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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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| 4. |
- Vishram, Julie K.K., et al.
(författare)
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Blood pressure variability predicts cardiovascular events independently of traditional cardiovascular risk factors and target organ damage : a LIFE substudy
- 2015
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 33:12, s. 2422-2430
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Tidskriftsartikel (refereegranskat)abstract
- Background: Assessment of antihypertensive treatment is normally based on the mean value of a number of blood pressure (BP) measurements. However, it is uncertain whether high in-treatment visit-to-visit BP variability may be harmful in hypertensive patients with left ventricular hypertrophy (LVH).Methods: In 8505 patients randomized to losartan vs. atenolol-based treatment in the LIFE study, we tested whether BP variability assessed as SD and range for BP6-24months measured at 6, 12, 18 and 24 months of treatment was associated with target organ damage (TOD) defined by LVH on ECG and urine albumin/creatinine ratio at 24 months, and predicted the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction (MI) or stroke occurring after 24 months (CEP=630 events).Results: In multiple regression models adjusted for mean BP6-24months and treatment allocation, neither high BP6-24months SD nor wide range were related to TOD at 24 months, except for a weak association between Sokolow-Lyon voltage and DBP6-24months SD and range (both b=0.04, P<0.01). Independently of mean BP6-24months, treatment allocation, TOD and baseline characteristics in Cox regression models, CEP after 24 months was associated with DBP6-24months SD [hazard ratio per 1mmHg increase1.04, 95% confidence interval (95% CI) 1.01-1.06, P=0.005], range (hazard ratio 1.02, 95% CI 1.01-1.03, P=0.004), SBP6-24months SD (hazard ratio 1.01, 95% CI 0.99-1.02, P=0.07) and range (hazard ratio 1.006, 95% CI 1.001-1.01, P=0.04). Adjusted for the same factors, stroke was associated with DBP6-24months SD (hazard ratio 1.06, 95% CI 1.02-1.10, P=0.001), range (hazard ratio 1.03, 95% CI 1.01-1.04, P=0.001), SBP6-24months SD (hazard ratio 1.02, 95% CI 1.002-1.04, P=0.04) and range (hazard ratio 1.008, 95% CI 1.001-1.02, P=0.05), but MI was not.Conclusion: In LIFE patients, higher in-treatment BP6-24months variability was independently of mean BP6-24months associated with later CEP and stroke, but not with MI or TOD after 24 months.
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| 5. |
- Okin, Peter M, et al.
(författare)
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Incidence of atrial fibrillation in relation to changing heart rate over time in hypertensive patients : the LIFE study
- 2008
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Ingår i: Circulation - Arrhythmia and Electrophysiology. - 1941-3149. ; 1:5, s. 337-343
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Tidskriftsartikel (refereegranskat)abstract
- Background— Onset of atrial fibrillation (AF) has been linked to changes in autonomic tone, with increasing heart rate (HR) immediately before AF onset in some patients suggesting a possible role of acute increases in sympathetic activity in AF onset. Although losartan therapy and decreasing ECG left ventricular hypertrophy are associated with decreased AF incidence, the relationship of HR changes over time to development of AF has not been examined. Methods and Results— HR was evaluated in 8828 hypertensive patients without AF by history or on baseline ECG in the Losartan Intervention for End Point Reduction in Hypertension (LIFE) study. Patients were treated with losartan- or atenolol-based regimens and followed with serial ECGs annually which were used to determine HR and ECG left ventricular hypertrophy by Cornell product and Sokolow-Lyon voltage criteria. During mean follow-up of 4.7±1.1 years, new-onset AF occurred in 701 patients (7.9%). Patients with new AF had smaller decreases in HR to last in-treatment ECG or last ECG before AF (−2.7±13.5 versus −5.2±12.5 bpm), whether on losartan- (−0.4±13.5 versus −2.2±11.7 bpm) or atenolol-based treatment (−5.3±12.8 versus −8.3±12.6 bpm, all P<0.001). In univariate Cox analyses, higher HR on in-treatment ECGs was associated with an increased risk of new-onset AF, with a 15% greater risk of AF for every 10 bpm higher HR (95% CI 8% to 22%). In alternative analyses, persistence or development of a HR≥84 (upper quintile of baseline HR) was associated with a 46% greater risk of developing AF (95% CI 19% to 80%). After adjusting for treatment with losartan versus atenolol, baseline risk factors for AF, baseline and in-treatment systolic and diastolic pressure and the known predictive value of baseline and in-treatment ECG left ventricular hypertrophy for new AF, higher in-treatment HR remained strongly associated with new AF with a 19% higher risk for every 10 bpm higher HR (95% CI 10% to 28%) or a 61% increased rate of AF in patients with persistence or development of a HR≥84 (95% CI 27% to 104%, all P<0.001). Conclusion— Higher in-treatment HR on serial ECGs is associated with an increased likelihood of new-onset AF, independent of treatment modality, blood pressure lowering, and regression of ECG left ventricular hypertrophy in patients with essential hypertension.
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- Okin, Peter M, et al.
(författare)
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Competing effects of hypokalemia and hydrochlororothiazide treatment on regression of Cornell product left ventricular hypertrophy in hypertensive patients : implications for the development of potassium-sparing diuretics
- 2009
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 120:Suppl. 18, s. s1015-s1015
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Hydrochlorothiazide (HCTZ) treatment is associated with blood pressure reduction and regression of left ventricular hypertrophy (LVH). HCTZ is also associated with hypokalemia (hypoK), which increases blood pressure and is associated with a greater likelihood and severity of electrocardiographic (ECG) LVH. However, the competing effects of HCTZ use and concomitant hypoK on LVH regression have not been examined. Methods: Baseline and yearly Cornell product (CP) ECG LVH levels were examined in relation to hypoK (serum K 3.90, the lowest quartile) and HCTZ use in 7816 patients in the LIFE study with baseline and year-1 K levels. Patients were randomized to losartan vs atenolol-based treatment and additional HCTZ as needed. Results: Patients on HCTZ had lower serum K levels at year 1 (4.05 ± 0.38 vs 4.24 ± 0.38), year 2 (4.04 ± 0.38 vs 4.25 ± 0.38), year 3 (4.04 ± 0.39 vs 4.27 ± 0.39) and year 4 (4.05 ± 0.41 vs 4.26 ± 0.38) of the study (all p < 0.001). In 2-way analysis of covariance adjusting for age, sex, race, prior and randomized treatment, yearly body mass index, serum glucose and creatinine, and for baseline and change in diastolic and systolic pressure, hypoK was associated with less mean reduction of CP LVH whereas HCTZ use was associated with greater regression of CP LVH between baseline and years 1 to 4. Multivariate logistic regression analyses with the same covariates revealed that hypoK was associated with a statistically significant 15 to 19% lower likelihood of median (236 mm·ms) reduction in CP LVH while HCTZ use was associated with an 18 to 33% greater likelihood of CP LVH regression of 236 mm·ms between baseline and years 1 to 4. Conclusions: HCTZ therapy is independently associated with a greater likelihood and magnitude of LVH regression whereas concomitant hypoK is associated with a competing lower likelihood and magnitude of LVH regression during antihypertensive therapy. These findings suggest that hypoK may blunt regression of LVH during treatment.
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| 10. |
- Okin, Peter M., et al.
(författare)
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The relationship of electrocardiographic left ventricular hypertrophy to decreased serum potassium
- 2012
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 21:3, s. 146-152
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Tidskriftsartikel (refereegranskat)abstract
- Background. Low serum potassium (K) is associated with increased blood pressure, impaired cardiac function and renal dysfunction. Although lower serum K is associated with cardiac hypertrophy in animal models, the relationship of low serum K to the presence and severity of electrocardiographic left ventricular hypertrophy (LVH) is unclear. Methods. Baseline and yearly Cornell product LVH levels were examined in relation to low serum K (serum K <= 3.90 mEq/l, the lowest quartile of baseline K levels) in 8586 patients with baseline K levels. Patients were randomized to losartan-vs atenolol-based treatment and additional hydrochlorothiazide (HCTZ) therapy as needed. Results. After adjusting for age, sex, race, prior antihypertensive treatment, losartan vs atenolol therapy, HCTZ use, baseline diastolic and systolic pressure, body mass index, serum creatinine and urine albumin/creatinine ratio, baseline serum K <= 3.90 was associated with significantly higher mean baseline Cornell product LVH (2898 vs 2801 mm.ms, p = 0.001) and a 24% higher risk of Cornell product LVH > 2440 mm.ms at baseline (OR 1.24, 95% CI 1.11-1.38, p < 0.001). After also adjusting for baseline Cornell product and changes in diastolic and systolic pressure between baseline and each year of measurement, in-treatment serum K <= 3.90 determined yearly was associated with significantly higher mean Cornell product LVH at years 1-3 and with statistically signifi cant 16-32% increased risks of LVH by Cornell product at years 1-4. Conclusions. A low serum K is independently associated with a greater likelihood and severity of Cornell product LVH during antihypertensive therapy.
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