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- Teo, Koon K., et al.
(författare)
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Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138 769 individuals The ARB Trialists Collaboration
- 2011
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 29:4, s. 623-635
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Forskningsöversikt (refereegranskat)abstract
- Background Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) reduce cardiovascular disease (CVD) events, but a recent meta-analysis of selected studies suggested that ARBs may increase cancer risks.Objective Candesartan, irbesartan, telmisartan, valsartan, and losartan were assessed for incident cancers in 15 large parallel long-term multicenter double-blind clinical trials of these agents involving 138 769 participants.Patients and methods Individuals at high CVD risk were randomized to telmisartan (three trials, n=51 878), irbesartan (three trials, n=14 859), valsartan (four trials, n=44 264), candesartan (four trials, n=18 566), and losartan (one trial, n=9193) and followed for 23-60 months. Incident cancer cases were compared in patients randomized to ARBs versus controls. In five trials (n=42 403), the ARBs were compared to ACEi and in 11 trials (n=63 313) to controls without ACEi. In addition, in seven trials (n=47 020), the effect of ARBs with ACEi was compared to ACEi alone and in two trials ARBs with ACEi versus ARB alone (n=25 712).Results Overall, there was no excess of cancer incidence with ARB therapy compared to controls in the 15 trials [ 4549 (6.16%) cases of 73 808 allocated to ARB versus 3856 (6.31%) of 61 106 assigned to non-ARB controls; odds ratio (OR) 1.00, 95% confidence interval (CI) 0.95-1.04] overall or when individual ARBs were examined. ORs comparing combination therapy with ARB along with ACEi versus ACEi was 1.01 (95% CI 0.94-1.10), combination versus ARB alone 1.02 (95% CI 0.91-1.13), ARB alone versus ACEi alone 1.06 (95% CI 0.97-1.16) and ARB versus placebo/control without ACEi 0.97 (95% CI 0.91-1.04). There was no excess of lung, prostate or breast cancer, or overall cancer deaths associated with ARB treatment.Conclusion There was no significant increase in the overall or site-specific cancer risk from ARBs compared to controls.
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- Wachtell, K., et al.
(författare)
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In-treatment reduced left atrial diameter during antihypertensive treatment is associated with reduced new-onset atrial fibrillation in hypertensive patients with left ventricular hypertrophy: The LIFE Study
- 2010
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Ingår i: Blood Pressure. - 0803-7051. ; 19:3, s. 169-175
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: It is unclear whether improvement of left atrial (LA) and ventricular (LV) structure results in reduction in new-onset atrial fibrillation (AF). The aim of the present study was to examine whether changes in-treatment LA diameter were related to changes in risk of new-onset AF. METHODS: We followed 939 hypertensive patients with electrocardiographic LV hypertrophy randomized to atenolol or losartan-based regimens in the LIFE Study for a mean of 4.8 years with echocardiograms at enrolment and annually during treatment. RESULTS: New-onset AF occurred in 46 patients (10.2/1000 patient-years of follow-up). At baseline, patients with new-onset AF were older, had higher systolic blood pressure and heart rate as well as higher prevalence of LA dilatation, but had similar prevalences of LV hypertrophy and mitral or aortic valve disease. In univariate Cox analysis baseline LA diameter (HR=4.67 per cm increase [95% CI 2.86-7.65], p<0.001) and LV mass index (HR=1.11 per 10 g/m(2) increase [95% CI 1.02-1.22], p<0.05) both predicted new-onset AF. In multivariate analysis, increased baseline LA diameter increased the risk of new-onset AF (HR=5.16 per cm [95% CI 2.85-9.35], p<0.001) whereas reduction of in-treatment LA diameter reduced the risk (HR=0.21 per cm lower LA diameter during treatment [95% CI 0.14-0.32], p<0.001) with adjustment for in-treatment LV mass in-treatment systolic blood pressure, age and Framingham risk score. CONCLUSION: LA diameter at baseline and during antihypertensive treatment were equally strong predictors of new-onset AF independent of the level of arterial pressure, LV mass and other covariates. Prevention of AF during antihypertensive treatment may be improved by antihypertensive therapy that reduces LA size in addition to controlling blood pressure.
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- Gerdts, E., et al.
(författare)
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Impact of overweight and obesity on cardiac benefit of antihypertensive treatment
- 2013
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Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 23:2, s. 122-129
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Tidskriftsartikel (refereegranskat)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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- Larstorp, A. C., et al.
(författare)
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Changes in electrocardiographic left ventricular hypertrophy and risk of major cardiovascular events in isolated systolic hypertension: The LIFE study
- 2011
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Ingår i: Journal of Human Hypertension. - 0950-9240. ; 25:3, s. 178-185
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Tidskriftsartikel (refereegranskat)abstract
- The predictive value of changes in the severity of electrocardiographic left ventricular hypertrophy (ECG-LVH) during antihypertensive therapy remains unclear in isolated systolic hypertension (ISH). In a Losartan Intervention For Endpoint reduction in hypertension substudy, we included 1320 patients aged 54-83 years with systolic blood pressure (BP) of 160-200 mm Hg, diastolic BP <90 mm Hg and ECG-LVH by Cornell voltage-duration product and/or Sokolow-Lyon voltage criteria, randomized to losartan- or atenolol-based treatment with a mean follow-up of 4.8 years. The composite end point of cardiovascular death, non-fatal myocardial infarction (MI) or stroke occurred in 179 (13.6%) patients. In Cox regression models controlling for treatment, Framingham risk score, as well as baseline and in-treatment BP, less severe in-treatment ECG-LVH by Cornell product and Sokolow-Lyon voltage was associated with 17 and 25% risk reduction for the composite end point (adjusted hazard ratio (HR) 0.83, 95% confidence interval (95% CI:) 0.75-0.92, P=0.001 per 1050 mm x ms (1 s.d.) lower Cornell product; and HR 0.75, 95% CI: 0.65-0.87, P<0.001 per 10.5 mm (1 s.d.) lower Sokolow-Lyon voltage). In parallel analyses, lower Cornell product and Sokolow-Lyon voltage were associated with lower risks of cardiovascular mortality and MI, and lower Sokolow-Lyon voltage with lower risk of stroke. Lower Cornell product and Sokolow-Lyon voltage during antihypertensive therapy are associated with lower likelihoods of cardiovascular events in patients with ISH.Journal of Human Hypertension advance online publication, 27 May 2010; doi:10.1038/jhh.2010.52.
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- Mancusi, C., et al.
(författare)
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Impact of isolated systolic hypertension on normalization of left ventricular structure during antihypertensive treatment in patients with electrocardiographic left ventricular hypertrophy (LIFE)
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 34:Supplement: 1, s. 597-597
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objective: Hypertension is associated with changes in left ventricular(LV) mass and geometry. We tested the impact of isolated systolichypertension (ISH) on normalization of LV structure during antihypertensive treatment.Methods: Baseline and annual echocardiograms were recorded in 875 hypertensive patients with electrocardiographic signs of LV hypertrophy during 4.8 years randomized losartan or atenolol-based antihypertensive treatment in the Losartan Intervention For Endpoint (LIFE) reduction inhypertension study.Results: Patients with ISH at baseline (n=128) were older, included more women, patients with diabetes or previous myocardial infarctioncompared to non-ISH patients (n=747) (all p<0.05). Baseline systolicblood pressure (BP), LV mass and ejection fraction (EF) did not differ between groups, while pulse pressure/stroke volume index (PP/SVi, an index of arterial stiffness) was higher in the ISH group (p<0.01). At the final study visit, systolic BP, LV mass, relative wall thickness (RWT) and PP/SVi were higher in the ISH group (all p<0.05). In particular, ISH patients had less reduction in LV mass and more residual LV hypertrophy compared to non-ISH patients (p<0.05). In multivariate analysis, ISH at baseline predicted higher LV mass at study end (β=0.53) independent ofhigher baseline LV mass (β=0.54) body mass index (β=0.10), atenolol-based treatment (β=0.09), and higher systolic BP (β=0.07), RWT (β=0.23) and lower LV EF (β=-0.24) at the final visit (all p<0.05), while age, historyof diabetes and PP/SVi were not significant covariates in the model.Conclusions: Antihypertensive treatment is associated with impairednormalization of LV mass and LV geometry in ISH patients with ECG LV hypertrophy. The findings may help explain the higher cardiovascular event-rate previously reported in LIFE ISH-patients.
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- Smink, P. A., et al.
(författare)
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A prediction of the renal and cardiovascular efficacy of aliskiren in ALTITUDE using short-term changes in multiple risk markers
- 2014
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 21:4, s. 434-441
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Tidskriftsartikel (refereegranskat)abstract
- Introduction We recently developed and validated in existing trials a novel algorithm (PRE score) to predict long-term drug efficacy based on short-term (month-6) drug-induced changes in multiple risk markers. To show the value of the PRE score for ongoing and planned clinical trials, we here report the predicted long-term cardio-renal efficacy of aliskiren in type 2 diabetes, which was investigated in the ALTITUDE trial, but unknown at the time this study was conducted. Methods We established the relation between multiple risk markers and cardio-renal endpoints (as defined in ALTITUDE) using a background database from past clinical trials. The short-term effect of aliskiren on multiple risk markers was taken from the AVOID trial. A PRE score was developed by multivariate Cox analysis in the background population and was then applied to the baseline and month-6 measurements of the aliskiren treatment arm of the AVOID trial to predict cardio-renal risk. The net risk difference at these time-points, after correction for placebo effects, was taken to indicate the estimated long-term cardio-renal risk change. Results Based on the PRE score, we predicted that aliskiren treatment in ALTITUDE would confer a relative risk change of -7.9% (95% CI -2.5 to -13.4) for the cardio-renal endpoint, a risk change of -5.1% (-1.2 to -9.0) for the CV endpoint and a non-significant risk change of -19.9% (-42.1 to +2.1) for the renal endpoint. Conclusions PRE score estimations suggested that aliskiren has only a marginal additive protective effect on cardio-renal endpoints. These predictions were validated by the results of the ALTITUDE trial, confirming the potential of the PRE score to prospectively predict drug efficacy on cardio-renal outcomes.
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