Savvato 5a Nikolaou by SAN PUBLICATIONS

ΥΠΟΛΙΠΙΔΑΙΜΙΚΗ ΑΓΩΓΗ ΣΕ ΑΣΘΕΝΕΙΣ ΜΕ ΚΑΡΔΙΑΚΗ ΑΝΕΠΑΡΚΕΙΑ

Classification of HF: Comparison Between ACC/AHA HF Stage and NYHA Functional Class ACC/AHA HF Stage1

NYHA Functional Class2 None

A At high risk for heart failure but without structural heart disease or symptoms of heart failure (eg, patients with hypertension or coronary artery disease) B Structural heart disease but without symptoms of heart failure

C Structural heart disease with prior or current symptoms of heart failure

D Refractory heart failure requiring specialized interventions

1Hunt

Asymptomatic

II Symptomatic with moderate exertion III Symptomatic with minimal exertion

IV Symptomatic at rest

SA et al. J Am Coll Cardiol. 2001;38:2101–2113.

2New York

Heart Association/Little Brown and Company, 1964. Adapted from: Farrell MH et al. JAMA. 2002;287:890–897.

Συμπτωματική καρδιακή ανεπάρκεια στο 2 % των ενηλίκων >45 ετών. Κίνδυνος εμφάνισης καρδιακής ανεπάρκειας κατά τη διάρκεια της ζωής περίπου 20 %.

ΣΥΧΝΟΤΗΤΑ ΚΑΡΔΙΑΚΗΣ ΑΝΕΠΑΡΚΕΙΑΣ ΑΝΑΛΟΓΑ ΜΕ ΤΟ ΦΥΛΟ ΚΑΙ ΤΗΝ ΗΛΙΚΙΑ NHANES 1999-2004

Epidemiology of Heart Failure in the US Heart Failure Patients in US (Millions)

10 8

• 550,000 new cases/year

6 4

• More deaths from heart failure than from all forms of cancer combined

4.7

• 4.7 million symptomatic patients; estimated 10 million in 2037

3.5

2 0

1991

2000

2037*

*Rich M. J Am Geriatric Soc. 1997;45:968–974. American Heart Association. 2001 Heart and Stroke Statistical Update. 2000.

Τάσεις μεταβολής του επιπολασμού της καρδιακής ανεπάρκειας Γυναίκες

Περιστατικά ανά 1.000 έτη ασθενών

Άνδρες

Ηλικιακή ομάδα (έτη)

Θνησιμότητα στο 1 έτος ρυθμισμένη ως προς την ηλικία

Τάσεις μεταβολής της επιβίωσης στην καρδιακή ανεπάρκεια

Άνδρες

Γυναίκες

Τεκμηριωμένες θεραπείες στη συστολική καρδιακή ανεπάρκεια Θεραπεία

μείωση σχετικός κινδύυνου θνησιμότητας από οποιοδήποτε αίτιο

α-ΜΕΑ /ARB

17-25%

β-Αποκλειστές

34-35%

Ανταγωνιστές αλδοστερόνης

15-30%

(ALDACTONE, INSPRA) Υδραλαζίνη (NEPREZOL)

43%

ICD

23%



Αντιπηκτικά, Ασπιρίνη, Αντιαρρυθμικά, Ινότροπα .



Στατίνες, ω3 ;

Στόχοι της θεραπείας Βελτίωση των συμπτωμάτων

Επιβράδυνση της εξέλιξης Μακροχρόνια επιβίωση

ΚΑΡΔΙΑΚΗ ΑΝΕΠΑΡΚΕΙΑ & ΣΤΑΤΙΝΕΣ ! • Μελέτη 4S : ΚΑ, στην ομάδα εικονικού φαρμάκου 10,3% και στην ομάδα της σιμβαστατίνης 8,3% , (19%) (P<0,015). • Μελέτη CARE : ΚΑ, 13,8% και 10,9% για το εικονικό φάρμακο και την πραβαστατίνη αντίστοιχα, (21%) (P=0,10).

• Μελέτη 4S : Στην ομάδα του εικονικού φαρμάκου, 52% των ασθενών που ανέπτυξαν ΚΑ παρουσίασαν ΟΕΜ μετά την τυχαιοποίηση, ενώ στην ομάδα των ασθενών που δεν ανέπτυξαν ΚΑ, το ποσοστό του ΕΜ ήταν μόνο 16%. • SOLVD 6 : το ΟΕΜ και η ασταθής στηθάγχη αυξάνουν τον κίνδυνο θανάτου και της εισαγωγής σε νοσοκομείο για ΧΚΑ. Aronow WS, Am J Cardiol 1999;84: 611-612.

Study

Study design

HF included patients

Conclusions

IDEAL

8888 AMI. atorva 80 vs

537 patients (simva 5.5% and atorva 6.6%)

Atorva vs simva, 19% reductions (in hospitalisation for HF [HR (95% CI): 0.81, p = 0.11]

TNT

10,001 (stable CHD and

781 patients (10 mg 7.6% and 80 mg 8.1%)

80 mg vs 10 mg of atorva, 26% reductions (in hospitalisation for HF [HR (95% CI): 0.74 , p = 0.01]. In a post hoc analysis, this benefit was observed only in patients with a history of HF.

162 patients (5.8% in the atorva vs. 7.4% in the usual care)

There was a 27% reduction hospitalisation for HF in atorvastatin [HR (95% CI): 0.73); p = NS]

simva 20). FU: 4.8 years. Primary endpoint: occurrence of a major coronary event

LDL cholesterol <130 mg/dL), 10 mg vs 80 mg of atorva. FU: 4.9 years. Primary end point: occurrence of a first major cardiovascular event

ALLIANCE 2442 CHD, atorva vs usual care. FU : 51.5 months Primary efficacy parameter: time to first CDV event

Study

Study design

HF included patients

Conclusions

LIPID

9014 (MI or unstable angina), prava 40 mg vs placebo. FU : 6.1 years. Primary endpoint: mortality from CHD.

There were no patients with HF at baseline

There were more deaths from HF in the placebo group (46) compared with the pravastatin group (36) (p < 0.05).

A to Z

ACS simv, placebo & 20 mg/d vs 40 mg/d & 80 mg/d . FU : 6– 24 months. Primary end point: CDV death, nonfatal MI, readmission for ACS, and stroke

221 patients (4% vs 6%)

New onset HF was reduced by 18% (from 5.0% in the placebo plus simvastatin group to 3.7% in the simvastatin only group) [HR (95% CI): 0.72 (0.53–0.98); (p = 0.04).

HYRIM

568 hypertensive men were fluvastatin, 40 mg vs placebo. FU : 4 years. Primary endpoint: the IMT and secondary endpoint: left ventricular mass progression

There were no patients with HF at baseline

Fluvastatin reduced left ventricular mass over 2 years compared with placebo (p = 0.0144).

GREACE

1600 CHD, atorva (10 to 80 mg) vs ‘‘usual’’ medical care. FU : 3 years Primary endpoint: death, nonfatal MI, unstable angina, HF, revascularisation (coronary morbidity) and stroke.

118 patients (63 in atorva group vs 55 usual care group) with NYHA class I or II.

There was a large reduction in the primary endpoint in the atorvastatin group when compared with the ‘‘usual care’’ group (_50%, p = 0.021) within the subgroup of HF patients.

Retrospective sub-group analysis of 4S trial 19% reduction

Mortality (%)

placebo simvastatin

31.9%

25.5%

25 20

28% reduction

9.2%

6.6% 5 0 n=228

n=184

Heart failure Statistical tests Kjekshus J etnot al. performed J Card Fail 1997;3:249â&#x20AC;&#x201C;254

n=1995

n=2037

No heart failure

Heart Failure Hospitalizations in the Treating to New Targets (TNT) Study Proportion of patients experiencing CHF with hospitalization

0.10

0.08

0.06

Hazard ratio = 0.74 95% CI 0.59-0.94 P=0.012

0.04

atorvastatin 10 mg

atorvastatin 80 mg

0.02

0.00 0

Months

Number at risk: ATV 10 mg

5006

4972

4877

4840

4791

4746

4692

4645

4586

2451

514

ATV 80 mg

4995

4969

4937

4895

4861

4825

4778

4735

4687

4611

2453

483

Khush KK et al. Circulation 2007:115;576â&#x20AC;&#x201C;583

Post-hoc analysis of Treating to New Targets (TNT) Study Proportion of patients experiencing CHF with hospitalization

0.20

Patients with prior CHF atorvastatin 10 mg (N=404) atorvastatin 80 mg (N=377)

0.18

Hazard ratio = 0.59 (95% CI 0.40-0.88) P=0.008

0.16 0.14

0.12 0.10 0.08 Patients without prior CHF atorvastatin 10 mg (N=4602) atorvastatin 80 mg (N=4818)

0.06

0.04

Hazard ratio = 0.87 (95% CI 0.84-1.16) P=0.34

0.02 0.00 0

Months CHFKhush â&#x20AC;&#x201C; chronic failure 2007:115;576â&#x20AC;&#x201C;583 KK etheart al. Circulation

Statins and Risks for Death and Heart Failure Hospitalisation in 25,000 heart failure patients northern California , 2.4 years

Rate per 100 person-years

Rate of Death

Rate of Hospitalization

0 No.

Overall

Baseline CHD

24598

19705

No Baseline CHD 4893 No Statin

Go A et al. JAMA 2006;296:2105â&#x20AC;&#x201C;2111

0 No.

Overall

Baseline CHD

No Baseline CHD

24598

19705

4893

Statin

ΑΗΑ 07

FREE NEJM E-TOC

CORONA study Controlled rosuvastatin multinational trial in heart failure Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Hydroxymethylglutaryl–coenzyme A reductase inhibitors (statins) represent one of the most important pharmacologic advances in the prevention of cardiovascular disease in decades. Since the publication of the Scandinavian Simvastatin Survival Study in 1994,1 several trials have demonstrated important benefits of statins in patients with established coronary disease. These findings have resulted in strong recommendations for the use of statins in clinical-practice guidelines.2 Statins are one of the few classes of drugs that are embedded in clinicalperformance measures for coronary artery disease, which indicates that clinicians should be considered remiss if they do not prescribe these agents for all their eligible patients.3

Philip J Barter MBBS, PhD, John J V McMurray MD, Christie M Ballantyne MD

Study design 371 centres in 21 countries (Europe, Russia, S. Africa) - Systolic HF of ischemic etiology - Age ≥60 years - Ejection fraction ≤0.40 (NYHA III/IV) or ≤0.35 (NYHA II) - Receiving optimal HF therapy

0 to 4 weeks

Eligibility Optimal HF treatment instituted

Rosuvastatin 10 mg

n=2514

Placebo

n=2497

Randomization 2 to 4 weeks Placebo run-in

Follow-up visits 6weeks

3 monthly

Closing date 20 May 2007

Median follow-up 2.7 years Kjekshus J et al. Eur J Heart Fail 2005;7:1059-69. Kjekshus J et al. N Engl J Med 2007;357:in press.

CORONA - Study Design rosuvastatin 10 mg (n=2514) vs placebo (n=2497), 3 years

Primary • Time to the first occurrence of cardiovascular death or non-fatal MI or non-fatal stroke (time to first event) Secondary

• Total mortality • Time to first event any coronary event • Cardiovascular mortality • Number of hospitalisations for cardiovascular causes

CORONA study Placebo n=2497

Rosuvastatin n=2514

Mean age (years) Female sex (%)

73 24

NYHA class (%) II III IV Ejection Fraction

37 62 1.6 0.31

37 61 1.4 0.31

Myocardial infarction (%) Angina pectoris (%) CABG or PCI (%) Diabetes mellitus (%) Atrial fibrillation or flutter Stroke (%)

60 72 26 29 23 12

60 73 26 30 24 13

3.56 1.23 1.99

3.54 1.24 2.01

LDL cholesterol (mmol/L) HDL cholesterol (mmol/L) Triglycerides (mmol/L)

(%)

Kjekshus J et al. N Eng J Med 2007; 357 doi 10.1056/NEJMoa0706201

Primary endpoint CV death or non-fatal MI or non-fatal stroke 35 Placebo n = 732 (29.3%)

Rosuvastatin n = 692 (27.5%)

Per cent

25 20 15

Hazard ratio = 0.92 95% CI 0.83 to 1.02 p = 0.12

5 0

No. at risk Placebo Rosuvastatin

12 18 24 30 Months of follow-up 2497 2514

2315 2345

2156 2207

2003 2068

36 1851 1932

1431 1484

811 855

Any coronary event endpoint Sudden death, fatal or non-fatal MI, PCI, CABG, defibrillation by an ICD, resuscitation after cardiac arrest or hospitalization for unstable angina

30 Placebo n = 588 (23.5%)

Per cent

Rosuvastatin n = 554 (21.6%)

20 15

Hazard ratio = 0.92 95% CI 0.82 to 1.04 p = 0.18

5 0 0 Kjekshus J et al. N Engl J Med 2007

No. at risk Placebo Rosuvastatin

12 18 24 30 Months of follow-up 2497 2514

2299 2332

2127 2174

1974 2029

36 1819 1871

1405 1427

789 817

CORONA - Secondary Endpoints Total number of hospitalizations

Placebo (n=2,497) Rosuvastatin 10 mg (n=2,514)

4,074

No. hospitalisations

4,000

3,694

3,000 2,464

2,193 2,000 1,299

1,510

1,501

1,109

1,000 0

All cause p=0.007

CV cause p<0.001

Heart failure p=0.01

Non-CV cause

Kjekshus J et al. N Eng J Med 2007; 357 doi 10.1056/NEJMoa0706201

CORONA Post hoc analysis of the number fatal/non-fatal MI or stroke in the primary endpoint 15

Placebo

Percent of patients with event

Rosuvastatin 10 mg 9

Hazard ratio = 0.84 95% CI 0.70 to 1.00 p = 0.05

0 0

Months of follow-up No. at risk Placebo Rosuvastatin

2497 2514

2315 2345

2156 2207

2003 2068

1851 1932

1431 1484

811 855

CORONA- Secondary Endpoints Non-cardiovascular Mortality

Non-CV mortality Infections Cancer Organ failure deaths2 Suicide/accidents GI bleeding Other non-CV deaths Unknown cause

Placebo

Rosuvastatin

[n=2497]

[n=2514]

n (rate)1

159 68 50 11 10 9 11 7

(2.6) (1.1) (0.8) (0.2) (0.2) (0.2) (0.2) (0.1)

138 54 52 10 8 1 13 9

(2.2) (0.9) (0.8) (0.2) (0.1) (<0.1) (0.2) (0.1)

Events per 100 patient-years of follow-up 2 No cases attributed to study drug, assessed by adjudication committee

Kjekshus J et al. N Eng J Med 2007; 357 doi 10.1056/NEJMoa0706201

CORONA Tolerability and safety data Placebo [n=2497]

[n=2514]

no. of pts Discontinuation of study drug1 adverse event2 patient unwilling to continue other reason 1Hazard 2Hazard

Rosuvastatin

546 302 162 82

no. of pts 490 241 187 62

ratio 0.88; 95 CI 0.78 to 0.99; p= 0.03 ratio 0.78; 95 CI 0.66 to 0.92; p= 0.004

Kjekshus J et al. N Eng J Med 2007; 357 doi 10.1056/NEJMoa0706201

CORONA Laboratory safety data Placebo

Rosuvastatin

[n=2497]

[n=2514]

no. of pts

CK > 10 x ULN CK > 10 x ULN CK > 10 x ULN and muscle symptoms

3 1

1 0

ALT > 3 x ULN At least one occasion >1 occasion

24 5

25 3

Serum creatinine Doubling of serum creatinine Baseline mg/dL (µmol/L) Last visit mg/dL (µmol/L)

1n=1553

32 1.30 (115)1 1.45 (128)1

23 1.30 (115)2 1.41 (125)2

2n=1619

Kjekshus J et al. N Eng J Med 2007; 357 doi 10.1056/NEJMoa0706201

CORONA – summary and perspectives • In summary, in elderly (mean age 73) patients with advanced heart failure, the addition of a statin to optimized heart failure therapy did not provide an incremental benefit and cannot prevent the deterioration of a failing heart muscle • The results from CORONA highlight the importance and need for early intervention in cardiovascular risk management and in the the progression of atherosclerosis to prevent its worst consequence, heart failure

Kjekshus J et al. N Eng J Med 2007; 357 doi 10.1056/NEJMoa0706201

GISSI-Prevenzione : Ο Aιφνίδιος θάνατος μετά ΟΕΜ Αιφνίδιος θάνατος Μη αιφνίδιος θάνατος

>11.000 ασθενείς με πρόσφατο ΟΕΜ σε παρακολούθηση ~3,5 έτη

Το χαμηλό LVEF συνδέεται με κακή πρόγνωση και αυξημένο κίνδυνο αιφνίδιου θανάτου

Macchia A et al. Eur J Heart Fail 2005;7:904–9.

Θνησιμότητα (%)

Μελέτη GISSI-P

GISSI – Heart Failure Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico

All treatments of proven efficacy for chronic HF (e.g., ACE-inhibitors, beta-blockers, diuretics, digitalis, spironolactone) were positively recommended.

6,975 patients

ω3 1g (3,494) Placebo (3,481)

 356 centers in Italy

 HF, receiving optimized therapy

4,574 Patients

rosuvastatin 10 mg (2,285)

2,401 pts not eligible • 1,576 treated with statins • 395 contraindications to statins • 430 Investigator’s decision

Placebo (2,289)

3.9 years of follow-up 1, 3, 6, 12 months and then every 6 months until the end of the trial

THE LANCET Volume 372, Issue 9645, Pages 1231 - 1239, 4 October 2008 Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial Summary Background Large observational studies, small prospective studies and post-hoc analyses of randomised clinical trial have suggested that statins could be beneficial in patients with chronic heart failure. However, previous studies have been methodologically weak. We investigated the efficacy and safety of the statin rosuvastatin in patients with heart failure. Methods • We undertook a randomised, double-blind, placebo-controlled trial in 326 cardiology and 31 internal medicine centres in Italy. We enrolled patients aged 18 years or older with chronic heart failure of New York Heart Association class II—IV, irrespective of cause and left ventricular ejection fraction, and randomly assigned them to rosuvastatin 10 mg daily (n=2285) or placebo (n=2289) by a concealed, computerised telephone randomisation system. Patients were followed up for a median of 3·9 years (IQR 3·0—4·4). Primary endpoints were time to death, and time to death or admission to hospital for cardiovascular reasons. Analysis was by intention to treat. Findings • We analysed all randomised patients. 657 (29%) patients died from any cause in the rosuvastatin group and 644 (28%) in the placebo group (adjusted hazard ratio [HR] 1·00 [95·5% CI 0·898—1·122], p=0·943). 1305 (57%) patients in the rosuvastatin group and 1283 (56%) in the placebo group died or were admitted to hospital for cardiovascular reasons (adjusted HR 1·01 [99% CI 0·908—1·112], p=0·903). In both groups, gastrointestinal disorders were the most frequent adverse reaction (34 [1%] rosuvastatin group vs 44 [2%] placebo group). Interpretation • Rosuvastatin 10 mg daily did not affect clinical outcomes in patients with chronic heart failure of any cause, in whom the drug was safe.

THE LANCET The Lancet, Volume 372, Issue 9645,

Pages 1223 - 1230, 4 October 2008

Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial Summary Background Several epidemiological and experimental studies suggest that n-3 polyunsaturated fatty acids (PUFA) can exert favourable effects on atherothrombotic cardiovascular disease, including arrhythmias. We investigated whether n-3 PUFA could improve morbidity and mortality in a large population of patients with symptomatic heart failure of any cause. Methods We undertook a randomised, double-blind, placebo-controlled trial in 326 cardiology and 31 internal medicine centres in Italy. We enrolled patients with chronic heart failure of New York Heart Association class II—IV, irrespective of cause and left ventricular ejection fraction, and randomly assigned them to n-3 PUFA 1 g daily (n=3494) or placebo (n=3481) by a concealed, computerised telephone randomisation system. Patients were followed up for a median of 3·9 years (IQR 3·0—4·5). Primary endpoints were time to death, and time to death or admission to hospital for cardiovascular reasons. Analysis was by intention to treat. Findings We analysed all randomised patients. 955 (27%) patients died from any cause in the n-3 PUFA group and 1014 (29%) in the placebo group (adjusted hazard ratio [HR] 0·91 [95·5% CI 0·833—0·998], p=0·041). 1981 (57%) patients in the n-3 PUFA group and 2053 (59%) in the placebo group died or were admitted to hospital for cardiovascular reasons (adjusted HR 0·92 [99% CI 0·849—0·999], p=0·009). In absolute terms, 56 patients needed to be treated for a median duration of 3·9 years to avoid one death or 44 to avoid one event like death or admission to hospital for cardiovascular reasons. In both groups, gastrointestinal disorders were the most frequent adverse reaction (96 [3%] n-3 PUFA group vs 92 [3%] placebo group). Interpretation A simple and safe treatment with n-3 PUFA can provide a small beneficial advantage in terms of mortality and admission to hospital for cardiovascular reasons in patients with heart failure in a context of usual care

GISSI-HF: Results Overall Death

Death + CV hospitalization

Rosuvastatin: 657/2285 (28·8%)

Rosuvastatin: 1305/2285 (57·1%)

Placebo: 644/2289 (28·1%)

Placebo: 1283/2289 (56·1%)

HR (95·5% CI)* 1·00 (0·90 – 1·12) p value 0·943 HR (99% CI)* 1·01 (0·91 – 1·11)

p value 0·903

Αποτελέσματα της GISSI-HF Η ροσουβαστατίνη είναι ωφέλιμη στη χρόνια καρδιακή ανεπάρκεια;

ΟΧΙ  Συνολικός αριθμός θανάτων: Ροσουβαστατίνη n=657 (29%), εικονικό φάρμακο n=644 (28%). – Προσαρμοσμένος λόγος κινδύνου 1,00, P=0,943

 Συνολικός αριθμός θανάτων ή νοσηλειών για καρδιαγγειακά αίτια: Ροσουβαστατίνη n=1305 (57%), εικονικό φάρμακο n=1283 (56%). – Προσαρμοσμένος λόγος κινδύνου 1,0, P=0,903

GISSI – Heart Failure Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico

All treatments of proven efficacy for chronic HF (e.g., ACE-inhibitors, beta-blockers, diuretics, digitalis, spironolactone) were positively recommended.

6,975 patients

ω3 1g (3,494) Placebo (3,481)

 356 centers in Italy

 HF, receiving optimized therapy

4,574 Patients

rosuvastatin 10 mg (2,285)

2,401 pts not eligible • 1,576 treated with statins • 395 contraindications to statins • 430 Investigator’s decision

Placebo (2,289)

3.9 years of follow-up 1, 3, 6, 12 months and then every 6 months until the end of the trial

Σχεδιασμός της GISSI-HF Τελικά σημεία  Δύο κύρια τελικά σημεία  



χρόνος μέχρι τον θάνατο από οποιοδήποτε αίτιο χρόνος μέχρι τον θάνατο από οποιοδήποτε αίτιο ή τη νοσηλεία για καρδιαγγειακά αίτια

Δευτερεύοντα τελικά σημεία   

θνησιμότητα από καρδιαγγειακά αίτια αιφνίδιος καρδιακός θάνατος νοσηλεία για καρδιακή ανεπάρκεια ή άλλα καρδιαγγειακά αίτια

Προφίλ καρδιακής ανεπάρκειας των ασθενών στην GISSI-HF:

Αιτιολογία (%) Ισχαιμική Διατατική Υπερτασική Άλλη Άγνωστη Τάξη NYHA (%) II III-IV LVEF % (μέση+ΤΑ) LVEF >40% (%)

ω3 (n=3.494)

placebo (n=3.481)

1.717 (49) 1.053 (30) 493 (14) 107 (3) 124 (4)

1.750 (50) 972 (28) 543 (16) 89 (3) 127 (4)

2.226 (64) 1.268 (36) 33,0+8,5 333 (9,5)

2.199 (63) 1.282 (37) 33,2+8,5 3,2 (9,2)

Πληθυσμός της μελέτης GISSI-HF  Αντιπροσωπευτικός πληθυσμός ασθενών με χρόνια καρδιακή ανεπάρκεια – Σχετικά ηλικιωμένοι (>40% ηλικίας >70) – Οι περισσότεροι (περίπου 66%) με ήπια ανεπάρκεια (NYHA II) – Πολλοί (περίπου 50%) με ΚΑ ισχαιμικής αιτιολογίας – Οι περισσότεροι (περίπου 90%) με LVEF <40% – Πολλοί λάμβαναν «τριπλή θεραπεία» ΚΑ (αναστολέα ACE ή ARB + β-αποκλειστή + διουρητικό)

Φαρμακευτικές αγωγές που ελάμβαναν οι ασθενείς στην GISSI-HF ω3 (n=3.494)

Εικ. φάρμακο (n=3.481)

Αναστολέας ACE/ARB

3.268 (93,5)

3.252 (93,4)

β-Αποκλειστής

2.275 (65,1)

2.247 64,6)

Σπιρονολακτόνη

1.347 (38,6)

1.393 (40)

Διουρητικό

3.127 (89,5)

3.133 (90)

Δακτυλίτιδα

1.296 (37,1)

1.282 (37,1)

Αντιπηκτικά από το στόμα

1.027 (29,4)

982 (28,2)

Ασπιρίνη

1.673 (47,9)

1.685 (48,4)

Νιτρώδη

1.236 (35,4)

1.236 (35,5)

343 (9,8)

366 (10,5)

Αμιοδαρόνη n (%)

668 (39,1)

690 (19,8)

Στατίνες (ανοικτή θεραπεία)

778 (22,3)

801 (23)

n (%)

Αποκλειστές διαύλων ασβεστίου

Αποτελέσματα της GISSI-HF (1) Επίδραση των ω 3 στη συνολική θνησιμότητα

Επιπρόσθετη μείωση κινδύνου με το ω

3 κατά 9% (p=0.041)

NNT=56

Αποτελέσματα της GISSI-HF (2)

Επίδραση των ω 3 στην καρδ/κη θνησιμότητα και νοσηλεία NNT=44

Επιπρόσθετη μείωση κινδύνου με το ω

3 κατά 8% (p=0.009)

Αποτελέσματα της GISSI-HF Επίδραση των ω 3 στα περιστατικά αρρυθμίας placebo των ω 3 (n=3.494) (n=3.481) Θάνατοι από πιθανολογούμενη αρρυθμία n,(%) Πρώτη νοσηλεία για κοιλιακή αρρυθμία n,(%)

95% CI

Τιμή P

274 (7,8)

304 (8,7)

0,88

0,75-1,04

0,14

97 (2,8)

132 (3,8)

0,72

0,55-0,93

0,01

Τεκμηριωμένες θεραπείες στη συστολική Καρδιακή Ανεπάρκεια Θεραπεία α-ΜΕΑ / ARB

Μείωση Κινδύνου (+ η – διουρητικό) 17 - 25%

β-Αποκλειστές

34 - 35%

Ανταγωνιστές αλδοστερόνης*

15 - 30%

Συνδ. υδραλαζίνης-ισοσορβίδης

43%

ICD

23%

ω3

Lancer, online 31 Αυγούστου 2008

;

HFSA 2010 Practice Guideline PUFA Recommendation 7.41 (NEW in 2010)

n-3 polyunsaturated fatty acids (PUFA) may be considered to reduce mortality in HF patients with NYHA class II-IV symptoms and reduced LVEF. Strength of Evidence = B

ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 Omega-3 polyunsaturated fatty acids The small treatment effect of n-3 polyunsaturated fatty acids (PUFAs) in the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico-heart failure (GISSI-HF) trial was only detected after covariate adjustment in the statistical analysis and there was no effect on HF hospitalization.

The effect of n-3 PUFAs after myocardial infarction is uncertain. Treatments not recommended (unproven benefit) 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (‘statins’) Although there is a wealth of robust evidence supporting the value of statins in patients with atherosclerotic (arterial) disease, most trials excluded patients with HF (because it was uncertain that they would benefit ). Two recent trials studied statin treatment specifically in patients with chronic HF and did not demonstrate convincing evidence of benefit (although there was little evidence of harm).

Statin treatment and did not demonstrate evidence of benefit

ΠΟΙΟΣ ΕΙΝΑΙ Ο ΣΤΟΧΟΣ ΜΑΣ ;

ΕΥΧΑΡΙΣΤΩ !

άνδρας 67 ετών, κάπνισμα (διακοπή 1998), κληρονομικό : πατέρας ΣΝ, ατομικό αναμνηστικό : ΑΥ (11 χρόνια), έμφραγμα μυοκαρδίου (2006), δύσπνοια προσπαθείας από διμήνου (NYHA II). BMI : 27, W : 92cm, σάκχαρο 98, κρεατινίνη ορού : 0,9mg/dl, Ch : 212mg/dl, LDL : 140mg/dl, HDL : 45mg/dl, TG : 135mg/dl,

EF > 32%

1η ΕΡΩΤΗΣΗ Θα συνταγογραφήσουμε στατινη ; 1. 2. 3. 4.

atorva 10mg Atorva 40mg Υγειονοδιατιτική αγωγή Δεν χρειάζεται κάποια παρέμβαση

2η ΕΡΩΤΗΣΗ Θα συνταγογραφήσουμε PUFA; 1. 2. 3. 4.

1gr 4gr Μόνο υγειονοδιατιτική αγωγή Δεν χρειάζεται κάποια παρέμβαση

άνδρας 67 ετών, κάπνισμα (διακοπή 1998), κληρονομικό : πατέρας ΣΝ, ατομικό αναμνηστικό : ΑΥ (11 χρόνια), ΣΔ (2009), δύσπνοια προσπαθείας από διμήνου (NYHA II). BMI : 27, W : 92cm, σάκχαρο 135, κρεατινίνη ορού : 0,9mg/dl, Ch : 188mg/dl, LDL : 115mg/dl, HDL : 38mg/dl, TG : 175mg/dl,

EF > 38%

1η ΕΡΩΤΗΣΗ Θα συνταγογραφήσουμε ; 1. 2. 3. 4.

atorva pufa Υγειονοδιατιτική αγωγή Δεν χρειάζεται κάποια παρέμβαση

άνδρας 69 ετών, κάπνισμα (διακοπή 1998), κληρονομικό : πατέρας ΣΝ, ατομικό αναμνηστικό : ΑΥ (11 χρόνια), δύσπνοια προσπαθείας από διμήνου (NYHA II). BMI : 24, W : 89cm, 78kgr σάκχαρο 98, κρεατινίνη ορού : 1,7mg/dl, Ch : 198mg/dl, LDL : 108mg/dl, HDL : 40mg/dl, TG : 250mg/dl,

EF > 40%

1η ΕΡΩΤΗΣΗ Θα συνταγογραφήσουμε ; 1. 2. 3. 4. 5.

Στατινη μικρη δοση Στατίνη μεγαλη δοση Στατινη και εζετιμιμπη PUFA PUFA & στατινη