Intravenous magnesium sulphate and sotalol for prevention of atrial fibrillation

134 Pages·2008·0.81 MB·English

H Health Technology Assessment 2008;Vol. 12: No. 28
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June 2008
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Intravenous magnesium sulphate and
sotalol for prevention of atrial
fibrillation after coronary artery bypass
surgery: a systematic review and
economic evaluation
* †
J Shepherd, J Jones, GK Frampton,´ L Tanajewski,
D Turner and A Price
Southampton Health Technology Assessments Centre (SHTAC),
University of Southampton, UK
* Corresponding author
† Present address: Department of Health Technology Assessment, The Agency for Health
Technology Assessment in Poland (AHTAPol), Poland
Declared competing interests of authors:none
Published June 2008
This report should be referenced as follows:
Shepherd J, Jones J, Frampton GK, Tanajewski ´L, Turner D, Price A. Intravenous
magnesium sulphate and sotalol for prevention of atrial fibrillation after coronary artery
bypass surgery: a systematic review and economic evaluation. Health Technol Assess
2008;12(28).
Health Technology Assessmentis indexed and abstracted in Index Medicus/MEDLINE,
Excerpta Medica/EMBASE and Science Citation Index Expanded (SciSearch®)and
Current Contents®/Clinical Medicine.
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Health Technology Assessment2008; Vol. 12: No. 28
Abstract
Intravenous magnesium sulphate and sotalol for prevention
of atrial fibrillation after coronary artery bypass surgery:
a systematic review and economic evaluation
J Shepherd,* J Jones, GK Frampton,´ L Tanajewski,† D Turner and A Price
Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, UK
* Corresponding author
† Present address: Department of Health Technology Assessment, The Agency for Health Technology Assessment
in Poland (AHTAPol), Poland
Objectives: To assess the clinical and cost- p= 0.0005). Two randomised controlled trials (RCTs)
effectiveness of magnesium sulphate compared with were notable as they had relatively lower ORs in
sotalol, and to assess the clinical effectiveness of favour of magnesium sulphate. When these were
magnesium sulphate compared with placebo in the removed from the analyses the pooled OR remained
prevention of atrial fibrillation (AF) in patients who statistically significant, but heterogeneity no longer
have had a coronary artery bypass graft (CABG). remained significant. These two studies tended to
Data sources: Major electronic databases were impart a highly significant reduction in the odds of AF
searched from December 2003 to May 2007. to whichever subgroup they were analysed in. When
Review methods: Selected studies were assessed, studies were ordered by total duration of prophylaxis,
subjected to data extraction using a standard template an apparent relationship between duration and odds of
and quality assessment using published criteria. AF was evident, with decreasing odds of AF as duration
A simple short-term economic model was developed, of prophylaxis increased. This was confirmed by linear
informed by a systematic review of economic regression analysis (R2= 0.743, p< 0.001). When the
evaluations and populated with data from a review of data were grouped into three classes according to
costing/resource-use studies and other published duration, a statistically significant intervention effect
studies. The cost-effectiveness of magnesium sulphate was only present for the longest duration (OR = 0.12,
as prophylaxis was estimated for a set of base-case 95% CI 0.06 to 0.23, p= 0.00001). Statistically
assumptions and the robustness of these results was significant intervention effects were associated with the
assessed using deterministic and probabilistic sensitivity initiation of prophylaxis 12 hours or more before
analysis. surgery (OR 0.26; 95% CI 0.16 to 0.44, test for overall
Results: Twenty-two papers met the inclusion criteria effect p= 0.00001, fixed-effects model) and less than
reporting 15 trials which all compared magnesium 12 hours before surgery or during the surgery itself
sulphate with placebo or control. They ranged in size (OR = 0.73, 95% CI 0.56 to 0.97, test for overall
from 15 to 176 patients randomised, and were effect p= 0.03, fixed-effects model), but not when
conducted in Europe, the USA and Canada. The prophylaxis was initiated at the end of surgery or
standard of reporting was generally poor, with details postsurgery (OR = 0.85, 95% CI 0.59, 1.22, p= 0.37,
of key methodological attributes difficult to elucidate. fixed-effects model). When studies were ordered by
No trials were identified that specifically aimed to total dose of intravenous magnesium sulphate (<25 g),
compare magnesium sulphate with sotalol. Of 1070 the odds of AF were independent of the dose.
patients in the pooled magnesium group, 230 (21%) A notable exception was that for a total dose of 9 g
developed postoperative AF, compared with 307 of magnesium sulphate; here the odds of AF were
1031 (30%) patients in the placebo or (control) group. significantly reduced relative to the control group,
Meta-analysis using a fixed-effects model generated a although this may be explained by the fact that these
pooled odds ratio (OR) that was significantly less than studies had excluded patients who were on
1.0 [OR = 0.65, 95% confidence interval (CI) 0.53 to antiarrhythmic drugs and so may have been at higher
0.79, test for overall effect p< 0.0001], but with risk of AF. Sixty-three potentially relevant references
statistically significant heterogeneity (I2= 63.4%, about cost-effectiveness were identified, but no iii
© Queen’s Printer and Controller of HMSO 2008. All rights reserved.
Abstract
economic evaluations of intravenous magnesium alone probability of being cost-effective was 99% at a
as prophylaxis against AF following CABG, compared willingness to pay (WTP) threshold of £2000 per AF
with sotalol as prophylaxis or no prophylaxis, were case avoided and 100% at a WTP threshold of £5000
identified. Studies reporting resource use by patients per AF case avoided under the base-case assumptions.
with AF following CABG suggest that while AF Under the alternative scenario of longer preoperative
significantly increased inpatient stays, by up to 2.3 days stays the probability of being cost-effective at these
in the intensive care unit (ICU) and 3.4 days on the two threshold values fell to 48% and 93%,
ward, differences in length of stay and costs between respectively. It is unclear what the appropriate decision
patients receiving prophylaxis and those not receiving threshold should be, given that this model used
prophylaxis were not statistically significant. In the intermediate rather than final outcomes.
base-case analysis, magnesium sulphate prophylaxis Conclusions: No RCTs were identified that specifically
resulted in 0.081 fewer cases of AF at an incremental aimed to compare intravenous magnesium with sotalol
cost of £2.55. The incremental cost-effectiveness ratio as prophylaxis for AF in patients undergoing CABG.
(ICER) was £32 per AF case avoided. The estimated Intravenous magnesium, compared with placebo or
difference in average length of stay between the control, is effective in preventing postoperative AF, as
prophylaxis and no-prophylaxis strategies was only 0.24 confirmed by a statistically significant intervention effect
days, despite a large assumed difference of 3 days for based on pooled analysis of 15 RCTs. It was also found
patients experiencing AF in each group (1 extra day in that AF was less likely to occur when a longer duration
the ICU and 2 extra days on the ward). In a of prophylaxis was used, and the earlier that
deterministic sensitivity analysis the greatest variation in prophylaxis is started; however, this finding was
ICERs was observed for input parameters relating to associated with two RCTs that had more favourable
the baseline risk of AF following CABG and the results than the other trials. No clear relationship
effectiveness of prophylaxis, cost of prophylaxis and the between dose and AF was observed, although a lower
resource consequences of postoperative AF. The constant dose rate was associated with the lowest odds
largest ICER (£2092) in the sensitivity analysis was of AF. Further research should investigate the
associated with increasing the length of patients’ relationship between dose, dose rate, duration of
preoperative stay. In the base case it was assumed that prophylaxis, timing of initiation of therapy and patient
admission routines would be identical under both characteristics, such as degree of risk for AF. This will
strategies. However, patients receiving prophylaxis by provide stronger evidence for the optimum delivery of
intravenous infusion may have longer preoperative intravenous magnesium in patients undergoing CABG.
stays. In a probabilistic analysis the majority of the In the base-case analysis in the economic model,
simulations were associated with improved outcomes magnesium sulphate prophylaxis reduced the number
(in this case fewer cases of AF), but also higher costs. of postoperative AF cases at a modest increase in cost.
Prophylaxis was the dominant strategy (better outcome The results of the economic analysis are highly sensitive
at lower cost) in about 41% of the simulations using to variation in certain key parameters. Prophylaxis is
the base-case assumptions. Under an alternative less likely to be a cost-effective option if it requires
scenario where patients receiving prophylaxis are changes in admission routines that result in longer
admitted for longer before their operation, to receive preoperative stays than would be the case without
their initial infusion, the proportion of simulations prophylaxis.
where prophylaxis dominates fell to around 5%. The
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Health Technology Assessment2008; Vol. 12: No. 28
Contents
Glossary and list of abbreviations ............. vii 7 Conclusions ................................................ 43
Executive summary .................................... ix Acknowledgements .................................... 45
1 Aim of the review ...................................... 1 References .................................................. 47
2 Background ................................................ 3 Appendix 1 Search strategy for RCTs and
Description of the underlying health systematic reviews ....................................... 51
problem ...................................................... 3
Current service provision ........................... 3 Appendix 2 Decision tree for screening
Description of the intervention ................. 4 abstracts and full papers ............................ 55
3 Methods of assessing clinical Appendix 3 Data extraction templates for
effectiveness ............................................... 5 the 15 RCTs included in this review .......... 57
Inclusion and exclusion criteria ................. 5
Search strategy ........................................... 5 Appendix 4 Studies screened and included
Study inclusion ........................................... 5 in the current review .................................. 85
Data extraction ........................................... 6
Quality assessment ..................................... 6 Appendix 5 Detection and definitions of
Data synthesis ............................................. 6 atrial fibrillation given in the included
RCTs ........................................................... 87
4 Clinical effectiveness results ...................... 9
Quantity and quality of research available 9 Appendix 6 Exclusion criteria reported
Systematic reviews ...................................... 9 for the selection of patients in RCTs ......... 89
Characteristics of the included RCTs ......... 10
Assessment of effectiveness ........................ 10 Appendix 7 Search strategy for economic
evaluations .................................................. 91
5 Economic analysis ...................................... 23
Methods for economic analysis .................. 23 Appendix 8 Inclusion criteria for
Results of the systematic review of economic review ......................................... 95
economic evaluations ................................. 23
SHTAC economic model methods ............ 26 Health Technology Assessment reports
Results of the economic model .................. 33 published to date ....................................... 97
6 Discussion ................................................... 39 Health Technology Assessment
Clinical effectiveness .................................. 39 Programme ................................................ 115
Cost-effectiveness ....................................... 40
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Health Technology Assessment2008; Vol. 12: No. 28
Glossary and list of abbreviations
Technical terms and abbreviations are used throughout this report. The meaning is usually clear from
the context, but a glossary is provided for the non-specialist reader. In some cases, usage differs in the
literature, but the term has a constant meaning throughout this review.
Glossary
Atrial arrhythmia Altered atrial rhythm PQ interval (ECG) The time between the
(includes atrial fibrillation, atrial flutter and beginning of atrial depolarisation and the
atrial tachycardia). beginning of ventricular depolarisation.
Atrial fibrillation Uncoordinated atrial QRS complex (ECG) Deflections in the
pulsation. tracing comprising the Q, R and S waves
indicating currents generated when the
Atrial flutter Increased but coordinated atrial ventricles depolarise before their contraction.
pulsation.
QT interval The time between the start of
Atrial tachycardia Increased atrial beat rate. the Q wave and the end of the T wave in the
heart’s electrical cycle.
F waves (ECG) Regular, rapid atrial waves
indicative of atrial flutter. Supraventricular arrhythmia A rhythmic
abnormality of the heart caused by impulses
Left ventricular ejection fraction The originating above the ventricles, e.g. in the
fraction of blood pumped out of a ventricle atrioventricular (sinoatrial) node; may be
with each heart beat; one of the most synonymous with atrial arrhythmia.
important predictors of prognosis.
P wave (ECG) The wave of depolarisation
that spreads from the sinoatrial node
throughout the atria.
vii
© Queen’s Printer and Controller of HMSO 2008. All rights reserved.
Glossary and list of abbreviations
List of abbreviations
ACE angiotensin-converting enzyme i.v. intravenous
AF atrial fibrillation LVEF left ventricular ejection fraction
BMI body mass index MI myocardial infarction
BNF British National Formulary NA not applicable
BP blood pressure NICE National Institute for Health and
Clinical Excellence
bpm beats per minute
NR not reported
BSA body surface area
ns not significant
CABG coronary artery bypass graft
NYHA New York Heart Association
CDSR Cochrane Database of Systematic
Reviews OR odds ratio
CEAC cost-effectiveness acceptable curve PCV pharmacological cardioversion
CI confidence interval POAT postoperative atrial tachycardia
COPD chronic obstructive pulmonary PSA probabilistic sensitivity analysis
disease
PVD peripheral vascular disease
CPB cardiopulmonary bypass
QALY quality-adjusted life-year
CRD Centre for Reviews and
Dissemination RCT randomised controlled trial
D W 5% dextrose water solution SD standard deviation
5
df degrees of freedom SDU step-down unit
ECV electrical cardioversion SHTAC SouthamptonHealth Technology
Assessments Centre
FEV forced expiratory volume in
1
1second SR systematic review
HRG Healthcare Resource Group SVA supraventricular arrhythmia
ICER incremental cost-effectiveness ratio SVT supraventricular tachycardia
ICU intensive care unit WTP willingness to pay
ITT intention-to-treat
All abbreviations that have been used in this report are listed here unless the abbreviation is well known (e.g. NHS), or
it has been used only once, or it is a non-standard abbreviation used only in figures/tables/appendices in which case
the abbreviation is defined in the figure legend or at the end of the table.
viii