Renin-angiotensin inhibition in systolic heart failure and chronic kidney disease.

BACKGROUND: The role of renin-angiotensin inhibition in older patients with systolic heart failure with chronic kidney disease remains unclear. METHODS: Of the 1665 patients (aged≥65 years) with systolic heart failure (ejection fraction<45%) and chronic kidney disease (estimated glomerular filtration rate<60 mL/min/1.73 m(2)), 1046 received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Propensity scores for the receipt of these drugs, estimated for each of the 1665 patients, were used to assemble a matched cohort of 444 pairs of patients receiving and not receiving these drugs who were balanced on 56 baseline characteristics. RESULTS: During more than 8 years of follow-up, all-cause mortality occurred in 75% and 79% of matched patients with chronic kidney disease receiving and not receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, respectively (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.74-0.996; P=.045). There was no significant association with heart failure hospitalization (HR, 0.86; 95% CI, 0.72-1.03; P=.094). Similar mortality reduction (HR, 0.83; 95% CI, 0.70-1.00; P=.046) occurred in a subgroup of matched patients with estimated glomerular filtration rate less than 45 mL/min/1.73 m(2). Among 171 pairs of propensity-matched patients without chronic kidney disease, the use of these drugs was associated with a significant reduction in all-cause mortality (HR, 0.72; 95% CI, 0.55-0.94; P=.015) and heart failure hospitalization (HR, 0.71; 95% CI, 0.52-0.95; P=.023). CONCLUSION: Discharge prescription of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant modest reduction in all-cause mortality in older patients with systolic heart failure with chronic kidney disease, including those with more advanced chronic kidney disease.

Effect of warfarin on outcomes in septuagenarian patients with atrial fibrillation.

Anticoagulation has been shown to decrease ischemic stroke in atrial fibrillation (AF). However, concerns remain regarding their safety and efficacy in those ≥70 years of age who constitute most patients with AF. Of the 4,060 patients (mean age 65 years, range 49 to 80) in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, 2,248 (55% of 4,060) were 70 to 80 years of age, 1,901 of whom were receiving warfarin. Propensity score for warfarin use, estimated for each of the 2,248 patients, was used to match 227 of the 347 patients not on warfarin (in 1:1, 1:2, or 1:3 sets) to 616 patients on warfarin who were balanced in 45 baseline characteristics. All-cause mortality occurred in 18% and 33% of matched patients receiving and not receiving warfarin, respectively, during up to 6 years (mean 3.4) of follow-up (hazard ratio [HR] when warfarin use was compared to its nonuse 0.58, 95% confidence interval [CI] 0.43 to 0.77, p <0.001). All-cause hospitalization occurred in 64% and 67% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use 0.93, 95% CI 0.77 to 1.12, p = 0.423). Ischemic stroke occurred in 4% and 8% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use 0.57, 95% CI 0.31 to 1.04, p = 0.068). Major bleeding occurred in 7% and 10% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use 0.73, 95% CI 0.44 to 1.22, p = 0.229). In conclusion, warfarin use was associated with decreased mortality in septuagenarian patients with AF but had no association with hospitalization or major bleeding.

A propensity-matched study of the comparative effectiveness of angiotensin receptor blockers versus angiotensin-converting enzyme inhibitors in heart failure patients age ≥ 65 years.

The comparative effectiveness of angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II type 1 receptor blockers (ARBs) in real-world older heart failure (HF) patients remains unclear. Of the 8,049 hospitalized HF patients aged ≥ 65 years discharged alive from 106 Alabama hospitals, 4,044 received discharge prescriptions of either ACE inhibitors (n = 3,383) or ARBs (n = 661). Propensity scores for ARB use, calculated for each of 4,044 patients, were used to match 655 (99% of 661) patients receiving ARBs with 661 patients receiving ACE inhibitors. The assembled cohort of 655 pairs of patients was well balanced on 56 baseline characteristics. During >8 years of follow-up, all-cause mortality occurred in 63% and 68% of matched patients receiving ARBs and ACE inhibitors, respectively (hazard ratio [HR] associated with ARB use 0.86, 95% confidence interval [CI] 0.75 to 0.99, p = 0.031). Among the 956 matched patients with data on the left ventricular ejection fraction (LVEF), the association between ARB (vs ACE inhibitor) use was significant in only 419 patients with LVEFs ≥ 45% (HR 0.65, 95% CI 0.51 to 0.84, p = 0.001) but not in the 537 patients with LVEFs < 45% (HR 1.00, 95% CI 0.81 to 1.23, p = 0.999; p for interaction = 0.012). HRs for HF hospitalization associated with ARB use were 0.99 (95% CI 0.86 to 1.14, p = 0.876) overall, 0.80 (95% CI 0.63 to 1.03, p = 0.080) in those with LVEFs ≥45%, and 1.14 (95% CI 0.91 to 1.43, p = 0.246) in those with LVEFs <45% (p for interaction = 0.060). In conclusion, in older HF patients with preserved LVEFs, discharge prescriptions of ARBs (vs ACE inhibitors) were associated with lower mortality and a trend toward lower HF hospitalization, findings that need replication in other HF populations.

A propensity-matched study of the effects of chronic diuretic therapy on mortality and hospitalization in older adults with heart failure.

BACKGROUND: Non-potassium-sparing diuretics may increase mortality and hospitalizations in heart failure patients. Most heart failure patients are older adults, yet the effect of diuretics on cause-specific mortality and hospitalizations in older adults with heart failure is unknown. The objective of this propensity-matched study was to determine the effect of diuretics on mortality and hospitalizations in heart failure patients >or=65 years. METHODS: Of the 7788 Digitalis Investigation Group participants, 4036 were >or=65 years and 3271 (81%) were receiving diuretics. Propensity scores for diuretic use for each of the 4036 patients were calculated using a non-parsimonious multivariable logistic regression model incorporating all measured baseline covariates, and were used to match 651 (85%) patients not receiving diuretics with 651 patients receiving diuretics. Effects of diuretics on mortality and hospitalization at 37 months of median follow-up were assessed using matched Cox regression models. RESULTS: All-cause mortality occurred in 173 patients not receiving diuretics and 208 patients receiving diuretics respectively during 2056 and 1943 person-years of follow-up (hazard ratio {HR}=1.36; 95% confidence interval {CI}=1.08-1.71; p=0.009). All-cause hospitalizations occurred in 413 patients not receiving and 438 patients receiving diuretics respectively during 1255 and 1144 person-years of follow-up (HR=1.18; 95% CI=0.99-1.39; p=0.063). Diuretic use was associated with significant increased risk of cardiovascular mortality (HR=1.50; 95% CI=1.15-1.96; p=0.003).and heart failure hospitalization (HR=1.48; 95% CI=1.13-1.94; p=0.005). CONCLUSIONS: Chronic diuretic use was associated with significant increased mortality and hospitalization in ambulatory older adults with heart failure receiving angiotensin converting enzyme inhibitor and diuretics.