Adoption of Spironolactone Therapy for Older Patients With Heart Failure and Left Ventricular Systolic Dysfunction in the United States, 1998–2001

Yale University, New Haven, Connecticut, United States
Circulation (Impact Factor: 14.43). 07/2005; 112(1):39-47. DOI: 10.1161/CIRCULATIONAHA.104.527549
Source: PubMed


Concerns have been raised about the appropriateness of spironolactone use in some patients with heart failure. We studied the adoption of spironolactone therapy after publication of the Randomized Aldactone Evaluation Study (RALES) in national cohorts of older patients hospitalized for heart failure.
This is a study of serial cross-sectional samples of Medicare beneficiaries > or =65 years old discharged after hospitalization for the primary diagnosis of heart failure and with left ventricular systolic dysfunction. The first sample was discharged before (April 1998 to March 1999, n=9758) and the second sample after (July 2000 to June 2001, n=9468) publication of RALES in September 1999. We assessed spironolactone prescriptions at hospital discharge in patient groups defined by enrollment criteria for the trial. Using multivariable logistic regression, we identified factors independently associated with prescriptions not meeting these criteria. Spironolactone use increased >7-fold (3.0% to 21.3% P<0.0001) after RALES. Of patients meeting enrollment criteria, 24.1% received spironolactone, as compared with 17.4% of those not meeting the criteria. Of all prescriptions after RALES, 30.9% were provided to patients not meeting enrollment criteria. Spironolactone was prescribed to 22.8% of patients with a serum potassium value > or =5.0 mmol/L, to 14.1% with a serum creatinine value > or =2.5 mg/dL, and to 17.3% with severe renal dysfunction (estimated glomerular filtration rate <30 mL.min(-1).1.73 m(-2)). In multivariable analyses, factors associated with prescriptions not meeting enrollment criteria included advanced age, noncardiovascular comorbidities, discharge to skilled nursing facilities, and care provided by physicians without board certification.
Spironolactone prescriptions increased markedly after the publication of RALES, and many treated patients were at risk for hyperkalemia. Simultaneously, many patients who might have benefited were not treated. These findings demonstrate the importance of balancing efforts to enhance use among appropriate patients and minimizing use in patients at risk for adverse events.

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    • "Rates of hyperkalemia admissions and mortality were increased following RALES publication [25], which could also be attributed to the increasing utilization of β-blockers at that time. Several reports showed a high rate of inappropriate use of spironolactone [10] [18] [26], and inadequate follow-up of renal function and potassium levels [27], with rates of hyperkalemia reaching 15% of patients treated with spironolactone, and even higher in renal failure patients. Thus, the present findings regarding underutilization of MRAs in eligible post-MI patients with a history of renal disease may be due to concerns raised by prior reports. "
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    ABSTRACT: Following the EPHESUS trial in 2003, mineralocorticoid receptor antagonist (MRA) therapy received a class I indication for the management of eligible high-risk post-MI patients. Our goal was to examine temporal trends in MRA use in eligible post-myocardial infarction (MI) patients. We investigated temporal trends and factors associated with MRA utilization among eligible patients enrolled in the biannual Acute Coronary Syndrome Israeli Surveys (ACSIS) 2004-2010. Among 7696 patients enrolled in the ACSIS surveys from 2004, 955 (12%) were eligible for MRA therapy. In this population, prescription of MRAs at discharge from the index event showed a modest increase from 21% to 25% over the six-year period, whereas utilization of other guideline recommended drugs, including angiotensin converting enzyme inhibitors/receptor blockers and β-blockers was >2-fold higher. Multivariate logistic regression analysis showed that independent predictors of MRA prescription at discharge included a higher degree of left ventricular dysfunction (LVEF ≤30% vs. 31-40%: OR=2.19; p=0.02), history of heart failure prior to admission (OR=1.92; p<0.004), admission Killip≥II (OR=1.78; p=0.004), and an anterior location of the index MI (OR=1.54; p=0.03). MRA utilization was not associated with an increased risk for adverse events or rehospitalization at 30days of follow-up. In a real world setting, approximately one quarter of eligible post-MI patients are treated with an MRA following the index event, without a significant time-dependent change in this management strategy. MRAs are more likely to be underutilized in eligible lower-risk patients.
    Full-text · Article · Jul 2013 · International journal of cardiology
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    • "A recent study has reported that most clinical guidelines did not modify or discuss the applicability of their recommendations for older patients with multiple comorbidities, suggesting that strict adhesion to current clinical guidelines in caring for an older patient with several comorbidities may have undesirable effects [23]. In patients with heart failure it has been estimated that one third of patients older than 65 years receiving spironolactone in the United States do not meet the enrollment criteria of the primary RCT [24], and that this inappropriate prescription is associated with an increase of hyperkalemia-induced mortality [25]. In patients with acute coronary syndromes, the results from the CRUSADE registry show that one fourth of the patients receive excess dosing of antithrombotic agents, especially patients with comorbidities, and that these patients had an increased risk of bleeding and a higher mortality [26]. "
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    ABSTRACT: To determine the long-term mortality of patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) that are eligible versus those not eligible in randomized controlled trials (RCT), and how each exclusion criteria is associated with outcome. Common causes of exclusion in six published RCT on intravenous antithrombotic therapy were prospectively assessed in a cohort of 452 consecutive patients with NSTEACS that were followed for up to 3 years. Forty-one percent of patients had one or more exclusion criteria establishing the ineligible group. These patients were older, more likely to have coronary risk factors, ischemic ECG changes, heart failure at admission, higher creatinine levels and a lower ejection fraction than eligible patients. There were no differences between both groups in the antithrombotic treatment received or in the performance of revascularization procedures during hospitalization or in the prescription of antiplatelet treatment and beta-blockers at discharge. Cumulative 3-year mortality rate was 25% in ineligible patients compared to 9% in eligible patients (p<0.001). The hazard ratio (HR) of mortality was of 9.1 (95% CI: 4.5-18.7) for severe renal dysfunction; 6.0 (3.3-11.4) for concomitant non-vascular diseases; 3.0 (1.6-5.5) for contraindications to anticoagulation; 2.5 (1.1-5.7) for heart failure; and 2.3 (1.1-4.6) for prior cerebrovascular disease. After adjusting for baseline differences, ineligible patients had a HR of total mortality of 1.88 (1.04-3.38), and of cardiac mortality of 2 (1.01-3.98). Patients with NSTEACS who are ineligible in RCT have a higher risk profile and a two-fold adjusted long-term mortality than eligible patients, especially those with comorbid conditions and those with contraindications to anticoagulation.
    Full-text · Article · Feb 2008 · International journal of cardiology

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