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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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- Kjeldsen, Sverre E, et al.
(författare)
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Predictors of cardiovascular events in patients with hypertension and left ventricular hypertrophy : the losartan inventervention for endpoint reduction in hypertension study
- 2009
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Ingår i: Blood Pressure. - 0803-7051 .- 1651-1999. ; 18:6, s. 348-361
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Tidskriftsartikel (refereegranskat)abstract
- Objective. We assessed readily available patient characteristics, including albuminuria (not included in traditional cardiovascular risk scores), as predictors of cardiovascular events in hypertension with left ventricular hypertrophy (LVH) and developed risk algorithms/scores for outcomes. Methods. The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study compared effects of losartan-based versus atenolol-based therapy on cardiovascular events in 9193 patients with hypertension and LVH. Univariate and multivariate analyses identified baseline variables with significant impact on development of the primary composite endpoint (cardiovascular death, stroke and myocardial infarction) and its components. Multivariate analysis used a Cox regression model with stepwise selection process. Risk scores were developed from coefficients of risk factors from the multivariate analysis, validated internally using naïve and jack-knife procedures, checked for discrimination and calibration, and compared with Framingham coronary heart disease and other risk scores. Results. LIFE risk scores showed increasing endpoint rates with increasing quintile (first to fifth quintile, composite endpoint 2.8–26.7%, cardiovascular death 0.5–14.4%, stroke 1.2–11.3%, myocardial infarction 1.4–8.1%) and were confirmed with a jack-knife approach that adjusts for potentially optimistic bias. The Framingham coronary heart disease and other risk scores overestimated risk in lower risk patients and underestimated risk in higher risk patients, except for myocardial infarction. Conclusion. A number of patient characteristics predicted cardiovascular events in patients with hypertension and LVH. Risk scores developed from these patient characteristics, including albuminuria, strongly predicted outcomes and may improve risk assessment of patients with hypertension and LVH and planning of clinical trials.
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- Olsen, Michael H., et al.
(författare)
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Changes in subclinical organ damage vs. in Framingham risk score for assessing cardiovascular risk reduction during continued antihypertensive treatment : a LIFE substudy
- 2011
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 29:5, s. 997-1004
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate whether in-treatment measurements of subclinical organ damage (SOD) assessed by elevated urine albumin/creatinine ratio (UACR) or electrocardiographic left ventricular hypertrophy improved the prediction of the composite cardiovascular endpoint of cardiovascular death, nonfatal myocardial infarction and stroke beyond in-treatment Framingham risk score (FRS).Methods: Excluding patients with a composite cardiovascular endpoint within the first year of treatment, 598 endpoints occurred in 6460 patients from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study with baseline and 1 year values for UACR, left ventricular hypertrophy by electrocardiography and FRS available.Results: Using Cox-regression analyses, FRS1year [hazard ratio = 1.006 (0.98-1.04)] did not predict the endpoint independently of history of cardiovascular disease [hazard ratio = 1.76 (1.49-2.08)], FRSbaseline [hazard ratio = 1.07 (1.04-1.11)], UACR(baseline) [hazard ratio = 1.15 (1.07-1.23), all three P < 0.001], Sokolow-Lyon(baseline) [hazard ratio = 1.01 (1.006-1.02), P < 0.01] and treatment allocation, whereas Cornell product(1yea)r [hazard ratio = 1.01 (1.006-1.02), P < 0.001] and to some degree UACR(1year) [hazard ratio = 1.05 (0.99-1.10), P = 0.09] predicted the endpoint independently of history of cardiovascular disease [hazard ratio = 1.71 (1.44-2.02)], FRSbaseline [hazard ratio = 1.08 (1.06-1.10)], Sokolow-Lyon(baseline) [hazard ratio = 1.01 (1.007-1.02), both P < 0.001], UACR(baseline) [hazard ratio = 1.11 (1.03-1.20), P < 0.01] and treatment allocation decreasing -2 Log likelihood significantly (P < 0.01).Presence of left ventricular hypertrophy by Cornell product1year or UACR(1year) at least 1 mmol/l [hazard ratio = 1.40 (1.15-1.70), P = 0.001] but not FRS1year above the median baseline value of 20 [hazard ratio = 1.22 (0.94-1.57), not significant] was associated with higher risk of subsequent endpoint after adjustment for history of cardiovascular disease [hazard ratio = 1.82 (1.54-2.15)], FRSbaseline at least 20 [hazard ratio = 1.67 (1.30-2.16)], left ventricular hypertrophy by Sokolow-Lyonbaseline or UACR(baseline) at least 1 mmol/l [hazard ratio = 1.61 (1.33-1.94), all P < 0.001] and treatment allocation [hazard ratio = 0.93 (0.79-1.09), not significant]. In contrast to FRS1year at least 20 decreased, SOD1year decreased -2Log likelihood significantly (P < 0.01).Conclusion: Cornell product(1year) and UACR(1year) improved in contrast to FRS1year risk prediction based on FRSbaseline, Sokolow-Lyon(baseline) and UACR(baseline) significantly in LIFE patients during antihypertensive treatment.
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