Guideline Development Tool

Author(s): Liis Rooväli

Question: Kas kõigile kõigile vähenenud väljutusfraktsiooniga kroonilise südamepuudulikkusega täiskasvanud patsientidele, kellel ei ole vastunäidustusi,tuleb parema ravitulemuse saamiseks määrata mineralokortikoidide antagonist (MRA) või mitte?

Setting: Kas kõigile kõigile vähenenud väljutusfraktsiooniga kroonilise südamepuudulikkusega täiskasvanud patsientidele, kellel ei ole vastunäidustusi, tuleb parema ravitulemuse saamiseks määrata mineralokortikoidide antagonist (MRA) või mitte?

Bibliography:

Certainty assessment	№ of patients	Effect	Certainty	Importance
kardiovaskulaarsuremus (follow-up: mean 15 months)
6^1,^2,^3,^4,^5,^6,^7,^a	randomised trials	serious^8,^b	not serious	not serious	not serious	none	788/5820 (13.5%)	998/5850 (17.1%)	RR 0.79 (0.73 to 0.86)	36 fewer per 1,000 (from 46 fewer to 24 fewer)	⨁⨁⨁◯ Moderate	KRIITILINE
üldsuremus (follow-up: mean 15 months)
8^1,^2,^3,^4,^5,^6,^7,^9,^10,^a	randomised trials	serious^c	not serious	not serious	not serious	none	950/5932 (16.0%)	1177/5960 (19.7%)	RR 0.81 (0.75 to 0.87)	38 fewer per 1,000 (from 49 fewer to 26 fewer)	⨁⨁⨁◯ Moderate	KRIITILINE
hospitaliseerimine kardiovaskulaarhaiguste tõttu (follow-up: mean 15 months)
7^1,^2,^3,^4,^5,^6,^10,^11,^a	randomised trials	serious^d	serious^e	not serious	not serious	none	1192/5862 (20.3%)	1443/5892 (24.5%)	RR 0.76 (0.64 to 0.90)	59 fewer per 1,000 (from 88 fewer to 24 fewer)	⨁⨁◯◯ Low	KRIITILINE
Füüsiline võimekud (VO2 max) (follow-up: mean 12 months; assessed with: ml/min/kg)
1¹⁰	randomised trials	serious^f	not serious	not serious	not serious	none	Maksimaalne hapnikutarbimine kasvas 50 mg spiroonolaktooni tarvitanutel , samal ajal kui kontrollrühmas see vähenes (17.7 +/- 5.2 -> 18.5 +/- 5.9 ml/min/kg vs. 19.1 +/- 5.6 -> 17.9 +/- 5.3 ml/min/kg; p = 0.01).	⨁⨁⨁◯ Moderate	KRIITILINE
hüperkaleemia (follow-up: mean 15 months)
11^1,^2,^3,^4,^5,^6,^7,^9,^10,^11,^12,^13,^a	randomised trials	serious^g	not serious	not serious	not serious	none	293/6135 (4.8%)	143/6159 (2.3%)	RR 2.01 (1.65 to 2.45)	23 more per 1,000 (from 15 more to 34 more)	⨁⨁⨁◯ Moderate	KRIITILINE
günekomastia (selektiivsed ja mitteselektivsed MRAd) (follow-up: mean 15 months)
8^1,^3,^5,^6,^9,^10,^14,^15,^16,^a	randomised trials	serious^h	not serious	seriousⁱ	not serious	none	120/3205 (3.7%)	15/3227 (0.5%)	RR 7.37 (4.42 to 12.30)	30 more per 1,000 (from 16 more to 53 more)	⨁⨁◯◯ Low	KRIITILINE
günekomastia (mitteselektiivsed MRAd) (follow-up: mean 15 months)
3^1,^2,^4,^17,^a	randomised trials	serious^j	not serious	seriousⁱ	serious^18,^19,^k	none	23/4708 (0.5%)	31/4709 (0.7%)	RR 0.74 (0.43 to 1.27)	2 fewer per 1,000 (from 4 fewer to 2 more)	⨁◯◯◯ Very low	KRIITILINE

Certainty assessment

№ of patients

Effect

Certainty

Importance

№ of studies

Study design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

mineralokortikoidide antagonisti

mitte

Relative
(95% CI)

Absolute
(95% CI)

kardiovaskulaarsuremus (follow-up: mean 15 months)

6^1,^2,^3,^4,^5,^6,^7,^a

randomised trials

serious^8,^b

not serious

none

788/5820 (13.5%)

998/5850 (17.1%)

RR 0.79
(0.73 to 0.86)

36 fewer per 1,000
(from 46 fewer to 24 fewer)

⨁⨁⨁◯
Moderate

KRIITILINE

üldsuremus (follow-up: mean 15 months)

8^1,^2,^3,^4,^5,^6,^7,^9,^10,^a

randomised trials

serious^c

not serious

none

950/5932 (16.0%)

1177/5960 (19.7%)

RR 0.81
(0.75 to 0.87)

38 fewer per 1,000
(from 49 fewer to 26 fewer)

⨁⨁⨁◯
Moderate

KRIITILINE

hospitaliseerimine kardiovaskulaarhaiguste tõttu (follow-up: mean 15 months)

7^1,^2,^3,^4,^5,^6,^10,^11,^a

randomised trials

serious^d

serious^e

not serious

none

1192/5862 (20.3%)

1443/5892 (24.5%)

RR 0.76
(0.64 to 0.90)

59 fewer per 1,000
(from 88 fewer to 24 fewer)

⨁⨁◯◯
Low

KRIITILINE

Füüsiline võimekud (VO2 max) (follow-up: mean 12 months; assessed with: ml/min/kg)

1¹⁰

randomised trials

serious^f

not serious

none

Maksimaalne hapnikutarbimine kasvas 50 mg spiroonolaktooni tarvitanutel , samal ajal kui kontrollrühmas see vähenes (17.7 +/- 5.2 -> 18.5 +/- 5.9 ml/min/kg vs. 19.1 +/- 5.6 -> 17.9 +/- 5.3 ml/min/kg; p = 0.01).

⨁⨁⨁◯
Moderate

KRIITILINE

hüperkaleemia (follow-up: mean 15 months)

11^1,^2,^3,^4,^5,^6,^7,^9,^10,^11,^12,^13,^a

randomised trials

serious^g

not serious

none

293/6135 (4.8%)

143/6159 (2.3%)

RR 2.01
(1.65 to 2.45)

23 more per 1,000
(from 15 more to 34 more)

⨁⨁⨁◯
Moderate

KRIITILINE

günekomastia (selektiivsed ja mitteselektivsed MRAd) (follow-up: mean 15 months)

8^1,^3,^5,^6,^9,^10,^14,^15,^16,^a

randomised trials

serious^h

not serious

seriousⁱ

not serious

none

120/3205 (3.7%)

15/3227 (0.5%)

RR 7.37
(4.42 to 12.30)

30 more per 1,000
(from 16 more to 53 more)

⨁⨁◯◯
Low

KRIITILINE

günekomastia (mitteselektiivsed MRAd) (follow-up: mean 15 months)

3^1,^2,^4,^17,^a

randomised trials

serious^j

not serious

seriousⁱ

serious^18,^19,^k

none

23/4708 (0.5%)

31/4709 (0.7%)

RR 0.74
(0.43 to 1.27)

2 fewer per 1,000
(from 4 fewer to 2 more)

⨁◯◯◯
Very low

KRIITILINE

a. Berbenetz et al 2016 metaanalüüs

b. Akbulut 2003 ja Pitt 2013 uuringutes esineb potentsiaalne nihke risk uuritavate rühmadesse jaotamise puuduliku kirjelduse ning Akbulut 2003 ja Vizzardi 2014 uuringutes ühekordse pimendamise tõttu

c. Akbulut 2003, Cicora 2002 ja Pitt 2013 uuringutes esineb potentsiaalne nihke risk uuritavate rühmadesse jaotamise puuduliku kirjelduse ning Akbulut 2003 ja Vizzardi 2014 uuringutes ühekordse pimendamise tõttu

d. Cicora 2002, Chan 2007 ja Pitt 2013 uuringutes esineb potentsiaalne nihke risk uuritavate rühmadesse jaotamise puuduliku kirjelduse ning Vizzardi 2014 uuringus ühekordse pimendamise tõttu

e. tulemuste suur heterogeensus I-ruut 68%

f. potentsiaalne nihke risk uuritavate rühmadesse jaotamise puuduliku kirjelduse tõttu

g. Akbulut 2003, Cicora 2002, Chan 2007 ja Pitt 2013 uuringutes esineb potentsiaalne nihke risk uuritavate rühmadesse jaotamise puuduliku kirjelduse ning Akbulut 2003 ja Vizzardi 2014 uuringutes ühekordse pimendamise tõttu

h. Cicora 2002 ja Edwards 2009 uuringutes esineb potentsiaalne nihke risk uuritavate rühmadesse jaotamise puuduliku kirjelduse tõttu; Edwards 2009 uuringus esineb potentsiaalne nihke risk sest ei kasutatud intention to treat analüüsi, ja Vizzardi 2014 uuringus on potentsiaalne nihke risk ühekordse pimendamise tõttu.

i. metaanalüüsis olid koos nii vähenenud kui säilunud väljtutusfraktsiooniga patsiendid

j. Deswal 2011 uuringutes esineb potentsiaalne nihke risk sest ei kasutatud intention to treat analüüsi

k. usaldusvahemik läbib väärtust 1 - puudub kliiniliselt oluline mõju

1.Berbenetz NM, Mrkobrada M.. Mineralocorticoid receptor antagonists for heart failure: systematic review and meta-analysis. BMC Cardiovasc Disord; 2016.

2.Zannad F, McMurray JJ,Krum H,Van Veldhuisen DJ,Swedberg K,Shi H,Vincent J,Pocock SJ,Pitt B,EMPHASIS-HF Study Group.. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med; 2011.

3.Vizzardi E, Nodari S,Caretta G,D’Aloia A,Pezzali N,Faden G,Lombardi C,Raddino R,Metra M,Dei CL. Effects of spironolactone on long-term mortality and morbidity in patients with heart failure and mild or no symptoms. Am J Med Sci; 2014.

4.Pitt B, Remme W,Zannad F,Neaton J,Martinez F,Roniker B,Bittman R,Hurley S,Kleiman J,Gatlin M.. Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.. N Engl J Med; 2003.

5.Pitt B, Zannad F,Remme WJ,Cody R,Castaigne A,Perez A,Palensky J,Wittes J.. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med; 1999.

6.Boccanelli A, Mureddu GF,Cacciatore G,Clemenza F,Di LA,Gavazzi A,Porcu M,Latini R,Lucci D,Maggioni AP,Masson S,Vanasia M,de Simone G,AREA INC. Anti-remodelling effect of canrenone in patients with mild chronic heart failure (AREA IN-CHF study): final results. Eur J Heart Fail; 2009.

7.Akbulut M, Ozbay Y,Ilkay E,Karaca I,Arslan N. Effects of spironolactone and metoprolol on QT dispersion in heart failure. Jpn Heart J; 2003.

8.Khan MS, Khan MS,Moustafa A,Anderson AS,Mehta R,Khan SS. Efficacy and Safety of Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Chronic Kidney Disease. Am J Cardiol; 2020.

9.Gao X, Peng L,Adhikari CM,Lin J,Zuo Z. Spironolactone reduced arrhythmia and maintained magnesium homeostasis in patients with congestive heart failure. J Card Fail; 2007.

10.Cicoira M, Zanolla L,Rossi A,Golia G,Franceschini L,Brighetti G,Marino P,Zardini P. Long-term, dose-dependent effects of spironolactone on left ventricular function and exercise tolerance in patients with chronic heart failure. J Am Coll Cardiol; 2002.

11.Chan AK, Sanderson JE,Wang T,Lam W,Yip G,Wang M,Lam YY,Zhang Y,Yeung L,Wu EB,Chan WW,Wong JT,So N,Yu CM. Aldosterone receptor antagonism induces reverse remodeling when added to angiotensin receptor blockade in chronic heart failure. J Am Coll Cardiol; 2007.

12.Udelson JE, Feldman AM,Greenberg B,Pitt B,Mukherjee R,Solomon HA,Konstam MA. Udelson JE, Feldman AM, GreeRandomized, double-blind, multicenter, placebo-controlled study evaluating the effect of aldosterone antagonism with eplerenone on ventricular remodeling in patients with mild-to-moderate heart failure and left ventricular systolic dysfunction. Circ Heart Fail.; 2010.

13.Pitt B, Kober L,Ponikowski P,Gheorghiade M,Filippatos G,Krum H,Nowack C,Kolkhof P,Kim SY,Zannad F. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94–8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J; 2013.

14.Edwards NC, Steeds RP,Stewart PM,Ferro CJ,Townend JN. Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial. . J Am Coll Cardiol; 2009.

15.Edelmann F, Wachter R,Schmidt AG,Kraigher-Krainer E,Colantonio C,Kamke W,Duvinage A,Stahrenberg R,Durstewitz K,Loffler M,Dungen HD,Tschope C,Herrmann-Lingen C,Halle M,Hasenfuss G,Gelbrich G,Pieske B,Aldo-DHF I. Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. JAMA; 2013.

16.Pitt B, Pfeffer MA,Assmann SF,Boineau R,Anand IS,Claggett B,Clausell N,Desai AS,Diaz R,Fleg JL,Gordeev I,Harty B,Heitner JF,Kenwood CT,Lewis EF,O’Meara E,Probstfield JL,Shaburishvili T,Shah SJ,Solomon SD,Sweitzer NK,Yang S,McKinlay SM,TOPCAT I. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med; 2014.

17.Deswal A, Richardson P,Bozkurt B,Mann DL. Results of the Randomized Aldosterone Antagonism in Heart Failure with Preserved Ejection Fraction trial (RAAM-PEF). J Card Fail; 2011.

18.Negi PC, Dev M,Paul P,Pal Singh D,Rathoure S,Kumar R,Dhiman A,Kandoria A,Ganju N,Sharma R,Bhardwaj R,Merwaha R,Asotra S,Mahajan K,Sondhi S,Rao S.. Prevalence, risk factors, and significance of iron deficiency and anemia in nonischemic heart failure patients with reduced ejection fraction from a Himachal Pradesh heart failure registry.. Indian Heart J.; 2018.

19.Beale AL, Warren JL,Roberts N,Meyer P,Townsend NP,Kaye D.. Iron deficiency in heart failure with preserved ejection fraction: a systematic review and meta-analysis.. Open Heart.; 2019.

Explanations

References