DRUGS IN HEART FAILURE

1. DRUGS IN HEART FAILURE Mari Fotherby & Emma Clingan Heart Failure Specialist Nurses Gloucestershire Heart Failure Service

2. Introduction • Drug management aims to provide symptomatic relief for the patient while also preventing further deterioration in cardiac function (Cowie & Kirby, 2003)

3. The Vicious Cycle of Heart Failure CARDIAC INJURY Pump failure • Vasoconstriction • Na+ H2O retention NeurohormonalActivation Renin Angiotensin, Aldosterone system Sympathetic Nervous system Others e.g. Natriuetic peptides

5. Diuretics • Effective at treating & controlling fluid retention, but do not prevent disease progression. • If used alone can stimulate renin-angiotensin system & accelerate disease process (SOLVD trial 1991). • No randomised trials to support

6. Uses • Goal to achieve dry weight – using as low a dose of diuretic as possible. • Titrate to weight & symptoms • Flexible regime • Self management / titration

7. Loop Diuretics • Furosemide & Bumetanide • Reduce symptoms of congestion by reducing preload • Act on Ascending Loop of Henle to increase the secretion & inhibit reabsoprtion of Na, Chloride and H2O • Long term use lowers B/P by arteriolar vasodilatation • Less likely to cause worsening renal function than Thiazides • Heart Failure Guidelines – 3 day increases.

8. Thiazide Diuretics • Bendroflumethiazide or Metolazone • Prevent Na reabsorption by kidneys • Cause reduced blood volume • Long-term use lowers B/P, by arteriolar vasodilatation

9. Cautions with Diuretics • Hyponatraemia • Hypokalaemia & low Mg • Hypovolaemia & hypotension • Drug Interaction – reduce hypoglycaemic effect of oral hypoglycaemics > hyperglycaemia Increased concentration Lithium • Gout • Concordance • Long-term resistance

10. ACE Inhibitors • Cornerstone of heart failure management • Blockade of the renin-angiotensin-aldosterone system • Decrease cardiac preload & afterload • Prevention of ventricular remodelling

11. ACE Inhibitors…2 • Approximately 7000 patients evaluated in placebo-controlled clinical trials • Consistent improvement in cardiac function, symptoms and clinical status • Decrease in all-cause mortality by 20-25% • Decrease in combined risk of death and hospitalisation by 20-25%

12. Clinical Trials • CONSENSUS- Enalapril 1987 • SOLVD- Enalapril 1991 • SAVE- Captopril 1992 • AIRE - Ramipril 1993 • ATLAS- Lisinopril 1999 • HOPE – Ramipril 2000

13. Effects • Symptomatic improvement may take weeks • Most benefit to more severe LVSD/NYHA class • Benefit to asymptomatic LVSD • Slow up titration, no less than 2 weekly until optimum dose or target achieved

14. Management • At least 20% of patients with chronic heart failure are not receiving ACE Is • About 10% of these are due to ACE I intolerance • Sell benefits- RARELY necessary to discontinue completely • Glos. Heart Failure Service 2005- 92.2%

15. Managing Complications • Cough (decreased catabolism of bradykinin) • Hypotension ??symptomatic, discontinue nitrates, calcium channel blockers, ?reduce diuretic dose • Taste disturbance • Seek specialist advice before stopping

16. Managing Renal Complications • Deteriorating renal function- eGFR!!! • Some deterioration is inevitable with chronic heart failure • Get broad parameters agreed at outset • ?remove NSAIDS, nitrates, calcium channel blockers • ?reduce diuretics (ACE I is alternative pathway for Na & water retention • Treat the patient, not the blood test

17. Angiotensin II Receptor Blocker • Block the renin-angiotensin system directly at the angiotensin II receptor level • complete blockade of the effects of angiotensin II- vasodilatation • CHARM study (2003) Candesartan, licensed for the treatment of heart failure

18. Indications • To date, ARBs are not superior to ACE inhibitors • Lack the bradykinin-related side effects of ACE I • Used if the patient is intolerant of an ACE Inhibitor due to a persistent cough or angioedema • ??combination therapy- little evidence/experience (Val-HeFT, 1999)

19. Beta Blockers • Activation of the sympathetic nervous system is a contributory factor in the pathophysiology of heart failure. • Beta Blockers prevent stimulation of the sympathetic nervous system by inhibiting the action of catecholamines (noradrenaline and adrenaline) at beta-adrenergic receptors.

20. Beta Adrenergic Blockers can be selective or non-selective. • Nonselective e.g. Carvedilol, Labetolol, Sotalol, Propranolol, affect receptors at Beta1 sites (mainly heart) ,and Beta2 sites (bronchi, blood vessels, and uterus). • Selective e.g. Bisoprolol, Metoprolol, Nebivolol and Atenolol, affect primarily Beta1 sites (heart).

21. Action • Increase peripheral vascular resistance • Decrease B/P • Reduce heart rate, automaticity and excitability (reduce arrhythmias) • Slow conduction through A-V node • Decrease force of contraction • Decrease Myocardial Oxygen consumption • Constriction of bronchioles • Constriction of peripheral blood vessels

22. Effects In Heart Failure • Reduce mortality and morbidity • Improve Left Ventricular function & symptoms • Reduce hospital admissions • Aim nationally for 70 – 80% • Glos. Heart Failure Service 2005 – 58%

23. Trial Evidence • CIBIS I - Bisoprolol improves LV function • CIBIS II -1999 • MERIT - HF, 1999 - Metoprolol – reduce morbidity & mortality; reduce healthcare costs in mild - mod heart failure. • COPERNICUS study, 2001 - use of Carvedilol in severe HF. 35% survival benefit • COMET study, 2003 - suggests Carvedilol vs Metoprolol increases mortality. • SENIORS, 2005 - Placebo vs Nebivolol

24. Indications • LVSD on ECHO • Mild to Severe LVSD of ischaemic or non –ischaemic aetiology • Clinically stable – no fluid • Can precipitate Asthma, but can be tolerated in COPD if have reversible airways disease -HFS/Cardiologist. • Drug interactions possible • Heart rate, ECG >60; B/P >100 mmHg • Bisoprolol used if ongoing ischaemia

25. Patient Advice • Bisoprolol 1.25 mg – 10 mg daily • Carvedilol 3.125 BD to 25mg BD* • Slow up titration, 2 – 4 weekly, from small initial dose to target or max tolerated dose – SOME is better than none. • Informed consent • Initial symptomatic deterioration possible • Long term benefits • Encourage self monitoring • Regular follow up and access for advice

26. Managing Complications • Worsening Heart Failure - up diuretics • Worsening breathlessness (bronchospasm related) • Symptomatic Hypotension- look at other meds before reducing B-Blocker. • Excessive Bradycardia • Fatigue; cold extremities; sleep disturbance • Glucose tolerance in Diabetics

27. Spironolactone • Aldosterone plays an important role in the pathophysiology of heart failure • Aldosterone has adverse effects on cardiac structure and function • Low dose spironolactone (aldesterone antagonist) reduces mortality in moderate to severe heart failure patients (RALES mortality trial, 1999)

28. Indications • NYHA class III-IV • Despite optimal treatment • Irrespective of aetiology • ??same effect on mild LVSD (NYHA class II) or asymptomatic LVSD • Glos. Heart Failure Service 2005- 73%

29. Management • Starting dose 12.5mg OD • Close monitoring of K+ & renal function (bloods 10, 20, 30 days) • Increase dose to 25mg OD if tolerated (bloods 10,20,30 days) • Inform GP need to check bloods every 4/52 for 3/12, 3/12 for 1 year, 6/12 thereafter- IMPORTANT

30. Complications • Discontinue and seek advice if: • Creatinine >200 (or 30% from baseline) • Potassium  to >5.5 • Potassium 5-5.5 reduce dose by 50% • Monitor for signs of sodium & water depletion e.g. diarrhoea & vomiting

31. Complications…2 • Gynaecomastia- 10% in the RALES study • May need to be discontinued • Consider Eplerenone (EPHESUS, 2003)- same precautions and side effects • Starting dose of 25mg Od, aiming to increase to 50mg Od after 4 weeks • Close monitoring of renal function applies

32. Digoxin • Cardiac glycosides are indicated in AF to control ventricular rate • In sinus rhythm it is recommended to improve clinical status of patients with persisting HF symptoms despite optimum treatment • Most benefit to pts with more severe HF

33. Management • DIG Trial/ESC guidelines (2001)- ↓risk of hospitalisations without an impact on survival • Monitor heart rate (especially when used with beta blockers) but do not withdraw suddenly • Drug interactions

34. Digoxin Toxicity • In the elderly the signs & symptoms may be less specific • Falls, confusion, ↓mobility- reduce dose • Monitor renal function- this can lead to dig toxicity • Digoxin induced arrhythmias are common in hypokalemic patients

35. Hydralazine with Nitrate • For patients truly intolerant of ACE / ARB • Hypertensive • Symptomatic despite therapy

36. Morphine • Relief of breathlessness in pulmonary oedema & left sided heart failure • Acts by peripheral dilatation and decreasing afterload • Renally excreted • Side effects • Not only for palliative care!

37. Concordance • About ½ of the medicines prescribed for patients with long term conditions are not taken as prescribed • Poor treatment adherence = worsening HF symptoms • More tablets= greater the risk of non-adherence • ? Dosette box- but remember extra diuretics

38. Remember… • Is continence an issue? • Dizziness? • Gout? • Hyperglycaemia? • Taste disturbance? • Cognitive impairment? Simplify the regime • Social isolation?

40. Heart Failure Service • Heart Failure Nurse can play pivotal role in drug management • Specialist knowledge in initiating & titrating HF medications • Monitoring – home & clinic • Patient education • Nurse Prescribing • Communication with multidisciplinary team

41. Any Questions?