ACE in hypotensive HF patients

1. ACE in hypotensive HF patients Kwame O Akosah MD Associate Clinical Professor of Medicine University of Wisconsin - Madison Director, Heart Failure Clinic Gundersen Lutheran Medical Center La Crosse, WI

2. Congestive heart failure • Congestive heart failure (CHF) is a major public health challenge • Morbidity and mortality are substantial (1997 mortality: 45,419) • Prevalence is increasing (4,600,000) • people are living longer • CHF is more prevalent in the elderly population American Heart Association. 2000 Heart and Stroke Statistical Update, 1999

3. Heart failure therapy ACE inhibitors • ACE (angiotensin converting enzyme) inhibitors are the mainstay of heart failure therapy • several large trials have proven the benefits of ACE inhibitors in the treatment of CHF • unfortunately, most patients do not receive ACE inhibitors; those who do often get inadequate doses • no multicenter trials have included patients with symptomatic hypotension

4. The CHF clinic • The heart failure clinic was established in April 1999 as an outpatient service for patients with severe heart failure • A significant number of patients referred to the clinic had symptomatic hypotension along with severe heart failure

5. The CHF clinic Study objectives • To determine efficacy, safety, and tolerability of ACE inhibitors in heart failure patients with symptomatic hypotension • To examine the effect of ACE inhibitors on symptoms of hypotension and functional status • To study the hemodynamic responses to ACE inhibitors as measured by blood pressure (BP) at optimal and maximal doses of ACE inhibitors

6. The CHF clinic Study population • 104 of the 220 patients seen in the clinic have been discharged • 27 of these meet the criteria for symptomatic hypotension • 20 were men • mean age was 64  10 years (45–85) • 7 (26%) could not tolerate ACE inhibitors and were prescribed angiotensin receptor blockers (ARBs) • all 20 on ACE inhibitors were optimized and 15 (75%) were maximized at their last visit

7. The CHF clinic Assessment • Inclusion criteria • those who had been discharged from the clinic • those with systolic BP  100 mm Hg and symptoms of hypotension at their first visit • Assessment • BP was assessed at presentation, on optimal and maximal doses of ACE inhibitor, at discharge, and at most recent clinic visit • maximal dose: 40 mg lisinopril or equivalent • optimal dose: >20 and <40 mg lisinopril or equivalent • New York Heart Association (NYHA) class was assessed on presentation and at discharge

8. The CHF clinic BP with ACE inhibitor therapy 112  15mm Hg‡ 103  11mm Hg† 101  13mm Hg* 120 86  12mm Hg 100 80 SBP (mm Hg) 60 40 20 0 baseline optimaldose maximaldose 6-monthfollow-up *p = 0.003 from baseline †p = 0.004 from baseline ‡p = 0.002 from baseline Akosah KO, et al. October 25, 2000

9. The CHF clinic Treatment and functional class • All patients showed improvement in symptoms of hypotension • The mean NYHA functional class at baseline was 3.5  0.6 • At follow-up, the mean NYHA functional class was 2.5  0.6 • None of the patients were in NYHA class IV by the end of the study

10. The CHF clinic Early improvement in hypotension • The hemodynamic effects of the stresses associated with heart failure may be more deleterious than the hypotensive effects of ACE inhibitors • An analogy would be giving epinephrine to someone with asthma • epinephrine would be expected to increase the heart rate further • but because epinephrine relieves the stress of breathing, the heart rate actually goes down

11. The CHF clinic Late improvement in hypotension • The late improvement is probably related to the effect of ACE inhibitors on reverse remodeling of the heart • As the heart remodeling is attenuated and perhaps reversed, shape, volume, and BP of the heart also improve

12. The CHF clinic Monitoring and titrating • All the people who had symptomatic hypotension were started on a very low dose of ACE inhibitor (eg, 2.5 mg of lisinopril) • Dose was titrated up very slowly • Patients were seen as frequently as needed — sometimes every day

13. The CHF clinic Discharge to care of family physician • Records and instructions were sent to the family physician at discharge • Patients received instructions on specific issues (eg, the clinic should be contacted before a physician stops or changes any of their medications) • The clinic makes follow-up calls to the primary care physician to monitor the progress of patients • Communication with primary care physicians is very important

14. The CHF clinic ACE intolerance • Some patients develop an intolerance to ACE inhibitors • patients who develop allergic reactions • patients who continue to have symptomatic hypotension • patients who develop angioedema • patients who develop intolerant cough • In this study, 7 people who were ACE intolerant were prescribed ARBs

15. The CHF clinic ACE inhibitors vs ARBs Akosah KO, et al. Presented at the meeting of the American College of Chest Physicians, October 25, 2000, San Fransico, CA

16. The CHF clinic Conclusions • CHF patients with symptomatic hypotension can be successfully treated with ACE inhibitors • Hypotension is not a legitimate reason to deny CHF patients life-saving medications such as ACE inhibitors • Functional status improves with therapy in CHF patients • With ARBs, improvements in BP are not significant; however symptoms of hypotension do improve • To try to duplicate these results in a wider groups of patients from various clinical practices, we are currently looking for other centers to collaborate in a larger study

17. HF and sudden death The use of AICDs • The use of automatic implantable cardioverter defibrillators (AICD) in heart failure patients is becoming more common • Objective • To evaluate the impact of AICD in patients enrolled in the heart failure clinic • Method • A retrospective review of shocks in patients with an AICD device was conducted • Data were analyzed for the number of shocks before enrollment and after optimization of medical management Akosah KO, et al. Presented at the meeting of the American College of Chest Physicians, October 25, 2000, San Fransico, CA

18. HF and sudden death Results • Of the first 100 consecutive patients enrolled in the clinic, 22 had an AICD • Cardiac death occurred in 1 patient (fatal MI) • Of the remaining 21, 6 patients (29%) had 23 shocks before enrollment in the clinic, 1 of which was inappropriate • 2 shocks occurred after enrollment (90% reduction) • 1 shock was inappropriate and the other shock occurred within a week of enrollment • No shocks occurred after medical therapy was optimized Akosah KO, et al. Presented at the meeting of theAmerican College of Chest Physicians, October 25, 2000, San Fransico, CA

19. HF and sudden death Conclusions • Results suggest that malignant arrhythmias are common in decompensated heart failure patients and that aggressive medical therapy may have incremental value in preventing sudden death in high-risk heart failure patients with an AICD • Clinical implications • Heart failure patients with an AICD will benefit from aggressive medical therapy Akosah KO, et al. Presented at the meeting of theAmerican College of Chest Physicians, October 25, 2000, San Fransico, CA