Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials

Teo, Koon; Yusuf, Salim; Sleight, Peter; Anderson, Craig S.; Mookadam, Farouk; Ramos, Barbara; Hilbrich, Lutz; Pogue, Janice; Schumacher, Helmut; Ontarget,; Investigators, Transcend

doi:10.1016/j.ahj.2004.03.020

Cited by 336 publications

(28 citation statements)

References 34 publications

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“…The ONTARGET and TRANSCEND studies were previously described [9]–[11]. Briefly, these studies included patients 55 years and older with atherosclerotic vascular disease or diabetes and retinopathy, left ventricular hypertrophy, micro- or macro-albuminuria, or a history of cardiac or vascular disease.…”

Section: Methodsmentioning

confidence: 99%

A Gene Variant in CERS2 Is Associated with Rate of Increase in Albuminuria in Patients with Diabetes from ONTARGET and TRANSCEND

Shiffman¹,

Paré

Oberbauer

et al. 2014

PLoS ONE

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Although albuminuria and subsequent advanced stage chronic kidney disease are common among patients with diabetes, the rate of increase in albuminuria varies among patients. Since genetic variants associated with estimated glomerular filtration rate (eGFR) were identified in cross sectional studies, we asked whether these variants were also associated with rate of increase in albuminuria among patients with diabetes from ONTARGET and TRANSCEND—randomized controlled trials of ramipril, telmisartan, both, or placebo. For 16 genetic variants associated with eGFR at a genome-wide level, we evaluated the association with annual rate of increase in albuminuria estimated from urine albumin:creatinine ratio (uACR). One of the variants (rs267734) was associated with rate of increase in albuminuria. The annual rate of increase in albuminuria among risk homozygotes (69% of the study population) was 11.3% (95%CI; 7.5% to 15.3%), compared with 5.0% (95%CI; 3.3% to 6.8%) for heterozygotes (27% of the population), and 1.7% (95%CI; −1.7% to 5.3%) for non-risk homozygotes (4% of the population); P = 0.0015 for the difference between annual rates in the three genotype groups. These estimates were adjusted for age, sex, ethnicity, and principal component of genetic heterogeneity. Among patients without albuminuria at baseline (uACR<30 mg/g), each risk allele was associated with 50% increased risk of incident albuminuria (OR = 1.50; 95%CI 1.15 to 1.95; P = 0.003) after further adjustment for traditional risk factors including baseline uACR and eGFR. The rs267734 variant is in almost perfect linkage-disequilibrium (r2 = 0.94) with rs267738, a single nucleotide polymorphism encoding a glutamic acid to alanine change at position 115 of the ceramide synthase 2 (CERS2) encoded protein. However, it is unknown whether CERS2 function influences albuminuria. In conclusion, we found that rs267734 in CERS2 is associated with rate of increase in albuminuria among patients with diabetes and elevated risk of cardiovascular disease.

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Section: Methodsmentioning

confidence: 99%

A Gene Variant in CERS2 Is Associated with Rate of Increase in Albuminuria in Patients with Diabetes from ONTARGET and TRANSCEND

Shiffman¹,

Paré

Oberbauer

et al. 2014

PLoS ONE

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“…Incidentstroke was determinedby an adjudicationcommittee Significant association betweenatrial fibrillation and cognitivedecline ( multivariate HR[95%CI]=1.14 [1.03, 1.26)Significant association betweenatrial fibrillation and dementia( multivariate HR [95%CI]=1.30[1.14,1.49]) Age; education; sex; baseline MMSE score;blood pressure; history of stroke or transientischemic attack, hypertension, diabetes andmyocardial infarction; levels ofmicroalbuminuria, macroalbuminuria andcreatinine; statins, beta-blockers,angiotensin-converting enzyme inhibitors,antiplatelets or oral anticoagulants; changesin systolic blood pressure during follow-up;smoking; BMI; physical activity; sleepapnea; and alcohol consumption

Studies are ordered based on the publication year. * At entry all participants underwent physical examination by a neurologist and a cardiologist and the patient records were collected. † Per contact with the authors. ‡ Data obtained from rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials (53).

…”

Section: Search Strategymentioning

confidence: 99%

“… * At entry all participants underwent physical examination by a neurologist and a cardiologist and the patient records were collected. † Per contact with the authors. ‡ Data obtained from rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials (53). …”

Section: Search Strategymentioning

confidence: 99%

Cognitive Impairment Associated With Atrial Fibrillation

Kalantarian

Stern²,

Mansour³

et al. 2013

Ann Intern Med

364

243

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Background Atrial fibrillation (AF) has been linked with an increased risk of cognitive impairment and dementia. Purpose To complete a meta-analysis of studies examining the association between AF and cognitive impairment. Data Sources Electronic search of 5 large databases and hand search of article references. Study Selection Prospective and non-prospective studies reporting adjusted risk estimates for the relationship between AF and cognitive impairment. Data Extraction Two abstracters independently extracted data on study characteristics, risk estimates, methods of AF and outcome ascertainment, and methodological quality. Data Synthesis Twenty one studies were included in the meta-analysis. AF was significantly associated with a higher risk of cognitive impairment independent of stroke history (relative risk (RR) [95% confidence interval (CI)] =1.34 [1.13, 1.58]), in patients with first-ever or recurrent stroke (RR [95%] =2.7 [1.82, 4.00]) and in a broader population including patients with or without a history of stroke (RR [95% CI] =1.4 [1.19, 1.64]). However, there was significant heterogeneity among studies of the broader population (I2 =69.4 %). Limiting the analysis to prospective studies yielded similar results (RR [95% CI] =1.36 [1.12, 1.65]). Restricting the analysis to studies of dementia eliminated the significant heterogeneity (P value =0.137) but did not alter the pooled estimate substantially (RR [95% CI] = 1.38 [1.22, 1.56]). Limitations There is an inherent bias due to confounding variables in observational studies. There was significant heterogeneity among included studies. Conclusions Evidence suggests that AF is associated with a higher risk of cognitive impairment and dementia, with or without a history of clinical stroke. Further studies are required to elucidate the relationship between AF and subtypes of dementia as well as the etiology of cognitive impairment.

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“…The HOPE trial was not intended to be a hypertension study; at randomization, only 46.6% of patients were hypertensive (≥140/90 mm Hg), with a mean baseline blood pressure of 139/79 mm Hg in both groups [23]. In ONTARGET and TRANSCEND, blood pressure >160/100 mm Hg was an exclusion criterion and a higher proportion of patients had mild-to-moderate hypertension when compared with HOPE (table 2) [39]. …”

Section: The Ontarget Trial Programmentioning

confidence: 99%

From Evidence to Rationale: Cardiovascular Protection by Angiotensin II Receptor Blockers Compared with Angiotensin-Converting Enzyme Inhibitors

Böhm

Baumhäkel²,

Mahfoud³

et al. 2010

Cardiology

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Clinical trials have shown the efficacy of angiotensin II receptor blockers (ARBs) in patients with hypertension and have suggested that ARBs are noninferior to angiotensin-converting enzyme (ACE) inhibitors in patients with ischemic heart disease and heart failure. The Heart Outcomes Prevention Evaluation (HOPE), a landmark study in high cardiovascular risk management, demonstrated the cardioprotection of the ACE inhibitor ramipril. Thus, in the recent Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET®) ramipril was selected as a comparator when exploring the cardioprotective potential of telmisartan in the first head-to-head comparison of an ACE inhibitor and an ARB in a broad cross-sectional cohort of cardiovascular high-risk patients. ONTARGET showed that telmisartan is as effective as ramipril in the management of these patients but is better tolerated. The combination of ramipril and telmisartan did not confer a further benefit but did bring about an increased rate of adverse events such as renal dysfunction. In previous ARB outcome trials, cardiovascular risk profile, nature and severity of the underlying cardiovascular disease, dosing regimens and concomitant therapies, follow-up, and endpoints have varied greatly so that caution is warranted in extrapolating evidence gained from high-risk patients to other conditions such as acute myocardial infarction or chronic heart failure.

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Cited by 336 publications

References 34 publications

A Gene Variant in CERS2 Is Associated with Rate of Increase in Albuminuria in Patients with Diabetes from ONTARGET and TRANSCEND

A Gene Variant in CERS2 Is Associated with Rate of Increase in Albuminuria in Patients with Diabetes from ONTARGET and TRANSCEND

Cognitive Impairment Associated With Atrial Fibrillation

From Evidence to Rationale: Cardiovascular Protection by Angiotensin II Receptor Blockers Compared with Angiotensin-Converting Enzyme Inhibitors

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