Perioperative angiotensin‐converting enzyme inhibitors or angiotensin II type 1 receptor blockers for preventing mortality and morbidity in adults

Zui Zou<sup>a</sup>; Hong B Yuan<sup>a</sup>; Bo Yang<sup>a</sup>; Fengying Xu; Xiao Y Chen; Guan J Liu; Xue Y Shi

doi:10.1002/14651858.CD009210.pub2

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Figure 1

Flow diagram of study selection process.

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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 4

Forest plot of comparison: 1 All‐cause mortality, outcome: 1.1 All‐cause mortality.

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Figure 5

Forest plot of comparison: 1 ACEIs or ARBs versus placebo, outcome: 1.2 ST‐elevation or new Q wave in ECG test.

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Figure 6

Forest plot of comparison: 1 ACEIs or ARBs versus placebo, outcome: 1.3 Cardiac index.

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Figure 7

Forest plot of comparison: 1 ACEIs or ARBs versus placebo, outcome: 1.4 Rate of perioperative cerebrovascular complications.

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Figure 8

Forest plot of comparison: 1 ACEIs or ARBs versus placebo, outcome: 1.5 Length of hospital stay.

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Analysis 1.1

Comparison 1 ACEIs or ARBs versus placebo, Outcome 1 All cause mortality.

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Analysis 1.2

Comparison 1 ACEIs or ARBs versus placebo, Outcome 2 ST‐elevation or new Q wave in ECG test.

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Analysis 1.3

Comparison 1 ACEIs or ARBs versus placebo, Outcome 3 Cardiac index.

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Analysis 1.4

Comparison 1 ACEIs or ARBs versus placebo, Outcome 4 Rate of perioperative cerebrovascular complications.

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Analysis 1.5

Comparison 1 ACEIs or ARBs versus placebo, Outcome 5 Length of hospital stay.

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Summary of findings for the main comparison. ACEIs or ARBs compared to placebo for preventing surgery‐related mortality and morbidity in adults

ACEIs or ARBs compared to placebo for preventing surgery‐related mortality and morbidity in adults
Patient or population: Patients undergoing any type of surgery under general anaesthesia receiving ACEIs or ARBs perioperatively Settings: All settings Intervention: ACEIs or ARBs Comparison: Placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	ACEIs or ARBs
All‐cause mortality	Study population		RR 1.61 (0.44 to 5.85)	419 (3 studies)	⊕⊝⊝⊝ very low¹	All the included trials were at high risk of bias. Total sample size is lower than the calculated. Duration of follow‐up: until discharge from hospital
	16 per 1000	25 per 1000 (7 to 90)
	Moderate
	7 per 1000	11 per 1000 (3 to 41)
Risk of acute myocardial ischaemia	Study population		RR 0.55 (0.14 to 2.26)	345 (2 studies)	⊕⊝⊝⊝ very low¹	All the included trials were at high risk of bias. Total sample size is lower than the calculated. Duration of follow‐up: until discharge from hospital
	30 per 1000	16 per 1000 (4 to 67)
	Moderate
	56 per 1000	31 per 1000 (8 to 127)
Congestive heart failure		The mean cardiac index in the intervention groups was 0.6 higher (0.7 to 0.5 higher)	‐	34 (2 studies)	⊕⊝⊝⊝ very low¹	All the included trials were at high risk of bias. Total population size is less than 400. Duration of follow‐up: not specified
Hypotension	‐		RR 1.95 (0.86 to 4.41)	298 (1 study)	⊕⊝⊝⊝ very low¹	All the included trials were at high risk of bias. Total population size is less than 400. Duration of follow‐up: not specified
Rate of perioperative cerebrovascular complications	Study population		RR 0.48 (0.18 to 1.28)	459 (3 studies)	⊕⊝⊝⊝ very low¹	All the included trials were at high risk of bias. Duration of follow‐up: until discharge from hospital (Billings 2012; Pretorius 2012); 90 days after surgery (Flesch 2009)
	50 per 1000	24 per 1000 (9 to 65)
	Moderate
	71 per 1000	34 per 1000 (13 to 92)
Length of hospital stay		The mean length of hospital stay in the intervention groups was 0.54 lower (0.93 lower to 0.16 lower)	‐	372 (2 studies)	⊕⊝⊝⊝ very low¹	All the included trials were at high risk of bias. Total population size is less than 400. Duration of follow‐up: until discharge from hospital
Treatment related adverse events	‐	‐	‐	385 (2 studies)	⊕⊝⊝⊝ very low¹	All the included trials were at high risk of bias. Total population size is less than 400. Authors did not provided detailed information on adverse events, which made the synthesis of the results less clinically relevant.
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ACEIs: angiotensin‐converting enzyme inhibitors; ARBs: angiotensin II type 1 receptor blockers; CI: confidence interval; ECG: electrocardiograph; RR: risk ratio
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹Downgraded by three levels due to very serious study limitations (all the trials included were at high risk of bias) and serious imprecision (total population size is less than 400).

Summary of findings for the main comparison. ACEIs or ARBs compared to placebo for preventing surgery‐related mortality and morbidity in adults

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Table 1. Rate of hypotension

Outcome or subgroup	Studies	Participants	Statistical method	Effect estimate
Rate of hypotension	1	298	Risk Ratio (M‐H, Fixed, 95% CI)	1.95 [0.86, 4.41]
Risk ratio < 1 favours angiotensin‐converting enzyme inhibitors and angiotensin II type 1 receptor blockers group. Risk ratio > 1 favours control group.

Table 1. Rate of hypotension

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Table 2. Glomerular filtration rate

Outcome or subgroup	Studies	Participants	Statistical method	Effect estimate
Glomerular filtration rate	1	16	Mean Difference (IV, Random, 95% CI)	‐1.40 [‐10.30, 7.50]
IV ‐ inverse variance IV: intravenous

Table 2. Glomerular filtration rate

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Comparison 1. ACEIs or ARBs versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All cause mortality Show forest plot	3	419	Risk Ratio (M‐H, Fixed, 95% CI)	1.61 [0.44, 5.85]

2 ST‐elevation or new Q wave in ECG test Show forest plot	2	345	Risk Ratio (M‐H, Fixed, 95% CI)	0.55 [0.14, 2.26]

3 Cardiac index Show forest plot	2	34	Mean Difference (IV, Random, 95% CI)	‐0.60 [‐0.70, ‐0.50]

4 Rate of perioperative cerebrovascular complications Show forest plot	3	459	Risk Ratio (M‐H, Fixed, 95% CI)	0.48 [0.18, 1.28]

5 Length of hospital stay Show forest plot	2	372	Mean Difference (IV, Fixed, 95% CI)	‐0.54 [‐0.93, ‐0.16]

Comparison 1. ACEIs or ARBs versus placebo

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