Mechanisms of cardiovascular risk reduction with ramipril: insights from HOPE and HOPE substudies

Lonn, Eva; Gerstein, Hertzel C.; Śmieja, Marek; Mann, J.; Yusuf, Salim

doi:10.1016/s1520-765x(03)90063-0

Cited by 28 publications

(14 citation statements)

References 38 publications

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“…Moreover, drugs that inhibit the RAS (ACE inhibitors and Ang-receptor blockers) unexpectedly produce clinical benefits even in normotensive individuals [156]. Although there is a disagreement on the exact mechanism by which cardiovascular benefits in normotensive patients are produced [157,158], these findings have opened new avenues for investigation of additional therapeutic possibilities for manipulation of the RAS.…”

Section: Perspective Of Pharmacological Im-munological and Gene Tarmentioning

confidence: 99%

Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease

Igić¹,

Behnia²

2007

CPD

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Effective blood pressure control with a large arsenal of conventional antihypertensive drugs, such as diuretics, beta-adrenergic blockers, and calcium channel blockers, significantly reduce the morbidity and mortality associated with cardiovascular disease. However, blood pressure control with these drugs does not reduce cardiovascular disease risks to the levels in normotensive persons. Only two drug classes that inhibit or antagonize portions of the renin-angiotensin system (RAS), angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor type-1 (AT(1) receptor) blockers, have protective and beneficial effects unrelated to the degree of blood pressure reduction. These drugs may prevent the blood pressure related functional and structural abnormalities of the cardiovascular system and reduce the end organ-damage. The first part of this review presents the components of the RAS, biological actions of angiotensin peptides, and the functions of the enzymes that generate and metabolize angiotensins, including the likely effect of manipulating them. Special attention is devoted to renin, ACE, ACE2, chymase, and neprilysin. The second part of this review presents the rationale for targeting the RAS, based on clinical studies of the ACE inhibitors and AT(1) receptor blockers. Finally, we present the investigational agents acting on the RAS that have a potential for clinical usage, and give the perspective of pharmacological, immunological and gene targeting of the RAS for treatment of cardiovascular disease.

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Section: Perspective Of Pharmacological Im-munological and Gene Tarmentioning

confidence: 99%

Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease

Igić¹,

Behnia²

2007

CPD

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“…The effects of bradykinin in the vasculature oppose many of the actions of angiotensin II; it stimulates synthesis of vasodilators, such as NO, hyperpolarizing factor and prostacyclin, which improve endothelial function; it inhibits platelet adhesion and smooth muscle cell proliferation and enhances the fibrinolytic balance by stimulating tissue plasminogen activator (tPA) synthesis. ACE inhibitors act by dual pathways to prevent angiotensin II formation and to block the degradation of bradykinin into inactive peptides and, thus, exert multiple effects that protect the coronary and peripheral vasculature ( Table 3) [101][102][103][104].…”

Section: Angiotensin Converting Enzyme (Ace) Inhibitors and Other Drumentioning

confidence: 99%

Drug Therapies in the Secondary Prevention of Cardiovascular Diseases:Successes, Shortcomings and Future Directions

Lonn

Grewal²

2006

CVP

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Cardiovascular diseases are the major cause of death and a significant cause of disability in the Western world and more recently threaten to pose an increasing health burden on developing nations. People with pre-existent vascular disease are those at highest risk for adverse cardiovascular outcomes and require aggressive secondary preventive therapies. Large strides have been made in the development of pharmacologic agents that intervene on various pathways implicated in atherogenesis, thus offering the ability to greatly impact on disease progression and to prevent events. Compelling data derived primarily from randomized controlled trials have shown the benefits of aspirin (or antiplatelet agents) and angiotensin converting enzyme (ACE) inhibitors (A), beta-blockers and blood pressure (B) and cholesterol-lowering drugs (C), particularly statins, in preventing recurrent events and improving survival. Taken together these data are the foundation for the simple, but important advice for secondary prevention - the ABCs. In addition, the evidence for the central role of lifestyle factors as determinants of risk has lead to increased efforts towards developing interventions aimed at modifying lifestyle patterns. Today, the biggest challenge remains in the implementation of proven effective therapies. Our focus should turn to educating physicians and patients alike regarding available therapies and their indications. In addition systematic, sustainable and globally applicable approaches to the secondary prevention of cardiovascular diseases need to be developed to truly realize the vast potential benefits of existing therapies.

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“…2 A number of therapies are available, but angiotensin-converting enzyme (ACE) inhibitors have been the preferred first-line therapy for hypertension, congestive heart failure, left ventricular (LV) systolic dysfunction and MI. 3,4 ACE inhibitors (ACEis) have been in use for the past two decades, and the interest in them is still growing. Recently, the discovery of domain-selective ACEis and new members of the renin-angiotensin system (RAS) (that is, angiotensin-converting enzyme 2) have again fueled the interest of researchers.…”

Section: Introductionmentioning

confidence: 99%

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

2009

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Since their inception, angiotensin-converting enzyme (ACE) inhibitors have been used as first-line therapy for the treatment of cardiovascular and renal diseases. They restore the balance between the vasoconstrictive salt-retentive and hypertrophy-causing peptide angiotensin II (Ang II) and bradykinin, a vasodilatory and natriuretic peptide. As ACE is a promiscuous enzyme, ACE inhibitors alter the metabolism of a number of other vasoactive substances. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have been proven effective in the treatment of hypertension, and reduce mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction. They inhibit ischemic events and stabilize plaques. Furthermore, they delay the progression of diabetic nephropathy and neuropathy and act as antioxidants. Ongoing studies have elucidated protective roles for them in both memory-related disorders and cancer. INTRODUCTIONIn recent years, stressful and fiercely competitive lifestyles and food habits have compounded the problems of hypertension. Long-standing and stressful, progressively rising hypertension can lead to many disorders, including myocardial infarction (MI), cerebrovascular events, congestive heart failure, peripheral arterial insufficiency, premature mortality 1 and renal dysfunction leading to glomerulosclerosis and kidney artery aneurysm. 2 A number of therapies are available, but angiotensin-converting enzyme (ACE) inhibitors have been the preferred first-line therapy for hypertension, congestive heart failure, left ventricular (LV) systolic dysfunction and MI. 3,4 ACE inhibitors (ACEis) have been in use for the past two decades, and the interest in them is still growing. Recently, the discovery of domain-selective ACEis and new members of the renin-angiotensin system (RAS) (that is, angiotensin-converting enzyme 2) have again fueled the interest of researchers. Some new studies have expanded the already impressive clinical profile of ACEis. This review traces some already known and new facets of ACE inhibition and introduces new advances in the designing of a new generation of ACEis.

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Mechanisms of cardiovascular risk reduction with ramipril: insights from HOPE and HOPE substudies

Cited by 28 publications

References 38 publications

Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease

Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease

Drug Therapies in the Secondary Prevention of Cardiovascular Diseases:Successes, Shortcomings and Future Directions

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

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