Yusuf, S. et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet 372, 1174-1183

The Lancet (Impact Factor: 45.22). 09/2008; 372:1174-83. DOI: 10.1016/S0140-6736(08)61242-8
Source: OAI


BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce major cardiovascular events, but are not tolerated by about 20% of patients. We therefore assessed whether the angiotensin-receptor blocker telmisartan would be effective in patients intolerant to ACE inhibitors with cardiovascular disease or diabetes with end-organ damage. METHODS: After a 3-week run-in period, 5926 patients, many of whom were receiving concomitant proven therapies, were randomised to receive telmisartan 80 mg/day (n=2954) or placebo (n=2972) by use of a central automated randomisation system. Randomisation was stratified by hospital. The primary outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure. Analyses were done by intention to treat. This trial is registered with, number NCT00153101. FINDINGS: The median duration of follow-up was 56 (IQR 51-64) months. All randomised patients were included in the efficacy analyses. Mean blood pressure was lower in the telmisartan group than in the placebo group throughout the study (weighted mean difference between groups 4.0/2.2 [SD 19.6/12.0] mm Hg). 465 (15.7%) patients experienced the primary outcome in the telmisartan group compared with 504 (17.0%) in the placebo group (hazard ratio 0.92, 95% CI 0.81-1.05, p=0.216). One of the secondary outcomes-a composite of cardiovascular death, myocardial infarction, or stroke-occurred in 384 (13.0%) patients on telmisartan compared with 440 (14.8%) on placebo (0.87, 0.76-1.00, p=0.048 unadjusted; p=0.068 after adjustment for multiplicity of comparisons and overlap with primary outcome). 894 (30.3%) patients receiving telmisartan were hospitalised for a cardiovascular reason, compared with 980 (33.0%) on placebo (relative risk 0.92, 95% CI 0.85-0.99; p=0.025). Fewer patients permanently discontinued study medication in the telmisartan group than in the placebo group (639 [21.6%] vs 705 [23.8%]; p=0.055); the most common reason for permanent discontinuation was hypotensive symptoms (29 [0.98%] in the telmisartan group vs 16 [0.54%] in the placebo group). INTERPRETATION: Telmisartan was well tolerated in patients unable to tolerate ACE inhibitors. Although the drug had no significant effect on the primary outcome of this study, which included hospitalisations for heart failure, it modestly reduced the risk of the composite outcome of cardiovascular death, myocardial infarction, or stroke. FUNDING: Boehringer Ingelheim.

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    • "than in the ramipril treatment arm, although this difference was not significant [26]. In the TRANSCEND trial, high-risk cardiovascular patients intolerant to ACE inhibitors were enrolled, and the ratio of those with a coronary disease reached 75 % [27]. Reductions in the risk of MI were not significant (p = 0.059) with telmisartan relative to placebo treatment. "
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    ABSTRACT: The renin-angiotensin-aldosterone system plays a major role in the pathophysiology of hypertension and closely related cardio- and cerebrovascular events. Although both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) are equally important in the treatment of hypertension, according to the results of recent years, there might be substantial differences in their cardiovascular protective effects, and these differences might be explained by our increasing knowledge of their non-overlapping mechanisms of action. The number of studies investigating how ACE inhibitors and ARB agents differ will certainly be increasing in the future. ACE inhibitors are the safe therapeutic opportunity for hypertensive patients at high risk, with a cardiological comorbidity.
    Full-text · Article · Jan 2014 · American Journal of Cardiovascular Drugs
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    • "The Survival of Myocardial Infarction Long-Term Evaluation (SMILE) study found a benefit, whereas the Valsartan Antihypertensive Long-term Use Evaluation trial (VALUE) found no difference and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) showed no difference [46] [55] [56]. The Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (TRANSCEND) showed the benefit of telmisartan [36]. The Captopril Prevention Project (CAPPP) showed a benefit in diabetics [41]. "
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    ABSTRACT: Renin-angiotensin system (RAS) inhibition by angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) has been shown to reduce cardiovascular mortality and non-fatal myocardial infarction (MI) in high-risk surgical patients. However, their effect in spinal surgery has not been explored. Our objective was to determine the effect of RAS inhibitors on postoperative troponin elevation in spinal fusions, and to examine their correlation with hospital stay. We retrospectively analyzed 208 consecutive patients receiving spinal fusions ⩾5 levels between 2007-2010 with a mean follow-up of 1.7years. Inclusion criteria were age ⩾18years, elective fusions for kyphoscoliosis, and semi-elective fusions for tumor or infection. Exclusion criteria were trauma and follow-up <1year. Descriptives, frequencies, and logistic and linear regression were used to analyze troponin elevation (⩾0.04ng/mL), peak troponin level, and hospital stay. The results featured 208 patients with a mean body mass index (BMI) 28.5kg/m(2) who underwent 345 spinal fusions. ACEI/ARB were withheld the day prior to surgery in 121 patients with 11 patients noteworthy for intra-operative electrocardiogram changes, 126 patients with troponin elevation, and 14 MI identified prior to discharge. Multivariate logistic regression identified BMI (p=0.04), estimated blood loss (p=0.015), and preoperative ACEI/ARB (p=0.015, odds ratio=2.7) as significant independent predictors for postoperative troponin elevation. Multivariate linear regression showed preoperative Oswestry Disability Index (p=0.002), unplanned return to operating room (p=0.007), pneumonia prior to hospital discharge (p<0.01), and preoperative ACEI/ARB to be associated with hospital stay. In patients with spinal fusions ⩾5 levels, ACEI/ARB are independently associated with postoperative troponin elevation and increased hospital stay.
    Full-text · Article · Nov 2013 · Journal of Clinical Neuroscience
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    • "ARBs are widely preferred over other antihypertensive medications because of their placebo-like tolerability [19]. As such, this study exhibited a rate of adverse events related to the medication of approximately 2.35 %, and no life-threatening adverse reactions were noted. "
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    ABSTRACT: Background Angiotensin II receptor blockers (ARBs) play a key role in hypertension therapy. Recently, fimasartan, the ninth ARB, was developed, but its safety and efficacy have not been well established. Objective The objective of this study was to determine whether age, sex, concomitant disease, and current antihypertensive medications affect the safety and efficacy of fimasartan in patients with arterial hypertension. Methods This was a large-scale, open-label observational study to determine the safety and efficacy of fimasartan in patients with hypertension. Patients who were treated for more than 2 months with fimasartan (60 or 120 mg, once daily) were recruited, and the data were systematically collected using electronic case report forms. Written informed consent forms were obtained from all patients. Results A total of 14,151 patients (50.7 % males; mean age 59 ± 12 years) were evaluated, of whom 37.9 % were never treated with fimasartan, 53.5 % were switched to fimasartan, and 8.5 % had fimasartan added to their treatment. Overall, fimasartan reduced systolic blood pressure (SBP) from 145.4 ± 18.1 to 126.8 ± 12.6 mmHg and diastolic blood pressure (DBP) from 88.7 ± 11.8 to 79.0 ± 8.7 mmHg (all p < 0.001). The pulse rate decreased from 74.4 ± 10.3 to 71.9 ± 9.2 beats/min in comparison with before treatment (p < 0.001). The reductions were similar between sexes, age groups, and patients with and without co-morbidities, and were not dependent on prior or concomitant treatment with other antihypertensive drugs. Adverse events were reported in 3.31 % (treatment-emergent) and 2.35 % (drug-related) of patients; there were no dose differences for adverse events. The most frequent adverse events were dizziness (1.55 %) and headache (0.52 %); other adverse events were rare. The responder rate (DBP to <90 mmHg or a reduction of ≥10 mmHg) and the goal rate (combined SBP/DBP <140/90 mmHg) were 85.0 and 75.6 %, respectively. Global drug compliance was rated as excellent, very good, good, and poor in 68.1, 26.9, 3.4, and 1.7 % of patients, respectively. Conclusion The safety, efficacy, and compliance of fimasartan were found to be excellent in a large patient population that included patients potentially at higher risk for adverse events.
    Full-text · Article · Jan 2013 · American Journal of Cardiovascular Drugs
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