Konstantinos Dimopoulos a,b, *, Tushar V. Salukhe a,b, Andrew J.S. Coats a,c, Jamil Mayet a,d, Massimo Piepoli a,e, Darrel P. Francis a,d.

Size: px
Start display at page:

Download "Konstantinos Dimopoulos a,b, *, Tushar V. Salukhe a,b, Andrew J.S. Coats a,c, Jamil Mayet a,d, Massimo Piepoli a,e, Darrel P. Francis a,d."

Transcription

1 International Journal of Cardiology 93 (2004) Review Meta-analyses of mortality and morbidity effects of an angiotensin receptor blocker in patients with chronic heart failure already receiving an ACE inhibitor (alone or with a h-blocker) Konstantinos Dimopoulos a,b, *, Tushar V. Salukhe a,b, Andrew J.S. Coats a,c, Jamil Mayet a,d, Massimo Piepoli a,e, Darrel P. Francis a,d a National Heart and Lung Institute, London, UK b Heart Failure Unit, Royal Brompton Hospital, Sydney St., London SW3 6NP, UK c Sydney University Medical School, Sydney, Australia d St. Mary s Hospital, London, UK e Ospedale Civile di Piacenza, Italy Received 1 October 2003; accepted 9 October Abstract Background: While treatment with either angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) is clearly superior to placebo in the treatment of heart failure patients, controversy still surrounds the effects of ARBs in patients already receiving an ACEi. Even more controversial is the wisdom of administering ARBs in patients already on an ACEi and h-blocker. Methods: We present meta-analyses of the available randomised controlled trials to date (October 2003) of angiotensin II receptor antagonists versus placebo in patients with symptomatic chronic heart failure in which both groups received ACEi. The two largest eligible trials were CHARM- Added and Val-HeFT. We examined two endpoints: mortality and a combined endpoint of mortality and morbidity. Results: In the first metaanalysis, covering all patients regardless of h-blocker use, we found a significant reduction in the combined endpoint (odds ratio [OR] = 0.89; 95% confidence interval [CI] ), but no significant reduction in mortality itself (OR = 0.97; CI: ). In the second metaanalysis, covering patients concomitantly on h-blockers, we found no significant effect on mortality (OR = 1.08; CI: ) or on the combined endpoint (OR = 0.94; CI: ). In the third meta-analysis, covering patients not on concomitant h-blockers, there is clear evidence of a reduction in the combined endpoint (OR = 0.83; CI: ), but not on mortality (OR = 0.93; CI: ). Conclusion: There is now good evidence for the use of ARBs to prevent events in patients with heart failure on ACEi who are not suitable for h-blockers. D 2004 Published by Elsevier Ireland Ltd. Keywords: Meta-analysis; Heart failure; Angiotensin receptor II antagonists 1. Introduction Controversy surrounds the use of angiotensin receptor blockers (ARBs) in patients with chronic heart failure who are already receiving angiotensin converting enzyme inhibitors (ACEi). Theoretically, ARBs can antagonise angiotensin II produced by enzymes other than ACE and therefore could potentially further suppress the effects of overactivation of the renin angiotensin aldosterone system. * Corresponding author. Heart Failure Unit, Royal Brompton Hospital, Sydney St., London SW3 6NP, UK. Tel.: ; fax: address: k.dimopoulos@ic.ac.uk (K. Dimopoulos). In particular, in patients already receiving both a h- blocker and an ACEi, it is especially controversial whether the effect of adding an ARB is harmful or beneficial. Data is now available from large randomised controlled trials that should help to evaluate whether the theoretical benefit of ARBs in patients already taking ACEi translates into reduced clinical events. From two large studies (Val- HeFT, CHARM), there are also data stratifying the patients according to whether they were receiving h- blockers. Quantitative synthesis by meta-analysis is the most reliable way of putting together results of large randomised controlled trials. We performed a meta-analysis of trials of ARBs versus placebo in patients receiving ACEi for chronic /$ - see front matter D 2004 Published by Elsevier Ireland Ltd. doi: /j.ijcard IJCA-05331; No of Pages 7

2 2 Table 1 Randomised controlled trials involving ARBs and ACEi therapy versus placebo plus ACEi, mean treatment duration >6 months, primary outcome mortality, or mortality morbidity Study Population ARBS ACEi Control Primary endpoint Hamroff [3] NYHA III IV losartan various (enalapril, captopril, fosinopril, lisinopril) RESOLVD [4] Val-HeFT[5,27] CHARM-Added [6] NYHA II IV, 6 MWD < 500 m, EF < 40% II IV, EF < 40% LVEDD>2.9 cm/m 2 NYHA III IV, NYHA II plus hospitalization last 6 months placebo candesartan enalapril placebo vs. candesartan vs. enalapril valsartan candesartan various (enalapril, lisinopril, quinazil, ramipril, captopril) various (enalapril, lisinopril, captopril, ramipril, etc.) placebo placebo peak VO2, NYHA class 6-min walk test, EF, LV volumes, neurohormones, QOL, clinical events mortality/mortality and morbidity (hospitalization, SCD with resuscitation, IV vasodilators or inotropes >4 h) mortality or hospitalization Total number of patients Patients in ARB arm Mean follow-up (months) Mortality (%) Mortality per year of follow-up (%) Overall ACEi=ACE inhibitor; ARBs=angiotensin receptor blocker; EF=ejection fraction; LV=left ventricle; LVEDD=left ventricular end diastolic diameter; NYHA=New York Heart Association; VO 2 =Oxygen consumption; 6MWD=6-min walk distance; QOL=Quality of Life; SCD=sudden cardiac death. K. Dimopoulos et al. / International Journal of Cardiology 93 (2004)

3 K. Dimopoulos et al. / International Journal of Cardiology 93 (2004) heart failure. We also performed separate meta-analyses of subgroups of patients according to whether they were receiving concomitant beta-blockade. 2. Methods We assessed the available randomised controlled trials to date (October 2003) of ARBs versus placebo in patients with symptomatic chronic heart failure in which both groups received ACEi. Our primary endpoint was mortality. Secondarily, we evaluated the effect on the combined endpoint of mortality and morbidity. Since the trials used different definitions of this combined endpoint, we decided that the only unbiased solution was to use the prespecified combined endpoint within the individual trials Presence of concomitant b-blocker therapy We performed one analysis (a) pooling all patients irrespective of whether they were on concomitant h-blockade. Where studies reported separate results for patients with and without concomitant h-blockade, we were able to include those studies in additional meta-analyses of (b) patients on concomitant ACEi and h-blocker and (c) patients on concomitant ACEi without h-blocker Study selection A systematic MEDLINE search was performed using key search words: angiotensin receptor antagonist (or blocker), heart failure, angiotensin converting enzyme (or ACE) inhibitor and randomised controlled trial. We specifically identified (i) double-blinded randomised controlled studies of combined ARB and ACEi therapy versus ACEi therapy alone in patients with symptomatic heart failure (NYHA II IV); (ii) studies with mortality and morbidity as a primary outcome; and (iii) with duration of follow-up of at least 6 months. Data were extracted by two readers independently, and a third reviewer was used in the eventuality of disagreement between the two Statistical analysis For each of the three meta-analyses (all patients; patients on h-blockers; patients not on h-blockers), we calculated the effects of added ARB on (i) mortality and (ii) a combined endpoint of mortality and morbidity. The odds ratio (OR) method was used to combine the individual study effect sizes into a single overall effect size, expressed as odds ratio and 95% confidence interval (CI).[1] A fixed effect model was used initially, but if there was evidence of heterogeneity by the Cochran Q method [2] ( p < 0.05 by v 2 ), we moved on to the random effects model. 3. Results 3.1. Trial characteristics A total of four randomised controlled studies met the entrance criteria, with a total of 7666 patients (Table 1). All were double-blind, randomised placebocontrolled studies in which comparison between combined ARBs plus ACEi therapy was compared to ACEi alone. Three types of ARBs were being tested in these studies: losartan, valsartan and candesartan. As for the ACEi used as background therapy, in only one trial was the ACEi constant (enalapril in the RESOLVD trial). Patients in the remaining studies were on treatment with various open-label ACEi. In one study (RESOLVD), we considered the ACEi alone and ACEi plus ARB arms only. All-cause mortality was reported in all studies. Combined endpoint expressed as mortality or morbidity was reported in all but one study [3]. Mortality and morbidity characteristics of the subgroups with and without concomitant h-blockers were reported in two studies (Val-HeFT and CHARM- Added). In the RESOLVD and Val-HeFT studies, not all patients were treated with an ACEi, and only the subgroups that were are included in this meta-analysis (Table 2). Table 2 Baseline demographic data and clinical characteristics Study Mean age (years) Male (%) NYHA Class II/III/IV (mean) Mean LVEF (%) Ischemic/idiopathic etiology (%) %on digoxin %on diuretic Hamroff NA 26 30: RESOLVD :35:2 (2.3) 28 71: Val-HeFT :36:2 (2.3) 27 57: CHARM :73:3 (2.7) 28 62: Added Overall :48.3:2.3 (2.5) : NYHA= New York Heart Association, LVEF = left ventricular ejection fraction, NA= not available. %on h-blocker

4 4 K. Dimopoulos et al. / International Journal of Cardiology 93 (2004) Fig. 1. Effect of ARBs on mortality and the combined endpoint mortality morbidity in patients with heart failure taking ACE inhibitors, regardless of h-blocker therapy. The OR and 95% confidence interval are shown for each study and overall ARB versus no ARB in patients taking ACEi (regardless of b-blocker therapy) A total of 3950 patients were randomised to combined ARB and ACEi therapy, whereas 3716 patients were randomised to ACEi plus placebo. Mean age was 63.2 years and 79.8% were men. Mean NYHA class was 2.5, and 59.6% had heart failure of ischemic aetiology. Only 40.5% were on h-blocker therapy. All-cause mortality was not significantly affected by ARB treatment (OR = 0.97; 95% CI: ) (Fig. 1). The combined endpoint showed subtle evidence of benefit from ARB treatment in the fixed effects model (OR = 0.89; 95% CI: ). There was no evidence of heterogeneity with either endpoint. Fig. 3. Effect of ARBs on mortality and the combined endpoint of mortality morbidity in patients with heart failure taking ACEi but not h- blockers. The odds ratio and 95% confidence interval are shown for each study and overall ARB versus no ARB in patients taking ACEi and b-blocker A total of 3163 patients were on h-blocker therapy, of which 1569 were randomised to ARB and 1594 to no ARB in the Val-HeFT and CHARM-Added trials. Mortality in the two groups was 23.3% and 24.1%, respectively. No significant difference in mortality was seen between the two groups by the fixed effects model (OR = 1.08; 95% CI: , Fig. 2). Because of evidence of heterogeneity [v 2 =6.8, p < 0.05], the random effects model was also calculated, which confirmed no significant treatment effect (OR = 1.12; 95% CI: ). Combined mortality and morbidity was also not significantly different (OR = 0.94; 95% CI: ) by the fixed effects model. Because of evidence of heterogeneity [v 2 =9.2, p < 0.05], the random effects model was also calculated, and this confirmed no significant treatment effect (OR = 0.95; 95% CI: ) ARB versus no ARB in patients taking ACEi but not b-blocker A total of 4029 patients were in the non-h-blockers subgroups of the Val-HeFT and CHARM-Added trials. Mortality was not significantly different between the ARB and non-arb arms (OR = 0.93; 95% CI: , fixed model; no evidence of heterogeneity). The combined endpoint of mortality and morbidity was significantly reduced in the ARB arm (OR = 0.83; 95% CI: , fixed model; no evidence of heterogeneity) (Fig. 3). Fig. 2. Effect of ARBs on mortality and the combined endpoint of mortality morbidity in patients with heart failure taking ACE inhibitors and h-blockers. The odds ratio and 95% confidence interval are shown for each study and overall. 4. Discussion In these meta-analyses, we have found that ARBs have a beneficial effect in patients who are taking ACEi, as long as

5 K. Dimopoulos et al. / International Journal of Cardiology 93 (2004) they are not taking h-blockers. The reduction in the combined endpoint is not accompanied by reduction in mortality, suggesting that the benefit might be largely through reduction in hospitalization. The deleterious effects of neurohormonal activation in the context of chronic heart failure have been the dominant treatment targets of recent decades. High levels of catecholamines, renin and aldosterone have negative effects on the cardiovascular system producing progressive impairment of left ventricular structure and function as well as vascular damage.[5,7 11] ACEi are clearly beneficial for prognosis, even though doubts remain on optimal dosage and interactions with other drugs.[12 13] However, ACEi alone, even if at full recommended doses, does not provide complete inhibition of the renin angiotensin converting enzyme system (RAS), thus permitting angiotensin to exert its negative systemic effects. [14 17]. ARBs, on the other hand, have been shown to be safe and have similar efficacy to ACEi in heart failure. [18 21] A combined approach using both ACEi and ARBs could provide a more effective blockade of the RAS than either drug alone. [22] Moreover, the beneficial effects of ACEi and ARBs may go beyond inhibition of the RAS [23 24]. ACEi increase kinin levels since ACE is also a potent kininase. ARBs may enhance the activation of ATII receptors by inducing circulating levels of angiotensin, thus triggering kinin generation and nitric oxide production. [23 24] Studies of ARB on a background of ACEi The first clinical trial to compare ACEi treatment to the combination ACEi plus ARBs in patients with heart failure was published by Hamroff et al. Even though the study was underpowered for survival analysis, a clear beneficial effect on the primary endpoints of exercise capacity and functional class was seen after a mean observation time of 6 months, suggesting an additive effect of ACEi and ARBs [3]. The RESOLVD pilot study showed a beneficial effect of the combination strategy on blood pressure, left ventricular dimensions and neurohormonal factors (renin, epinephrine, N-terminal pro-atrial natriuretic peptide). [4] The ACEi plus ARB arm also showed the greatest increase in renin and greatest decrease in aldosterone, suggesting a more effective blockage of the RAS. No significant differences were seen in mortality and morbidity, leaving doubts on the long-term survival benefits of the combination therapy. It is nevertheless noteworthy that the ACEi arm consisted of only 109 patients and a significantly lower proportion of patients took h-blockers in the ARB arm than in the non-arb arm, possibly affecting survival analysis in this study. The Val-HeFT Study compared valsartan to placebo in heart failure patients, the vast majority of which were on ACEi. [5] Even though a large population of patients was included and mean observation period was nearly 2 years, a significant effect of the combination therapy was only seen on morbidity expressed as hospitalization, whereas mortality was similar in the two groups. An unexpected increase in mortality emerged during post hoc analysis in the subgroup of patients on triple therapy (ARB, ACEi and h-blocker): 129 versus 97 deaths, HR 1.42, 95% CI: Doubts were raised on whether this was a true harmful effect of excessive neurohormonal blockade by the triple therapy or a manifestation of the random play of chance. The CHARM-Added Study was recently published, comparing candesartan to placebo in a large population of heart failure patients already on ACEi. It was large and had a long mean observation period of more than 3 years and was thus potentially capable of answering the questions that Val-HeFT had raised. There was a significant decrease in the primary endpoint of death or hospitalization for worsening heart failure in the ARB plus ACEi arm, which had not been seen in Val-HeFT. In mortality, however, there was no significant difference. Subgroup analysis showed that the addition of h-blockers to the combination ACEi-ARB as well as administration of the maximum recommended doses of ACEi were the two factors that conferred the maximum benefit. Paradoxically, therefore, the CHARM-Added results favoured triple therapy (ACEi-ARBS-h-blocker), while Val- HeFT had suggested that such combination could be harmful. The present meta-analysis was largely dependent on these two discordant studies since, as the largest two trials ever on this question, they were responsible for the vast majority of events Quantitative synthesis by meta-analysis Across the trials as a whole, all-cause mortality is not significantly affected by ARB. There is a borderline reduction in combined endpoint, which is significant by the fixed effect model, but nonsignificant in the random effects model, which is more appropriate in a meta-analysis with this degree of heterogeneity. Our conclusion is therefore that at present, there is not good endpoint-based evidence for routine administration of ARB across all patients receiving ACEi for heart failure. Within the subgroup taking h-blockers, there is no evidence of reduced mortality nor of reduce combined endpoint. The apparent increase in mortality seen in Val- HeFT is neutralised by the nonsignificant trend to reduce mortality in CHARM-Added. In a mirror-image situation, the reduced combine endpoint in CHARM-Added is neutralised by a nonsignificant trend to increased combined endpoint in Val-HeFT. We conclude that there are no grounds to recommend routine ARBs receiving both ACEi and h-blockers. Those patients not taking h-blockers, however, had clear evidence of reduction, the combined endpoint of morbidity and mortality when ARB was added to a background of ACEi, although mortality itself was not significantly re-

6 6 K. Dimopoulos et al. / International Journal of Cardiology 93 (2004) duced. We can therefore conclude that for patients not taking h-blockers, adding an ARB reduces the clinical events, largely (or entirely) by reducing hospital admissions/morbidity. Our meta-analysis thus furthers the previous meta-analysis by Jong et al. [25], since data newly available (CHARM-Added) demonstrate a significant benefit of double treatment on the combined endpoint of mortality and morbidity Possible mechanisms Why does adding ARBs to ACEi only seem to help those patients not on h-blockers? It could be a consequence of an interaction between AT1 receptors and h-adrenergic receptors.[26] It has been shown that selective AT1 receptor blockade inhibits downstream signalling of h-adrenergic receptors, thus producing a h-blocker effect. It may be that the benefit derives mainly from the h-blocking properties of ARBs. Why was there such a contrast between the results of Val- HeFT and CHARM-Added in the subset of patients on h- blockers? Differences in baseline characteristics of these two large trials that could explain the difference. First, being a more recent study, CHARM-Added had a significantly higher proportion of patients on h-blockers than Val-HeFT (Table 1). Second, the vast majority of patients in the Val- HeFT were in NYHA class II, whereas the majority of patients in CHARM-Added were in class III. The sicker CHARM-Added patients may have had more neurohormonal activation and therefore more opportunity to benefit from a more complete neurohormonal blockade provided by the triple therapy. Our meta-analysis combines the two populations, producing a more homogeneous distribution between the two main functional classes (II and III, 49.3% and 48.3%, respectively) of chronic heart failure. Perhaps triple therapy may in the future be proved beneficial in the more impaired patients. More studies would be required to clarify this question Study limitations The key limitation was the small number of studies available on combined ACEi and ARBs treatment. Moreover, there was evidence of heterogeneity in some of the analyses. Nevertheless, the overall population was large enough to permit analysis and identify certain key results, and recalculations (as presented in Results) using a randomeffects model in those analyses showing heterogeneity did not affect the conclusions. Secondly, three different ARBs were used in the studies included in this meta-analysis, and only one used a uniform ACEi, whereas the rest used several ACEi, as long as treatment was optimal. We are therefore indirectly considering ACEi to have a class effect. While this viewpoint would be widely held by clinicians to be valid, there is no proof of a uniform class effect. Thirdly, the proportion of patients on h-blockers varied depending on the age of the study, from 6% in the Hamroff et al., to 55.4% in the most recent CHARM-Added. Fourthly, the prespecified combined mortality and morbidity endpoint differed between trials. Specifically, the morbidity element varied significantly. As detailed data to standardise morbidity was not available, the only unbiased solution was to use the prespecified combined endpoint definition. Finally, as pointed out above, the studies differed in their distributions of functional classes of the patients. CHARM- Added seems to have included patients with greater degree of impairment than Val-HeFT and SOLVD. However, this adds breadth to the range of patients studied Conclusions There is now satisfactory evidence that patients with heart failure who are taking ACEi but not h-blockers would benefit from routine administration of an ARB. The evidence supporting this is a significant reduction in combined morbidity mortality, without evidence of reduced mortality. For those already taking both ACEi and h-blockers, there is not convincing evidence of benefit nor of harm from giving additional ARBs. We are in equipoise for both mortality and combined morbidity mortality. Beta-blockade can no longer be considered a contraindication for combined ACEi-ARB therapy. Acknowledgements Dr. Dimopoulos is supported by the European Society of Cardiology; Dr. Salukhe is supported by the Robert Luff Fellowship; Dr. Francis was supported by the British Heart Foundation. References [1] Hedges LV, Olkin I. Statistical methods for meta-analysis. San Diego: Academic Press; Chapter 5. [2] Cochran WG. The combination of estimates from different experiments. Biometrics 1954;10: [3] Hamroff G, Katz SD, Mancini D, et al. Addition of angiotensin II receptor blockade to maximal angiotensin-converting enzyme inhibition improves exercise capacity in patients with severe congestive heart failure. Circulation 1999;99: [4] McKelvie RS, Yusuf S, Pericak D, et al. Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation 1999;100: [5] Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001;345: [6] McMurray JJ, Ostergren J, Swedberg K. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic

7 K. Dimopoulos et al. / International Journal of Cardiology 93 (2004) function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003;362: [7] Dzau VJ. Tissue renin angiotensin system in myocardial hypertrophy and failure. Arch Intern Med 1993;153: [8] CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999; 353:9 13. [9] Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 1996;334: [10] MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF). Lancet 1999;353: [11] Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone in morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341: [12] Williams SG, Cooke GA, Wright DJ, Tan LB. Disparate results of ACE inhibitor dosage on exercise capacity in heart failure: a reappraisal of vasodilator therapy and study design. Int J Cardiol 2001; 77: [13] Harjai KJ, Solis S, Prasad A, Loupe J. Use of aspirin in conjunction with angiotensin-converting enzyme inhibitors does not worsen longterm survival in heart failure. Int J Cardiol 2003;88: [14] Rousseau MF, Konstam MA, Benedict CR, et al. Progression of left ventricular dysfunction secondary to coronary artery disease, sustained neurohormonal activation and effects of ibopamine therapy during long-term therapy with angiotensin-converting enzyme inhibitor. Am J Cardiol 1994;73: [15] Francis GS, Cohn JN, Johnson G, Rector TS, Goldman S, Simon A. the V-HeFT VA Cooperative Studies Group. Plasma norepinephrine, plasma renin activity, and congestive heart failure: relations to survival and the effects of therapy in V-HeFT II. Circulation 1993;87(Suppl VI):VI [16] Jorde UP, Ennezat PV, Lisker J, Suryadevara V, Infeld J, Cukon S, et al. Maximally recommended doses of angiotensin-converting enzyme (ACE) inhibitors do not completely prevent ACE-mediated formation of angiotensin II in chronic heart failure. Circulation 2000;101: [17] St. John Sutton M, Pfeffer MA, Moye L, et al. Cardio-vascular death and left ventricular remodeling two years after myocardial infarction: baseline predictors and impact of long-term use of captopril: information from the Survival and Ventricular Enlargement (SAVE) trial. Circulation 1997;96: [18] Willenheimer R, Helmers C, Pantev E, Rydberg E, Lofdahl P, Gordon A. Safety and efficacy of valsartan versus enalapril in heart failure patients. Int J Cardiol 2002;85: [19] Pitt B, Poole-Wilson PA, et al. Effect of Losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial the Losartan Heart Failure Survival Study ELITE II. Lancet 2000;355: [20] Sharma D, Buyse M, Pitt B, Rucinska EJ. Meta-analysis of observed mortality data from all-controlled, double-blind, multiple-dose studies of losartan in heart failure. Losartan Heart Failure Mortality Metaanalysis Study Group. Am J Cardiol 2000;85: [21] Coats AJ. Angiotensin receptor blockers finally the evidence is coming in: IDNT and RENAAL. Int J Cardiol 2001;79: [22] Azizi M, Chatellier G, Guyene TT, et al. Additive effects of combined angiotensin-converting enzyme inhibition and angiotensin II antagonism on blood pressure and renin release in sodium-depleted normotensives. Circulation 1995;92: [23] Wollert KC, Drexler H. The renin angiotensin system and experimental heart failure. Cardiovasc Res 1999;43: [24] Yu G, Liang X, Xie X, Su M, Zhao S. Diverse effects of chronic treatment with losartan, fosinopril, and amlodipine on apoptosis, angiotensin II in the left ventricle of hypertensive rats. Int J Cardiol 2001;81: [25] Jong P, Demers C, McKelvie RS, Liu PP. Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials. Am Coll Cardiol 2002;39: [26] Barki-Harrington L, Luttrell LM, Rockman HA. Dual inhibition of {beta}-adrenergic and angiotensin II receptors by a single antagonist: a functional role for receptor receptor interaction in vivo. Circulation 2003;108:r [27] J.N. Cohn,Val-HeFT efficacy subgroup analyses (presentation). US Food and Drug Administration Web site. Available at ohrms/dockets/ac/01/slides/3793s1_03_efficacy%20 subgroups.pdf.

Optimal blockade of the Renin- Angiotensin-Aldosterone. in chronic heart failure

Optimal blockade of the Renin- Angiotensin-Aldosterone. in chronic heart failure Optimal blockade of the Renin- Angiotensin-Aldosterone Aldosterone- (RAA)-System in chronic heart failure Jan Östergren Department of Medicine Karolinska University Hospital Stockholm, Sweden Key Issues

More information

Understanding and Development of New Therapies for Heart Failure - Lessons from Recent Clinical Trials -

Understanding and Development of New Therapies for Heart Failure - Lessons from Recent Clinical Trials - Understanding and Development of New Therapies for Heart Failure - Lessons from Recent Clinical Trials - Clinical trials Evidence-based medicine, clinical practice Impact upon Understanding pathophysiology

More information

The role of angiotensin II receptor blockers in the management of heart failure

The role of angiotensin II receptor blockers in the management of heart failure European Heart Journal Supplements (2005) 7 (Supplement J), J10 J14 doi:10.1093/eurheartj/sui057 The role of angiotensin II receptor blockers in the management of heart failure John J.V. McMurray* Department

More information

I know the trials in heart failure but how do I manage my patient? Dosing of neurohormones antagonists

I know the trials in heart failure but how do I manage my patient? Dosing of neurohormones antagonists I know the trials in heart failure but how do I manage my patient? Dosing of neurohormones antagonists Alessandro Fucili (Ferrara, IT) Massimo F Piepoli (Piacenza, IT) Clinical Case: 82 year old woman

More information

Mayo Clin Proc, March 2003, Vol 78 Role of ARBs in Treatment of Heart Failure 335 system, tissue-based RAS has long-term effects that can modify cardi

Mayo Clin Proc, March 2003, Vol 78 Role of ARBs in Treatment of Heart Failure 335 system, tissue-based RAS has long-term effects that can modify cardi 334 Concise Review for Clinicians Therapeutic Role of Angiotensin II Receptor Blockers in the Treatment of Heart Failure Concise Review for Clinicians PRERANA MANOHAR, MD, AND ILEANA L. PIÑA, MD Angiotensin

More information

ESC Guidelines for the Diagnosis and Treatment of Chronic Heart Failure

ESC Guidelines for the Diagnosis and Treatment of Chronic Heart Failure ESC Guidelines for the Diagnosis and Treatment of Chronic Heart Failure - 2005 Karl Swedberg Professor of Medicine Department of Medicine Sahlgrenska University Hospital/Östra Göteborg University Göteborg

More information

The value of angiotensin-converting enzyme (ACE) inhibitors

The value of angiotensin-converting enzyme (ACE) inhibitors New Drugs and Technologies Which Inhibitor of the Renin Angiotensin System Should Be Used in Chronic Heart Failure and Acute Myocardial Infarction? John J.V. McMurray, MD; Marc A. Pfeffer, MD, PhD; Karl

More information

Checklist for Treating Heart Failure. Alan M. Kaneshige MD, FACC, FASE Oklahoma Heart Institute

Checklist for Treating Heart Failure. Alan M. Kaneshige MD, FACC, FASE Oklahoma Heart Institute Checklist for Treating Heart Failure Alan M. Kaneshige MD, FACC, FASE Oklahoma Heart Institute Novartis Disclosure Heart Failure (HF) a complex clinical syndrome that arises secondary to abnormalities

More information

Therapeutic Targets and Interventions

Therapeutic Targets and Interventions Therapeutic Targets and Interventions Ali Valika, MD, FACC Advanced Heart Failure and Pulmonary Hypertension Advocate Medical Group Midwest Heart Foundation Disclosures: 1. Novartis: Speaker Honorarium

More information

CKD Satellite Symposium

CKD Satellite Symposium CKD Satellite Symposium Recommended Therapy by Heart Failure Stage AHA/ACC Task Force on Practice Guideline 2001 Natural History of Heart Failure Patients surviving % Mechanism of death Sudden death 40%

More information

ACE inhibitors: still the gold standard?

ACE inhibitors: still the gold standard? ACE inhibitors: still the gold standard? Session: Twenty-five years after CONSENSUS What have we learnt about the RAAS in heart failure? Lars Køber, MD, D.Sci Department of Cardiology Rigshospitalet University

More information

The Role of Angiotensin Receptor Blockers in Heart Failure

The Role of Angiotensin Receptor Blockers in Heart Failure ARBS IN HF CHF MARCH/APRIL 2000 103 The Role of Angiotensin Receptor Blockers in Heart Failure The effectiveness of ACE inhibitors in reducing morbidity and mortality in patients with heart failure is

More information

RAS Blockade Across the CV Continuum

RAS Blockade Across the CV Continuum A Summary of Recent International Meetings RAS Blockade Across the CV Continuum Copyright New Evidence Presented at the 2009 Congress of the European Society of Cardiology (August 29-September 2, Barcelona)

More information

heart failure John McMurray University of Glasgow.

heart failure John McMurray University of Glasgow. A to Z of RAAS blockade in heart failure John McMurray BHF Cardiovascular Research Centre University of Glasgow. RAAS inhibition in CHF ACE inhibition in patients with low LVEF CHF CONSENSUS Enalapril

More information

The Therapeutic Potential of Novel Approaches to RAAS. Professor of Medicine University of California, San Diego

The Therapeutic Potential of Novel Approaches to RAAS. Professor of Medicine University of California, San Diego The Therapeutic Potential of Novel Approaches to RAAS Inhibition in Heart Failure Barry Greenberg, M.D. Professor of Medicine University of California, San Diego Chain of Events Leading to End-Stage Heart

More information

Two landmark clinical trials, CONSEN-

Two landmark clinical trials, CONSEN- Heart 2001;86:97 103 HEART FAILURE Angiotensin receptor blockers for chronic heart failure and acute myocardial infarction John J V McMurray Clinical Research Initiative in Heart Failure, Wolfson Building,

More information

Drugs acting on the reninangiotensin-aldosterone

Drugs acting on the reninangiotensin-aldosterone Drugs acting on the reninangiotensin-aldosterone system John McMurray Eugene Braunwald Scholar in Cardiovascular Diseases, Brigham and Women s Hospital, Boston & Visiting Professor, Harvard Medical School

More information

ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure

ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure Patients t with acute heart failure frequently develop chronic heart failure Patients with chronic heart failure frequently decompensate acutely ESC Guidelines for the Diagnosis and A clinical response

More information

Heart Failure Update John Coyle, M.D.

Heart Failure Update John Coyle, M.D. Heart Failure Update 2011 John Coyle, M.D. Causes of Heart Failure Anderson,B.Am Heart J 1993;126:632-40 It It is now well-established that at least one-half of the patients presenting with symptoms and

More information

Heart failure. Complex clinical syndrome. Estimated prevalence of ~2.4% (NHANES)

Heart failure. Complex clinical syndrome. Estimated prevalence of ~2.4% (NHANES) Heart failure Complex clinical syndrome caused by any structural or functional impairment of ventricular filling or ejection of blood Estimated prevalence of ~2.4% (NHANES) Etiology Generally divided into

More information

Evidence Supporting Post-MI Use of

Evidence Supporting Post-MI Use of Addressing the Gap in the Management of Patients After Acute Myocardial Infarction: How Good Is the Evidence Supporting Current Treatment Guidelines? Michael B. Fowler, MB, FRCP Beta-adrenergic blocking

More information

Congestive Heart Failure 2015

Congestive Heart Failure 2015 Definition Congestive Heart Failure 215 JP Mehegan/ Mercy Cardiology n Cardiac failure; Congestive heart failure; Chronic heart failure (synonyms) n When the heart is unable to pump sufficiently and at

More information

Online Appendix (JACC )

Online Appendix (JACC ) Beta blockers in Heart Failure Collaborative Group Online Appendix (JACC013117-0413) Heart rate, heart rhythm and prognostic effect of beta-blockers in heart failure: individual-patient data meta-analysis

More information

Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensinconverting-enzyme

Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensinconverting-enzyme Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensinconverting-enzyme inhibitors: the CHARM-Added trial John J V McMurray, Jan

More information

Treating HF Patients with ARNI s Why, When and How?

Treating HF Patients with ARNI s Why, When and How? Treating HF Patients with ARNI s Why, When and How? 19 th Annual San Diego Heart Failure Symposium for Primary Care Physicians January 11-12, 2019 La Jolla, CA Barry Greenberg M.D. Distinguished Professor

More information

Angiotensin receptor blockers in the treatment of heart failure

Angiotensin receptor blockers in the treatment of heart failure Heart Failure: Pharmacologic Management Edited by Arthur M. Feldman Copyright 2006 by Blackwell Publishing 4 CHAPTER 4 Angiotensin receptor blockers in the treatment of heart failure Anita Deswal, MD,

More information

Scientific conclusions and detailed explanation of the scientific grounds for the differences from the PRAC recommendation

Scientific conclusions and detailed explanation of the scientific grounds for the differences from the PRAC recommendation Annex I Scientific conclusions, grounds for variation to the terms of the marketing authorisations and detailed explanation of the scientific grounds for the differences from the PRAC recommendation 1

More information

Effects of Valsartan on Morbidity and Mortality in Patients With Heart Failure Not Receiving Angiotensin-Converting Enzyme Inhibitors

Effects of Valsartan on Morbidity and Mortality in Patients With Heart Failure Not Receiving Angiotensin-Converting Enzyme Inhibitors Journal of the American College of Cardiology Vol. 40, No. 8, 2002 2002 by the American College of Cardiology Foundation ISSN 0735-1097/02/$22.00 Published by Elsevier Science Inc. PII S0735-1097(02)02304-5

More information

Heart Failure Management Update

Heart Failure Management Update Heart Failure Management Update Rafique Ahmed, MD, PhD, FACC, FCPS Consultant Cardiac Electrophysiologist Baltimore, Maryland, USA Heart Failure - Definition The situation when the heart is incapable of

More information

Cost effectiveness of beta blocker therapy for patients. with chronic severe heart failure. in Ireland. M. Barry

Cost effectiveness of beta blocker therapy for patients. with chronic severe heart failure. in Ireland. M. Barry IMJ June 2002;95(6):174-177 Cost effectiveness of beta blocker therapy for patients with chronic severe heart failure in Ireland M. Barry Irish National Centre for Pharmacoeconomics Address for correspondence

More information

Impact of the African American Heart Failure Trial (A-HeFT): Guideline-based Therapy in Blacks with Heart Failure 2016

Impact of the African American Heart Failure Trial (A-HeFT): Guideline-based Therapy in Blacks with Heart Failure 2016 Impact of the African American Heart Failure Trial (A-HeFT): Guideline-based Therapy in Blacks with Heart Failure 2016 National Minority Quality forum APRIL 11, 2016 Washington,D.C. Keith C. Ferdinand,

More information

Data Alert #2... Bi o l o g y Work i n g Gro u p. Subject: HOPE: New validation for the importance of tissue ACE inhibition

Data Alert #2... Bi o l o g y Work i n g Gro u p. Subject: HOPE: New validation for the importance of tissue ACE inhibition Vascular Bi o l o g y Work i n g Gro u p c/o Medical Education Consultants, In c. 25 Sy l van Road South, We s t p o rt, CT 06880 Chairman: Carl J. Pepine, MD Professor and Chief Division of Cardiovascular

More information

A patient with decompensated HF

A patient with decompensated HF A patient with decompensated HF Professor Michel KOMAJDA University Pierre & Marie Curie Pitie Salpetriere Hospital Department of Cardiology Paris (France) Declaration Of Interest 2010 Speaker : Servier,

More information

Heart Failure and Cardiomyopathy Center, Division of Cardiology, North Shore University Hospital, Manhasset, NY

Heart Failure and Cardiomyopathy Center, Division of Cardiology, North Shore University Hospital, Manhasset, NY NEUROHORMONAL ANTAGONISTS IN THE POST-MI PATIENT New Evidence from the CAPRICORN Trial: The Role of Carvedilol in High-Risk, Post Myocardial Infarction Patients Jonathan D. Sackner-Bernstein, MD, FACC

More information

Update on pharmacological treatment of heart failure. Aldo Pietro Maggioni, MD, FESC ANMCO Research Center Firenze, Italy

Update on pharmacological treatment of heart failure. Aldo Pietro Maggioni, MD, FESC ANMCO Research Center Firenze, Italy Update on pharmacological treatment of heart failure Aldo Pietro Maggioni, MD, FESC ANMCO Research Center Firenze, Italy Presenter Disclosures Dr. Maggioni : Serving in Committees of studies sponsored

More information

Definition of Congestive Heart Failure

Definition of Congestive Heart Failure Heart Failure Definition of Congestive Heart Failure A clinical syndrome of signs & symptoms resulting from the heart s inability to supply adequate tissue perfusion. CHF Epidemiology Affects 4.7 million

More information

CT Academy of Family Physicians Scientific Symposium October 2012 Amit Pursnani, MD

CT Academy of Family Physicians Scientific Symposium October 2012 Amit Pursnani, MD CT Academy of Family Physicians Scientific Symposium October 2012 Amit Pursnani, MD Clinical syndrome resulting from a structural or functional cardiac disorder that impairs the ability of the heart to

More information

Contemporary Advanced Heart Failure Therapy

Contemporary Advanced Heart Failure Therapy Contemporary Advanced Heart Failure Therapy Andrew Boyle, MD Professor of Medicine Medical Director of Advanced Heart Failure Thomas Jefferson University Philadelphia, PA Audience Response Question 40

More information

Heart Failure. Mortality and Morbidity Reduction With Candesartan in Patients With Chronic Heart Failure and Left Ventricular Systolic Dysfunction

Heart Failure. Mortality and Morbidity Reduction With Candesartan in Patients With Chronic Heart Failure and Left Ventricular Systolic Dysfunction Heart Failure Mortality and Morbidity Reduction With Candesartan in Patients With Chronic Heart Failure and Left Ventricular Systolic Dysfunction Results of the CHARM Low Left Ventricular Ejection Fraction

More information

LXIV: DRUGS: 4. RAS BLOCKADE

LXIV: DRUGS: 4. RAS BLOCKADE LXIV: DRUGS: 4. RAS BLOCKADE ACE Inhibitors Components of RAS Actions of Angiotensin i II Indications for ACEIs Contraindications RAS blockade in hypertension RAS blockade in CAD RAS blockade in HF Limitations

More information

Optimal Adrenergic Blockades in Heart Failure. Jae-Joong Kim MD, PhD Asan Medical Center, University of Ulsan, Seoul, Korea

Optimal Adrenergic Blockades in Heart Failure. Jae-Joong Kim MD, PhD Asan Medical Center, University of Ulsan, Seoul, Korea Optimal Adrenergic Blockades in Heart Failure Jae-Joong Kim MD, PhD Asan Medical Center, University of Ulsan, Seoul, Korea Contents Harmful effects of adrenergic system in heart failure Clinical studies

More information

Position Statement on ALDOSTERONE ANTAGONIST THERAPY IN CHRONIC HEART FAILURE

Position Statement on ALDOSTERONE ANTAGONIST THERAPY IN CHRONIC HEART FAILURE Position Statement on ALDOSTERONE ANTAGONIST THERAPY IN CHRONIC HEART FAILURE Over 8,000 patients have been studied in two well-designed placebo-controlled outcome-driven clinical trials to evaluate the

More information

Heart Failure Clinician Guide JANUARY 2016

Heart Failure Clinician Guide JANUARY 2016 Kaiser Permanente National CLINICAL PRACTICE GUIDELINES Heart Failure Clinician Guide JANUARY 2016 Introduction This evidence-based guideline summary is based on the 2016 National Heart Failure Guideline.

More information

Review Article. Pharmacotherapy of Heart Failure with Reduced LVEF. Sachin Mukhedkar, Ajit Bhagwat

Review Article. Pharmacotherapy of Heart Failure with Reduced LVEF. Sachin Mukhedkar, Ajit Bhagwat Review Article Vidarbha Journal of Internal Medicine Volume 22 January 2017 Pharmacotherapy of Heart Failure with Reduced LVEF 1 2 Sachin Mukhedkar, Ajit Bhagwat ABSTRACT Heart failure with reduced ejection

More information

ESC Guidelines for diagnosis and management of HF 2012: What s new? John Parissis, MD Athens, GR

ESC Guidelines for diagnosis and management of HF 2012: What s new? John Parissis, MD Athens, GR ESC Guidelines for diagnosis and management of HF 2012: What s new? John Parissis, MD Athens, GR Disclosures ALARM INVESTIGATOR RESEARCH GRANTS BY ABBOTT USA AND ORION PHARMA The principal changes from

More information

Heart Failure Clinician Guide JANUARY 2018

Heart Failure Clinician Guide JANUARY 2018 Kaiser Permanente National CLINICAL PRACTICE GUIDELINES Heart Failure Clinician Guide JANUARY 2018 Introduction This evidence-based guideline summary is based on the 2018 National Heart Failure Guideline.

More information

Pharmacological Treatment for Chronic Heart Failure. Dr Elaine Chau HK Sanatorium & Hospital, Hong Kong 3 August 2014

Pharmacological Treatment for Chronic Heart Failure. Dr Elaine Chau HK Sanatorium & Hospital, Hong Kong 3 August 2014 Pharmacological Treatment for Chronic Heart Failure Dr Elaine Chau HK Sanatorium & Hospital, Hong Kong 3 August 2014 1 ACC/AHA 2005 guideline update for Diagnosis & management of CHF in the Adult -SA Hunt

More information

Combination of renin-angiotensinaldosterone. how to choose?

Combination of renin-angiotensinaldosterone. how to choose? Combination of renin-angiotensinaldosterone system inhibitors how to choose? Karl Swedberg Professor of Medicine Sahlgrenska Academy University of Gothenburg karl.swedberg@gu.se Disclosures Research grants

More information

Satish K Surabhi, MD.FACC,FSCAI,RPVI Medical Director, Cardiac Cath Labs AnMed Health Heart & Vascular Care

Satish K Surabhi, MD.FACC,FSCAI,RPVI Medical Director, Cardiac Cath Labs AnMed Health Heart & Vascular Care Satish K Surabhi, MD.FACC,FSCAI,RPVI Medical Director, Cardiac Cath Labs AnMed Health Heart & Vascular Care None Fig. 1. Progression of Heart Failure.With each hospitalization for acute heart failure,

More information

Heart Failure: Combination Treatment Strategies

Heart Failure: Combination Treatment Strategies Heart Failure: Combination Treatment Strategies M. McDonald MD, FRCP State of the Heart Symposium May 28, 2011 None Disclosures Case 69 F, prior MIs (LV ejection fraction 25%), HTN No demonstrable ischemia

More information

Disclosures. Overview. Goal statement. Advances in Chronic Heart Failure Management 5/22/17

Disclosures. Overview. Goal statement. Advances in Chronic Heart Failure Management 5/22/17 Disclosures Advances in Chronic Heart Failure Management I have nothing to disclose Van N Selby, MD UCSF Advanced Heart Failure Program May 22, 2017 Goal statement To review recently-approved therapies

More information

Beta-blockers in heart failure: evidence put into practice

Beta-blockers in heart failure: evidence put into practice Beta-blockers in heart failure: evidence put into practice John McMurray Professor of Medical Cardiology, University of Glasgow & Consultant Cardiologist,Western Infirmary, Glasgow, UK Eugene Braunwald

More information

eplerenone 25, 50mg film-coated tablets (Inspra ) SMC No. (793/12) Pfizer Ltd

eplerenone 25, 50mg film-coated tablets (Inspra ) SMC No. (793/12) Pfizer Ltd eplerenone 25, 50mg film-coated tablets (Inspra ) SMC No. (793/12) Pfizer Ltd 08 June 2012 The Scottish Medicines Consortium (SMC) has completed its assessment of the above product and advises NHS Boards

More information

Metoprolol CR/XL in Female Patients With Heart Failure

Metoprolol CR/XL in Female Patients With Heart Failure Metoprolol CR/XL in Female Patients With Heart Failure Analysis of the Experience in Metoprolol Extended-Release Randomized Intervention Trial in Heart Failure (MERIT-HF) Jalal K. Ghali, MD; Ileana L.

More information

Heart Failure Treatments

Heart Failure Treatments Heart Failure Treatments Past & Present www.philippelefevre.com Background Background Chronic heart failure Drugs Mechanical Electrical Background Chronic heart failure Drugs Mechanical Electrical Sudden

More information

Disclosures for Presenter

Disclosures for Presenter A Comparison of Angiotensin Receptor- Neprilysin Inhibition (ARNI) With ACE Inhibition in the Long-Term Treatment of Chronic Heart Failure With a Reduced Ejection Fraction Milton Packer, John J.V. McMurray,

More information

Since the initial description of angiotensin II mediated

Since the initial description of angiotensin II mediated CLINICAL CARDIOLOGY: PHYSICIAN UPDATE Manipulation of the Renin-Angiotensin System Michael M. Givertz, MD Since the initial description of angiotensin II mediated hypertension 40 years ago, basic and clinical

More information

DISCLAIMER: ECHO Nevada emphasizes patient privacy and asks participants to not share ANY Protected Health Information during ECHO clinics.

DISCLAIMER: ECHO Nevada emphasizes patient privacy and asks participants to not share ANY Protected Health Information during ECHO clinics. DISCLAIMER: Video will be taken at this clinic and potentially used in Project ECHO promotional materials. By attending this clinic, you consent to have your photo taken and allow Project ECHO to use this

More information

Entresto Development of sacubitril/valsartan (LCZ696) for the treatment of heart failure with reduced ejection fraction

Entresto Development of sacubitril/valsartan (LCZ696) for the treatment of heart failure with reduced ejection fraction Cardio-Metabolic Franchise Entresto Development of sacubitril/valsartan (LCZ696) for the treatment of heart failure with reduced ejection fraction Randy L Webb, PhD Rutgers Workshop October 21, 2016 Heart

More information

Report on the Expert Group Meeting of Paediatric Heart Failure, London 29 November 2010

Report on the Expert Group Meeting of Paediatric Heart Failure, London 29 November 2010 Report on the Expert Group Meeting of Paediatric Heart Failure, London 29 November Clinical trials in Paediatric Heart Failure List of participants: Michael Burch, Hugo Devlieger, Angeles Garcia, Daphne

More information

ACE inhibitors vs ARBs: Is one class better for heart failure?

ACE inhibitors vs ARBs: Is one class better for heart failure? HEART FAILURE UPDATE MARK E. DUNLAP, MD * Associate Professor of Medicine, Physiology, and Biophysics, Case Western Reserve University School of Medicine, and Louis B. Stokes Cleveland VA Medical Center,

More information

MEDICAL MANAGEMENT OF PATIENTS WITH HEART FAILURE AND REDUCED EJECTION FRACTION

MEDICAL MANAGEMENT OF PATIENTS WITH HEART FAILURE AND REDUCED EJECTION FRACTION MEDICAL MANAGEMENT OF PATIENTS WITH HEART FAILURE AND REDUCED EJECTION FRACTION FRANCIS X. CELIS, D.O. OPSO FALL CONFERENCE PORTLAND, OR 16 SEPTEMBER 2017 OVERVIEW What are the ACC/AHA Stages of HF? What

More information

Disclosures. Advances in Chronic Heart Failure Management 6/12/2017. Van N Selby, MD UCSF Advanced Heart Failure Program June 19, 2017

Disclosures. Advances in Chronic Heart Failure Management 6/12/2017. Van N Selby, MD UCSF Advanced Heart Failure Program June 19, 2017 Advances in Chronic Heart Failure Management Van N Selby, MD UCSF Advanced Heart Failure Program June 19, 2017 I have nothing to disclose Disclosures 1 Goal statement To review recently-approved therapies

More information

Rate of Heart failure guideline adherence in a tertiary care center in India after accounting for the therapeutic contraindications.

Rate of Heart failure guideline adherence in a tertiary care center in India after accounting for the therapeutic contraindications. Article ID: WMC004618 ISSN 2046-1690 Rate of Heart failure guideline adherence in a tertiary care center in India after accounting for the therapeutic contraindications. Peer review status: No Corresponding

More information

Introduction: Clinical Trials: Assessing Safety and Efficacy for a Diverse Population

Introduction: Clinical Trials: Assessing Safety and Efficacy for a Diverse Population Introduction: Clinical Trials: Assessing Safety and Efficacy for a Diverse Population FDA and JHU-CERSI White Oak, Maryland Wednesday, December 2, 2015 Keith C. Ferdinand, MD, FACC,FAHA,FNLA,FASH Professor

More information

Review. Renin Inhibitors in Chronic Heart Failure: The Aliskiren Observation of Heart Failure Treatment Study in Context

Review. Renin Inhibitors in Chronic Heart Failure: The Aliskiren Observation of Heart Failure Treatment Study in Context Review Renin Inhibitors in Chronic Heart Failure: The Aliskiren Observation of Heart Failure Treatment Study in Context Address for correspondence: HenryKrum,MBBS,PhD,FRACP Centre of Cardiovascular Research

More information

Beyond neuro-hormonal blockade

Beyond neuro-hormonal blockade Beyond neuro-hormonal blockade Giuseppe M.C. Rosano, MD, PhD, MSc, FESC, FHFA St George s Hospitals NHS Trust University of London KCS Congress: Impact through collaboration CONTACT: Tel. +254 735 833

More information

The burden of disease in patients with. What s New. Heart Failure? In this article:

The burden of disease in patients with. What s New. Heart Failure? In this article: What s New in Heart Failure? A large part of the population is at risk for congestive heart failure. With one-year mortality rates approaching 40%, it is crucial to understand the newest and best treatment

More information

Treating Heart Failure in Biodiverse Patient Populations: Best Practices and Unveiling Disparities in Blacks

Treating Heart Failure in Biodiverse Patient Populations: Best Practices and Unveiling Disparities in Blacks Treating Heart Failure in Biodiverse Patient Populations: Best Practices and Unveiling Disparities in Blacks 12th Annual Leadership Summit on Health Disparities & Congressional Black Caucus Spring Health

More information

Effects of heart rate reduction with ivabradine on left ventricular remodeling and function:

Effects of heart rate reduction with ivabradine on left ventricular remodeling and function: Systolic Heart failure treatment with the If inhibitor ivabradine Trial Effects of heart rate reduction with ivabradine on left ventricular remodeling and function: results of the SHIFT echocardiography

More information

The Management of Heart Failure after Biventricular Pacing

The Management of Heart Failure after Biventricular Pacing The Management of Heart Failure after Biventricular Pacing Juan M. Aranda, Jr., MD University of Florida College of Medicine, Division of Cardiovascular Medicine, Gainesville, Florida Approximately 271,000

More information

Φαρμακευτική θεραπεία της μετεμφραγματικής καρδιακής ανεπάρκειας. Α. Καραβίδας Υπεύθυνος ιατρείου καρδιακής ανεπάρκειας Γ.Ν.Α Γ.

Φαρμακευτική θεραπεία της μετεμφραγματικής καρδιακής ανεπάρκειας. Α. Καραβίδας Υπεύθυνος ιατρείου καρδιακής ανεπάρκειας Γ.Ν.Α Γ. Φαρμακευτική θεραπεία της μετεμφραγματικής καρδιακής ανεπάρκειας Α. Καραβίδας Υπεύθυνος ιατρείου καρδιακής ανεπάρκειας Γ.Ν.Α Γ.Γεννηματάς Clinical Trials on Fibrinolysis N = 61.41 AMI pts, ( GUSTO I, GUSTOIIb,

More information

HEART FAILURE SUMMARY. and is associated with significant morbidity and mortality. the cornerstone of heart failure treatment.

HEART FAILURE SUMMARY. and is associated with significant morbidity and mortality. the cornerstone of heart failure treatment. HEART FAILURE SUMMARY + Heart Failure is a condition affecting a large number of Irish people and is associated with significant morbidity and mortality. + ACE inhibitors, in combination with diuretics,

More information

Guideline-Directed Medical Therapy

Guideline-Directed Medical Therapy Guideline-Directed Medical Therapy Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation OPTIMAL THERAPY (As defined in

More information

National Horizon Scanning Centre. Irbesartan (Aprovel) for heart failure with preserved systolic function. August 2008

National Horizon Scanning Centre. Irbesartan (Aprovel) for heart failure with preserved systolic function. August 2008 Irbesartan (Aprovel) for heart failure with preserved systolic function August 2008 This technology summary is based on information available at the time of research and a limited literature search. It

More information

Heart Failure Council of Thailand (HFCT) 2019 Heart Failure Guideline: Pharmacologic Treatment of Chronic Heart Failure - Part I

Heart Failure Council of Thailand (HFCT) 2019 Heart Failure Guideline: Pharmacologic Treatment of Chronic Heart Failure - Part I Clinical Practice Guideline Heart Failure Council of Thailand (HFCT) 2019 Heart Failure Guideline: Pharmacologic Treatment of Chronic Heart Failure - Part Buakhamsri, MD¹, Chirakarnjanakorn S, MD², Sanguanwong

More information

LCZ696 A First-in-Class Angiotensin Receptor Neprilysin Inhibitor

LCZ696 A First-in-Class Angiotensin Receptor Neprilysin Inhibitor The Angiotensin Receptor Neprilysin Inhibitor LCZ696 in Heart Failure with Preserved Ejection Fraction The Prospective comparison of ARNI with ARB on Management Of heart failure with preserved ejection

More information

The benefit of treatment with -blockers in heart failure is

The benefit of treatment with -blockers in heart failure is Heart Rate and Cardiac Rhythm Relationships With Bisoprolol Benefit in Chronic Heart Failure in CIBIS II Trial Philippe Lechat, MD, PhD; Jean-Sébastien Hulot, MD; Sylvie Escolano, MD, PhD; Alain Mallet,

More information

Neprilysin Inhibitor (Entresto ) Prior Authorization and Quantity Limit Program Summary

Neprilysin Inhibitor (Entresto ) Prior Authorization and Quantity Limit Program Summary Neprilysin Inhibitor (Entresto ) Prior Authorization and Quantity Limit Program Summary FDA APPROVED INDICATIONS DOSAGE 1 Indication Entresto Reduce the risk of cardiovascular (sacubitril/valsartan) death

More information

Cardiovascular Guideline-Driven Pharmacotherapies: Optimizing Management

Cardiovascular Guideline-Driven Pharmacotherapies: Optimizing Management Cardiovascular Guideline-Driven Pharmacotherapies: Optimizing Management David Parra, Pharm.D., FCCP, BCPS Clinical Pharmacy Program Manager in Cardiology/Anticoagulation VISN 8 Pharmacy Benefits Management

More information

Heart Failure New Drugs- Updated Guidelines

Heart Failure New Drugs- Updated Guidelines Heart Failure New Drugs- Updated Guidelines Eileen Handberg, PhD, ANP-BC, FAHA, FACC Professor of Medicine Division of Cardiovascular Medicine University of Florida Disclosures 1. 3 2. 6 3. 8 4. 11 Dunlay

More information

How do heart failure patients die?

How do heart failure patients die? European Heart Journal Supplements (2002) 4 (Supplement D), D59-D65 How do heart failure patients die? University of Bergen and Cardiology Division, Central Hospital in Rogaland, Stavanger, Norway Approximately

More information

Changes in Brain Natriuretic Peptide and Norepinephrine Over Time and Mortality and Morbidity in the Valsartan Heart Failure Trial (Val-HeFT)

Changes in Brain Natriuretic Peptide and Norepinephrine Over Time and Mortality and Morbidity in the Valsartan Heart Failure Trial (Val-HeFT) Changes in Brain Natriuretic Peptide and Norepinephrine Over Time and Mortality and Morbidity in the Valsartan Heart Failure Trial (Val-HeFT) Inder S. Anand, MD, DPhil; Lloyd D. Fisher, PhD; Yann-Tong

More information

2017 Summer MAOFP Update

2017 Summer MAOFP Update 2017 Summer MAOFP Update. Cardiology Update 2017 Landmark Trials Change Practice Guidelines David J. Strobl, DO, FNLA Heart Failure: Epidemiology More than 4 million patients affected 400,000 new cases

More information

Management of Myocardial Infarction & Congestive Heart Failure. Dr. Dionne Dames-Rahming

Management of Myocardial Infarction & Congestive Heart Failure. Dr. Dionne Dames-Rahming Management of Myocardial Infarction & Congestive Heart Failure Dr. Dionne Dames-Rahming Myocardial Infarction Objectives of Medical Management Decrease morbidity Reduce further myocardial damage or injury

More information

Treatment of Heart Failure: Current Recommendation Waiz A

Treatment of Heart Failure: Current Recommendation Waiz A Treatment of Heart Failure: Current Recommendation Waiz A The impaired left ventricular emptying that characterizes heart failure may result from a variety of cardiac diseases, including myocardial ischaemia

More information

Aldosterone Antagonism in Heart Failure: Now for all Patients?

Aldosterone Antagonism in Heart Failure: Now for all Patients? Aldosterone Antagonism in Heart Failure: Now for all Patients? Inder Anand, MD, FRCP, D Phil (Oxon.) Professor of Medicine, University of Minnesota, Director Heart Failure Program, VA Medical Center 111C

More information

Module 1: Evidence-based Education for Health Care Professionals

Module 1: Evidence-based Education for Health Care Professionals Module 1: Evidence-based Education for Health Care Professionals Heart Failure is a HUGE Problem Prevalence Incidence Mortality Hospital Discharges Cost 1 5,300,000 660,000 284,965 1,084,000 $34.8 billion

More information

By Prof. Khaled El-Rabat

By Prof. Khaled El-Rabat What is The Optimum? By Prof. Khaled El-Rabat Professor of Cardiology - Benha Faculty of Medicine HT. Introduction Despite major worldwide efforts over recent decades directed at diagnosing and treating

More information

ANGIOTENSIN-CONVERTING

ANGIOTENSIN-CONVERTING BRIEF REPORT Impact of on Nonfatal Myocardial Infarction and Cardiovascular Death in Patients With Heart Failure Catherine Demers, MD, MSc John J. V. McMurray, MD Karl Swedberg, MD, PhD Marc A. Pfeffer,

More information

Trials Enrolled subjects Findings Fox et al. 2014, SIGNIFY 1

Trials Enrolled subjects Findings Fox et al. 2014, SIGNIFY 1 Appendix 5 (as supplied by the authors): Published trials on the effect of ivabradine on outcomes including mortality in patients with different cardiovascular diseases Trials Enrolled subjects Findings

More information

Heart Failure Medical and Surgical Treatment

Heart Failure Medical and Surgical Treatment Heart Failure Medical and Surgical Treatment Daniel S. Yip, M.D. Medical Director, Heart Failure and Transplantation Mayo Clinic Second Annual Lakeland Regional Health Cardiovascular Symposium February

More information

Case 1: A 54-year-old man with

Case 1: A 54-year-old man with CLINICIAN UPDATE -Blockers in Chronic Heart Failure Mihai Gheorghiade, MD; Wilson S. Colucci, MD; Karl Swedberg, MD Case 1: A 54-year-old man with a history of myocardial infarction (MI) presented with

More information

CONGESTIVE HEART FAILURE

CONGESTIVE HEART FAILURE abstract CONGESTIVE HEART FAILURE Pharmacological Management of Systolic Heart Failure in Older Adults Heart failure is common in older adults and is associated with high mortality and hospitalization

More information

The Beneficial Role of Angiotensin- Converting Enzyme Inhibitor in Acute Myocardial Infarction

The Beneficial Role of Angiotensin- Converting Enzyme Inhibitor in Acute Myocardial Infarction The Beneficial Role of Angiotensin- Converting Enzyme Inhibitor in Acute Myocardial Infarction Cardiovascular Center, Korea University Guro Hospital 2007. 4. 20 Seung-Woon Rha, MD, PhD Introduction 1.

More information

Behandlungsalgorithmus bei Herzinsuffizienz mit reduzierter Auswurffraktion

Behandlungsalgorithmus bei Herzinsuffizienz mit reduzierter Auswurffraktion Behandlungsalgorithmus bei Herzinsuffizienz mit reduzierter Auswurffraktion Professor Dr. med. Roger Hullin Leiter Programm für Schwere Herzinsuffizienz, VAD & Herztransplantation Suisse Romande Klinik

More information

Do Cardiologists at a University Hospital Adopt the Guidelines for the Treatment of Heart Failure?

Do Cardiologists at a University Hospital Adopt the Guidelines for the Treatment of Heart Failure? Original Article Do Cardiologists at a University Hospital Adopt the Guidelines for the Treatment of Heart Failure? Antonio Carlos Pereira Barretto, Moacyr Roberto Cucê Nobre, Inês Lancarotte, Airton Roberto

More information

TERAPIA DELLO SCOMPENSO DAI BETA- BLOCCANTI AGLI ARNI (ARNI SI ARNI NO) Iseo 10 Novembre 2018

TERAPIA DELLO SCOMPENSO DAI BETA- BLOCCANTI AGLI ARNI (ARNI SI ARNI NO) Iseo 10 Novembre 2018 TERAPIA DELLO SCOMPENSO DAI BETA- BLOCCANTI AGLI ARNI (ARNI SI ARNI NO) Iseo 10 Novembre 2018 Carlo Lombardi Cattedra di Cardiologia Università e Spedali Civili di Brescia All-cause mortality in the European

More information

Metoprolol Succinate SelokenZOC

Metoprolol Succinate SelokenZOC Metoprolol Succinate SelokenZOC Blood Pressure Control and Far Beyond Mohamed Abdel Ghany World Health Organization - Noncommunicable Diseases (NCD) Country Profiles, 2014. 1 Death Rates From Ischemic

More information