Do ACE inhibitors or angiotensin II antagonists reduce total mortality and arrhythmic mortality? A critical review of controlled clinical trials

Naccarella, F; Naccarelli, Gerald V.; Maranga, Stefano Sdringola; Lepera, Giovannina; Grippo, M.C.; Melandri, Francesco; Gatti, Mauro; Pazzaglia, Stefano; Spinelli, Giovanna; Angelini, Vittorio; Ambrosioni, Ettore; Borghi, Claudio; Giovagnorio, Maria Teresa; Nisam, Seah

doi:10.1097/00001573-200201000-00002

Cited by 22 publications

(8 citation statements)

References 57 publications

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“…Despite recent advances in the treatment and the primary prevention of heart failure (1,115,168,178), the long-term prognosis for patients who present with this diagnosis remains dismal and the economic burden to the health care system is huge (47,133). In this perspective, a consideration of the role of the brain may be critically important in the development of effective therapeutic strategies.…”

Section: Translational Aspectsmentioning

confidence: 99%

Heart failure and the brain: new perspectives

Felder¹,

Francis²,

Zhang³

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

109

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Heart failure and the brain: new perspectives. Am J Physiol Regul Integr Comp Physiol 284: R259-R276, 2003; 10.1152/ajpregu.00317.2002.-Despite recent therapeutic advances, the prognosis for patients with heart failure remains dismal. Unchecked neurohumoral excitation is a critical element in the progressive clinical deterioration associated with the heart failure syndrome, and its peripheral manifestations have become the principal targets for intervention. The link between peripheral systems activated in heart failure and the central nervous system as a source of neurohumoral drive has therefore come under close scrutiny. In this context, the forebrain and particularly the paraventricular nucleus of the hypothalamus have emerged as sites that sense humoral signals generated peripherally in response to the stresses of heart failure and contribute to the altered volume regulation and augmented sympathetic drive that characterize the heart failure syndrome. This brief review summarizes recent studies from our laboratory supporting the concept that the forebrain plays a critical role in the pathogenesis of ischemiainduced heart failure and suggesting that the forebrain contribution must be considered in designing therapeutic strategies. Forebrain signaling by neuroactive products of the renin-angiotensin system and the immune system are emphasized.angiotensin; aldosterone; cytokines; tumor necrosis factor; immune system; renin; vasopressin; sympathetic; extracellular fluid volume; baroreflex THE IMPORTANCE OF AUTONOMIC dysfunction to the progression of heart failure is firmly established (55,113,120,152). The most effective treatments for heart failure specifically target the peripheral manifestations of neurohumoral activation (86,113). Yet the understanding of the mechanisms leading to neurohumoral excitation in heart failure is still quite limited.Over the last several decades, substantial evidence has been amassed to support the concept that peripheral afferent systems innervating the heart and vascular tree are altered in heart failure. Dysfunction has been described in all components of the reflexes mediated by these cardiovascular afferent systems-the afferent fibers themselves, the central processing of the afferent signals, the efferent innervation of the end organs, and the end organs themselves. In general, the influence of low-and high-pressure baroreceptors (40,42,191) that normally restrain sympathetic drive and vasopressin release is diminished, whereas the excitatory influences of arterial chemoreceptors (161) and cardiac sympathetic afferent fibers (100) are enhanced.Central nervous system (CNS) neurons affecting cardiovascular regulation respond to humoral as well neural signals. Blood-borne neuroactive peptides, too large to readily cross the blood-brain barrier, may influence the brain by activating sensory neurons at specific sites in hindbrain and forebrain that lack a blood-brain barrier (15,18) or by inducing the release of mediators that do penetrate the barrier (135). These neuroactive s...

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Section: Translational Aspectsmentioning

confidence: 99%

Heart failure and the brain: new perspectives

Felder¹,

Francis²,

Zhang³

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

109

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“…The ELITE study, which compared losartan versus captopril in patients with NYHA class II or III HF who had not previously received an ACE inhibitor, showed a lower rate of both all-cause mortality and SCD under losartan [42]. However, the far larger ELITE II study found a non-significant trend to more SCD with losartan [43], with similar findings in the OPTIMAAL trial of 5,477 patients with acute MI and HF [44]. ARBs are thus currently considered an alternative therapy in HF patients who cannot tolerate ACE inhibitors.…”

Section: Raas Inhibition and Scdmentioning

confidence: 69%

Primary Prevention of Sudden Cardiac Death in Patients with Heart Failure: How Effective is Current Pharmacologic Therapy?

Gavira¹,

García‐Bolao²,

Dı́ez³

2016

Cardiovasc Pharm Open Access

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Sudden cardiac death is the most common cause of death in the early stages of heart failure. Implantable cardioverter-defibrillator therapies substantially reduce sudden cardiac death but incur morbidity and are expensive, so are recommended only after failure of optimal medical therapy. Guidelines recommend simultaneous first-line therapy with an angiotensin converting enzyme inhibitor and a beta blocker for heart failure with reduced ejection fraction, with diuretic therapy for symptom relief. The all-cause mortality benefit of angiotensin converting enzyme inhibitors (or angiotensin receptor blockers) in this setting is largely attributable to reduced deaths related to disease progression. Addition of a beta blocker improves both all-cause survival and rates of sudden cardiac death. Where symptoms persist, introduction of a mineralocorticoid receptor antagonist is recommended and can reduce sudden cardiac death. If symptoms continue, substitution of the angiotensin converting enzyme inhibitor with the angiotensin receptor neprilysin inhibitor sacubitril/valsartan significantly reduces all-cause mortality, with the benefit arising from fewer deaths from both sudden cardiac death and worsening heart failure. Further medical interventions should be instituted in specific situations as required. Disappointingly, despite evidence-led guidelines, approximately a quarter of patients who have heart failure with reduced ejection fraction do not receive standard therapy with an angiotensin converting enzyme inhibitor and beta blocker. It remains to be seen if recent guidelines for successive interventions in the event of non-response to standard therapy are more effectively adopted.

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“…108 For example, in CONSENSUS there was a 50% relative risk reduction in death caused by progressive HF, but no change in sudden cardiac death after treatment with enalapril. 3 Aldosterone blockade reduces the risk of both atrial and ventricular arrhythmias, which may partly explain the reductions in sudden cardiac death observed in clinical trials.…”

Section: The Raas and Hf Pathophysiologymentioning

confidence: 99%