Author(s):
Question:
Setting:
Bibliography:
Certainty assessment№ of patientsEffectCertaintyImportance
№ of studiesStudy designRisk of biasInconsistencyIndirectnessImprecisionOther considerationsesmavalikuna ARNI-tAKE-t/ARB-iRelative
(95% CI)		Absolute
(95% CI)
Üldsuremus HFrEF
31,2,3
randomised trials
not serious
not serious
seriousa
not serious
none
722/4687 (15.4%)
850/4711 (18.0%)
RR 0.86
(0.78 to 0.93)
25 fewer per 1,000
(from 40 fewer to 13 fewer)
⨁⨁⨁◯
Moderate
OLULINE
Südamepuudulikkusega seotud hospitaliseerimine
31,2,3
randomised trials
not serious
not serious
seriousa
not serious
none
575/4687 (12.3%)
724/4711 (15.4%)
RR 0.80
(0.72 to 0.89)
31 fewer per 1,000
(from 43 fewer to 17 fewer)
⨁⨁⨁◯
Moderate
Kardiovaskulaarsuremus HFrEF
31,2,3
randomised trials
not serious
not serious
seriousa
not serious
none
564/4687 (12.0%)
704/4711 (14.9%)
RR 0.81
(0.72 to 0.90)
28 fewer per 1,000
(from 42 fewer to 15 fewer)
⨁⨁⨁◯
Moderate
Sümptomaatline hüpotensioon
32,3,4
randomised trials
seriousb
not serious
seriousa
not serious
none
663/4858 (13.6%)
448/4886 (9.2%)
RR 1.49
(1.33 to 1.67)
45 more per 1,000
(from 30 more to 61 more)
⨁⨁◯◯
Low
Neerufunktsioon langus
62,3,4
randomised trials
seriousb
not serious
seriousa
not serious
none
221/4858 (4.5%)
267/4886 (5.5%)
RR 0.79
(0.67 to 0.95)
11 fewer per 1,000
(from 18 fewer to 3 fewer)
⨁⨁◯◯
Low
Oluline hüperkaleemia K>6,0 mmol/L
61,2,3,4,5,6
randomised trials
seriousc
not serious
seriousd
not serious
none
261/6722 (3.9%)
343/6731 (5.1%)
RR 0.76
(0.65 to 0.89)
12 fewer per 1,000
(from 18 fewer to 6 fewer)
⨁⨁◯◯
Low
Hüperkaleemia (K >5.5 mmol/l)
32,3,4
randomised trials
very seriousb
not serious
not serious
not serious
none
762/4858 (15.7%)
798/4886 (16.3%)
RR 1.04
(0.84 to 1.29)
7 more per 1,000
(from 26 fewer to 47 more)
⨁⨁◯◯
Low
Angioödeem
52,3,4,5,6
randomised trials
seriouse
not serious
seriousd
not serious
none
35/7414 (0.5%)
21/7427 (0.3%)
RR 1.42
(0.52 to 3.87)
1 more per 1,000
(from 1 fewer to 8 more)
⨁⨁◯◯
Low
NYHA klass
27,8
observational studies
not serious
not serious
not serious
seriousf
none
293
293
-
mean 0.82 NYHA klass lower
(0.91 lower to 0.72 lower)
⨁◯◯◯
Very low
Füüsiline võimekus (assessed with: 6 MKT)
79,10,11,12,13,14,15,g
observational studies
not serious
serioush
seriousi
seriousj
none
325
325
-
MD 27.62 m higher
(39.48 higher to 15.76 higher)
⨁◯◯◯
Very low

CI: confidence interval; MD: mean difference; RR: risk ratio

Explanations

a. 97.9% metaanalüüsi haaratud patsientidest ei olnud AKE/ARB ravinaiivsed
b. 97,9% metaanalüüsi kaasatud patsientidest olid enne randomiseerimist läbinud run-in perioodi. Randomiseeriti ainult need patsiendid, kes talusid run-in perioodi jooksul ravi AKE/ARB + ARNI-ga.
c. 88,3% metaanalüüsi kaasatud patsientidest olid enne randomiseerimist läbinud run-in perioodi. Randomiseeriti ainult need patsiendid, kes talusid run-in perioodi jooksul ravi AKE/ARB + ARNI-ga.
d. Analüüsi olid kaasatud ka HFpEF patsiendid (PARAMOUNT-HF ja PARAGON-HF)
e. 68,3 % metaanalüüsi kaasatud patsientidest olid enne randomiseerimist läbinud run-in perioodi. Randomiseeriti ainult need patsiendid, kes talusid run-in perioodi jooksul ravi AKE/ARB + ARNI-ga.
f. Kaks uuringut, milles vähe patsiente (250 ja 43)
g. Wang jt 2019.aasta metaanalüüsi kaasati 7 kohortuuringu andmeid
h. I2 = 55%
i. Jälgimisuuringus puudus kontroll-grupp
j. Väikese patsientide arvuga uuringud

References

1.DH, Kang, SJ, Park, SH, Shin, GR, Hong, S, Lee, MS, Kim, SC, Yun, JM, Song, SW, Park, JJ, Kim. Angiotensin Receptor Neprilysin Inhibitor for Functional Mitral Regurgitation.. Circulation; 2019.
2.McMurray, , M, Packer, AS, Desai, J, Gong, MP, Lefkowitz, AR, Rizkala, JL, Rouleau, VC, Shi, SD, Solomon, K, Swedberg, MR, Zile. Angiotensin-neprilysin inhibition versus enalapril in heart failure. PARADIGM-HF trial.. The New England journal of medicine; 2014.
3.EJ, Velazquez, DA, Morrow, AD, DeVore, CI, Duffy, AP, Ambrosy, K, McCague, R, Rocha, E, Braunwald, Investigators, PIONEER-HF. Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure.. The New England journal of medicine; 2019.
4.AS, Desai, SD, Solomon, AM, Shah, BL, Claggett, JC, Fang, J, Izzo, K, McCague, CA, Abbas, R, Rocha, GF, Mitchell, Investigators, EVALUATE-HF. Effect of Sacubitril-Valsartan vs Enalapril on Aortic Stiffness in Patients With . JAMA; 2019.
5.SD, Solomon, JJV, McMurray, IS, Anand, J, Ge, CSP, Lam, AP, Maggioni, F, Martinez, M, Packer, MA, Pfeffer, B, Pieske, MM, Redfield, JL, Rouleau, DJ, van,Veldhuisen, F, Zannad, MR, Zile, AS, Desai, B, Claggett, PS, Jhund, SA, Boytsov, J, Comin-Colet, J, Cleland, HD, Düngen, E, Goncalvesova, T, Katova, JF, Kerr,Saraiva, M, Lelonek, B, Merkely, M, Senni, SJ, Shah, J, Zhou, AR, Rizkala, J, Gong, VC, Shi, MP, Lefkowitz, Committees, PARAGON-HF,Investigators,and. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction.. The New England journal of medicine; 2019.
6.SD, Solomon, M, Zile, B, Pieske, A, Voors, A, Shah, E, Kraigher-Krainer, V, Shi, T, Bransford, M, Takeuchi, J, Gong, M, Lefkowitz, M, Packer, JJ, McMurray, , Prospective,comparison,of,ARNI,with,ARB,on,Management,Of,heart,failUre,with. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved . Lancet (London, England); 2012.
7.Gonzalez-Torres, L, De Diego, C, Centurion, R. Angiotensin-neprilysin inhibition further reverses cardiac remodeling as compared to angiotensin inhibition in reduced heart failure patients. Clin Cardiol J.; 2018.
8.Nazzari, Hamed, Yeung, Michael, Marceau, Aude, Luong, Michael, Clark, Catherine, Ahuja, Stephanie, Knoll, Jennifer, Koscal, Mirka, Davis, Margot, Virani, Sean. Left ventricular function improves in heart failure patients treated with sacubitril-valsartan. Circulation; 2017.
9.Mantis C, Anadiotis A,Patsilinakos S. Impact of sacubitril/valsartan on functional exercise capacity and quality of life in patients with heart failure with reduced ejection fraction. Eur J Prev Cardiol; 2018.
10.R, Rodil,Fraile, V, Malafarina, G, Tiberio,López. Sacubitril-valsartan in heart failure and multimorbidity patients.. ESC heart failure; 2018.
11.Hlavata, Katerina, Hoskova, Lenka, Franekova, Janka, Jabor, Antonin, Kautzner, Josef, Melenovsky, Vojtech, Benes, Jan. Transition from angiotensin-converting enzyme inhibitor/angiotensin-II-receptor-blocker to sacubitril/valsartan in chronic heart failure patients: Initial experiences in clinical practice. Cor et Vasa; 2018.
12.Mercedes Faraudo, M, Beltran, P, Freixa, R, Guri, O, Mena, E, Ceresuela, L, Masip, J. How does sacubitril/valsartan improve submaximal functional capacity measured through six-minute walk test?. EUROPEAN JOURNAL OF HEART FAILURE; 2017.
13.Kalantari S, Medvedofsky DM,Grinstein JG,Tayazime ST,Kim GK,Sarswat NS,Raikelkhar JR,Smith BS,Maffessanti FM,Beiser DB,Ward PW,Uriel NU. Remodel: demonstration of reverse remodeling effects of sacubitril/valsartan. Eur J Heart Fail; 2018.
14.Canu, A., Hebert, M., Gachet, A., Arabucki, F., Maurin, V., Picard, F., Santos, Pierre. Results of a single center experience on 110 consecutive patients treated with Entresto (sacubitril/valsartan). Archives of Cardiovascular Diseases Supplements; 2017.
15.P, Beltrán, P, Palau, E, Domínguez, M, Faraudo, E, Núñez, O, Guri, A, Mollar, J, Sanchis, A, Bayés-Genís, J, Núñez. Sacubitril/valsartan and short-term changes in the 6-minute walk test: A pilot . International journal of cardiology; 2018.