| 1. |
- Sacco, R. L., et al.
(author)
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Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke
- 2008
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In: New England Journal of Medicine. - Boston : Massachusetts medical society. - 1533-4406 .- 0028-4793. ; 359:12, s. 1238-51
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Journal article (peer-reviewed)abstract
- BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. RESULTS: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). CONCLUSIONS: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)
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| 2. |
- Yusuf, S., et al.
(author)
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Telmisartan to prevent recurrent stroke and cardiovascular events
- 2008
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In: New England Journal of Medicine. - : Massachusetts medical society. - 1533-4406 .- 0028-4793. ; 359:12, s. 1225-37
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Journal article (peer-reviewed)abstract
- BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. (ClinicalTrials.gov number, NCT00153062.)
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| 3. |
- Dahlöf, Björn, 1953, et al.
(author)
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Perindopril/indapamide combination more effective than enalapril in reducing blood pressure and left ventricular mass: the PICXEL study
- 2005
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In: J Hypertens. - 0263-6352. ; 23:11, s. 2063-70
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Few data are available comparing the effects of monotherapy and combination therapy on target organ damage. The PICXEL study compared the efficacy of a strategy based on first-line combination with perindopril/indapamide versus monotherapy with enalapril in reducing left ventricular hypertrophy (LVH) in hypertensive patients. METHODS: In this 1-year multicentre randomized double-blind study, patients received an increasing dosage of perindopril/indapamide (n = 284) or enalapril (n = 272). Changes in blood pressure and echocardiographic measures of LVH were assessed from baseline to the end of treatment. Reading of the echocardiograms was central and blinded for therapy, patient and sequence. RESULTS: Systolic and diastolic blood pressure decreased significantly more in the perindopril/indapamide than in the enalapril group (P < 0.0001 and P = 0.003). The left ventricular mass index decreased by 13.6 +/- 23.9 g/m(2) (mean +/- SD) with perindopril/indapamide (P < 0.0001) and 3.9 +/- 23.9 g/m(2) with enalapril (P < 0.005); these decreases were significantly different (P < 0.0001). The left ventricular internal diameter, posterior and interventricular septal wall thickness decreased significantly with perindopril/indapamide (P < or = 0.0001); the interventricular septal wall thickness decreased significantly with enalapril (P < 0.001). Both treatments were well tolerated. CONCLUSION: A strategy based on first-line combination with perindopril/indapamide achieved better blood pressure decrease with a significantly greater degree of LVH reduction than a strategy based on monotherapy with enalapril in hypertensive patients with LVH.
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| 4. |
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| 5. |
- Carr, A. A., et al.
(author)
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Hospitalizations for new heart failure among subjects with diabetes mellitus in the RENAAL and LIFE studies
- 2005
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In: Am J Cardiol. - : Elsevier BV. - 0002-9149. ; 96:11, s. 1530-6
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Journal article (peer-reviewed)abstract
- We sought to study the risk factors for heart failure (HF) and the relation between antihypertensive treatment with losartan and the first hospitalization for HF in patients with diabetes mellitus in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) and Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) studies. We evaluated 1,195 patients with hypertension, left ventricular hypertrophy, and diabetes from the LIFE study and 1,513 patients with type 2 diabetes and nephropathy from the RENAAL study. The comparative treatments were atenolol in the LIFE study and placebo in the RENAAL study. Patients with a history of HF were excluded from this analysis. Losartan significantly reduced the incidence of first hospitalizations for HF versus placebo in the RENAAL study (hazard ratio 0.74, p=0.037) and versus atenolol in the LIFE study (hazard ratio 0.57, p=0.019). Patients enrolled in the RENAAL study were at a higher risk of developing HF (hazard ratio for RENAAL vs LIFE diabetics 3.0, p<0.0001). The significant, independent baseline risk factors for the development of HF in the RENAAL study were urinary albumin/creatinine ratio, age, peripheral vascular disease, the Cornell product, body mass index, and previous angina; in the LIFE study they were the Cornell product, previous myocardial infarction, peripheral vascular disease, baseline atrial fibrillation, alcohol use (inverse relation), and urinary albumin/creatinine ratio. The beneficial effect of losartan on the reduction of risk for hospitalization for new HF was demonstrated in patients who were at high renal and/or high cardiovascular risk.
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| 6. |
- Dahlöf, Björn, 1953, et al.
(author)
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Felodipine-metoprolol combination tablet: maintained health-related quality of life in the presence of substantial blood pressure reduction
- 2005
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In: Am J Hypertens. - : Oxford University Press (OUP). - 0895-7061. ; 18:10, s. 1313-9
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Journal article (peer-reviewed)abstract
- BACKGROUND: Most treated hypertensive patients do not achieve adequate blood pressure (BP) control. Initiating therapy with two drugs has been suggested when BP is >20/10 mm Hg above goal. To ensure patients' compliance, such treatment needs to be well tolerated and must not compromise health-related quality of life (HRQL). The primary objective of this study was to compare the effects on HRQL of initiating treatment with felodipine + metoprolol (F+M) fixed combination tablets, or enalapril (E), or placebo (P). METHODS: A total of 947 patients of both sexes with primary hypertension (diastolic BP 95 to 110 mm Hg), aged 20 to 70 years, participated in this randomized, double-blind, parallel group, 12-week, multicenter trial. Treatment was initiated with F+M 5 + 50 mg, or E 10 mg, or P. Doses were doubled after 4 or 8 weeks if diastolic BP was >90 mm Hg. The HRQL was measured at baseline and at the last visit using two validated questionnaires: the Psychological General Well-being Index (PGWB) and the Subjective Symptom Assessment Profile (SSA-P). Office BP was measured at trough, that is, 24 h after the previous dose. RESULTS: The HRQL was high at baseline and generally well maintained during the study. For example, the mean (SD) PGWB total score was 104 (16) at baseline and 105 (16) at 12 weeks in all three treatment groups. The BP reductions after F+M (18/14 mm Hg) and E (12/9 mm Hg) were significantly greater than after P (7/7 mm Hg), and the reduction after F+M was significantly greater than after E. CONCLUSIONS: The HRQL is maintained in the presence of substantial BP reduction during antihypertensive treatment with F+M fixed combination tablets.
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| 7. |
- Fyhrquist, F., et al.
(author)
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Pulse pressure and effects of losartan or atenolol in patients with hypertension and left ventricular hypertrophy
- 2005
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In: Hypertension. - 1524-4563. ; 45:4, s. 580-5
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Journal article (peer-reviewed)abstract
- In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, the primary composite end point of cardiovascular death, stroke, and myocardial infarction was reduced by losartan versus atenolol in patients with hypertension and left ventricular hypertrophy. The objective of this post hoc analysis was to determine the influence of pulse pressure on outcome. Patients were divided into quartiles of baseline pulse pressure. Cox regression, including baseline Framingham risk score as a covariate, was used to compare risk in the quartiles. In the atenolol group, there were significantly higher risks in the highest versus lowest quartile for the composite end point 28% (confidence interval [CI], 2% to 62%; P=0.035), stroke 84% (CI, 32% to 157%; P<0.001), and total mortality 41% (CI, 7% to 84%; P=0.013). Risk for myocardial infarction was 44% higher (CI, -5% to 120%; P=0.089). The risks in the losartan group also increased with increasing quartile, but were lower than in the atenolol group, and differences between the highest and lowest quartiles were not significant: composite end point 12% (CI, -13% to 44%; P>0.2), stroke -5% (CI, -34% to 37%; P>0.2), myocardial infarction 30% (CI, -13% to 94%; P>0.2), and total mortality 32% (CI, -1% to 76%; P=0.062). In patients with hypertension and left ventricular hypertrophy in the LIFE study, there were significantly higher risks, adjusted for the Framingham risk score, for the primary composite end point, stroke, and total mortality in the highest versus lowest quartile of pulse pressure with atenolol-based treatment. The risks in the losartan group also increased with increasing pulse pressure quartile, but were lower than those in the atenolol group, and were not significant.
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| 8. |
- Gerdts, E., et al.
(author)
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Impact of overweight and obesity on cardiac benefit of antihypertensive treatment
- 2013
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In: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 23:2, s. 122-129
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Journal article (peer-reviewed)abstract
- Background and aims: Increased body mass index (BMI) has been associated with increased cardiovascular morbidity and mortality in hypertension. Less is known about the impact of BMI on improvement in left ventricular (LV) structure and function during antihypertensive treatment. Methods and results: Annual BMI, echocardiograms and cardiovascular events were recorded in 875 hypertensive patients with LV hypertrophy during 4.8 years randomized treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy. Patients were grouped by baseline BMI into normal (n = 282), overweight (n = 405), obese (n = 150) and severely obese groups (n = 38) (BMI <= 24.9, 25.0-29.9, 30.0-34.9, and >= 35.0 kg/m(2), respectively). At study end, residual LV hypertrophy was present in 54% of obese and 79% of severely obese patients compared to 31% of normal weight patients (both p < 0.01). In regression analyses, adjusting for initial LV mass/height(2.7), higher BMI predicted less LV hypertrophy reduction and more reduction in LV ejection fraction (both p < 0.05), independent of blood pressure reduction, diabetes and in-study weight change. During follow-up, 91 patients suffered cardiovascular death, myocardial infarction or stroke. In Cox regression analysis 1 kg/m(2) higher baseline BMI predicted a 5% higher rate of cardiovascular events and 10% higher cardiovascular mortality over 4.8 years (both p < 0.05). Conclusions: In hypertensive patients in the LIFE study, increased BMI was associated with less reduction of LV hypertrophy and less improvement in LV systolic function which may contribute to the observed higher cardiovascular event rate of treated hypertensive patients. (C) 2011 Elsevier B. V. All rights reserved.
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| 9. |
- Hacke, W., et al.
(author)
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Transcranial Laser Therapy in Acute Stroke Treatment Results of Neurothera Effectiveness and Safety Trial 3, a Phase III Clinical End Point Device Trial
- 2014
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In: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 45:11, s. 3187-3193
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Journal article (peer-reviewed)abstract
- Background and Purpose On the basis of phase II trials, we considered that transcranial laser therapy could have neuroprotective effects in patients with acute ischemic stroke. Methods We studied transcranial laser therapy in a double-blind, sham-controlled randomized clinical trial intended to enroll 1000 patients with acute ischemic stroke treated 24 hours after stroke onset and who did not undergo thrombolytic therapy. The primary efficacy measure was the 90-day functional outcome as assessed by the modified Rankin Scale, with hierarchical Bayesian analysis incorporating relevant previous data. Interim analyses were planned after 300 and 600 patients included. Results The study was terminated on recommendation by the Data Monitoring Committee after a futility analysis of 566 completed patients found no difference in the primary end point (transcranial laser therapy 140/282 [49.6%] versus sham 140/284 [49.3%] for good functional outcome; modified Rankin Scale, 0-2). The results remained stable after inclusion of all 630 randomized patients (adjusted odds ratio, 1.024; 95% confidence interval, 0.705-1.488). Conclusions Once the results of the interim futility analysis became available, all study support was immediately withdrawn by the capital firms behind PhotoThera, and the company was dissolved. Proper termination of the trial was difficult but was finally achieved through special efforts by former employees of PhotoThera, the CRO Parexel and members of the steering and the safety committees. We conclude that transcranial laser therapy does not have a measurable neuroprotective effect in patients with acute ischemic stroke when applied within 24 hours after stroke onset. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01120301.
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| 10. |
- Kjeldsen, S. E., et al.
(author)
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Targeting the renin-angiotensin system for the reduction of cardiovascular outcomes in hypertension: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers
- 2005
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In: Expert Opin Emerg Drugs. - 1744-7623. ; 10:4, s. 729-45
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Journal article (peer-reviewed)abstract
- Agents that counteract the negative impact of the renin-angiotensin-aldosterone system (RAAS) are effective antihypertensives and reduce the risk of developing Type 2 diabetes. Contrary to common perception, angiotensin-converting enzyme inhibitors do not share the apparent benefit of angiotensin II receptor blockers (ARBs) in reducing risk of cardiovascular-disease outcomes, particularly stroke, in randomised clinical trials. RAAS agents, especially ARBs, are well tolerated. Use of ARBs alone or in combination with other classes of antihypertensive agents to lower blood pressure and/or medications to control other conditions (e.g., insulin sensitivity) reduces risk of cardiovascular disease outcomes and Type 2 diabetes with excellent tolerability. Selected issues related to use of RAAS agents as antihypertensive therapies (e.g., Type 2 diabetes, global risk management, multiple drug therapy and coronary heart disease) are addressed.
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