Guidelines for the Management of Absolute CVD Risk Technical report

412 Pages·2012·4.25 MB·English

Absolute cardiovascular disease risk management

Inclusion, appraisal and summary of evidence for the National
evidence-based guideline for the management of absolute
cardiovascular disease risk

An initiative of the National Vascular Disease Prevention Alliance

The NVDPA is a group of four leading and well-known Australian charities: Kidney Health Australia, Diabetes Australia, the National Heart Foundation of Australia and the National Stroke Foundation. It
was established in 2000 and aims to reduce cardiovascular disease in Australia. Links to the full guidelines can be found on NVDPA member websites: www.strokefoundation.com.au,
www.kidney.org.au, www.diabetesaustralia.com.au and www.heartfoundation.org.au.

The NVDPA would like to acknowledge the international Centre for Allied Health Evidence (iCAHE), University of South Australia for their work in developing this report.
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Contents
1. Background ................................................................................................................................................................ 6
2. Methods ..................................................................................................................................................................... 6
Literature review ............................................................................................................................................................ 6
Evidence Tables and quality checks ............................................................................................................................... 7
Formulation of recommendations – Grades .................................................................................................................. 8
3. Absolute risk assessment (Q1-5) .............................................................................................................................. 11
Search results ............................................................................................................................................................... 11
Literature included ....................................................................................................................................................... 12
Evidence details ........................................................................................................................................................... 19
FORM framework Question 1 ...................................................................................................................................... 42
FORM framework Question 2 ...................................................................................................................................... 45
Questions 3-5 ............................................................................................................................................................... 47
4. Aims of treatment, monitoring and follow up (Q6-8) .............................................................................................. 49
Search results ............................................................................................................................................................... 49
Question 6 Summary ................................................................................................................................................... 49
Question 7 & 8 Summary ............................................................................................................................................. 54
5. Blood pressure lowering (Q9-13) ............................................................................................................................. 58
Search results ............................................................................................................................................................... 58
Literature included ....................................................................................................................................................... 59
Evidence details ........................................................................................................................................................... 62
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FORM framework Question 9 .................................................................................................................................... 109
FORM framework Question 10 .................................................................................................................................. 112
FORM framework Question 11 .................................................................................................................................. 115
FORM framework Question 12 .................................................................................................................................. 118
FORM framework Question 13 .................................................................................................................................. 120
6. Lipid lowering therapy (Q14-17) ............................................................................................................................ 127
Search results ............................................................................................................................................................. 127
Included literature ..................................................................................................................................................... 128
Evidence details ......................................................................................................................................................... 132
FORM framework Question 14 .................................................................................................................................. 194
FORM framework Question 15 .................................................................................................................................. 197
FORM framework Question 16 .................................................................................................................................. 200
FORM framework Question 17 .................................................................................................................................. 202
7. Antiplatelet therapy (Q18-19) ................................................................................................................................ 207
Search results ............................................................................................................................................................. 207
Literature Included ..................................................................................................................................................... 207
Evidence details ......................................................................................................................................................... 210
FORM framework Question 18 .................................................................................................................................. 246
FORM framework Question 19 .................................................................................................................................. 248
8. Weight reduction (Q20) ......................................................................................................................................... 254
Search results ............................................................................................................................................................. 254
Literature identified ................................................................................................................................................... 254
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Evidence details ......................................................................................................................................................... 255
FORM framework Question 20 .................................................................................................................................. 264
9. Dietary advice (Q21) .............................................................................................................................................. 267
Search results ............................................................................................................................................................. 267
Literature identified ................................................................................................................................................... 268
Evidence details ......................................................................................................................................................... 270
FORM framework Question 21 .................................................................................................................................. 286
10. Physical activity (Q22-23) ................................................................................................................................... 291
Search results ............................................................................................................................................................. 291
Literature identified ................................................................................................................................................... 291
Evidence details ......................................................................................................................................................... 293
FORM framework Question 22 & 23.......................................................................................................................... 327
11. Alcohol consumption (Q24) ............................................................................................................................... 330
Search results ............................................................................................................................................................. 330
Literature identified ................................................................................................................................................... 330
Evidence details ......................................................................................................................................................... 331
FORM framework Question 24 .................................................................................................................................. 354
12. Smoking cessation (Q25) .................................................................................................................................... 357
Search results ............................................................................................................................................................. 357
Literature identified ................................................................................................................................................... 357
Evidence details ......................................................................................................................................................... 362
FORM framework Question 25 .................................................................................................................................. 365
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13. Depression (Q26) ............................................................................................................................................... 368
Search results ............................................................................................................................................................. 368
Literature identified ................................................................................................................................................... 368
Evidence details ......................................................................................................................................................... 368
FORM framework Question 26 .................................................................................................................................. 374
Appendix 1. Additional evidence details ........................................................................................................................ 377
Appendix 2. Data extraction and critical appraisal templates ....................................................................................... 404

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1. Background
The international Centre for Allied Health Evidence (iCAHE) was engaged by the National Stroke Foundation (NSF) on
behalf of the National Vascular Disease Prevention Alliance (NVDPA) to conduct the systematic search and appraisal
for the development of these guidelines. The paradigm to be adopted a priori was one of absolute risk. Wherever
possible the protocol followed that of the Scottish Intercollegiate Guidelines Network (SIGN) Guideline 97 (Risk
estimation and the prevention of cardiovascular disease) to enable efficiencies. The original SIGN protocol was
adapted to:
 reflect the absolute risk approach;
 update the searches to June 2010 (SIGN searches were conducted in August 2004- June 2005);
 comply with NHMRC guideline procedures;
 reflect the questions modified/rewritten from the original SIGN questions by the NVDPA Expert Working
Group and to incorporate subgroups where appropriate.

A further update search for the Australian CVD Absolute Risk Assessment Guidelines was also conducted in particular
to cover absolute risk assessment for the under 45 and over 75 age groups. The search and appraisal process for
these questions followed the protocol reported by the guideline developers (NVDPA Technical report 2006).
2. Methods
Literature review
The clinical questions and literature review methodology is outlined in appendix 2: Guidelines development process
report, in the full guidelines document. In short, 26 clinical questions were developed to guide the literature search.
As noted above the current guideline development process built on two existing guidelines: The Guidelines for the
assessment of absolute cardiovascular disease risk (2009) and the SIGN Risk estimation and the prevention of
cardiovascular disease (2007). As such search dates updated those used in these two guidelines. Where possible the
highest level of evidence was selected (high quality, Level I studies). Where possible studies focussed specifically on
the primary prevention of CVD were selected however often there was a mix of primary and secondary prevention.
Where possible this is noted. Prespecified subgroups were used for specific questions. These included one or more of
the following:
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a. Those deemed clinically high risk as outlined in the assessment guidelines (those with SBP >180 or
DBP>110mmHg, diabetes >60yrs, diabetes with microalbuminuria, CKD [see levels below], familial
hypercholesterolaemia, cholesterol >7.5mmol/L)
b. Those with atrial fibrillation
c. High, medium and low absolute risk of CVD
d. Abnormal BP and normal BP
e. Hypercholesterol and normal cholesterol
f. Diabetes and no diabetes
g. Chronic kidney disease and no chronic kidney disease (break down into GFR <45 ml/min, GFR 45-60
ml/min and GFR >60 ml/min)

The primary outcomes for each question were cardiovascular events and all cause mortality. The secondary
outcomes of interest were surrogate outcomes as specified in the individual questions (e.g. BP control).
The search was undertaken in two phases based on the PICO questions. Initally the literature was searched
based on the population and intervention for each of the broad topics. Each study outcome and comparison
was then evaluated before the final section of included studies made relevant to each specific question
Evidence Tables and quality checks
Included studies had data abstracted into tables for each question including evidence summary, citation, study type,
evidence level (as per NHMRC), patient number and characteristics, intervention, comparison, length of follow-up,
outcome measure, effect size and funding source (as appropriate).

Two reviewers independently assessed the methodological quality of each included trial and resolved disagreements
by consensus, with reference to a third reviewer if necessary. This appraisal was included in the evidence table.
Methodological quality of included systematic reviews (SRs) was assessed using the SIGN Methodology checklist for
systematic reviews and meta-analyses or the NSF Methodological Checklist for systematic reviews (modified SIGN
checklist with Guidelines-International-Network template); included randomised controlled trials (RCTs) were
assessed using the NSF Methodological Checklist for randomised controlled trials (modified SIGN checklist with
Guidelines-International-Network template); included cohort studies were assessed using the SIGN Methodology
checklist for cohort studies.

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For Questions 1-5 the Monash group had applied critical appraisal questions related to diagnostic studies – this
practice was continued for the update for consistency, though it should be noted the studies retrieved were
methodologically more related to prognostic or screening designs.
Formulation of recommendations – FORM framework
To assist in the formulation of recommendations, where a body of evidence existed for each question, the NMHRC
FORM process was applied. This resulted in a preliminary Evidence Statement used by the expert working group in
their final recommendations and is supported by a ‘strength of recommendation’ grade (based on the NHMRC Body
of Evidence matrix).
The application of a grade to a recommendation is based on an assessment of all the included studies for that
recommendation (the ‘body of evidence’).

Table 1 Body of evidence assessment matrix
A B C D
Component
Excellent Good Satisfactory Poor
Volume of Several level I or One or two level Level III studies Level IV studies,
evidence II studies with low II studies with low with low risk of or level I to III
risk of bias risk of bias or a bias, or level I or II studies with high
SR/multiple level III studies with risk of bias
studies with moderate risk of
low risk of bias bias
Consistency All studies Most studies Some inconsistency Evidence is
consistent consistent and reflecting genuine inconsistent
inconsistency uncertainty
may be explained around clinical
question
Clinical impact Very large Substantial Moderate Slight or
restricted
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Generalisability Population/s Population/s Population/s Population/s
studied in body of studied in the studied in body of studied in body of
evidence are the body of evidence evidence are evidence are
same as the target are similar to the different to the different to the
population for target population target population target population
these for these for these and it is hard to
guidelines guidelines guidelines, but it judge whether it
is clinically is sensible to
sensible to apply generalise to the
this evidence to target population
the target
population
Applicability Directly Applicable to the Probably Not applicable to
applicable to the Australian applicable to the the Australian
Australian healthcare Australian healthcare
healthcare context, with few healthcare context
context caveats context, with
some caveats
Source: NHMRC additional levels of evidence and grades for recommendations for developers of guidelines PILOT PROGRAM
2005 – 2007.

Table 2 Overall grade of evidence based recommendation

Grade of Description
recommendation
A Body of evidence can be trusted to guide practice
B Body of evidence can be trusted to guide practice in most situations
C Body of evidence provides some support for recommendation(s) but care should be taken in its application
D Body of evidence is weak and recommendation must be applied with caution
Source: BMC Med Res Methodol. 2011 Feb 28;11:23.
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Additional guidance
Consensus-based recommendations (CBR) developed by the guidelines expert working group when a systematic review of the
CBR evidence found either an absence of direct evidence which answered the clinical question or poor quality evidence, which was
deemed not to be strong enough to formulate an evidence based recommendation.
Practice points (PP) developed by the guidelines expert working group where a systematic review had not been conducted but
PP there was a need to provide practical guidance to support the implementation of the evidence based and/or consensus based
recommendations.

Important consideration

The current guidelines take an absolute risk approach to the management of CVD risk which has posed some
challenges in formulation of the recommendations. This is because although there is robust and compelling evidence
in the published literature which clearly shows that pharmacotherapy reduces the levels of individual risk factors
(blood pressure and lipids) with consequent reduction in CVD mortality or CVD events, this evidence is based on a
single risk factor/relative risk approach. Therefore the expert panel carefully considered the literature before making
and grading the recommendations in an absolute risk paradigm. When examining the evidence, special consideration
was given to any heterogeneity found between subgroups and the generalisability of the findings. In general, the final
grading of these recommendations was downgraded to account for the uncertainty of applying evidence from a
relative risk approach to an absolute risk paradigm.
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