| 1. |
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| 2. |
- Connolly, S., et al.
(författare)
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Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events
- 2006
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Ingår i: American heart journal. - 1097-6744. ; 151:6, s. 1187-93
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.
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| 3. |
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| 4. |
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| 5. |
- O'Meara, E., et al.
(författare)
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Clinical correlates and consequences of anemia in a broad spectrum of patients with heart failure: results of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program
- 2006
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Ingår i: Circulation. - 1524-4539. ; 113:7, s. 986-94
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We wished to determine the prevalence of, potential mechanistic associations of, and clinical outcomes related to anemia in patients with heart failure and a broad spectrum of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: In multivariable analyses, we examined the associations between hemoglobin and baseline characteristics, laboratory variables, and outcomes in 2653 patients randomized in the CHARM Program in the United States and Canada. Anemia was equally common in patients with preserved (27%) and reduced (25%) LVEF but was more common in black and older patients. Anemia was associated with ethnicity, diabetes, low body mass index, higher systolic and lower diastolic blood pressure, and recent heart failure hospitalization. More than 50% of anemic patients had a glomerular filtration rate <60 mL.min(-1).1.73 m(-2) compared with <30% of nonanemic patients. Despite an inverse relationship between hemoglobin and LVEF, anemia was associated with an increased risk of death and hospitalization, a relationship observed in patients with both reduced and preserved LVEF. There were 133 versus 69 deaths and 527 versus 352 hospitalizations per 1000 patient-years of follow-up in anemic versus nonanemic patients (both P<0.001). The effect of candesartan in reducing outcomes was independent of hemoglobin. CONCLUSIONS: Anemia was common in heart failure, regardless of LVEF. Lower hemoglobin was associated with higher LVEF yet was an independent predictor of adverse mortality and morbidity outcomes. In heart failure, the causes of anemia and the associations between anemia and outcomes are probably multiple and complex.
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| 6. |
- Desai, A. S., et al.
(författare)
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Incidence and predictors of hyperkalemia in patients with heart failure: an analysis of the CHARM Program
- 2007
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Ingår i: J Am Coll Cardiol. - 1558-3597. ; 50:20, s. 1959-66
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We explored the incidence and predictors of hyperkalemia in a broad population of heart failure patients. BACKGROUND: When used in optimal doses to treat patients with heart failure, renin-angiotensin-aldosterone system (RAAS) inhibitors improve clinical outcomes but can cause hyperkalemia. METHODS: Participants in the CHARM (Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity) (n = 7,599) Program were randomized to standard heart failure therapy plus candesartan or placebo, titrated as tolerated to a target of 32 mg once daily with recommended monitoring of serum potassium and creatinine. We assessed the incidence and predictors of hyperkalemia associated with dose reduction, study drug discontinuation, hospitalization, or death over the median 3.2 years of follow-up. RESULTS: Independent of treatment assignment, the risk of hyperkalemia increased with age > or =75 years, male gender, diabetes, creatinine > or =2.0 mg/dl, K+ > or =5.0 mmol/l, and background use of angiotensin-converting enzyme inhibitors or spironolactone. Candesartan increased the rate of aggregate hyperkalemia from 1.8% to 5.2% (difference 3.4%, p < 0.0001) and serious hyperkalemia (associated with death or hospitalization) from 1.1% to 1.8% (difference 0.7%, p < 0.001), with hyperkalemia associated with death reported in 2 (0.05%) candesartan patients and 1 (0.03%) placebo patient. The benefit of candesartan in reducing cardiovascular death or heart failure hospitalization (relative risk reduction 16%, p < 0.0001) was uniform in these subgroups, as was the incremental risk of hyperkalemia. CONCLUSIONS: The risk of hyperkalemia is increased in symptomatic heart failure patients with advanced age, male gender, baseline hyperkalemia, renal failure, diabetes, or combined RAAS blockade. Although these groups derive incremental clinical benefit from candesartan, careful surveillance of serum potassium and creatinine is particularly important.
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| 7. |
- Kenchaiah, S., et al.
(författare)
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Body mass index and prognosis in patients with chronic heart failure: insights from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program
- 2007
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Ingår i: Circulation. - 1524-4539. ; 116:6, s. 627-36
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In individuals without known cardiovascular disease, elevated body mass index (BMI) (weight/height2) is associated with an increased risk of death. However, in patients with certain specific chronic diseases, including heart failure, low BMI has been associated with increased mortality. METHODS AND RESULTS: We examined the influence of BMI on prognosis using Cox proportional hazards models in 7599 patients (mean age, 65 years; 35% women) with symptomatic heart failure (New York Heart Association class II to IV) and a broad spectrum of left ventricular ejection fractions (mean, 39%) in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. During a median follow-up of 37.7 months, 1831 patients died. After adjustment for potential confounders, compared with patients with BMI between 30 and 34.9, patients in lower BMI categories had a graded increase in the risk of death. The hazard ratios (95% confidence intervals) were 1.22 (1.06 to 1.41), 1.46 (1.24 to 1.71), and 1.69 (1.43 to 2.01) among those with BMI of 25 to 29.9, 22.5 to 24.9, and < 22.5, respectively. The increase in risk of death among patients with BMI > or = 35 was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.95 to 1.43). The association between BMI and mortality was not altered by age, smoking status, or left ventricular ejection fraction (P for interaction >0.20). However, lower BMI was associated with a greater risk of all-cause death in patients without edema but not in patients with edema (P for interaction <0.0001). Lower BMI was associated with a greater risk of cardiovascular death and noncardiovascular death. Baseline BMI did not influence the risk of hospitalization for worsening heart failure or due to all causes. CONCLUSIONS: In patients with symptomatic heart failure and either reduced or preserved left ventricular systolic function, underweight or low BMI was associated with increased mortality, primarily in patients without evidence of fluid overload (edema).
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| 8. |
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| 9. |
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| 10. |
- O'Meara, E., et al.
(författare)
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Sex differences in clinical characteristics and prognosis in a broad spectrum of patients with heart failure: results of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program
- 2007
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Ingår i: Circulation. - 1524-4539. ; 115:24, s. 3111-20
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We wished to test previous hypotheses that sex-related differences in mortality and morbidity may be due to differences in the cause of heart failure or in left ventricular ejection fraction (LVEF) by comparing fatal and nonfatal outcomes in women and men with heart failure and a broad spectrum of left ventricular ejection fraction. METHODS AND RESULTS: We compared outcomes in 2400 women and 5199 men randomized in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program using multivariable regression analyses. A total of 1188 women (50%) had a low LVEF (< or = 0.40), and 1212 had a preserved LVEF (> 0.40). Among the men, 3388 (65%) had a low LVEF, and 1811 had a preserved LVEF. A total of 1216 women (51%) and 3465 men (67%) had an ischemic cause of their heart failure. All-cause mortality was 21.5% in women and 25.3% in men (adjusted hazard ratio [HR], 0.77; 95% CI, 0.69 to 0.86; P<0.001). Fewer women (30.4%) than men (33.3%) experienced cardiovascular death or heart failure hospitalization (adjusted HR, 0.83; 95% CI, 0.76 to 0.91; P<0.001). The risks of sudden death (HR, 0.70; 95% CI, 0.58 to 0.85) and death due to worsening heart failure (HR, 0.72; 95% CI, 0.58 to 0.89) were reduced to a comparable extent. The adjusted risk of cardiovascular hospitalization was also lower in women (HR, 0.88; 95% CI, 0.82 to 0.95), mainly because of a reduced risk of heart failure hospitalization (HR, 0.87; 95% CI, 0.78 to 0.97). Women had a lower risk of death irrespective of cause of heart failure or LVEF. CONCLUSIONS: Among patients with heart failure, women have lower risks of most fatal and nonfatal outcomes that are not explained, as previously suggested, by LVEF or origin of the heart failure.
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| 11. |
- Pocock, S. J., et al.
(författare)
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Weight loss and mortality risk in patients with chronic heart failure in the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) programme
- 2008
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 29:21, s. 2641-50
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The curiosity that leanness is associated with poor survival in patients with chronic heart failure (CHF) needs further insight by investigating the impact of weight loss on prognosis in a large sample of patients across a broad spectrum of both reduced and preserved left ventricular (LV) systolic function. METHODS AND RESULTS: We investigated the change in weight over 6 months in 6933 patients in the Candesartan in Heart failure: Reduction in Mortality and morbidity (CHARM) programme, and its association with subsequent mortality (1435 deaths) over a median 32.9 months follow-up using Cox proportional hazard models to account for the impact of body mass index and other risk predictors. We then used time-updated Cox models to relate each patient's ongoing data on annual weight change to their mortality hazard. The percentage weight loss over 6 months had a highly significant monotonically increasing association with excess mortality, both for cardiovascular and for other causes of death. Patients with 5% or greater weight loss in 6 months had over a 50% increase in hazard compared with those with stable weight. Weight loss carried a particularly high risk in patients who were already lean at study entry. Findings were similar in the presence of dependent oedema, preserved or reduced LV ejection fraction, and treatment with candesartan, although weight loss was significantly less common on candesartan. The time-updated analyses revealed an even stronger link between weight loss and short-term risk of dying, i.e. risk increased more than four-fold for patients whose last recorded annual weight loss exceeded 10%. Weight gain had a more modestly increased short-term mortality risk. Weight loss accelerates in the year prior to death. CONCLUSIONS: Weight loss and leanness are important predictors of poor prognosis in CHF. Being lean and losing weight is particularly bad. The detection of weight change, and particularly weight loss, should be considered as an adverse sign prompting further evaluation.
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| 12. |
- Rosengren, Annika, 1951, et al.
(författare)
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Education and risk for acute myocardial infarction in 52 high, middle and low-income countries: INTERHEART case-control study
- 2009
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Ingår i: Heart. - 1468-201X. ; 95:24, s. 2014-22
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the effect of education and other measures of socioeconomic status (SES) on risk of acute myocardial infarction (AMI) in patients and controls from countries with diverse economic circumstances (high, middle, and low income countries). DESIGN: Case-control study. SETTING: 52 countries from all inhabited regions of the world. PARTICIPANTS: 12242 cases and 14622 controls. MAIN OUTCOME MEASURES: First non-fatal AMI. RESULTS: SES was measured using education, family income, possessions in the household and occupation. Low levels of education (< or =8 years) were more common in cases compared to controls (45.0% and 38.1%; p<0.0001). The odds ratio (OR) for low education adjusted for age, sex and region was 1.56 (95% confidence interval 1.47 to 1.66). After further adjustment for psychosocial, lifestyle, other factors and mutually for other socioeconomic factors, the OR associated with education < or =8 years was 1.31 (1.20 to 1.44) (p<0.0001). Modifiable lifestyle factors (smoking, exercise, consumption of vegetables and fruits, alcohol and abdominal obesity) explained about half of the socioeconomic gradient. Family income, numbers of possessions and non-professional occupation were only weakly or not at all independently related to AMI. In high-income countries (World Bank Classification), the risk factor adjusted OR associated with low education was 1.61 (1.33 to 1.94), whereas it was substantially lower in low-income and middle-income countries: 1.25 (1.14 to 1.37) (p for interaction 0.045). CONCLUSION: Of the SES measures we studied, low education was the marker most consistently associated with increased risk for AMI globally, most markedly in high-income countries.
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| 13. |
- Sacco, R. L., et al.
(författare)
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Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke
- 2008
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Ingår i: New England Journal of Medicine. - Boston : Massachusetts medical society. - 1533-4406 .- 0028-4793. ; 359:12, s. 1238-51
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Tidskriftsartikel (refereegranskat)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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| 14. |
- Yusuf, S., et al.
(författare)
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Telmisartan to prevent recurrent stroke and cardiovascular events
- 2008
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Ingår i: New England Journal of Medicine. - : Massachusetts medical society. - 1533-4406 .- 0028-4793. ; 359:12, s. 1225-37
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Tidskriftsartikel (refereegranskat)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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| 15. |
- Abrahamsson, Putte, 1965, et al.
(författare)
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Impact of hospitalization for acute coronary events on subsequent mortality in patients with chronic heart failure
- 2009
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Ingår i: Eur Heart J. - 1522-9645. ; 30:3, s. 338-45
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: We explored the impact of having a hospital admission for an acute coronary syndrome (ACS) on the subsequent prognosis among patients with chronic heart failure (CHF). METHODS AND RESULTS: A total of 7599 patients with CHF, New York Heart Association Classes II-IV, were randomly assigned to candesartan or placebo. We assessed the risk of death after a first ACS using time-updated Cox proportional hazard models adjusted for baseline predictors. During a mean follow-up of 3.3 years, 1174 patients experienced at least one ACS. Myocardial infarction (MI) was the first ACS in 442 subjects and unstable angina (UA) in 732. After these events, 219 (49.5%) and 167 (22.8%) patients died during follow-up. The early risk of death was more pronounced after MI: 30.2% died within 30 days compared with 3.6% after UA. After an ACS event, the risk of death declined steadily over time, although 18 months after an MI the risk was still twice that of patients without an ACS. CONCLUSION: Patients with CHF, who develop an ACS, have markedly increased subsequent mortality, particularly in the early phase after an MI.
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| 16. |
- Allen, L. A., et al.
(författare)
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Liver function abnormalities and outcome in patients with chronic heart failure: data from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program
- 2009
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Ingår i: Eur J Heart Fail. - : Wiley. - 1388-9842. ; 11:2, s. 170-7
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The prevalence and importance of liver function test (LFT) abnormalities in a large contemporary cohort of heart failure patients have not been systematically evaluated. METHODS AND RESULTS: We characterized the LFTs of 2679 patients with symptomatic chronic heart failure from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity program (CHARM). We used multivariable modelling to assess the relationships between baseline LFT values and long-term outcomes. Liver function test abnormalities were common in patients with chronic heart failure, ranging from alanine aminotransferase elevation in 3.1% of patients to low albumin in 18.3% of patients; total bilirubin was elevated in 13.0% of patients. In multivariable analysis, elevated total bilirubin was the strongest LFT predictor of adverse outcome for both the composite outcome of cardiovascular death or heart failure hospitalization (HR 1.21 per 1 SD increase, P<0.0001) and all-cause mortality (HR 1.19 per 1 SD increase, P<0.0001). Even after adjustment for other variables, elevated total bilirubin was one of the strongest independent predictors of poor prognosis (by global chi-square). CONCLUSION: Bilirubin is independently associated with morbidity and mortality. Changes in total bilirubin may offer insight into the underlying pathophysiology of chronic heart failure.
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| 17. |
- Felker, G. M., et al.
(författare)
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Red cell distribution width as a novel prognostic marker in heart failure: data from the CHARM Program and the Duke Databank
- 2007
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Ingår i: J Am Coll Cardiol. - 1558-3597. ; 50:1, s. 40-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The goal of this study was to identify potentially novel laboratory markers of risk in chronic heart failure patients. BACKGROUND: Although a variety of prognostic markers have been described in heart failure, a systematic assessment of routine laboratory values has not been reported. METHODS: All 2,679 symptomatic chronic heart failure patients from the North American CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) program had a wide range of laboratory measures performed at a core facility, enabling us to assess the relationship between routine blood tests and outcomes using a Cox proportional hazards model. We then replicated our findings in a cohort of 2,140 heart failure patients from the Duke Databank. RESULTS: Among 36 laboratory values considered in the CHARM program, higher red cell distribution width (RDW) showed the greatest association with morbidity and mortality (adjusted hazard ratio 1.17 per 1-SD increase, p < 0.001). Higher RDW was among the most powerful overall predictors, with only age and cardiomegaly showing a better independent association with outcome. This finding was replicated in the Duke Databank, in which higher RDW was strongly associated with all-cause mortality (adjusted hazard ratio 1.29 per 1 SD, p < 0.001), second only to age as a predictor of outcome. CONCLUSIONS: In 2 large contemporary heart failure populations, RDW was found to be a very strong independent predictor of morbidity and mortality. Understanding how and why this marker is associated with outcome may provide novel insights into heart failure pathophysiology.
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| 18. |
- Hawkins, N. M., et al.
(författare)
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Prevalence and prognostic impact of bundle branch block in patients with heart failure: Evidence from the CHARM programme
- 2007
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Ingår i: European journal of heart failure. - : Wiley. - 1388-9842. ; 9:5, s. 510-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bundle branch block (BBB) is a powerful independent predictor of cardiovascular mortality in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). The prognostic implications in HF with preserved systolic function (HF-PSF) are less well understood. METHODS: The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme randomised 7599 patients with symptomatic HF to receive candesartan or placebo. The primary outcome comprised cardiovascular death or HF hospitalisation. The relative risk conveyed by BBB relative to a normal electrocardiogram was examined. RESULTS: The prevalence of BBB was significantly lower in patients with preserved compared with reduced systolic function (CHARM-Preserved 14.4%, Alternative 29.6%, Added 30.5%), p<0.0001. Overall, the adjusted hazard ratio for the primary outcome was 1.48 (95% confidence interval 1.22-1.78), p<0.0001, reflecting increased risk in patients with reduced LVEF (1.72 [1.28-2.31], p=0.0003). The apparently more modest risk among patients with HF-PSF was significant in unadjusted (1.80 [1.37-2.37], p<0.0001) but not adjusted analysis (1.16 [0.88-1.54], p=0.2897). However, no formal statistical difference was observed between the two cohorts, and interpretation is limited by the unknown prevalence of left and right BBB morphologies in each. Comparing BBB presence with absence yielded qualitatively similar results. CONCLUSION: The simple clinical finding of BBB is a powerful independent predictor of worse clinical outcomes in patients with HF and reduced LVEF. It is less frequent, with a more modest predictive effect, in patients with preserved systolic function.
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| 19. |
- Hawkins, N. M., et al.
(författare)
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Prevalence and prognostic implications of electrocardiographic left ventricular hypertrophy in heart failure: evidence from the CHARM programme
- 2007
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Ingår i: Heart. - : BMJ. - 1468-201X .- 1355-6037. ; 93:1, s. 59-64
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Electrocardiographic left ventricular hypertrophy (ECG LVH) is a powerful independent predictor of cardiovascular morbidity and mortality in hypertension. OBJECTIVE: To determine the contemporary prevalence and prognostic implications of ECG LVH in a broad spectrum of patients with heart failure with and without reduced left ventricular ejection fraction (LVEF). METHODS AND OUTCOME: The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme randomised 7599 patients with symptomatic heart failure to receive candesartan or placebo. The primary outcome comprised cardiovascular death or hospital admission for worsening heart failure. The relative risk (RR) conveyed by ECG LVH compared with a normal ECG was examined in a Cox model, adjusting for as many as 31 covariates of prognostic importance. RESULTS: The prevalence of ECG LVH was similar in all three CHARM trials (Alternative, 15.4%; Added, 17.1%; Preserved, 14.7%; Overall, 15.7%) despite a more frequent history of hypertension in CHARM-Preserved. ECG LVH was an independent predictor of worse prognosis in CHARM-Overall. RR for the primary outcome was 1.27 (95% confidence interval (CI) 1.04 to 1.55, p = 0.018). The risk of secondary end points was also increased: cardiovascular death, 1.50 (95% CI 1.13 to 1.99, p = 0.005); hospitalisation due to heart failure, 1.19 (95% CI 0.94 to 1.50, p = 0.148); and composite major cardiovascular events, 1.35 (95% CI 1.12 to 1.62, p = 0.002). CONCLUSION: ECG LVH is similarly prevalent in patients with symptomatic heart failure regardless of LVEF. The simple clinical finding of ECG LVH was an independent predictor of a worse clinical outcome in a broad spectrum of patients with heart failure receiving extensive contemporary treatment. Candesartan had similar benefits in patients with and without ECG LVH.
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| 20. |
- Jackson, C. E., et al.
(författare)
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Albuminuria in chronic heart failure: prevalence and prognostic importance
- 2009
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Ingår i: Lancet. - 1474-547X. ; 374:9689, s. 543-50
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increased excretion of albumin in urine might be a marker of the various pathophysiological changes that arise in patients with heart failure. Therefore our aim was to assess the prevalence and prognostic value of a spot urinary albumin to creatinine ratio (UACR) in patients with heart failure. METHODS: UACR was measured at baseline and during follow-up of 2310 patients in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Programme. The prevalence of microalbuminuria and macroalbuminuria, and the predictive value of UACR for the primary composite outcome of each CHARM study--ie, death from cardiovascular causes or admission to hospital with worsening heart failure--and death from any cause were assessed. FINDINGS: 1349 (58%) patients had a normal UACR, 704 (30%) had microalbuminuria, and 257 (11%) had macroalbuminuria. The prevalence of increased UACR was similar in patients with reduced and preserved left ventricular ejection fractions. Patients with an increased UACR were older, had more cardiovascular comorbidity, worse renal function, and a higher prevalence of diabetes mellitus than did those with normoalbuminuria. However, a high prevalence of increased UACR was still noted among patients without diabetes, hypertension, or renal dysfunction. Elevated UACR was associated with increased risk of the composite outcome and death even after adjustment for other prognostic variables including renal function, diabetes, and haemoglobin A1c. The adjusted hazard ratio (HR) for the composite outcome in patients with microalbuminuria versus normoalbuminuria was 1.43 (95% CI 1.21-1.69; p<0.0001) and for macroalbuminuria versus normoalbuminuria was 1.75 (1.39-2.20; p<0.0001). The adjusted values for death were 1.62 (1.32-1.99; p<0.0001) for microalbuminuria versus normoalbuminuria, and 1.76 (1.32-2.35; p=0.0001) for macroalbuminuria versus normoalbuminuria. Treatment with candesartan did not reduce or prevent the development of excessive excretion of urinary albumin. INTERPRETATION: Increased UACR is a powerful and independent predictor of prognosis in heart failure. FUNDING: AstraZeneca.
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| 21. |
- Lewis, E. F., et al.
(författare)
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Characterization of health-related quality of life in heart failure patients with preserved versus low ejection fraction in CHARM
- 2007
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Ingår i: European journal of heart failure. - : Wiley. - 1388-9842. ; 9:1, s. 83-91
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Limited comparative studies assessing the health-related quality of life (HRQL) in heart failure (HF) patients with preserved vs. low ejection fraction (LVEF) have been disparate. AIMS: The aims of this study were a) to characterize HRQL in a large population of HF patients with preserved and low LVEF and b) to determine the factors associated with worse HRQL. METHODS: Patients with symptomatic HF (NYHA Class II-IV) enrolled in the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) HRQL study completed the Minnesota Living with Heart Failure questionnaire at randomization. Patients were stratified into 2 HF cohorts: preserved LVEF (>40%) and low LVEF (
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| 22. |
- McMurray, J. J., et al.
(författare)
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Relationship of dose of background angiotensin-converting enzyme inhibitor to the benefits of candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial
- 2006
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Ingår i: American heart journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 151:5, s. 985-91
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Whether an angiotensin receptor blocker is of benefit when added to a full dose of angiotensin-converting enzyme (ACE) inhibitor in heart failure (HF) is uncertain. METHODS: The effect of candesartan, compared with placebo, in 2548 patients randomized in the CHARM-Added trial was analyzed according to (i) ACE inhibitor dose at baseline, (ii) ACE inhibitor dose during follow-up, and (iii) combination treatment with ACE inhibitor and beta-blocker at baseline. The main outcome was the composite of cardiovascular death or HF hospitalization. RESULTS: The benefit of candesartan was not modified by the dose of ACE inhibitor. In all patients (n = 2548), the candesartan/placebo hazard ratio (HR) for the primary outcome was 0.85 (95% CI 0.75-0.96). In patients taking a guideline recommended dose of ACE inhibitor at baseline (n = 1291), this HR was 0.79 (95% CI 0.67-0.95; interaction P value .26). In patients taking a Food and Drug Administration-designated maximum dose of ACE inhibitor (n = 529), this HR was 0.75 (95% CI 0.57-0.98; interaction P value .29). The benefit of candesartan was preserved in patients taking beta-blockers in addition to a higher dose of ACE inhibitor and in patients maintaining a high dose of ACE inhibitor throughout follow-up. CONCLUSIONS: These clinical findings support the pharmacologic evidence that ACE inhibitors and angiotensin receptor blockers have distinct mechanisms of action and show that their combined use improves outcomes in patients with HF more than an evidence-based dose of ACE inhibitor alone.
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| 23. |
- Meredith, P. A., et al.
(författare)
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Clinical outcomes according to baseline blood pressure in patients with a low ejection fraction in the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) Program
- 2008
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 1558-3597 .- 0735-1097. ; 52:24, s. 2000-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study sought to investigate the efficacy and tolerability of candesartan, according to baseline blood pressure (BP), in the 4,576 patients with a low ejection fraction (EF) (or=141 mm Hg) and 4 DBP categories (or=81 mm Hg). RESULTS: Low SBP and DBP were associated with worse clinical outcomes. Baseline BP did not modify the effects of candesartan on clinical outcomes: the interaction p value between SBP category and treatment was 0.38 (0.22 for DBP category). For both placebo and candesartan, study drug discontinuation for adverse effects (especially hypotension) was highest in patients in the lowest baseline BP categories. However, the relative risk of discontinuation for hypotension, renal dysfunction, and hyperkalemia in the candesartan compared with placebo group was not increased in patients with a low baseline BP. CONCLUSIONS: In patients with low EF heart failure, the relative risks and benefits of candesartan treatment were similar in patients with a low BP compared to those with a higher BP.
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| 24. |
- O'Meara, E., et al.
(författare)
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Patient perception of the effect of treatment with candesartan in heart failure. Results of the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) programme
- 2005
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Ingår i: European journal of heart failure. - : Wiley. - 1388-9842. ; 7:4, s. 650-6
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To evaluate the effect of the angiotensin receptor blocker candesartan on patients' perception of symptoms, using the McMaster Overall treatment evaluation (OTE), in a broad spectrum of patients with chronic heart failure (CHF). METHODS AND RESULTS: Patients with symptomatic CHF, randomised in the CHARM Programme in North America (n=2498), were studied. OTE was assessed at baseline, at 6, 14 and 26 months and the patient's final or closing visit. Patient's status was classified as "improved (score +1 to +7)", "unchanged (score 0)" or "deteriorated (score -1 to -7)" at the end of the study compared to baseline. Both a simple "last visit carried forward" (LVCF) analysis and "worst rank carried forward" (WRCF) analysis (where patients who died were allocated the worst OTE score) were used. In the LVCF analysis, compared to placebo, more candesartan patients improved (37.7% versus 33.5%) and fewer worsened (10.8% versus 12.0%) in OTE (p=0.017). The WRCF analysis also showed better overall OTE scores with candesartan compared to placebo (p=0.029). There was no heterogeneity in the response to candesartan between the CHARM component trials or across four exploratory sub-groups (age, sex, NYHA class and beta-blocker). CONCLUSIONS: Candesartan was shown to be better than placebo, when using the McMaster OTE to measure patient perception of treatment. More patients treated with candesartan reported improvement and fewer reported deterioration. This benefit was obtained when candesartan was added to extensive background therapy and is consistent with the benefits of candesartan on NYHA class, hospital admission for worsening heart failure and mortality.
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| 25. |
- Pocock, S. J., et al.
(författare)
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Predictors of mortality and morbidity in patients with chronic heart failure
- 2006
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Ingår i: Eur Heart J. - 0195-668X .- 0195-668X. ; 27:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: We aimed to develop prognostic models for patients with chronic heart failure (CHF). METHODS AND RESULTS: We evaluated data from 7599 patients in the CHARM programme with CHF with and without left ventricular systolic dysfunction. Multi-variable Cox regression models were developed using baseline candidate variables to predict all-cause mortality (n=1831 deaths) and the composite of cardiovascular (CV) death and heart failure (HF) hospitalization (n=2460 patients with events). Final models included 21 predictor variables for CV death/HF hospitalization and for death. The three most powerful predictors were older age (beginning >60 years), diabetes, and lower left ventricular ejection fraction (EF) (beginning <45%). Other independent predictors that increased risk included higher NYHA class, cardiomegaly, prior HF hospitalization, male sex, lower body mass index, and lower diastolic blood pressure. The model accurately stratified actual 2-year mortality from 2.5 to 44% for the lowest to highest deciles of predicted risk. CONCLUSION: In a large contemporary CHF population, including patients with preserved and decreased left ventricular systolic function, routine clinical variables can discriminate risk regardless of EF. Diabetes was found to be a surprisingly strong independent predictor. These models can stratify risk and help define how patient characteristics relate to clinical course.
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| 26. |
- Solomon, S. D., et al.
(författare)
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Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients
- 2005
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Ingår i: Circulation. - 1524-4539. ; 112:24, s. 3738-44
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Left ventricular function is a principal determinant of cardiovascular risk in patients with heart failure. The growing number of patients with preserved systolic function heart failure underscores the importance of understanding the relationship between ejection fraction and risk. METHODS AND RESULTS: We studied 7599 patients with a broad spectrum of symptomatic heart failure enrolled in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Program. All patients were randomized to candesartan at a target dose of 32 mg once daily or matching placebo and followed up for a median of 38 months. We related left ventricular ejection fraction (LVEF), measured before randomization at the sites, to cardiovascular outcomes and causes of death. Mean LVEF in patients enrolled in CHARM was 38.8+/-14.9% (median LVEF 36%). Patients with lower LVEF tended to have higher baseline New York Heart Association class. The hazard ratio for all-cause mortality increased by 39% for every 10% reduction in ejection fraction below 45% (hazard ratio 1.39, 95% CI 1.32 to 1.46), with adjustment for baseline covariates. All-cause mortality, cardiovascular death, and all components of cardiovascular death declined with increasing ejection fraction until an ejection fraction of 45%, after which the risk of these outcomes remained relatively stable with increasing LVEF. The absolute change in rate per 100 patient-years for each 10% reduction in LVEF was greatest for sudden death and heart failure-related death. The effect of candesartan in reducing cardiovascular outcomes was consistent across LVEF categories. CONCLUSIONS: LVEF is a powerful predictor of cardiovascular outcome in heart failure patients across a broad spectrum of ventricular function. Nevertheless, once elevated to a range above 45%, ejection fraction does not further contribute to assessment of cardiovascular risk in heart failure patients.
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| 27. |
- Solomon, S. D., et al.
(författare)
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Influence of nonfatal hospitalization for heart failure on subsequent mortality in patients with chronic heart failure
- 2007
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Ingår i: Circulation. - 1524-4539. ; 116:13, s. 1482-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with chronic heart failure (HF) are at increased risk of both fatal and nonfatal major adverse cardiovascular events. We used data from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) trials to assess the influence of nonfatal hospitalizations for HF on subsequent mortality rates in a broad spectrum of HF patients. METHODS AND RESULTS: In the present study, 7599 patients with New York Heart Association class II to IV HF and reduced or preserved left ventricular ejection fraction were randomized to placebo or candesartan. We assessed the risk of death after discharge from a first hospitalization for HF using time-updated Cox proportional-hazards models on 7572 patients for whom discharge data were available. Of 7572 patients, 1455 (19%) had at least 1 HF hospitalization, and 586 of 1819 deaths occurred after discharge from an HF hospitalization. The mortality rate was increased after HF hospitalizations, even after adjustment for baseline predictors of death (hazard ratio, 3.15; 95% confidence interval, 2.83 to 3.50). Longer duration of HF hospitalization enhanced the risk of dying, as did repeat HF hospitalizations. Moreover, risk of death was highest within a month of discharge and then declined progressively over time, particularly for death resulting from HF progression and for sudden cardiac death. We observed a similar pattern of risk associated with all-cause hospitalization, although the magnitude was less than that with HF hospitalization. CONCLUSIONS: In patients with chronic HF, the risk of death is greatest in the early period after discharge after a hospitalization for HF and is directly related to the duration and frequency of HF hospitalizations. These findings suggest a role for increased surveillance in the early postdischarge period of greatest vulnerability after an HF admission.
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| 28. |
- Demers, C., et al.
(författare)
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Impact of candesartan on nonfatal myocardial infarction and cardiovascular death in patients with heart failure
- 2005
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Ingår i: JAMA. - 1538-3598. ; 294:14, s. 1794-8
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Forskningsöversikt (refereegranskat)abstract
- CONTEXT: Angiotensin-converting enzyme (ACE) inhibitors reduce the risk of myocardial infarction (MI), but it is not known whether angiotensin receptor blockers have the same effect. OBJECTIVE: To assess the impact of the angiotensin receptor blocker candesartan on MI and other coronary events in patients with heart failure. DESIGN, SETTING, AND PARTICIPANTS: The Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program, a randomized, placebo-controlled study enrolling patients (mean age, 66 [SD, 11] years) with New York Heart Association class II to IV symptoms who were randomly allocated to receive candesartan (target dose, 32 mg once daily) or matching placebo given in addition to optimal therapy for heart failure. Patients were enrolled from March 1999 through March 2001. Of 7599 patients allocated, 4004 (53%) had experienced a previous MI, and 1808 (24%) currently had angina. At baseline, 3125 (41%) were receiving an ACE inhibitor; 4203 (55%), a beta-blocker; 3153 (42%), a lipid-lowering drug; 4246 (56%), aspirin; and 6286 (83%), a diuretic. MAIN OUTCOME MEASURE: The primary outcome of the present analysis was the composite of cardiovascular death or nonfatal MI in patients with heart failure receiving candesartan or placebo. RESULTS: During the median follow-up of 37.7 months, the primary outcome of cardiovascular death or nonfatal MI was significantly reduced in the candesartan group (775 patients [20.4%]) vs the placebo group (868 [22.9%]) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96; P = .004; number needed to treat [NNT], 40). Nonfatal MI alone was also significantly reduced in the candesartan group (116 [3.1%]) vs the placebo group (148 [3.9%]) (HR, 0.77; 95% CI, 0.60-0.98; P = .03; NNT, 118). The secondary outcome of fatal MI, sudden death, or nonfatal MI was significantly reduced with candesartan (459 [12.1%]) vs placebo (522 [13.8%]) (HR, 0.86; 95% CI, 0.75-0.97; P = .02; NNT, 59). Risk reductions in cardiovascular death or nonfatal MI were similar across predetermined subgroups and the component CHARM trials. There was no impact on hospitalizations for unstable angina or coronary revascularization procedures with candesartan. CONCLUSION: In patients with heart failure, candesartan significantly reduces the risk of the composite outcome of cardiovascular death or nonfatal MI.
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| 29. |
- Ducharme, A., et al.
(författare)
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Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program
- 2006
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Ingår i: American heart journal. - 1097-6744. ; 152:1, s. 86-92
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atrial fibrillation (AF) is frequent in patients with chronic heart failure (CHF). Experimental and small patient studies have demonstrated that blocking the renin-angiotensin-aldosterone system may prevent AF. In the CHARM program, the effects of the angiotensin receptor blocker candesartan on cardiovascular mortality and morbidity were evaluated in a broad spectrum of patients with symptomatic CHF. CHARM provided the opportunity to prospectively determine the effect of candesartan on the incidence of new AF in this CHF population. METHODS: 7601 patients with symptomatic CHF and reduced or preserved left ventricular systolic function were randomized to candesartan (target dose 32 mg once daily, mean dose 24 mg) or placebo in the 3 component trials of CHARM. The major outcomes were cardiovascular death or CHF hospitalization and all-cause mortality. The incidence of new AF was a prespecified secondary outcome. Median follow-up was 37.7 months. A conditional logistic regression model for stratified data was used. RESULTS: 6379 patients (83.9%) did not have AF on their baseline electrocardiogram. Of these, 392 (6.15%) developed AF during follow-up, 177 (5.55%) in the candesartan group and 215 (6.74%) in the placebo group (odds ratio 0.812, 95% CI 0.662-0.998, P = .048). After adjustment for baseline covariates, the odds ratio was 0.802 (95% CI 0.650-0.990, P = .039). There was no heterogeneity of the effects of candesartan in preventing AF between the 3 component trials (P = .57). CONCLUSIONS: Treatment with the angiotensin receptor blocker candesartan reduced the incidence of AF in a large, broadly-based, population of patients with symptomatic CHF.
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| 30. |
- Hillege, H. L., et al.
(författare)
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Renal function as a predictor of outcome in a broad spectrum of patients with heart failure
- 2006
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Ingår i: Circulation. - 1524-4539 .- 0009-7322. ; 113:5, s. 671-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Decreased renal function has been found to be an independent risk factor for cardiovascular outcomes in patients with chronic heart failure (CHF) with markedly reduced left ventricular ejection fraction (LVEF). The aim of this analysis was to evaluate the prognostic importance of renal function in a broader spectrum of patients with CHF. METHODS AND RESULTS: The Candesartan in Heart Failure:Assessment of Reduction in Mortality and Morbidity (CHARM) program consisted of three component trials that enrolled patients with symptomatic CHF, based on use of ACE inhibitors and reduced (< or =40%) or preserved LVEF (>40%). Entry baseline creatinine was required to be below 3.0 mg/dL (265 micromol/L). Routine baseline serum creatinine assessments were done in 2680 North American patients. An analysis of the estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease equation and LVEF on risk of cardiovascular death or hospitalization for heart failure, as well as on all-cause mortality, was conducted on these 2680 patients. The proportion of patients with eGFR <60 mL/min per 1.73 m2 was 36.0%; 42.6% for CHARM-Alternative, 33.0% for CHARM-Added, and 34.7% for CHARM-Preserved. During the median follow-up of 34.4 months (total 6493 person-years), the primary outcome of cardiovascular death or hospital admission for worsening CHF occurred in 950 of 2680 subjects. Both reduced eGFR and lower LVEF were found to be significant independent predictors of worse outcome after adjustment for major confounding baseline clinical characteristics. The risk for cardiovascular death or hospitalization for worsening CHF as well as the risk for all-cause mortality increased significantly below an eGFR of 60 mL/min per 1.73 m2 (adjusted hazard ratio, 1.54 for 45 to 60 mL/min per 1.73 m2 and 1.86 for <45 mL/min per 1.73 m2 for the primary outcome, both P<0.001, and hazard ratio of 1.50, P=0.006, and 1.91, P=0.001, respectively, for all-cause mortality). The prognostic value of eGFR was not significantly different among the three component trials. There was no significant interaction between renal function, the effect of candesartan, and clinical outcome. CONCLUSIONS: Impaired renal function is independently associated with heightened risk for death, cardiovascular death, and hospitalization for heart failure in patients with CHF with both preserved as well as reduced LVEF. There was no evidence that the beneficial effect of candesartan was modified by baseline eGFR.
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| 31. |
- McMurray, J. J., et al.
(författare)
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Resource utilization and costs in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme
- 2006
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 27:12, s. 1447-58
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: More treatments are needed to improve clinical outcomes in chronic heart failure (HF). It is, however, important that treatments for a condition as common as HF are affordable. We have carried out a prospective economic analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. METHODS AND RESULTS: Patients with NYHA class II-IV HF and LVEF < or =0.40 were randomized to CHARM-Alternative if intolerant of an ACE-inhibitor or to CHARM-Added if taking an ACE-inhibitor. Patients with a LVEF >0.40 were randomized in CHARM-Preserved. Each trial compared the effect of candesartan to placebo on the primary outcome of cardiovascular death or HF hospitalization. Detailed information was prospectively collected on hospital admissions, procedures/operations and drugs. A cost-consequence analysis was performed for France, Germany and the UK for CHARM-Overall and a cost-effectiveness analysis for the low LVEF trials. The cost of candesartan was substantially offset by a reduction in hospital admissions, especially for HF. In the cost-consequence analysis, candesartan was cost-saving in most scenarios for CHARM-Alternative and Added but the marginal annual net cost per patient was upto 372 euros per year in CHARM-Preserved, in which candesartan did not reduce the primary outcome significantly. In the cost-effectiveness analysis of patients with a LVEF < or = 0.40, candesartan was cost-saving in some scenarios and in the others the maximum cost per life year gained was 3881 euros. CONCLUSION: Candesartan improves functional class, reduces the risk of hospital admission, and increases survival in patients with a HF and a LVEF < or =0.40 at an acceptable cost.
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| 32. |
- Olsson, L. G., et al.
(författare)
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Atrial fibrillation and risk of clinical events in chronic heart failure with and without left ventricular systolic dysfunction: results from the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program
- 2006
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Ingår i: Journal of the American College of Cardiology. - 1558-3597. ; 47:10, s. 1997-2004
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We assessed the risk of adverse cardiovascular (CV) outcomes associated with atrial fibrillation (AF) in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program, which enrolled patients with chronic heart failure (CHF) and a broad range of ejection fractions (EFs). BACKGROUND: Atrial fibrillation is associated with an increased risk of adverse CV outcomes in patients with CHF and reduced EF. The risk of AF in patients with CHF and preserved left ventricular ejection fraction (PEF) is unknown. METHODS: A total of 7,599 patients with symptomatic CHF were randomized to candesartan or placebo. Patients were divided by baseline EF (< or =40% or >40%) in low or preserved EF groups. Major outcomes were cardiovascular death or hospitalization for worsening heart failure, and all-cause mortality. Median follow-up was 37.7 months. RESULTS: A total of 670 (17%) patients in the low EF group and 478 (19%) in the PEF group had AF at baseline. Atrial fibrillation predicted a high risk of cardiovascular morbidity and mortality regardless of baseline EF. Patients with AF and low EF had the highest absolute risk for adverse CV outcomes. However, AF was associated with greater relative increased risk of the major outcomes in patients with PEF than in patients with low EF: hazard ratio 1.72 (95% confidence interval [CI] 1.45 to 2.06) versus 1.29 (95% CI 1.14 to 1.46), respectively. The same was true for the risk of all-cause mortality. Candesartan was associated with similar treatment effects regardless of baseline rhythm. CONCLUSIONS: Atrial fibrillation is associated with an increased risk of CV outcomes in patients with CHF and either reduced EF or PEF. Candesartan improved outcomes similarly regardless of baseline rhythm.
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| 33. |
- Preiss, D., et al.
(författare)
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Predictors of development of diabetes in patients with chronic heart failure in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program
- 2009
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 32:5, s. 915-20
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The purpose of this study was to identify predictors of incident diabetes during follow-up of nondiabetic patients with chronic heart failure (CHF) in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program. RESEARCH DESIGN AND METHODS: A total of 1,620 nondiabetic patients had full baseline datasets. We compared baseline demographic, medication, and laboratory data for patients who did or did not develop diabetes and conducted logistic regression and receiver operator characteristic curve analyses. RESULTS: Over a median period of 2.8 years, 126 of the 1,620 patients (7.8%) developed diabetes. In multiple logistic regression analysis, the following baseline characteristics were independently associated with incident diabetes in decreasing order of significance by stepwise selection: higher A1C (odds ratio [OR] 1.78 per 1 SD increase; P < 0.0001), higher BMI (OR 1.64 per 1 SD increase; P < 0.0001), lipid-lowering therapy (OR 2.05; P = 0.0005), lower serum creatinine concentration (OR 0.68 per 1 SD increase; P = 0.0018), diuretic therapy (OR 4.81; P = 0.003), digoxin therapy (OR 1.65; P = 0.022), higher serum alanine aminotransferase concentration (OR 1.15 per 1 SD increase; P = 0.027), and lower age (OR 0.81 per 1 SD increase; P = 0.048). Using receiver operating characteristic curve analysis, A1C and BMI yielded areas under the curve of 0.723 and 0.712, respectively, increasing to 0.788 when combined. Addition of other variables independently associated with diabetes risk minimally improved prediction of diabetes. CONCLUSIONS: In nondiabetic patients with CHF in CHARM, A1C and BMI were the strongest predictors of the development of diabetes. Other minor predictors in part reflected CHF severity or drug-associated diabetes risk. Identifying patients with CHF at risk of diabetes through simple criteria appears possible and could enable targeted preventative measures.
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| 34. |
- Granger, B. B., et al.
(författare)
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Adherence to candesartan and placebo and outcomes in chronic heart failure in the CHARM programme: double-blind, randomised, controlled clinical trial
- 2005
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Ingår i: Lancet. - 1474-547X. ; 366:9502, s. 2005-11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic heart failure (CHF) is an important cause of hospital admission and death. Poor adherence to medication is common in some chronic illnesses and might reduce the population effectiveness of proven treatments. Because little is known about adherence in patients with CHF and about the consequences of non-adherence, we assessed the association between adherence and clinical outcome in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) programme. METHODS: CHARM was a double-blind, randomised, controlled clinical trial, comparing the effects of the angiotensin receptor blocker candesartan with placebo in 7599 patients with CHF. Median follow-up was 38 months. The proportion of time patients took more than 80% of their study medication was defined as good adherence and 80% or less as poor adherence. We used a Cox proportional hazards regression model, with adherence as a time-dependent covariate in the model, to examine the association between adherence and mortality in the candesartan and placebo groups. FINDINGS: We excluded 187 patients because of missing information on adherence. In the time-dependent Cox regression model, after adjustment for predictive factors (demographics, physiological and severity-of-illness variables, smoking history, and number of concomitant medications), good adherence was associated with lower all-cause mortality in all patients (hazard ratio [HR] 0.65, 95% CI 0.57-0.75, p<0.0001). The adjusted HR for good adherence was similar in the candesartan (0.66, 0.55-0.81, p<0.0001) and placebo (0.64, 0.53-0.78, p<0.0001) groups. INTERPRETATION: Good adherence to medication is associated with a lower risk of death than poor adherence in patients with CHF, irrespective of assigned treatment. This finding suggests that adherence is a marker for adherence to effective treatments other than study medications, or to other adherence behaviours that affect outcome. Understanding these factors could provide an opportunity for new interventions, including those aimed at improving adherence.
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| 35. |
- Granger, B. B., et al.
(författare)
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Adherence to medication according to sex and age in the CHARM programme
- 2009
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Ingår i: European Journal of Heart Failure. - 1879-0844. ; 11:11, s. 1092-8
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Although many patients with heart failure have incomplete adherence to prescribed medications, predisposing factors remain unclear. This analysis investigates factors associated with adherence, with particular emphasis on age and sex. METHODS AND RESULTS: A multivariable regression analysis of 7599 heart failure patients from the CHARM trial was done to evaluate factors associated with adherence. Adherence was measured as the proportion of time patients took more than 80% of study medication. The mean age was 66 years (SD 11) and 31.5% (n = 2400) were women. Women were slightly less adherent than men (87.3 vs. 89.8%, P = 0.002), even in adjusted, multivariable models (treatment, P = 0.006; placebo P = 0.004; and overall P < 0.001). However, all-cause mortality was lower in women (21.5%) than in men (25.3%) (adjusted hazard ratio, 0.77; 95% CI, 0.69-0.86; P < 0.001), but patients with a low adherence regardless of sex had a higher mortality. Age, severity of heart failure, number of medications, and smoking status were not associated with adherence. CONCLUSION: Women, particularly those <75 years of age, were less likely to be adherent in this large sample of patients with symptomatic heart failure. Understanding factors associated with adherence may provide opportunities for intervention.
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| 36. |
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Yusuf, S., et al.
(författare)
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Effects of candesartan on the development of a new diagnosis of diabetes mellitus in patients with heart failure
- 2005
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Ingår i: Circulation. - 1524-4539. ; 112:1, s. 48-53
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Diabetes is a risk factor for heart failure, and both conditions are increasing. Identifying treatments that prevent both conditions will be clinically important. We previously reported that candesartan (an angiotensin receptor blocker) reduces cardiovascular mortality and heart failure hospitalizations in heart failure patients (CHARM: Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity Program). METHODS AND RESULTS: We assessed the impact of candesartan versus placebo on the development of diabetes, a predefined secondary outcome in a randomized, controlled, double-blind study involving 5436 of the 7601 patients with heart failure, irrespective of ejection fraction, who did not have a diagnosis of diabetes at entry into the trial. Patients received candesartan (target of 32 mg once daily) or matching placebo for 2 to 4 years. One hundred sixty-three (6.0%) individuals in the candesartan group developed diabetes, as compared with 202 (7.4%) in the placebo group (hazard ratio [HR], 0.78 with a 95% confidence interval [CI] of 0.64 to 0.96; P=0.020). The composite end point of death or diabetes occurred in 692 (25.2%) and 779 (28.6%), respectively, in the candesartan and placebo groups (HR, 0.86; 95% CI, 0.78 to 0.95; P=0.004). The results were not statistically heterogeneous in the various subgroups examined, although the apparent magnitude of benefit appeared to be smaller among those treated concomitantly with angiotensin-converting enzyme inhibitors at trial entry (HR, 0.88; 95% CI, 0.65 to 1.20) compared with those not receiving these drugs (HR, 0.71; 95% CI, 0.53 to 0.93; P for heterogeneity, 0.28). CONCLUSIONS: The angiotensin receptor blocker candesartan appears to prevent diabetes in heart failure patients, suggesting that the renin-angiotensin axis is implicated in glucose regulation.
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