What is Heart Failure Therapy and the Role of Angiotensin Receptor Blockers, Beta Blockers and ACE Inhibitors?
Heart disease is extremely common in the USA. Over 600,000 people die from heart disease in the United States each year, accounting for 1 in 4 causes of death. Heart disease can progress into heart failure, from which it is difficult for patients to recover normal heart function.
Fortunately, thanks to advances in research, there are more treatment options and the number of available pharmacological therapies for treating heart failure, particularly for heart failure with reduced ejection fraction (HFrEF), have grown.
Efficacy of Multiple Drug Therapies for Heart Failure with Reduced Ejection Fraction
The use of new therapies as well as multiple drug therapies together has improved the overall prognosis of HFrEF.
Heart failure patients used to be treated with vasodilators and then clinical trials established that ACE inhibitors and angiotensin receptor blockers (ARBs) are crucial aspects for cardiac recovery of patients suffering from HFrEF. These medicines have been shown to reduce morbidity from heart failure and should be administered as the first line of therapy in heart failure patients.
In addition, these studies found that in patients who are being treated with ACE inhibitors and ARBs, adding beta-blockers and mineralocorticoid receptor antagonists (MRAs) to the treatment regimen provides additional benefits.
In recent developments, a study found that the use of angiotensin receptor neprilysin inhibitor in patients was shown to be superior in some circumstances to the traditional pharmaceutical ACE inhibitor usually used, called enalapril.
The Importance of ACE Inhibitors
ACE inhibitors work by chemically reducing peripheral resistance and reducing the load on the failing myocardium by inhibiting the conversion of angiotensin I to angiotensin II. Preventing this conversion inhibits vasoconstriction and allows the relaxation of the vasculature.
The CONSENSUS trial, which compared enalapril ACE inhibitor with placebo, showed that enalapril reduced patients’ overall mortality risk by 27%. Enalapril also slowed or stopped the progression of heart failure with reduced ejection fraction in these patients.
ACE inhibitors are generally well tolerated by patients. However, patients with conditions such as pre-existing hypotension, baseline hyperkalemia, those receiving concomitant potassium supplements or potassium-sparing diuretics, or previous angioedema from ACE inhibitor use, should use caution when taking these medications. In some cases, another pharmaceutical therapy should be chosen for patients that match this profile.
The Importance of Angiotensin Receptor Blockers
Similar to ACE inhibitors, ARBs inhibit the action of angiotensin II in patients with heart failure with reduced ejection fraction. However, instead of preventing the conversion from angiotensin I to angiotensin II, like ACE inhibitors do, ARBs work by blocking angiotensin II from binding to its receptor.
Blocking the action of angiotensin decreases vasoconstriction and relaxes vasculature. However, ARBs do not cause inhibition of kininase as ACE inhibitors do. For this reason, ARBs can be a suitable pharmaceutical therapy for patients who are intolerant of ACE inhibitors.
It’s been shown that ARBs have the same result as ACE inhibitors in heart disease therapy; they both reduce morbidity. In the 2003 Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM Alternative) study, ARBs showed great potential in cardiovascular outcomes compared with placebo groups. The study focused on cardiovascular death or hospital admission in patients with symptomatic heart failure with an ejection failure of 40% or less who were intolerant of ACE inhibitors. The outcome shows that 33% of patients who took the ARB therapy had passed away due to cardiovascular causes, compared to 40% in the placebo group.
The Importance of Beta Blockers in Heart Failure
The beneficial effects of beta-blockers in patients who have heart failure with reduced ejection fraction have been long studied. Since 1975, studies have shown that beta-blockers have decreased mortality in these patients.
So far, bisoprolol, carvedilol, and sustained-release metoprolol succinate are the beta-blockers that have been widely studied in large clinical trials. These three medicines all reduce mortality rates in patients with HFrEF. For this reason, beta-blockers are integrated as a first line of defense in many heart disease treatments.
These medicines all work in the same way: they block the β1 receptor located in the heart. By stopping β1 receptors, these beta-blockers prevent ventricular remodeling, thus enhancing a patient’s likelihood of recovery from heart disease. At first, beta blockers can decrease heart function, so need to be initiated carefully with low dosage that is increased slowly over time.
Final Thoughts on Heart Failure Therapies
In addition to ACE inhibitors, ARBs, and beta-blockers, there are many other pharmaceutical heart failure therapy options for patients today. These other therapies include aldosterone receptor antagonists, diuretics for fluid retention control, vasodilators, and digoxin.
Beta-blockers and ACE inhibitors have been found to greatly decrease the risk of morbidity in a wide array of patient demographics. However, the best results come from personalized therapy plans where medications are chosen for the specific patient and their unique needs.
Heart Failure Research at the Cardiovascular Research and Training Institute
The Investigators in the Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI) are pioneering the development of new drug therapies for heart failure. Over the past decade, we have been exploring molecular mechanisms underlying genetic dysregulation, proteomics alteration, insufficient energy supply, and metabolic abnormalities of the heart when it fails. By studying the fundamental biology of healthy and failing heart muscle cells, our Investigators are identifying critical molecules that can be targeted for the functional rescue of failing hearts. With many years of extensive research at the bench, researchers in the CVRTI now found two proteins (GJA1-20k and cBIN1 ) that can be used to treat injured hearts in both acute and chronic settings. GJA1-20k is a stress response protein which helps maintain normal heart rhythms and energy supply. During acute injury, GJA1-20k can maintain myocyte survival, thus limiting heart damage. cBIN1, on the other hand, is a protein organizing the excitation-contraction machinery in heart muscle cells to maintain normal pump function of the heart. A multidisciplinary team has been formed within the CVRTI to use gene transfer methods to deliver exogenous GJA1-20k or cBIN1 to failing hearts. The therapeutic effect of GJA1-20k and cBIN1 gene therapy is currently under advanced preclinical studies and toxicity and safety studies are underway in anticipation of clinical trials.
