Article Text

Systematic review
Regional and temporal variations of spontaneous coronary artery dissection care according to consensus recommendations: a systematic review and meta-analysis
  1. Quan Dang1,
  2. Farrah Othman2,3,
  3. Brodie Sheahen1,
  4. Simone Marschner1,
  5. Peter Psaltis4,5,6,
  6. Rasha Kadem Al-Lamee7,
  7. Richard Szirt8,
  8. James Chong9 and
  9. Sarah Zaman1,9
  1. 1Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Westmead, New South Wales, Australia
  2. 2The University of Western Australia, Perth, Western Australia, Australia
  3. 3Department of Cardiology, Fiona Stanley Hospital, Perth, Western Australia, Australia
  4. 4Vascular Research Centre, Lifelong Health Theme, South Australian Medical and Health Research Institute, Adelaide, South Australia, Australia
  5. 5Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia
  6. 6Department of Cardiology, Central Adelaide Local Health Network, Adelaide, South Australia, Australia
  7. 7National Heart and Lung Institute, Imperial College London, London, UK
  8. 8St George Hospital, Kogarah, New South Wales, Australia
  9. 9Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia
  1. Correspondence to Dr Sarah Zaman; sarah.zaman{at}sydney.edu.au

Abstract

Aim The first expert consensus documents on management of patients with spontaneous coronary artery dissection (SCAD) were published in 2018. Worldwide quality of care, as measured by adherence to these recommendations, has not been systematically reviewed. We aim to review the proportion of patients with SCAD receiving consensus recommendations globally, regionally and, determine differences in practice before and after 2018.

Methods and results A systematic review was performed by searching four main databases (Medline, Embase, SCOPUS, CINAHL) from their inception to 16 June 2022. Studies were selected if they included patients with SCAD and reported at least one of the consensus document recommendations. 53 studies, n=8456 patients (mean 50.1 years, 90.6% female) were included. On random effects meta-analysis, 92.1% (95% CI 89.3 to 94.8) received at least one antiplatelet, 78.0% (CI 73.5 to 82.4) received beta-blockers, 58.7% (CI 52.3 to 65.1) received ACE inhibitors or aldosterone receptor blockers (ACEIs/ARBs), 54.4% (CI 45.4 to 63.5) were screened for fibromuscular dysplasia (FMD), and 70.2% (CI 60.8 to 79.5) were referred to cardiac rehabilitation. Except for cardiac rehabilitation referral and use of ACEIs/ARBs, there was significant heterogeneity in all other quality-of-care parameters, across geographical regions. No significant difference was observed in adherence to recommendations in studies published before and after 2018, except for lower cardiac rehabilitation referrals after 2018 (test of heterogeneity, p=0.012).

Conclusion There are significant variations globally in the management of patients with SCAD, particularly in FMD screening. Raising awareness about consensus recommendations and further prospective evidence about their effect on outcomes may help improve the quality of care for these patients.

  • Acute Coronary Syndrome
  • Cardiac Rehabilitation
  • Coronary Artery Disease

Data availability statement

Data are available upon reasonable request. The data underlying this article will be shared on reasonable request to the corresponding author.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

WHAT IS ALREADY KNOWN ON THIS TOPIC

  • Consensus documents recommended five main interventions for patients with spontaneous coronary artery dissection (SCAD): (1) at least one antiplatelet agent, (2) beta-blocker, (3) ACE inhibitor or aldosterone receptor blocker for patient with left ventricular systolic dysfunction, (4) screening for fibromuscular dysplasia (FMD) and (5) cardiac rehabilitation.

WHAT THIS STUDY ADDS

  • This study provides a systematic review of the current practice in managing patients with SCAD worldwide. It identifies low adherence and likely under-reporting of FMD screening and cardiac rehabilitation.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

  • Raising awareness among clinicians about these recommendations may help improve the quality of care for these patients.

Introduction

Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction (MI), especially in young women.1 2 Once thought to be a rare condition, SCAD has been reported to be the cause of up to 4% of all acute coronary syndrome (ACS)3 and up to 35% of ACS among women less than 50 years of age.4 5 Despite its significance, our understanding about this potentially life-threatening condition remains incomplete. No randomised data have been published to guide treatment for SCAD, and clinicians have largely relied on standard ACS guidelines. This was not ideal as these guidelines are for atherosclerotic ACS.1

In 2018, the American Heart Association and the European Society of Cardiology published the world-first scientific statements on the management of SCAD.1 2 The recommendations of these documents were based on data from mostly observational studies and, where no data were available, expert opinions. Although there are some minor variations with regards to the use of antiplatelets, the consensus recommendations for SCAD treatment are similar and can be summarised as follows: (1) at least one antiplatelet agent, (2) beta-blocker, (3) ACE inhibitor (ACEI) or an angiotensin receptor blocker (ARB) in the presence of left ventricular (LV) systolic dysfunction, (4) referral to cardiac rehabilitation and (5) screening for fibromuscular dysplasia (FMD). So far, there have been no data about the effects of these treatments on major adverse cardiovascular events (MACE). The use of beta-blockers was found to be associated with lower risks of SCAD recurrence in a recent systematic review and meta-analysis.6 As the use of antiplatelets, beta-blockers, ACEI or ARB, and cardiac rehabilitation was also present in guidelines for atherosclerotic ACS, it is worth highlighting the following differences in SCAD consensus recommendations compared with atherosclerotic ACS guidelines: (1) optimal time for antiplatelet therapy was not defined in SCAD and dual-antiplatelets therapy was only recommended if coronary stents were used, (2) ACEIs or ARBs were only recommended in patients with impaired LV systolic function, (3) statins were not recommended in patients with SCAD, and (4) FMD screening was specific for patients with SCAD only and was not recommended in patients with atherosclerotic ACS.

Since the publication of these consensus recommendations, there has been no evaluation of the international implementation of these recommendations. Current optimal quality of care for patients with SCAD around the world is based on the proportion of patients who receive consensus-recommended treatment. The primary aim of this systematic review was to evaluate the quality of care of patients with SCAD, as measured by adherence to global consensus recommendations. Secondary aims included the time from symptom onset to angiography or revascularisation, comparison of adherence to recommendations between geographic regions and before versus after 2018 (the year when the positional papers were published). In addition, for patients presenting with acute MI (AMI), the time from presentation to angiography or revascularisation is an important marker of quality of care, irrespective of the diagnosis of SCAD. As patients with SCAD are often young and without traditional cardiovascular risk factors,7 we hypothesised that this time would be longer compared with patients with atherosclerotic MI.

Method

This systematic review complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements.8 Ethics approval was not required as only data from published literature was used. This systematic review was registered with the international prospective register of systematic reviews (PROSPERO), ID number CRD42022363414.

Search strategy

A search strategy was developed with a university librarian and performed using the following databases: Medline, Embase, SCOPUS and CINAHL, from their inception up to 16 June 2022. The search was restricted to literature published in English only and using the following search terms: ‘spontaneous coronary artery dissection’ and ‘spontaneous coronary dissection’. The full search strategy can be viewed in online supplemental table 1.

Study selection

To be included in the systematic review, studies either had to be an original cohort or original case series on consecutive patients diagnosed with SCAD and, report at least one of the quality-of-care parameters: that is, proportion of patients prescribed with antiplatelets, beta-blockers, ACEIs or ARBs (in the presence of LV systolic dysfunction) during index hospital admission or at the time of discharge, the proportion of patients screened for FMD, the proportion of patients referred to cardiac rehabilitation and, the time from symptom onset to coronary angiography or revascularisation (where appropriate). The sample size had to be more than 10 patients. Case reports, reviews including systematic reviews, editorials and comments, studies not in English and grey literature (eg, conference abstracts) were excluded.

Screening and data extraction

Literature screening using Covidence software (Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia. Available at www.covidence.org) was performed by two pairs of investigators (QD-FO and QD-BS) independently, using the inclusion and exclusion criteria as defined above. An investigator (QD) performed data extraction while another coauthor (FO/BS/SZ/RZ) checked for consistency. For each study included the following parameters were extracted: author name, year of publication, country of study, site of study, city of study, study name, study aim, type of ACS, sample size, parent SCAD cohort or registry, mean or median age, proportion of female, study design, data collection time, baseline comorbidities, quality of care parameters (the proportion of patients receiving antiplatelets, beta-blockers, ACEIs/ARBs, cardiac rehabilitation, FMD screening, time to angiogram/revascularisation), in-hospital and follow-up MACE (cardiovascular death, MI and stroke) and median or mean follow-up time. With regards to FMD screening, current guidelines recommended CT angiography or magnetic resonance angiography from brain to pelvis. We defined the parameter of FMD screening as having either complete or partial screening.

Included studies were evaluated independently by two investigators for bias using the Newcastle-Ottawa Scale (NOS), a scoring system to evaluate the quality of non-randomised studies in meta-analysis. The NOS scores studies in three domains, with higher scores mean higher quality thus lower risk of bias. The three domains of the NOS are: (1) selection, with a maximum of four points, (2) comparability, with a maximum of two points, and (3) exposure, with a maximum of three points. Included studies were classified based on their total NOS score: low risk for total score 7–9, medium risk for total score 4–6 and high risk for total score 0–3.

If there were multiple papers based on the same cohort (or registries) of SCAD patients, to avoid duplication, only the most recent publication and/or with the highest number of patients that reported the quality-of-care parameters was included in the meta-analysis. Although not included in the meta-analysis, multiple papers from the same cohort of patients offered an opportunity to assess how quality-of-care parameters for the same cohort changed with time. These studies were presented and discussed separately. If a study had a quality-of-care criterion as a selection requirement (e.g., a study on patients with SCAD who were screened for FMD), data for that criterion were not collected. At any stage of the screening and data extraction process, disagreements between two investigators were resolved by discussion and consensus, with the involvement of a third investigator (SZ) where required.

Statistical analysis

Descriptive statistics were reported using weighted means and SD. Random effects meta-analysis was used to estimate each quality-of-care parameter, reporting mean percentages and 95% CIs. The differences in these parameters across geographical regions and before and after 2018 were assessed using univariate metaregression. Heterogeneity was analysed using Cochran’s Q test, which tests whether the variability in the observed effect sizes is larger than would be expected based on sampling variability alone. All analysis was conducted in R (R Foundation for Statistical Computing, Vienna, Austria), using the rma function in the metafor package.

Results

The PRISMA flow chart is presented in figure 1. In total, 2554 articles were screened, and 398 articles were identified for full-text screening. From these, 325 articles were excluded (figure 1). From the remaining 73 articles, 29 were identified to have clear or potential duplicated data from the same cohorts/registries of patients (table 1), with the most appropriate study selected for inclusion. In total, 53 articles, published between 1989 and 2022, were included, with characteristics of the included studies shown in table 2. Overall, n=8456 individuals with SCAD were analysed, mean age 50.1, 90.6% female. Studies were performed in 22 countries which were grouped into 6 geographical regions: Europe, North America, Oceania, East Asia, Middle East and South Asia. Europe had the highest number of studies (20 studies) while North American studies included the highest number of patients (4401). Medical therapy was reported in 39 studies, FMD screening in 24 and cardiac rehabilitation in 3 studies. On assessment of the included studies for risk of bias using NOS, 21 studies were classified as low risk, 28 as medium risk, and 4 as high risk (online supplemental table 2).

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart. SCAD, spontaneous coronary artery dissection.

Table 1

Studies excluded due to data duplication

Table 2

Characteristics of included studies

Study inclusion and MACE outcomes

Table 3 provides the baseline characteristics of the included studies. Before 2018, there were only 15 studies (n=1065), compared with 39 studies (n=7509) after 2018. The majority of included studies were retrospective (28), followed by prospective (12), cross-sectional (10) and mixed-method (4) studies.

Table 3

Baseline statistics of included studies

Most studies reported MACE as a composite of death, non-fatal MI and revascularisation with stroke, heart failure, and recurrent or de novo SCAD also reported in some studies. MACE occurred in 7.3% of patients in-hospital and 12.4% on follow-up. Total mortality was reported in 20 studies. Follow-up time varied significantly between studies with mean follow-up ranging between 1 month and 49.2 months.

Time to angiography

Only three studies reported time to angiogram or revascularisation and the methods of report were highly heterogenous. Two studies reported the mean time from symptoms onset to angiogram, with one reported 95% CI (24 hours (4–48))9 and the other reported standard deviation (7±5.4 days).10 In another study,11 door-to-balloon time was reported with the difference between patients with SCAD and other causes of AMI being not statistically significant (median 142 min for SCAD vs 99 min for other AMI, p=0.301). Due to heterogeneity, meta-analysis was not performed for this parameter.

Medical management, FMD screening and cardiac rehabilitation referral

Using random effects meta-analysis, 92.1% of patients (95% CI 89.3% to 94.8%) received at least one antiplatelet, 78.0% (95% CI 73.5% to 82.4%) received beta-blockers, 58.7% (95% CI 52.3% to 65.1%) received ACEIs/ARBs, 54.4% (95% CI 45.4% to 63.5%) were screened for FMD and 70.2% (95% CI 60.8% to 79.5%) were referred to cardiac rehabilitation (figure 2). Left ventricular ejection fraction (LVEF) was not reported in most studies. Among the few studies that reported LVEF, none reported if ACEIs/ARBs were given to patients with impaired LVEF. One study12 reported the proportion of patients (29.6%) who received all consensus-document recommended treatments.

Figure 2

Meta-analysis of quality-of-care parameters—forest plot depiction for random effect meta-analysis of the proportion of patients received each of the recommended interventions using data from all included studies. Note: ARB, angiotensin receptor blocker; FMD, fibromuscular dysplasia.

Meta regression analysis of the quality-of-care parameters differed significantly between geographical regions (figure 3) except for the use of ACEIs/ARBs (p=0.088) and cardiac rehabilitation (data for this were only available for North America). Use of at least one antiplatelet was most consistent, with proportions close to 100% in most regions, except for North America (at 78.2%). Use of beta-blockers was also consistently higher than 63% in all regions, while ACEIs/ARBs ranged from 44.2% to 81.3%. Screening for FMD was the most inconsistent parameter, which was lowest in the Middle East (0.6%) and highest in North America (60.5%). North America was also the only region where the rate of cardiac rehabilitation attendance or referral was reported (70.2%, CI 60.9% to 79.5%).

Figure 3

Meta-analysis of quality-of-care parameters by regions—forest plot depiction of random effect meta-analysis of the proportion of patients received each of the recommended interventions, grouped by regions. Note: ARB, angiotensin receptor blocker; FMD, fibromuscular dysplasia.

Overall, no significant difference was observed in the proportion of patients receiving each of the recommended treatments between studies published before and after 2018 (figure 4), except for a small deterioration in the proportion of patients undergone cardiac rehabilitation (74.1% vs 60.0%, p=0.012). This parameter, however, was only reported on in North America.

Figure 4

Meta-analysis of quality-of-care parameters by year of publication—forest plot depiction of random effect meta-analysis of the proportion of patients received each of the recommended interventions, grouped by year of publication. Note: ARB, angiotensin receptor blocker; FMD, fibromuscular dysplasia.

Temporal changes within the same cohorts

The change of quality-of-care parameters within the same cohorts was explored in table 4. Apart from the use of antiplatelets, which consistently increased with time, other parameters fluctuated significantly between the cohorts. The greatest change was observed in the Kantonsspital St. Gallen cohort (drop in FMD screening rate from 62.5% to 38.1%) and Mayo Clinic SCAD Registry (rise in FMD screening rate from 45.5% to 68.1%). There were no data for the change in the rate of referral to cardiac rehabilitation.

Table 4

Change of quality-of-care parameters on the same cohorts with time

Discussion

This systematic review is the first to measure adherence to consensus recommendations in patients with SCAD. Overall, adherence to consensus recommendations in SCAD care was highest for antiplatelet therapy and lowest for FMD screening, with significant variations across geographical regions. There was little change in adherence to consensus recommendations before and after the publication of consensus recommendations in 2018.

Medical management and antiplatelet therapy

The proportions of patients with SCAD receiving antiplatelets, beta-blockers, FMD screening and cardiac rehabilitation were 94.5%, 78%, 54.6% and 70.5%, respectively. With regards to antiplatelet therapy, there is no quality evidence guiding the use of single versus dual antiplatelet, or the duration of therapy. In our review, the proportions of patients on single-antiplatelet therapy were provided in almost all studies which reported on this parameter (35 out of 37 studies), while the use of dual therapy was only provided in half (17 out of 37 studies).

Temporal and geographical trends in SCAD care

No significant change in practice was observed for studies published before and after 2018. The proportion of patients who received all of the recommended treatments would have been a good indicator of overall quality of care. Unfortunately, there was only one paper (Baechler et al13) that reported this composite parameter, with the number relatively low at 29.6%. Notably, there was significant heterogeneity across studies and regions in FMD screening, ranging from 0.6% to 60.6%. This is despite the well-known association between SCAD and FMD, with screening recommended in all patients to look for extracardiac vascular manifestations. Most of the studies included in our systematic review were from higher income countries, highlighting a paucity of data from lower income countries. It is possible that adherence would be lower than our current data, particularly for FMD screening and rehab referral, due to limitations in resources in these countries.

SCAD awareness and cardiac rehabilitation referral

SCAD is an increasingly recognised condition and, consistent with this, we found nearly eight times the number of patients studied in the past 4 years, compared with the 30 years prior. Although there was no significant change in most of the quality-of-care parameters in studies published before and after 2018, this was likely a consequence of later studies including patients recruited historically, diluting any change in the quality-of-care with time. The drop in the proportion of patients who underwent cardiac rehabilitation was related to under reporting and differences in type of reporting. Only 3/53 studies provided information on cardiac rehabilitation, with the method of reporting varied. While one provided the rate of referral to cardiac rehabilitation,14 the other two reported on the proportion of patients who attended cardiac rehabilitation.13 15

Limitations

This systematic review is limited by the under reporting of several quality-of-care measures, particularly cardiac rehabilitation and FMD screening. We were also unable to determine use of single vs dual antiplatelet therapy in many studies. The benefit of medical therapy in SCAD, such as antiplatelets and beta blockers remains controversial, with no randomised data to support their use. Most studies reported discharge medical therapy whereby adverse effects related to antiplatelets or beta blockers may have led to early cessation, and we cannot comment on adherence to such therapy. The included studies were heterogenous and were conducted with different aims. In a small number of studies, the percentage of females was low, and it is possible that some atherosclerotic dissections may have been included in these studies. There was an under-reporting of the practice of FMD screening (24 studies) and cardiac rehabilitation (three studies). The risk of reporting bias could not be excluded.

Conclusion

There are significant variations in the management of SCAD globally, particularly with regards to FMD screening and cardiac rehabilitation referral. An improvement in adherence to recommended therapies is thus needed. Raising awareness among clinicians about these recommendations, together with further prospective evidence on their effectiveness in reducing MACE, may help improve quality of care for patients with SCAD.

Data availability statement

Data are available upon reasonable request. The data underlying this article will be shared on reasonable request to the corresponding author.

Ethics statements

Patient consent for publication

Ethics approval

Not applicable.

Acknowledgments

Special thanks to all the co-authors who have contributed to this paper.

References

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Footnotes

  • Twitter @quan_m_dang

  • Presented at Findings from this study was presented at the 71st Annual Scientific Meeting of the Cardiac Society of Australia and New Zealand and the 2023 European Society of Cardiology Congress.

  • Contributors QD: conceptualisation, methodology, investigation, formal analysis, writing - original draft preparation, guarantor. FO, BS, RS: investigation, validation, writing – review and editing. SM: software, formal analysis, data curation, visualisation, writing – review and editing. PP and RKA: writing – review and editing. JC: writing – review and editing. SM: supervision, project administration, conceptualisation, methodology, writing - review and editing.

  • Funding QD received a Faculty of Medicine and Health Research Centres Stipend Scholarship from the University of Sydney. SZ was supported by a Heart Foundation Fellowship (ID 102627) and a New South Wales Health Cardiovascular Research Elite Postdoctoral Grant for this work. JJHC was supported by an Investigator grant APP1194139 from National Health & Medical Research Council of Australia. RAL is supported by a British Heart Foundation fellowship (FS/ICRF/22/26051).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.