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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular risk is determined by multiple risk factors, all of which greatly increase the chance of morbidity and mortality. So-called "normal" levels of these factors are not biologically normal, so current strategy is based on estimations of a person's global cardiovascular risk, and then using appropriate combinations of treatments in higher-risk people. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) provide multiple actions against many of the risk factors for cardiovascular disease and also show some evidence of an effect that is independent of blood pressure reduction. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) is designed to clarify whether an ARB (telmisartan), an ACE inhibitor (ramipril) or a combination of both confers blood pressure-independent cardioprotection in high-risk patients whose blood pressure is well controlled. The Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) trial has the same endpoints, but will compare telmisartan with placebo in patients who are intolerant to an ACE inhibitor. Primary endpoints for both trials are the composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for heart failure. Recruitment is now complete, with 25 620 patients randomised in ONTARGET and 5926 in TRANSCEND. Baseline patient characteristics are similar to those in the Heart Outcomes Prevention Evaluation (HOPE) study, except that the current trials have greater ethnic diversity (including an important cohort from Asia). The subjects are slightly older and mean blood pressure at randomisation is again normal, but slightly lower than in HOPE. The use of beta-blockers and lipid-lowering therapy, known to reduce mortality and morbidity, is also higher in ONTARGET/TRANSCEND. These trials are the largest comparisons to date of ARB and ACE-inhibitor therapy in high-risk patients with controlled blood pressure, and the results will contribute significantly to the future treatment of cardiovascular disease.
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PMID:The ONTARGET/TRANSCEND Trial Programme: baseline data. 1586 20

Ramipril is an angiotensin-converting enzyme inhibitor that has been extensively studied in randomised, controlled clinical trials in patients with cardiovascular diseases. Therapy with ramipril in patients with various cardiovascular disorders has demonstrated significant and clinically important reductions in cardiovascular death, myocardial infarction, stroke, congestive heart failure, progressive renal impairment and onset of diabetes. Ramipril is usually dosed at 2.5-10 mg/day. Beneficial effects of ramipril are observed in the treatment of hypertension and congestive heart failure, prevention of cardiovascular events in high-risk patients, prevention of congestive heart failure, diabetes and other vascular events.
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PMID:Ramipril in the treatment of vascular diseases. 1614 10

The Heart Outcomes Prevention Evaluation (HOPE) study demonstrated that the angiotensin-converting enzyme inhibitor, ramipril, significantly reduces mortality, myocardial infarction and stroke in high-risk cardiovascular patients, beyond the benefits from blood pressure lowering. The tolerability of ramipril 10 mg/day has been an important concern when applying these results. Following the same criteria as the HOPE study, we investigated the adverse effects profile and tolerability of 10 mg ramipril in high-risk patients at our institution. In total, 92 patients with high cardiovascular risk were eligible for this study. Initially, ramipril was prescribed 2.5 mg orally once daily, and then titrated up to 5.0, 7.5, and 10.0 mg/day at 1-month intervals. The target maintenance dose was 10 mg/day. All adverse events were recorded during at least 3 months of follow-up. After 4-6 months of the titration protocol, only 18 patients (25.3%) reached and remained on ramipril 10 mg/day; 11 (15.5%), 22 (30.9%), and 20 patients (28.2%) remained on 2.5, 5.0, and 7.5 mg/day, respectively. Twenty-one patients (22.6%) had at least one adverse event. Twelve patients (13.0%) stopped treatment because of adverse effects. A total of 23 episodes of adverse events were reported, including cough (15.1%), dizziness (6.0%), and hypotension (2.4%). Ramipril was relatively well tolerated in our study population. However, only one-quarter of our patients reached the target maintenance dose of 10 mg/day. Dry cough, dizziness, and hypotension were the major side effects. About 15% of our patients discontinued ramipril treatment, which is comparable with previous reports.
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PMID:Tolerability of ramipril 10 mg daily in high-risk cardiovascular patients in Taiwan: experience from Kaohsiung Medical University Chung-Ho Memorial Hospital. 1635 53

Clinical trials have shown that effective control of blood pressure reduces the risk of cardiovascular events in high-risk patients. For example, data from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study show significant reductions in the incidence of cardiac events, stroke and all-cause mortality in patients in whom blood pressure control was achieved compared with those in whom blood pressure remained uncontrolled. Although the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) demonstrated no significant difference in cardiovascular mortality and morbidity between patients receiving diuretics, calcium channel blockers or angiotensin-converting enzyme (ACE) inhibitors, this finding might have been confounded by differences in the blood pressure reductions achieved with the three treatments. Other studies have consistently shown that newer antihypertensive agents, such as ACE inhibitors and calcium channel blockers, reduce cardiovascular events to a similar, or possibly greater, extent as older therapies, such as diuretics and beta-blockers. In particular, ACE inhibitors appear to offer additional benefits beyond blood pressure reduction in terms of reducing cardiovascular events and producing renoprotective effects. Angiotensin II receptor blockers (ARBs) have been less extensively studied, but there is evidence already that they have heart failure, stroke and renoprotective benefits. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) is currently comparing the effects of the ARB telmisartan 80 mg and the ACE inhibitor ramipril 10 mg, alone and in combination, on cardiovascular events in high-risk patients.
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PMID:Hypertension treatment and implications of recent cardiovascular outcome trials. 1660 60

Ramipril is an oral, non-sulfhydryl ACE inhibitor thought to act in the renin-angiotensin-aldosterone system to decrease vasopressor activity, aldosterone secretion, and bradykinin degradation. Ramipril is generally well tolerated and effective in the treatment of patients aged > or =55 years at high risk for the development of cardiovascular (CV) events, in whom the risk of myocardial infarction (MI), stroke, and CV death can be significantly reduced. The risk of these CV outcomes may also be reduced with ramipril therapy in various subgroups; these include patients with diabetes mellitus, peripheral arterial disease (PAD) or renal insufficiency, and women. Thus, ramipril, in addition to lifestyle interventions, should be considered an important therapy in the prevention of CV outcomes in high-risk patients.
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PMID:Ramipril: a review of its use in preventing cardiovascular outcomes in high-risk patients. 1719 35

Cardiovascular disease represents a continuum that starts with risk factors, such as hypertension, and progresses to atherosclerosis, target organ damage, and ultimately leads to heart failure or stroke. Renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) has been shown to be beneficial at all stages of this continuum. Both classes of agent can prevent or reverse endothelial dysfunction and atherosclerosis, thereby potentially reducing the risk of cardiovascular events. Such a reduction has been shown with ACE inhibitors in patients with coronary artery disease, but no such data are currently available for ARBs. Both ACE inhibitors and ARBs have been shown to reduce damage in target organs, such as the heart and kidney, and to decrease cardiovascular mortality and morbidity in patients with congestive heart failure. Trials, such as the Ongoing Telmisartan Alone in Combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomised Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease (TRANSCEND), that compare telmisartan, ramipril, and their combination in high-risk patients with vascular end-organ damage, should provide important new insights into the benefits of intervention with RAS blockade along the cardiorenovascular continuum.
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PMID:Angiotensin receptor blockers versus angiotensin-converting enzyme inhibitors: where do we stand now? 1830 33

The role of angiotensin-converting enzyme (ACE) inhibitors in diabetic patients with preserved ventricular function is uncertain. Tissue ACE inhibitors have been defined by increased lipophilicity and structural characteristics that result in greater tissue-specific ACE binding when compared with plasma ACE inhibitors. A Bayesian meta-analysis of randomized trials was conducted to evaluate tissue ACE inhibitors in prevention of cardiovascular disease among patients with diabetes mellitus and preserved left ventricular function. Four trials were selected that evaluated 2 different ACE inhibitors and included 10,328 patients (43,517 patient-years). The Perindopril Substudy in Coronary Artery Disease and Diabetes (PERSUADE) and the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) compared the effects of perindopril vs a placebo, and the Heart Outcomes Prevention Evaluation (HOPE) and the Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) study investigated the impact of ramipril vs a placebo. Bayesian meta-analysis of sequential trials and sensitivity analysis of therapeutic response were subsequently computed. Bayesian meta-analysis determined reduced risk of cardiovascular mortality (PB=.991), myocardial infarction (PB=.999), and the need for invasive coronary revascularization (PB=.995) when compared with placebo. Total mortality was also decreased (PB=.967), while the risk of stroke (PB=.907) and hospitalization for heart failure (PB=.923) were impacted. Bayesian meta-analysis of randomized trials suggests that tissue ACE inhibitors decrease the probability that diabetic patients with preserved left ventricular function will experience myocardial infarctions and cardiovascular death and reduce overall mortality.
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PMID:Bayesian meta-analysis of tissue angiotensin-converting enzyme inhibitors for reduction of adverse cardiovascular events in patients with diabetes mellitus and preserved left ventricular function. 1832 70

Blockade of the renin-angiotensin system (RAS) by angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) plays an important role in the protection and prevention of cardiovascular disease. The Heart Outcomes Prevention Evaluation (HOPE) study established the significant effect of ACE inhibition on cardiovascular morbidity and mortality beyond blood pressure control. Smaller studies have demonstrated the efficacy of ARBs. In addition, a recent analysis from the Blood Pressure Lowering Treatment Trialists' Collaboration showed that ARB-based and ACE inhibitor-based treatment regimens were comparable in terms of the odds ratio for stroke and heart failure, independent of blood pressure reduction. There is an emerging body of evidence to suggest that a combination approach to RAS blockade with an ARB and an ACE inhibitor may further improve cardiovascular outcome compared with monotherapy with either agent alone. The large-scale ONgoing Telmisartan Alone or in combination with Ramipril Global Endpoint Trial (ONTARGET), comparing high-dose ramipril (HOPE study dosage) with telmisartan or a combination of the two, should provide important insight into the benefits of RAS blockade intervention. The results of ONTARGET are anticipated to be available in 2008.
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PMID:No HOPE without proof: do ARBs meet the standard for cardiovascular protection? 1844 79

Cardiovascular risk is determined by multiple risk factors. Blockade of the renin-angiotensin system is an important approach to the prevention of cardiovascular events. In the largest angiotensin receptor blocker cardiovascular outcome study to date, the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) program will compare the efficacy of therapy with telmisartan and ramipril, in reducing cardiovascular events in patients at high risk (history of coronary artery disease, stroke or transient ischemic attack, peripheral artery disease, or diabetes with evidence of end-organ damage). Recruited patients (n = 31,546) will be followed up for a period of 6 years, and more than 150,000 patient-years of data will be recorded. The primary endpoint is a composite of cardiovascular death, stroke, acute myocardial infarction, and hospitalization for congestive heart failure; secondary endpoints focus on reductions in newly diagnosed heart failure, new-onset type 2 diabetes, cognitive decline, atrial fibrillation, and nephropathy. In addition, an ambulatory blood pressure monitoring substudy will be conducted to assess the effect of treatment on endpoints after adjustment for 24-hour blood pressure values. Other substudies of the treatment effects on erectile dysfunction, blood markers, arterial stiffness, oral glucose tolerance, and the progression of target organ damage are also planned. The results of the ONTARGET program are due in 2008, and the findings are expected to have important clinical implications for the management of patients at high cardiovascular risk.
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PMID:Cardiac and vascular protection: the potential of ONTARGET. 1844 80

ONTARGET ("ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial") compared the angiotensin converting enzyme inhibitor ramipril (10 mg/day), the angiotensin-receptor blocker telmisartan 80 mg/day, and the combination of the two drugs in 25,620 patients with vascular disease or high-risk diabetes. After a median follow up of 56 months, no significant differences were observed between the three groups neither in the primary composite outcome (death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure), nor in each of its components, total mortality and other secondary outcomes. Telmisartan was equivalent to ramipril (non inferiority criterion), but was better tolerated (less cough and angioedema). The combination of the two drugs in this population (without congestive heart failure and proteinuric nephropathy) did not bring increased benefit (no superiority), but was associated with more adverse events (hypotension, syncope and renal dysfunction). In this population, the choice of the molecule in monotherapy remains optional and the use of a dual blockade is not justified in order to have a better cardiovascular protection.
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PMID:[ONTARGET: similar protection of telmisartan and ramipril and lack of benefit of combined therapy in patients at high risk for vascular events]. 1857 77


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