Telmisartan to Prevent Recurrent Stroke and Cardiovascular Events

Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
New England Journal of Medicine (Impact Factor: 55.87). 09/2008; 359(12):1225-37. DOI: 10.1056/NEJMoa0804593
Source: PubMed


Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke.
In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes.
The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10).
Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. ( number, NCT00153062.)

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Available from: Bernard Chan, Sep 30, 2015
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    • "HOPE: heart outcomes prevention evaluation; PROGRESS: perindopril protection against recurrent stroke study; QUIET: quinapril ischemic event trial; EUROPA: European trial on reduction of cardiac events with perindopril in stable coronary artery disease; CAMELOT: comparison of amlodipine versus enalapril to limit occurrences of thrombosis; PEACE: prevention of events with angiotensin converting enzyme inhibitors; JIKEI: valsartan in a Japanese population with hypertension and other cardiovascular disease; TRANSCEND: telmisartan randomized assessment study in ACE-intolerant subjects with cardiovascular disease; PROFESS: telmisartan to prevent recurrent stroke and cardiovascular events; NAVIGATOR: nateglinide and valsartan in impaired glucose tolerance outcomes research. HOPE [12] PROGRESS [15] QUIET [16] EUROPA [17] CAMELOT [18] PEACE [19] JIKEI [20] TRANSCEND [21] PROFESS [22] NAVIGATOR [23]. "
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    ABSTRACT: Context. Whether angiotensin converting-enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) are useful in high risk patients without heart failure is unclear. We perform a meta-analysis of prospective randomized placebo-controlled ACEI or ARB trials studying patients with a combination of risk factors to assess treatment impact on all cause mortality, cardiovascular mortality, nonfatal myocardial infarction (MI) and stroke. Method. A PubMed search was made for placebo-controlled trials recruiting at least 1,200 high risk patients randomized to either ACEI or ARB, with follow-up of at least 2 years. Meta-analysis was performed using the RevMan 5 program and Mantel-Haenszel analysis was done with a fixed effects model. Results. Ten trials recruiting 77,633 patients were reviewed. All cause mortality was significantly reduced by ACEI (RR 0.89; P = 0.0008), but not by ARB treatment (RR 1.00; P = 0.89). Cardiovascular mortality and nonfatal MI were also reduced in the ACEI trials but not with ARB therapy. Stroke was significantly reduced in the ACEI trials (RR 0.75; P < 0.00001) and more modestly reduced in the ARB trials (RR 0.90; P = 0.01). Conclusion. ACEI treatment reduced stroke, nonfatal MI, cardiovascular and total mortality in high risk patients, while ARB modestly reduced stroke with no effect on nonfatal MI, cardiovascular and total mortality.
    11/2013; 2013(5):478597. DOI:10.1155/2013/478597
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    • "It was assessed in the PRoFESS stroke secondary prevention megatrial although treatment was not associated with reduced stroke recurrence [16]. In this study, we examined the effect of telmisartan on BP, CBF, CPP, ZFP, and arterial compliance in patients with recent ischaemic stroke. "
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    ABSTRACT: High blood pressure (BP) is common in acute stroke and is independently associated with a poor outcome. Lowering BP might improve outcome if cerebral blood flow (CBF) is unaffected in the presence of dysfunctional autoregulation. We investigated the effect of telmisartan on systemic and cerebral haemodynamics in patients with recent stroke. Patients with ischaemic stroke (<5 days) were randomised to 90 days of telmisartan (80 mg) or placebo. CBF (primary outcome) was measured using xenon CT at baseline and 4 hours. BP and transcranial doppler (TCD) were performed at baseline, 4 hours after-treatment, and on days 4, 7, and 90. Cerebral perfusion pressure and zero filling pressure (ZFP) were calculated. Of a planned 24 patients, 17 were recruited. Telmisartan significantly accentuated the fall in systolic and diastolic BP over 90 days (treatment-time interaction , resp.) but did not alter BP at 4 hours after treatment (171/99 versus 167/87 mmHg), CBF, or CBF velocity. ZFP was significantly lower in the treatment group . Impairment at 7 days and dependency at 90 days did not differ between the groups. In this underpowered study, telmisartan did not significantly alter BP or CBF after the first dose. Telmisartan reduced BP over the subsequent 90 days and significantly lowered ZFP. This trial is registered with ISRCTN 41456162.
    06/2013; 2013(6624). DOI:10.1155/2013/587954
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    • "Secondly, the interrelationships between baseline BP, stroke severity, and administration of antihypertensive agents have not been well understood but an interaction could not be excluded; in the PRoFESS study the failure to show beneficial effect of telmisartan may reflect that patients had only mild hypertension and mild stroke. Thirdly, favourable effect of treatment may show a significant time interaction; a post hoc analysis of the main PRoFESS study indicated that recurrence was lower with telmisartan after the first six months of treatment [44], and in the ACCESS benefit on overall mortality and vascular events did not arise immediately but instead appeared to increase during follow up. The included studies presented followup ranging from 3 to 12 months and have not been designed to investigate long term effects of treatment. "
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    ABSTRACT: Raised blood pressure (BP) is common after stroke but its causes, effects, and management still remain uncertain. We performed a systematic review of randomized controlled trials that investigated the effects of the angiotensin receptor blockers (ARBs) administered in the acute phase (≤72 hours) of stroke on death and dependency. Trials were identified from searching three electronic databases (Medline, Cochrane Library and Web of Science Database). Three trials involving 3728 patients were included. Significant difference in BP values between treatment and placebo was found in two studies. No effect of the treatment was seen on dependency, death and vascular events at one, three or six months; the cumulative mortality and the number of vascular events at 12 months differed significantly in favour of treatment in one small trial which stopped prematurely. Evidence raises doubts over the hypothesis of a specific effect of ARBs on short- and medium-term outcomes of stroke. It is not possible to rule out that different drugs might have different effects. Further trials are desirable to clarify whether current findings are generalizable or there are subgroups of patients or different approaches to BP management for which a treatment benefit can be obtained.
    International Journal of Hypertension 01/2013; 2013:941783. DOI:10.1155/2013/941783
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