FPIN Journal Club
SYSTEMATIC REVIEW WORKSHEET
SPEAKER NOTES
Title: Statins for ACS
Author: Laura Morris MD MSPH
PURL Citation: GovAri H, Stevermer JJ. Prescribing statins for ACS? No need to wait. Journal of
Family Practice, 63(12) 2014: 735-738.
Original Article: Navarese EP, Kowalewski M, Andreotti F, et al. Meta-analysis of time related
benefits of statin therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Am J Cardiol.2014;113:1753-1764.
Definitions
Systematic review:
A review in which evidence on a topic or research question has been systematically identified, appraised and summarized according to predetermined criteria.
Meta-analysis:
A statistical technique. Summarizes the results of several studies into a single estimate, giving more weight to larger studies.
1. What question did the study attempt to answer?
Patients – Adults with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI)
Intervention – Statin use before or after PCI
Comparison – No statin or low dose statin
Outcome – Primary: 30 day mortality and 30 day MI (myocardial infarction) rate
Secondary: Major adverse cardiac events (MACE), major adverse cardiac and cerebrovascular events (MACCE)
Did the study address an appropriate and clearly focused question Yes No
2. Determining relevance:
a. Did the authors study a clinically meaningful
and/or a patient oriented outcome? Yes No
b. The patients covered by the review similar to your population Yes No
3. Determining validity:
a. What type of studies are included in the review? RCT
b. The literature search is sufficiently rigorous to identify all the relevant studies?
Look for Yes No
· Which bibliographic databases were used Yes
· Follow up from reference lists Yes
· Personal contact with experts Not specified
· Search for unpublished as well as published studies Yes—conference
abstracts, websites
· Search for non-English language studies Yes—no language restriction
c. Did the review’s authors do enough to assess the
quality of the included studies? Yes No
· The authors need to consider the rigor of the studies
they have identified. Often original articles include a table that judges the sources or risk of bias in the included studies.
d. If the results of the review have been combined, was it
reasonable to do so? Yes No
Consider whether
· The results were similar from study to study
· The results of all the included studies are clearly
displayed
· The results of the different studies are similar
· The reasons for any variations are discussed
4. What are the results?
a. What is the overall result of the review?
The 30-day incidence of MI was markedly lower when statins were administered before PCI (OR 0.38, 95% CI 0.24-0.59, p<0.0001) rather than after PCI (p=0.28). The direction and magnitude of the estimates for before and after PCI versus no statin or low-dose statin were sustained at long term, not reaching statistical significance for MI (OR 0.81, 95%CI 0.65-1.01, p=0.06) but with significant reductions in MACE (p=0.0002). By meta-regression, earlier statin administration correlated significantly with lower risk of MI, MACE, and MACCE at 30 days.
b. Consider:
Are we clear about the reviews ‘bottom line’ results Yes No
Are the results presented with confidence intervals, Yes No
NNT, odds ratio, etc
5. Applying the evidence:
a. If the findings are valid and relevant, will this change
your current practice? Yes No
b. Is the change in practice something that can be done in
a medical care setting of a family physician? Yes No
c. Can the results be implemented? Yes No
d. Are there any barrier to immediate implementation? Yes No
e. How was this study funded? Not exactly clear, authors are members of SIRIO research network, a collaboration of “senior scientists” doing international cardiovascular research. Authors state nothing to disclose. No pharma funding mentioned.
6. Teaching Points
Sensitivity Analysis-- Systematic reviews combine studies with different inclusion and exclusion criteria, study populations, and sometimes varying cutoffs for interventions or outcomes. For example, this SR of statins for ACS included studies using varying doses of different statins.
It may not be clear if some of the studies should have been included in the meta-analysis in the first place, perhaps because the authors judged them to be low-quality studies. Or perhaps the authors want to know if including only atorvastatin changes the results of the meta-analysis. To find out, they might undertake a sensitivity analysis.
We want to know that the findings from a systematic review or meta-analysis are not dependent on arbitrary or unclear decisions (such as the dose of statin in our example). A sensitivity analysis is a repeat of the primary analysis or meta-analysis, substituting alternative decisions or ranges of values for decisions that were unclear.
If the results do not change during the sensitivity analysis, this suggests that the results of the original meta-analysis are probably accurate. If the results do change, then the authors draw different conclusions for the “entire group” and “atorvastatin” only.
In this study, researchers were concerned that the effects might have varied based on the formulation of statin used or the dose. They conducted a sensitivity analysis which looked to see if one type of statin or one dose was responsible for the apparent statistical significance—in this study, no one statin seemed to stand out. Most RCTs used high dose statins, which may have eliminated differences, should they have been there at lower doses. They also performed sensitivity analyses to see if the results of the study were attributable to one individual study—performing the meta-analysis repeatedly, leaving out each study once, to see if the results changed, and found that they did not. This suggests that the overall results are accurate reflections of the pooled data, rather than a reflection of just 1 study’s influence.
Citation: http://handbook.cochrane.org/chapter_9/9_7_sensitivity_analyses.htm