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Mortality and morbi...
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Young, J. B.
(författare)
Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials
- Artikel/kapitelEngelska2004
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LIBRIS-ID:oai:gup.ub.gu.se/52249
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https://gup.ub.gu.se/publication/52249URI
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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BACKGROUND: Patients with symptomatic chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF) have a high risk of death and hospitalization for CHF deterioration despite therapies with angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and even an aldosterone antagonist. To determine whether the angiotensin-receptor blocker (ARB) candesartan decreases cardiovascular mortality, morbidity, and all-cause mortality in patients with CHF and depressed LVEF, a prespecified analysis of the combined Candesartan in Heart Failure Assessment of Reduction in Mortality and morbidity (CHARM) low LVEF trials was performed. CHARM is a randomized, double-blind, placebo-controlled, multicenter, international trial program. METHODS AND RESULTS: New York Heart Association (NYHA) class II through IV CHF patients with an LVEF of < or =40% were randomized to candesartan or placebo in 2 complementary parallel trials (CHARM-Alternative, for patients who cannot tolerate ACE inhibitors, and CHARM-Added, for patients who were receiving ACE inhibitors). Mortality and morbidity were determined in 4576 low LVEF patients (2289 candesartan and 2287 placebo), titrated as tolerated to a target dose of 32 mg once daily, and observed for 2 to 4 years (median, 40 months). The primary outcome (time to first event by intention to treat) was cardiovascular death or CHF hospitalization for each trial, with all-cause mortality a secondary end point in the pooled analysis of the low LVEF trials. Of the patients in the candesartan group, 817 (35.7%) experienced cardiovascular death or a CHF hospitalization as compared with 944 (41.3%) in the placebo group (HR 0.82; 95% CI 0.74 to 0.90; P<0.001) with reduced risk for both cardiovascular deaths (521 [22.8%] versus 599 [26.2%]; HR 0.84 [95% CI 0.75 to 0.95]; P=0.005) and CHF hospitalizations (516 [22.5%] versus 642 [28.1%]; HR 0.76 [95% CI 0.68 to 0.85]; P<0.001). It is important to note that all-cause mortality also was significantly reduced by candesartan (642 [28.0%] versus 708 [31.0%]; HR 0.88 [95% CI 0.79 to 0.98]; P=0.018). No significant heterogeneity for the beneficial effects of candesartan was found across prespecified and subsequently identified subgroups including treatment with ACE inhibitors, beta-blockers, an aldosterone antagonist, or their combinations. The study drug was discontinued because of adverse effects by 23.1% of patients in the candesartan group and 18.8% in the placebo group; the reasons included increased creatinine (7.1% versus 3.5%), hypotension (4.2% versus 2.1%), and hyperkalemia (2.8% versus 0.5%), respectively (all P<0.001). CONCLUSIONS: Candesartan significantly reduces all-cause mortality, cardiovascular death, and heart failure hospitalizations in patients with CHF and LVEF < or =40% when added to standard therapies including ACE inhibitors, beta-blockers, and an aldosterone antagonist. Routine monitoring of blood pressure, serum creatinine, and serum potassium is warranted.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Dunlap, M. E.
(författare)
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Pfeffer, M. A.
(författare)
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Probstfield, J. L.
(författare)
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Cohen-Solal, A.
(författare)
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Dietz, R.
(författare)
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Granger, C. B.
(författare)
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Hradec, J.
(författare)
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Kuch, J.
(författare)
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McKelvie, R. S.
(författare)
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McMurray, J. J.
(författare)
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Michelson, E. L.
(författare)
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Olofsson, B.
(författare)
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Ostergren, J.
(författare)
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Held, P.
(författare)
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Solomon, S. D.
(författare)
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Yusuf, S.
(författare)
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Swedberg, Karl,1944Gothenburg University,Göteborgs universitet,Hjärt-kärlinstitutionen,Cardiovascular Institute(Swepub:gu)xsweka
(författare)
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Göteborgs universitetHjärt-kärlinstitutionen
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Circulation110:17, s. 2618-261524-4539
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Young, J. B.
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Dunlap, M. E.
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Pfeffer, M. A.
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Probstfield, J. ...
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Cohen-Solal, A.
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Dietz, R.
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visa fler...
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Granger, C. B.
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Hradec, J.
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Kuch, J.
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McKelvie, R. S.
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McMurray, J. J.
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Michelson, E. L.
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Olofsson, B.
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Ostergren, J.
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Held, P.
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Solomon, S. D.
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Yusuf, S.
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Swedberg, Karl, ...
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Circulation
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