years reduction in life expectancy compared to those without diabetes.
The new Heart Failure Association Clinical Practice Update 2019 recommendations state that canagliflozin and dapagliflozin should be considered in patients with type 2 diabetes and established cardiovascular disease or those with high cardiovascular risk to reduce onset and hospitalisation due to heart failure, but no recommendation could be made on the use of SGLT2 inhibitors in patients with heart failure.
New results from the AMBER trial, which investigated the use of spironolactone with patiromer in the treatment of resistant hypertension in patients with chronic kidney disease, have indicated that the use of patiromer helped to keep patients on spironolactone to derive benefit.
Heart failure medicines remain sub-optimal in both the acute setting and in the outpatient setting, despite recommendations being made
Also relating to potassium binders, the Heart Failure Association Clinical Practice Update 2019 states that patiromir and sodium zirconium cyclosilicate may be considered in patients with heart failure and hyperkalaemia in the presence and absence ofchronic kidney disease. These agents may be used to ‘enable’ up-titration of the renin angiotensin and aldosterone system inhibitors (RAASi’s: a new term which includes angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor antagonists (ARB) and mineralocorticoid receptor antagonists (MRAs)) when the up-titration is limited by hyperlkalaemia. However, it is not known if such a strategy would improve patient outcomes.
Several sessions referred to the use of rivaroxaban in heart failure, with particular focus on the COMMANDER-HF trial in which rivaroxaban (2.5mg BD) was shown to reduce stroke in patients with heart failure and ‘sinus rhythm’ when combined with baseline aspirin. This was without increasing haemorrhagic major events.
The Heart Failure Association Clinical Practice Update 2019 states that rivaroxaban (2.5mg BD) combined with baseline aspirin may be considered in patients who have coronary artery disease with heart failure, left ventricular ejection fraction>30%, and NYHA I/II (New York Heart Association functional classification of heart failure)to reduce risk of stroke and cardiovascular death. This is not applicable to patients with atrial fibrillation and/or those who have had recent heart failure related hospitalisation or persistent NYHA III/IV.
There were plenty of discussions and poster presentations about sacubitril/valsartan. The most interesting and relevant highlights were as follows:
- The need to optimise diuretic dose after initiating sacubitril/valsartan. Several studies and audits seem to show the need to reduce the diuretic dose after introducing sacubitril/valsartan.
- It is thought that sacubitril/valsartan improved the functional class and NT-proBNP values within three months of reaching the optimal dose. This dose was associated with a decrease in loop diuretic requirements.
The Heart Failure Association Clinical Practice Update 2019 states that:
- Sacubitril/valsartan is recommended as a replacement for ACEi or ARBs to reduce the risk of heart failure hospitalisation and death in ambulatory patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal therapy (with ACEi, beta blockers, MRAs).
- Initiation of sacubitril/valsartan rather than ACEi or ARB may be considered for patients hospitalised with new onset heart failure or decompensated chronic heart failure to reduce the short term risk of adverse events and to simplify management by avoiding the need to titrate ACEi first and then switch to sacubitril/valsartan.
The impact of community pharmacy
Results of the PHARM-CHF study, which evaluated a pharmacy-based interdisciplinary intervention for patients with chronic heart failure, were presented at the congress. This randomised controlled trial involved over 200 ambulatory chronic heart failure patients aged 60 years or over who were randomly allocated to usual care or a pharmacy intervention. The intervention involved patients bringing their medication to a pharmacist who then provided a medication plan, checked for drug interactions and double medications, and contacted the physician about any risks. Patients visited the pharmacy every eight to ten days to discuss adherence and symptoms and have their blood pressure and pulse rate measured. Patients receiving the pharmacy intervention reported improved adherence to heart failure medications and increased quality of life.
Cardiac rehabilitation and lifestyle modification
The benefits of cardiac rehabilitation for patients with heart failure continued to be highlighted. In addition, several presentations reminded us about the importance of a healthy lifestyle to prevent heart failure, such as walking at a pace of at least two miles per hour, not smoking, and avoiding obesity. These health behaviours contribute a powerful relative risk reduction of 50 percent.
We also heard about the usefulness of exercise-based cardiac rehabilitation in patients with heart failure and chronic total occlusions (of a coronary artery), that lonely patients with heart failure are least likely to follow treatment recommendations, and that patients with heart failure require continued person-centred care.
Adherence to heart failure medicines
Several poster presentations reported on adherence to medicines among patients with heart failure. The message was clear: non-adherence to pharmacological therapy is prevalent among patients with all types of heart failure, and that there are many missed opportunities that need to be addressed.
Medication adherence and alteration remain a challenge despite the emphasis of self-education and care. One study reported that 85 percent of patients with heart failure with preserved ejection fraction(HFpEF) and hypertension were non-adherent. In addition, only 60 percent of patients with heart failure with reduced ejection fraction (HFrEF) were adherent to their pharmacological therapy. Some of the factors associated with poor adherence included loneliness, number of hospitalisations, and treatment with diuretics.
Studies report that heart failure medicines remain sub-optimal
Several poster presentations reported that heart failure medicines remain sub-optimal in both the acute setting and in the outpatient setting, despite recommendations being made.
Statins in patients with heart failure and myocardial Infarction
A few studies highlighted data which suggest that withdrawal of statins within a year in post-MI patients with heart failure was associated with poor outcome.
The latest results from the ReBIC-1 study, the first multicentre randomised trial on de-prescribing diuretics show complete diuretic withdrawal to be safe in stable chronic heart failure. Others reported that early urinary sodium can be a marker for diuretic resistance and possible need for a more intensive treatment strategy, and that an inappropriately high dose of loop diuretics in decongested patients can hamper up-titration of disease modifying drugs.
Heart failure with preserved ejection fraction
Heart failure with preserved ejection fraction (HFpEF) had a lot of coverage during the congress. The key messages focussed on dispelling the myths about this condition. The following are the main points highlighted, despite that these claims are still not fully substantiated:
- HFpEF does exist
- HFpEF is not a pre-stage of HFrEF
- The pathophysiology of HFpEF and HFrEF are different
- The aetiology of HFpEF is varied
- Diastolic dysfunction is not the hallmark of HFpEF
- Patients with HFpEF do not always have elevated NPs
- Obese HFpEF is real HFpEF
- Treatments for HFrEF do not benefit patients with HFpEF
Until new evidence emerges on medicines that reduce mortality in patients with HFpEF, the medicines optimisation needs of these patients should be met by optimising diuretics and therapy for co-morbidities. HFpEF is on the increase and it is estimated that by 2020, 65 percent of hospitalised heart failure patients will have HFpEF. It is associated with a lower mortality and heart failure hospitalisation compared to HFrEF but is more than those without heart failure.
The future: emerging therapies
So, what should we look out for in terms of pharmacological heart failure management? For me, there were four key areas:
- The role of apelin in heart failure
- Beta3 agonists in heart failure (mirabegron is being tested)
- The new drug vericiguat, a novel oral soluble guanylate cyclase (sGC) stimulator
- Iron, trimetazidine, and Bendavia (elamipretide) for targeting cardiac metabolism in heart failure.
This is a personal account of the key highlights that I thought important and relevant to those interested in heart failure medicines optimisation. This article summarises the topics that I tweeted about during my time in the conference. It is by no means comprehensive, nor does it cover all the areas that were addressed in the congress. In addition, I do not express my opinion, so I do not necessarily endorse what is included in the summary or the tweets. You can see all my tweets, slides, photos and references @DrRaniKhatib.