Aims: To determine the effects of digoxin on all-cause mortality and heart failure(HF) hospitalizations, regardless of ejection fraction, accounting for serum digoxin concentration(SDC). Methods and results: This comp...Aims: To determine the effects of digoxin on all-cause mortality and heart failure(HF) hospitalizations, regardless of ejection fraction, accounting for serum digoxin concentration(SDC). Methods and results: This comprehensive post-hoc analysis of the randomized controlled Digitalis Investigation Group trial(n=7788) focuses on 5548 patients: 1687 with SDC, drawn randomly at 1 month, and 3861 placebo patients, alive at 1 month. Overall, 33% died and 31% had HF hospitalizations during a 40-month median follow-up. Compared with placebo, SDC 0.5- 0.9 ng/mL was associated with lower mortality[29 vs. 33% placebo; adjusted hazard ratio(AHR), 0.77; 95% confidence interval(CI), 0.67- 0.89], all-cause hospitalizations(64 vs. 67% placebo; AHR, 0.85; 95% CI, 0.78- 0.92) and HF hospitalizations(23 vs. 33% placebo; AHR, 0.62; 95% CI, 0.54- 0.72). SDC ≥ 1.0 ng/mL was associated with lower HF hospitalizations(29 vs. 33% placebo; AHR, 0.68; 95% CI, 0.59- 0.79), without any effect on mortality. SDC 0.5- 0.9 reduced mortality in a wide spectrum of HF patients and had no interaction with ejection fraction >45% (P=0.834) or sex(P=0.917). Conclusions: Digoxin at SDC 0.5- 0.9 ng/mL reduces mortality and hospitalizations in all HF patients, including those with preserved systolic function. At higher SDC, digoxin reduces HF hospitalization but has no effect on mortality or all-cause hospitalizations.展开更多
Aims: Non-potassium-sparing diuretics are commonly used in heart failure(HF). They activate the neurohormonal system,and are potentially harmful. Yet, the long-term effects of chronic diuretic use in HF are largely un...Aims: Non-potassium-sparing diuretics are commonly used in heart failure(HF). They activate the neurohormonal system,and are potentially harmful. Yet, the long-term effects of chronic diuretic use in HF are largely unknown. We retrospectively analysed the Digitalis Investigation Group(DIG) data to determine the effects of diuretics on HF outcomes. Methods and results: Propensity scores for diuretic use were calculated for each of the 7788 DIG participants using a non-parsimonious multivariable logistic regression model, and were used to match 1391(81%) no-diuretic patients with 1391 diuretic patients. Effects of diuretics on mortality and hospitalization at 40 months of median follow-up were assessed using matched Cox regression models. All-cause mortality was 21%for nodiuretic patients and 29%for diuretic patients[hazard ratio(HR) 1.31; 95%confidence interval(CI) 1.11-1.55; P=0.002]. HF hospitalizations occurred in 18%of no-diuretic patients and 23%of diuretic patients(HR 1.37; 95%CI 1.13-1.65; P=0.001). Conclusion: Chronic diuretic use was associated with increased long-term mortality and hospitalizations in a wide spectrum of ambulatory chronic systolic and diastolic HF patients. The findings of the current study challenge the wisdom of routine chronic use of diuretics in HF patients who are asymptomatic or minimally symptomatic without fluid retention, and are on complete neurohormonal blockade. These findings, based on a non-randomized design, need to be further studied in randomized trials.展开更多
文摘Aims: To determine the effects of digoxin on all-cause mortality and heart failure(HF) hospitalizations, regardless of ejection fraction, accounting for serum digoxin concentration(SDC). Methods and results: This comprehensive post-hoc analysis of the randomized controlled Digitalis Investigation Group trial(n=7788) focuses on 5548 patients: 1687 with SDC, drawn randomly at 1 month, and 3861 placebo patients, alive at 1 month. Overall, 33% died and 31% had HF hospitalizations during a 40-month median follow-up. Compared with placebo, SDC 0.5- 0.9 ng/mL was associated with lower mortality[29 vs. 33% placebo; adjusted hazard ratio(AHR), 0.77; 95% confidence interval(CI), 0.67- 0.89], all-cause hospitalizations(64 vs. 67% placebo; AHR, 0.85; 95% CI, 0.78- 0.92) and HF hospitalizations(23 vs. 33% placebo; AHR, 0.62; 95% CI, 0.54- 0.72). SDC ≥ 1.0 ng/mL was associated with lower HF hospitalizations(29 vs. 33% placebo; AHR, 0.68; 95% CI, 0.59- 0.79), without any effect on mortality. SDC 0.5- 0.9 reduced mortality in a wide spectrum of HF patients and had no interaction with ejection fraction >45% (P=0.834) or sex(P=0.917). Conclusions: Digoxin at SDC 0.5- 0.9 ng/mL reduces mortality and hospitalizations in all HF patients, including those with preserved systolic function. At higher SDC, digoxin reduces HF hospitalization but has no effect on mortality or all-cause hospitalizations.
文摘Aims: Non-potassium-sparing diuretics are commonly used in heart failure(HF). They activate the neurohormonal system,and are potentially harmful. Yet, the long-term effects of chronic diuretic use in HF are largely unknown. We retrospectively analysed the Digitalis Investigation Group(DIG) data to determine the effects of diuretics on HF outcomes. Methods and results: Propensity scores for diuretic use were calculated for each of the 7788 DIG participants using a non-parsimonious multivariable logistic regression model, and were used to match 1391(81%) no-diuretic patients with 1391 diuretic patients. Effects of diuretics on mortality and hospitalization at 40 months of median follow-up were assessed using matched Cox regression models. All-cause mortality was 21%for nodiuretic patients and 29%for diuretic patients[hazard ratio(HR) 1.31; 95%confidence interval(CI) 1.11-1.55; P=0.002]. HF hospitalizations occurred in 18%of no-diuretic patients and 23%of diuretic patients(HR 1.37; 95%CI 1.13-1.65; P=0.001). Conclusion: Chronic diuretic use was associated with increased long-term mortality and hospitalizations in a wide spectrum of ambulatory chronic systolic and diastolic HF patients. The findings of the current study challenge the wisdom of routine chronic use of diuretics in HF patients who are asymptomatic or minimally symptomatic without fluid retention, and are on complete neurohormonal blockade. These findings, based on a non-randomized design, need to be further studied in randomized trials.
