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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in blood pressure regulation and hypertension-related complications. Angiotensin-converting enzyme inhibitors (ACEIs) were the first to be used to block the RAAS and now have many compelling indications in the treatment of hypertension and its cardiovascular and renal complications. Angiotensin II receptor blockers (ARBs), introduced 20 years later, have been shown to be equally as effective as antihypertensive treatment and are also associated with a lower number of side effects. Furthermore, in clinical trials ARBs and ACEIs were associated with comparable benefits for their most typical indications. This was confirmed in the 2007 New European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines for the management of hypertension by comparable specific recommendations for ARB and ACEI treatment. There is sufficient theoretical background and, in some cases, also clinical evidence that combination therapy with ACEIs and ARBs may be more beneficial than monotherapy with either of the groups alone, both in uncomplicated hypertension and with concomitant heart failure or renal dysfunction. However, the combination of ACEI and ARB was not recommended in the ESH/ESC 2007 Guidelines. This may change after the publication of the Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial (ONTARGET) study, the preliminary results of which have just been presented. In heart failure, recent studies have shown that the combination of ACEI and ARB decreases cardiovascular mortality and the number of hospitalizations due to aggravation of heart failure. These results have been reflected in the newest ESC guidelines of the heart failure treatment. Nephroprotective properties of the combination of ACEs and ARBs have been proved both in studies on nondiabetic and diabetic nephropathy. The potential benefits, indications in prespecified groups of patients, the most recent data from clinical trials and latest research regarding dual blockade of RAAS will be reviewed in this article.
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PMID:Current possibilities of ACE inhibitor and ARB combination in arterial hypertension and its complications. 1851 Apr 91

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

1. Epidemiological aspects: There is evidence that the pandemic of DM is entering a stabilization phase, with a slight downturn in the rates of ESRD attributed to DM in the United States. 2. New pathogenic and progression mechanisms of renal disease are proposed: 1) Intraglomerular hyperpressure with phenotypical cell changes, inducing TGF-beta activation; 2) Genetic polymorphisms, with candidate genes in chromosomes 18q, 3q, 7p and others; 3) Endothelial dysfunction as an injury initiating mechanism, demonstrated in the eNOS knockout rat; 4) Isoforms of PKC molecules that favor progression of nephropathy. 3. Importance of metabolic syndrome as a progression factor of chronic renal disease. 4. Increased CV risk in patients treated with thiazolidinediones (glitazones) -Hydrosaline retention and heart failure. 5. Recent studies: ADVANCE study: Combined treatment with an ACE inhibitor (perindropil) and a diuretic (indapamide) in fixed doses helps to reduce CV risk and overall mortality.DREAM study: Ramipril does not reduce the occurrence of DM2, but does improve reversion to normoglycemia. AVOID study: Direct renin inhibitors add greater antihypertensive and antiproteinuric efficacy. 6. New therapeutic targets: Antifibrotic, anti-inflammatory and antiproteinuric effects of sulodexide, isosorbide mononitrate, PKC inhibitors and others. 7. The most effective strategy continues to be intensive, multifactorial and multidisciplinary management of the type 2 diabetic patient, as shown by long-term follow-up in the Steno-2 study.
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PMID:[Advances in diabetes mellitus, diabetic nephropathy, metabolic syndrome and cardio-vascular-renal risk]. 1884 25

Physicians have embraced the concept of dual renin-angiotensin system (RAS) blockade hoping that it would translate into better blood pressure control as well as incremental nephroprotective and cardioprotective effects. With regard to blood pressure, a small additional fall with dual RAS blockade was observed when compared with that seen in monotherapy. Numerous studies have shown a reduction of albuminuria with dual RAS blockade. However, the recent findings in the ONTARGET (Renal Outcomes With Telmisartan, Ramipril, or Both, in People at High Vascular Risk) study of significantly more doubling of the creatinine and dialysis in the combination arm despite lesser albuminuria emphasized the fallacy of surrogate end points and argue against nephroprotective effects of dual RAS blockade. In heart failure, dual RAS blockade was associated with more hypotension, worsening of renal function, and hyperkalemia than was angiotensin-converting enzyme inhibitor therapy alone. In conclusion, recent outcome and safety data have shattered the halo of dual RAS blockade for hypertension, nephroprotection, and heart failure. Unless data emerge to the contrary, dual RAS blockade should no longer be used in clinical practice.
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PMID:The sudden demise of dual renin-angiotensin system blockade or the soft science of the surrogate end point. 1958 45

The recently published Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) in patients with vascular disease or high-risk diabetes, as the largest published comparative trial of these agent classes, provides further evidence concerning the comparison between the angiotensin-receptor blockers (ARBs) and the angiotensin-converting enzyme inhibitors (ACEIs). In this trial, telmisartan (an ARB) was non-inferior to ramipril (an ACEI) in reducing fatal and nonfatal cardiovascular events. Moreover, ONTARGET is an example of a high-quality noninferiority trial. However, the combination of the 2 agents was associated with more adverse effects without an increase in benefit. The study differed from several other comparative studies in which the dose and choice of ACEI was left to individual physicians. Further, in ONTARGET, the ACEI was not titrated to the maximum dose and patients with heart failure were excluded.
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PMID:Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET): implications for reduced cardiovascular risk. 1930 91

Renin-angiotensin-aldosterone system (RAAS) overactivity is associated with increased cardiovascular risk, a finding that may be explained by the key role of the RAAS in stimulating vascular and cardiac remodeling. Inhibition of RAAS activity with the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) has been shown to reduce cardiovascular mortality in patients with heart failure. ACE inhibitors have also been shown to reduce the incidence of stroke, myocardial infarction (MI), and heart failure in high-risk patients without heart failure. These findings led to the evaluation of the ARB telmisartan versus the ACE inhibitor ramipril in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), a cardioprotection trial conducted in high-risk patients without left ventricular dysfunction or heart failure. The results of this trial showed that the ACE inhibitor ramipril and the ARB telmisartan are equally effective in reducing the incidence of cardiovascular death, MI, stroke, and hospitalization for heart failure in patients without heart failure or left ventricular dysfunction but at high risk for cardiovascular disease (CVD). These results confirm that RAAS inhibition, using ACE inhibitors or ARBs, is an effective approach to reducing cardiovascular mortality and morbidity in patients without heart failure who are at high risk for CVD.
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PMID:Recent advances in cardiovascular risk reduction: implications of ONTARGET. 1940 52

In patients with arterial hypertension and/or high cardiovascular risk, including patients with diabetes, chronic ischemic heart disease and kidney disease, the risk of heart failure decreases with blood pressure reduction and the use of drugs that inhibit the renin-angiotensin system (RAS) [angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)]. The heart failure incidence seen in ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) is in line with this observation. In ONTARGET, telmisartan and ramipril were equally effective in heart failure prevention and with the same blood pressure reduction. The low event rate, including the low incidence of heart failure in TRANSCEND with the greater use of diuretics in the placebo arm, may help to explain the absence of significant differences between telmisartan and placebo.
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PMID:The question of heart failure in ONTARGET and TRANSCEND: implications for clinical practice. 1949 21


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