“Escape” of aldosterone production in patients with left ventricular dysfunction treated with an angiotensin converting enzyme inhibitor: Implications for therapy

Despite the findings in randomized trials of a significant effect of angiotensin-converting enzyme (ACE) inhibitors in reducing morbidity and mortality of patients with symptomatic left ventricular dysfunction, the morbidity and mortality of these patients remains relatively high. One potential strategy to further improve morbidity and mortality in these patients is blockade of aldosterone. Many clinicians have assumed that ACE inhibitors would block both angiotensin II and aldosterone. However, there are data to suggest that aldosterone production may “escape” despite the use of an ACE inhibitor. An escape of aldosterone production has several important consequences, including: sodium retention, potassium and magnesium loss, myocardial collagen production, ventricular hypertrophy, myocardial norepinephrine release, endothelial dysfunction, and a decrease in serum high density lipoprotein cholesterol. Due to the potential importance of these mechanisms, the finding that there is a significant correlation between aldosterone production and mortality in patients with heart failure, as well as evidence that an aldosterone antagonist, spironolactone, when administered to patients with heart failure treated with conventional therapy including an ACE inhibitor results in increased diuresis and symptomatic improvement, an international prospective multicenter study has been organized, the Randomized Aldactone Evaluation Study (RALES Pilot Study), to evaluate the safety of blocking the effects of aldosterone in patients with heart failure treated with an ACE inhibitor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44631/1/10557_2004_Article_BF00877755.pd

Age-Related Differences in Management of Heart Disease: A Study of Cardiac Medication Use in an Older Cohort

BackgroundPrevious studies have suggested suboptimal use of cardiac medications for secondary prevention after myocardial infarction (MI) and atrial fibrillation (AF), especially among older people.ObjectiveTo determine whether patients older than 75 years are less likely than those aged 65 to 74 to be prescribed medications with evidence-based indications, including angiotensin-converting enzyme (ACE) inhibitors for left ventricular dysfunction (LVD) and/or diabetes mellitus (DM), aspirin and/or beta-blockers for those with a history of MI, and warfarin for chronic AF.DesignA retrospective cohort study.SettingTwenty-nine hospitals, predominantly tertiary-care institutions.ParticipantsA total of 407 patients randomized to ventricular or dual-chamber pacing from February 26, 1993, to September 30, 1994, in the Pacemaker Selection in the Elderly (PASE) trial.MeasurementsA review of the patient's medical history and a physical exam at study enrollment, three follow-up timepoints, and a study closeout.ResultsPatients older than 75 years with LVD and/or DM were less likely to be prescribed ACE inhibitors (OR = .56 (0.31-1.00)); patients older than 75 with a history of MI were less likely to be taking aspirin (OR = .43 (0.19-.95)), and patients older than 75 with AF were less likely to be prescribed warfarin (OR = .18 (0.05-.61)). Patients older than 75 years of age with any or all of the conditions studied were less likely to be prescribed indicated medications than those ages 65 to 74 (OR = .35 (0.18-.70)), after controlling for between-group differences in comorbidity, gender, and number of noncardiac medications.ConclusionOlder age is a significant independent negative correlate of evidence-based cardiac medication use in this cohort. Causes for this finding need to be explored