Alpha‐2 adrenergic agonists for the prevention of cardiac complications among patients undergoing surgery

Duminda N Wijeysundera; Jennifer S Bender; W Scott Beattie

doi:10.1002/14651858.CD004126.pub2

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Figure 1

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Figure 2

Funnel plot of comparison: Alpha‐2 agonists versus control in all surgery (outcome: all‐cause mortality).

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Figure 3

Funnel plot of comparison: Alpha‐2 agonists versus control in all surgery (outcome: cardiac mortality).

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Figure 4

Funnel plot of comparison: Alpha‐2 agonists versus control in all surgery (outcome: myocardial infarction).

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Figure 5

Funnel plot of comparison: Alpha‐2 agonists versus control in all surgery (outcome: myocardial ischaemia).

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Analysis 1.1

Comparison 1 Alpha‐2 agonists versus control in all surgery, Outcome 1 All‐Cause Mortality.

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Analysis 1.2

Comparison 1 Alpha‐2 agonists versus control in all surgery, Outcome 2 Cardiac Mortality.

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Analysis 1.3

Comparison 1 Alpha‐2 agonists versus control in all surgery, Outcome 3 Myocardial Infarction.

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Analysis 1.4

Comparison 1 Alpha‐2 agonists versus control in all surgery, Outcome 4 Myocardial Ischaemia.

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Analysis 1.5

Comparison 1 Alpha‐2 agonists versus control in all surgery, Outcome 5 Supraventricular Tachyarrhythmia.

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Analysis 1.6

Comparison 1 Alpha‐2 agonists versus control in all surgery, Outcome 6 Congestive Heart Failure.

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Analysis 1.7

Comparison 1 Alpha‐2 agonists versus control in all surgery, Outcome 7 Hypotension.

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Analysis 1.8

Comparison 1 Alpha‐2 agonists versus control in all surgery, Outcome 8 Bradycardia.

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Analysis 1.9

Comparison 1 Alpha‐2 agonists versus control in all surgery, Outcome 9 Acute Stroke.

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Analysis 1.10

Comparison 1 Alpha‐2 agonists versus control in all surgery, Outcome 10 Preoperative Beta‐Blocker Use.

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Analysis 1.11

Comparison 1 Alpha‐2 agonists versus control in all surgery, Outcome 11 Preoperative Calcium Channel Blocker Use.

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Analysis 2.1

Comparison 2 Alpha‐2 agonist (stratified by drug) versus control in all surgery, Outcome 1 All‐Cause Mortality.

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Analysis 2.2

Comparison 2 Alpha‐2 agonist (stratified by drug) versus control in all surgery, Outcome 2 Cardiac Mortality.

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Analysis 2.3

Comparison 2 Alpha‐2 agonist (stratified by drug) versus control in all surgery, Outcome 3 Myocardial Infarction.

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Analysis 2.4

Comparison 2 Alpha‐2 agonist (stratified by drug) versus control in all surgery, Outcome 4 Myocardial Ischaemia.

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Analysis 2.5

Comparison 2 Alpha‐2 agonist (stratified by drug) versus control in all surgery, Outcome 5 Hypotension.

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Analysis 3.1

Comparison 3 Alpha‐2 agonist versus control in cardiac surgery, Outcome 1 All‐Cause Mortality.

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Analysis 3.2

Comparison 3 Alpha‐2 agonist versus control in cardiac surgery, Outcome 2 Myocardial Infarction.

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Analysis 3.3

Comparison 3 Alpha‐2 agonist versus control in cardiac surgery, Outcome 3 Myocardial Ischaemia.

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Analysis 3.4

Comparison 3 Alpha‐2 agonist versus control in cardiac surgery, Outcome 4 Supraventricular Tachyarrhythmia.

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Analysis 3.5

Comparison 3 Alpha‐2 agonist versus control in cardiac surgery, Outcome 5 Bradycardia.

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Analysis 4.1

Comparison 4 Alpha‐2 agonist versus control in non‐cardiac surgery, Outcome 1 All‐Cause Mortality.

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Analysis 4.2

Comparison 4 Alpha‐2 agonist versus control in non‐cardiac surgery, Outcome 2 Cardiac Mortality.

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Analysis 4.3

Comparison 4 Alpha‐2 agonist versus control in non‐cardiac surgery, Outcome 3 Myocardial Infarction.

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Analysis 4.4

Comparison 4 Alpha‐2 agonist versus control in non‐cardiac surgery, Outcome 4 Myocardial Ischaemia.

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Analysis 4.5

Comparison 4 Alpha‐2 agonist versus control in non‐cardiac surgery, Outcome 5 Bradycardia.

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Analysis 5.1

Comparison 5 Alpha‐2 agonist versus control in vascular surgery, Outcome 1 All‐Cause Mortality.

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Analysis 5.2

Comparison 5 Alpha‐2 agonist versus control in vascular surgery, Outcome 2 Cardiac Mortality.

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Analysis 5.3

Comparison 5 Alpha‐2 agonist versus control in vascular surgery, Outcome 3 Myocardial Infarction.

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Analysis 5.4

Comparison 5 Alpha‐2 agonist versus control in vascular surgery, Outcome 4 Myocardial Ischaemia.

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Analysis 6.1

Comparison 6 Alpha‐2 agonist versus control in non‐vascular, non‐cardiac surgery, Outcome 1 All‐Cause Mortality.

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Analysis 6.2

Comparison 6 Alpha‐2 agonist versus control in non‐vascular, non‐cardiac surgery, Outcome 2 Myocardial Infarction.

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Analysis 6.3

Comparison 6 Alpha‐2 agonist versus control in non‐vascular, non‐cardiac surgery, Outcome 3 Myocardial Ischaemia.

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Analysis 7.1

Comparison 7 Alpha‐2 agonist versus control in patients receiving epidural or spinal anaesthesia, Outcome 1 Myocardial infarction.

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Analysis 8.1

Comparison 8 Alpha‐2 agonists versus control in studies with blinding and concealed allocation, Outcome 1 All‐Cause Mortality.

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Analysis 8.2

Comparison 8 Alpha‐2 agonists versus control in studies with blinding and concealed allocation, Outcome 2 Myocardial Infarction.

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Analysis 8.3

Comparison 8 Alpha‐2 agonists versus control in studies with blinding and concealed allocation, Outcome 3 Myocardial Ischaemia.

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Analysis 9.1

Comparison 9 Alpha‐2 agonists versus control in studies that used strict definitions of myocardial infarction or ischaemia, Outcome 1 Myocardial Infarction.

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Analysis 9.2

Comparison 9 Alpha‐2 agonists versus control in studies that used strict definitions of myocardial infarction or ischaemia, Outcome 2 Myocardial Ischaemia.

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Analysis 10.1

Comparison 10 Alpha‐2 agonists versus control in all surgery, excluding Oliver 1999, Outcome 1 All‐Cause Mortality.

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Analysis 10.2

Comparison 10 Alpha‐2 agonists versus control in all surgery, excluding Oliver 1999, Outcome 2 Cardiac Mortality.

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Analysis 10.3

Comparison 10 Alpha‐2 agonists versus control in all surgery, excluding Oliver 1999, Outcome 3 Myocardial Infarction.

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Comparison 1. Alpha‐2 agonists versus control in all surgery

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐Cause Mortality Show forest plot	18	3828	Risk Ratio (M‐H, Fixed, 95% CI)	0.66 [0.44, 0.98]

2 Cardiac Mortality Show forest plot	6	2590	Risk Ratio (M‐H, Fixed, 95% CI)	0.53 [0.30, 0.95]

3 Myocardial Infarction Show forest plot	16	3603	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.65, 1.10]

4 Myocardial Ischaemia Show forest plot	20	1650	Risk Ratio (M‐H, Fixed, 95% CI)	0.68 [0.57, 0.81]

5 Supraventricular Tachyarrhythmia Show forest plot	8	1056	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.65, 1.58]

6 Congestive Heart Failure Show forest plot	11	1203	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.47, 1.19]

7 Hypotension Show forest plot	17	3600	Risk Ratio (M‐H, Random, 95% CI)	1.32 [1.07, 1.62]

8 Bradycardia Show forest plot	18	3933	Risk Ratio (M‐H, Random, 95% CI)	1.66 [1.14, 2.41]

9 Acute Stroke Show forest plot	5	713	Risk Ratio (M‐H, Fixed, 95% CI)	0.68 [0.31, 1.52]

10 Preoperative Beta‐Blocker Use Show forest plot	17	3338	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [1.01, 1.22]

11 Preoperative Calcium Channel Blocker Use Show forest plot	16	3293	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.89, 1.03]

Comparison 1. Alpha‐2 agonists versus control in all surgery

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Comparison 2. Alpha‐2 agonist (stratified by drug) versus control in all surgery

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐Cause Mortality Show forest plot	18		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Clonidine	8	848	Risk Ratio (M‐H, Fixed, 95% CI)	0.34 [0.13, 0.94]
1.2 Dexmedetomidine	8	783	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.40, 2.54]
1.3 Mivazerol	2	2197	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.42, 1.15]
2 Cardiac Mortality Show forest plot	5		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Clonidine	3	363	Risk Ratio (M‐H, Fixed, 95% CI)	0.75 [0.17, 3.37]
2.2 Mivazerol	2	2197	Risk Ratio (M‐H, Fixed, 95% CI)	0.51 [0.27, 0.98]
3 Myocardial Infarction Show forest plot	16		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Clonidine	9	881	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.26, 1.33]
3.2 Dexmedetomidine	5	525	Risk Ratio (M‐H, Fixed, 95% CI)	0.68 [0.24, 1.87]
3.3 Mivazerol	2	2197	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.68, 1.21]
4 Myocardial Ischaemia Show forest plot	19		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 Clonidine	15	1077	Risk Ratio (M‐H, Fixed, 95% CI)	0.62 [0.51, 0.76]
4.2 Dexmedetomidine	4	273	Risk Ratio (M‐H, Fixed, 95% CI)	0.71 [0.48, 1.05]
5 Hypotension Show forest plot	17		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

5.1 Clonidine	8	525	Risk Ratio (M‐H, Random, 95% CI)	1.51 [1.11, 2.04]
5.2 Dexmedetomidine	7	878	Risk Ratio (M‐H, Random, 95% CI)	1.57 [1.16, 2.12]
5.3 Mivazerol	2	2197	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.82, 1.10]

Comparison 2. Alpha‐2 agonist (stratified by drug) versus control in all surgery

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Comparison 3. Alpha‐2 agonist versus control in cardiac surgery

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐Cause Mortality Show forest plot	7	546	Risk Ratio (M‐H, Fixed, 95% CI)	0.70 [0.21, 2.31]

2 Myocardial Infarction Show forest plot	8	776	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.46, 2.21]

3 Myocardial Ischaemia Show forest plot	10	589	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.50, 0.85]

4 Supraventricular Tachyarrhythmia Show forest plot	4	583	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.65, 1.71]

5 Bradycardia Show forest plot	6	657	Risk Ratio (M‐H, Random, 95% CI)	1.91 [1.11, 3.29]

Comparison 3. Alpha‐2 agonist versus control in cardiac surgery

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Comparison 4. Alpha‐2 agonist versus control in non‐cardiac surgery

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐Cause Mortality Show forest plot	9	2851	Risk Ratio (M‐H, Fixed, 95% CI)	0.61 [0.39, 0.96]

2 Cardiac Mortality Show forest plot	4	2515	Risk Ratio (M‐H, Fixed, 95% CI)	0.51 [0.27, 0.93]

3 Myocardial Infarction Show forest plot	8	2817	Risk Ratio (M‐H, Random, 95% CI)	0.49 [0.22, 1.09]

4 Myocardial Ischaemia Show forest plot	10	1061	Risk Ratio (M‐H, Random, 95% CI)	0.73 [0.54, 1.00]

5 Bradycardia Show forest plot	10	2845	Risk Ratio (M‐H, Random, 95% CI)	1.44 [0.89, 2.31]

Comparison 4. Alpha‐2 agonist versus control in non‐cardiac surgery

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Comparison 5. Alpha‐2 agonist versus control in vascular surgery

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐Cause Mortality Show forest plot	7	1648	Risk Ratio (M‐H, Fixed, 95% CI)	0.47 [0.25, 0.90]

2 Cardiac Mortality Show forest plot	4	1522	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.16, 0.79]

3 Myocardial Infarction Show forest plot	6	1616	Risk Ratio (M‐H, Fixed, 95% CI)	0.66 [0.46, 0.94]

4 Myocardial Ischaemia Show forest plot	5	715	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.64, 1.34]

Comparison 5. Alpha‐2 agonist versus control in vascular surgery

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Comparison 6. Alpha‐2 agonist versus control in non‐vascular, non‐cardiac surgery

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐Cause Mortality Show forest plot	2	1013	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.52, 2.09]

2 Myocardial Infarction Show forest plot	2	1021	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.20, 4.16]

3 Myocardial Ischaemia Show forest plot	3	96	Risk Ratio (M‐H, Fixed, 95% CI)	0.23 [0.04, 1.30]

Comparison 6. Alpha‐2 agonist versus control in non‐vascular, non‐cardiac surgery

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Comparison 7. Alpha‐2 agonist versus control in patients receiving epidural or spinal anaesthesia

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Myocardial infarction Show forest plot	2	526	Risk Ratio (M‐H, Fixed, 95% CI)	0.72 [0.29, 1.81]

Comparison 7. Alpha‐2 agonist versus control in patients receiving epidural or spinal anaesthesia

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Comparison 8. Alpha‐2 agonists versus control in studies with blinding and concealed allocation

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐Cause Mortality Show forest plot	5	2699	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.37, 0.95]

2 Myocardial Infarction Show forest plot	5	2326	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.68, 1.21]

3 Myocardial Ischaemia Show forest plot	3	394	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.41, 0.85]

Comparison 8. Alpha‐2 agonists versus control in studies with blinding and concealed allocation

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Comparison 9. Alpha‐2 agonists versus control in studies that used strict definitions of myocardial infarction or ischaemia

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Myocardial Infarction Show forest plot	9	3064	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.64, 1.11]

2 Myocardial Ischaemia Show forest plot	13	1340	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.54, 0.79]

Comparison 9. Alpha‐2 agonists versus control in studies that used strict definitions of myocardial infarction or ischaemia

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Comparison 10. Alpha‐2 agonists versus control in all surgery, excluding Oliver 1999

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐Cause Mortality Show forest plot	17	1931	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.37, 1.28]

2 Cardiac Mortality Show forest plot	5	693	Risk Ratio (M‐H, Fixed, 95% CI)	0.61 [0.18, 2.04]

3 Myocardial Infarction Show forest plot	15	1706	Risk Ratio (M‐H, Fixed, 95% CI)	0.53 [0.30, 0.94]

Comparison 10. Alpha‐2 agonists versus control in all surgery, excluding Oliver 1999

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