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Background: In the Studies of Left Ventricular Dysfunction (SOLVD) treatment trial, similar clinical benefits were observed between starting doses of enalapril and the target dose achieved by postrandomization up-titration. In our current analysis, protecting the randomization, we examined the early effects of starting doses of enalapril.Methods: There were 2569 patients with mild-to-moderate chronic heart failure with reduced ejection fraction (ejection fraction ≤35%) randomized to receive starting doses (5-10 mg/day) of placebo (n = 1284) or enalapril (n = 1285). At day 14, both study drugs were blindly up-titrated to the target dose (20 mg/day). Overall, 96% (2458/2569) of the patients returned for dose up-titration, which was achieved in 59% (1444/2458), 48% (696/1444) of whom were in the enalapril group. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes in the enalapril group were estimated.Results: HRs (95% CIs) for all-cause mortality, heart failure hospitalization, and the combined endpoint of heart failure hospitalization or all-cause mortality at 14 days after randomization were 0.80 (0.32-2.03), 0.63 (0.35-1.12), and 0.65 (0.39-1.06), respectively. Corresponding HRs (95% CIs) at 30 days were 0.82 (0.41-1.67), 0.43 (0.27-0.68), and 0.43 (0.27-0.68), respectively. The magnitude of these early effects of starting doses of enalapril is similar to its previously reported long-term effects at the target dose.Conclusion: These data suggest that in stable ambulatory patients with heart failure with reduced ejection fraction, the magnitude of the early effect of starting doses of enalapril is similar to that observed during longer-term therapy with the target doses of the drug. [ABSTRACT FROM AUTHOR]

Background: Beta-blockers in high target doses are recommended for heart failure with reduced ejection fraction (HFrEF) but not for preserved ejection fraction (HFpEF). Treatment benefits are often more pronounced in high-risk subgroups, and patients with HFpEF with heart rate ≥70 beats per minute have emerged as such a high-risk subgroup. We examined the associations of high-dose beta-blocker use with outcomes in these patients.Methods: Of the 8462 hospitalized patients with heart failure with ejection fraction ≥50% in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, 5422 had a discharge heart rate ≥70 beats per minute. Of these, 4537 had no contraindications to beta-blocker use, of which 2797 (2592 with dose data) received prescriptions for beta-blockers. Of the 2592, 730 received high-dose beta-blockers, defined as atenolol ≥100 mg/day, carvedilol ≥50 mg/day, metoprolol tartrate or succinate ≥200 mg/day, or bisoprolol ≥10 mg/day, and 1740 received no beta-blockers. Using propensity scores for the receipt of high-dose beta-blockers, we assembled a matched cohort of 1280 patients, balanced on 58 characteristics.Results: All-cause mortality occurred in 63% and 68% of matched patients receiving high-dose beta-blocker vs no beta-blocker, respectively, during 6 years (median, 2.8) of follow-up (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98; P = .027). The hazard ratios (95% confidence intervals) for all-cause readmission and the combined endpoint of all-cause readmission or all-cause mortality associated with high-dose beta-blocker use were 0.90 (0.81-1.02) and 0.89 (0.80-1.00), respectively.Conclusions: In patients with HFpEF and heart rate ≥70 beats per minute, high-dose beta-blocker use was associated with a significantly lower risk of death. Future randomized controlled trials are needed to examine this association. [ABSTRACT FROM AUTHOR]

Background: Older people are predisposed to hyperkalemia because of impaired renal function, comorbid conditions, and polypharmacy. Renin-angiotensin-aldosterone system inhibitors (RAASi), which are recommended to treat chronic kidney disease and heart failure augment the risk. Patiromer, a nonabsorbed potassium binder, was shown in the phase 3 OPAL-HK study to decrease serum potassium in patients with chronic kidney disease taking RAASi. We studied the efficacy and safety of patiromer in a prespecified subgroup of patients aged ≥65 years from OPAL-HK.Methods: Chronic kidney disease patients with mild or moderate-to-severe hyperkalemia received patiromer, initially 8.4 g/d or 16.8 g/d, respectively, for 4 weeks (treatment phase, part A). Eligible patients entered an 8-week randomized withdrawal phase (part B) and continued patiromer or switched to placebo.Results: Mean ± standard error change in serum potassium from baseline to week 4 of part A (primary endpoint) in patients aged ≥65 years was -1.01 ± 0.05 mEq/L (P < .001); 97% achieved serum potassium 3.8-<5.1 mEq/L. The serum potassium increase during the first 4 weeks of part B was greater in patients taking placebo than in those taking patiromer (P < .001). Fewer patients taking patiromer (30%) than placebo (92%) developed recurrent hyperkalemia (serum potassium ≥5.1 mEq/L). Mild-to-moderate constipation occurred in 15% (part A) and 7% (part B) of patients aged ≥65 years. Serum potassium <3.5 mEq/L and serum magnesium <1.4 mg/dL were infrequent (4% each in patients aged ≥65 years in part A).Conclusions: Patiromer reduced recurrent hyperkalemia and was well tolerated in older chronic kidney disease patients taking RAASi. [ABSTRACT FROM AUTHOR]