Angiotensin II Receptor Blockers in Heart Failure
Angiotensin II Receptor Blockers in Heart Failure
Heart failure remains a significant cause of morbidity and mortality, despite major advances in therapy. Angiotensin II, the principal mediator of the renin-angiotensin system, exerts both short-term (e.g., hemodynamic, renal) and long-term (e.g., inflammation, cardiac remodeling) effects in the pathophysiology of cardiovascular disease. The effects of angiotensin II appear to be more completely inhibited by angiotensin II receptor blockers (ARBs), which act at the subtype 1 receptor level, than by angiotensin-converting enzyme (ACE) inhibitors because pathways other than that of ACE contribute to the generation of angiotensin II. Evidence demonstrates that ARBs, when added to conventional treatment for patients with heart failure, are associated with a reduction in morbidity and mortality as well as an improvement in quality of life. Clinical trials of ARB therapy indicate that these agents are generally well tolerated, both alone and in combination with other neurohormonal inhibitors. The current role of ARBs in heart failure is as an alternative for patients who cannot tolerate therapy with an ACE inhibitor. A number of ongoing clinical studies are likely to further define or expand the role of ARBs in the treatment of cardiovascular disease.
Despite advances in treatment, heart failure continues to cause significant morbidity and mortality. Nearly 5 million Americans have heart failure, with about 550,000 new cases each year and 287,200 deaths annually attributable to heart failure. Patients with heart failure are 6-9 times more likely to die from sudden cardiac death than the general population. The public health economic burden of heart failure is significant: in 1998, Medicare paid $3.6 billion for heart failure claims. Because the prevalence of heart failure increases sharply after age 54 in both men and women, these costs are expected to rise.
The prognosis for patients with heart failure remains poor: 80% of men and 70% of women under age 65 diagnosed with heart failure will die within 8 years. In part, this poor prognosis is related to inadequate treatment with newer agents that target the pathophysiology of heart failure, such as
-blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs). Activation of endogenous neurohormonal systems after injury to the heart, particularly the sympathetic nervous system and the renin-angiotensin system (RAS), exerts deleterious hemodynamic effects and has a direct toxic effect on the myocardium. This toxic effect is progressive and is independent of hemodynamic effects. Treatment with agents that target neurohormonal systems may alter the course of heart failure.
Although the neurohormonal basis of heart failure was proposed 2 decades ago, neurohormonal agents are underprescribed in terms of both usage and dosage, possibly because of unnecessary concern regarding the use of
-blockers in patients with heart failure and intolerance to common side effects of ACE inhibitors (e.g., cough induced by bradykinin or substance P). An increasing body of clinical trial evidence supports the use of ARBs, the newest class of therapeutic agents, as alternatives to ACE inhibitors in the treatment of heart failure.
Heart failure remains a significant cause of morbidity and mortality, despite major advances in therapy. Angiotensin II, the principal mediator of the renin-angiotensin system, exerts both short-term (e.g., hemodynamic, renal) and long-term (e.g., inflammation, cardiac remodeling) effects in the pathophysiology of cardiovascular disease. The effects of angiotensin II appear to be more completely inhibited by angiotensin II receptor blockers (ARBs), which act at the subtype 1 receptor level, than by angiotensin-converting enzyme (ACE) inhibitors because pathways other than that of ACE contribute to the generation of angiotensin II. Evidence demonstrates that ARBs, when added to conventional treatment for patients with heart failure, are associated with a reduction in morbidity and mortality as well as an improvement in quality of life. Clinical trials of ARB therapy indicate that these agents are generally well tolerated, both alone and in combination with other neurohormonal inhibitors. The current role of ARBs in heart failure is as an alternative for patients who cannot tolerate therapy with an ACE inhibitor. A number of ongoing clinical studies are likely to further define or expand the role of ARBs in the treatment of cardiovascular disease.
Despite advances in treatment, heart failure continues to cause significant morbidity and mortality. Nearly 5 million Americans have heart failure, with about 550,000 new cases each year and 287,200 deaths annually attributable to heart failure. Patients with heart failure are 6-9 times more likely to die from sudden cardiac death than the general population. The public health economic burden of heart failure is significant: in 1998, Medicare paid $3.6 billion for heart failure claims. Because the prevalence of heart failure increases sharply after age 54 in both men and women, these costs are expected to rise.
The prognosis for patients with heart failure remains poor: 80% of men and 70% of women under age 65 diagnosed with heart failure will die within 8 years. In part, this poor prognosis is related to inadequate treatment with newer agents that target the pathophysiology of heart failure, such as
-blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs). Activation of endogenous neurohormonal systems after injury to the heart, particularly the sympathetic nervous system and the renin-angiotensin system (RAS), exerts deleterious hemodynamic effects and has a direct toxic effect on the myocardium. This toxic effect is progressive and is independent of hemodynamic effects. Treatment with agents that target neurohormonal systems may alter the course of heart failure.
Although the neurohormonal basis of heart failure was proposed 2 decades ago, neurohormonal agents are underprescribed in terms of both usage and dosage, possibly because of unnecessary concern regarding the use of
-blockers in patients with heart failure and intolerance to common side effects of ACE inhibitors (e.g., cough induced by bradykinin or substance P). An increasing body of clinical trial evidence supports the use of ARBs, the newest class of therapeutic agents, as alternatives to ACE inhibitors in the treatment of heart failure.
