In a blog for medical trainees, Chris McAloon, a cardiology specialty trainee, reflects on evidence and practice for treating someone with ST elevation myocardial infarction (STEMI)
It is just after 2am and I have only just closed my eyes, then I hear the ear piercing bleep of the ST elevation myocardial infarction (STEMI) pager. I phone the switchboard to be told the patient is 10 minutes out. I start the walk to the emergency department, thinking about what to expect…
How do we treat a STEMI in the UK?
The majority of the United Kingdom is now covered by a primary percutaneous coronary A treatment, procedure or programme of health care that has the potential to change the course of events of a healthcare condition. Examples include a drug, surgery, exercise or counselling. (PPCI) network. A PPCI is a procedure in cardiology where pictures of the coronary arteries can be taken by inserting catheters into the blood vessels. These catheters can be inserted into the coronary arteries and radiopaque dye injected and pictures taken using x-rays. If a culprit narrowing or blockage is found Something done with the aim of improving health or relieving suffering. For example, medicines, surgery, psychological and physical therapies, diet and exercise changes. can be implemented in the procedure; the clot can be removed and narrowings can be opened with balloons and stents (angioplasty). All patients suspected of having a STEMI and who are within 90 minutes of a PPCI centre are brought in 24 hours a day, 7 days a week, 365 days a year. Over the last two decades the shift in treatment for STEMIs has been from thrombolysis (clot busting drugs) to PPCI due to persistently reported superior patient Outcomes are measures of health (for example quality of life, pain, blood sugar levels) that can be used to assess the effectiveness and safety of a treatment or other intervention (for example a drug, surgery, or exercise). In research, the outcomes considered most important are ‘primary outcomes’ and those considered less important are ‘secondary outcomes’. in the latter.1,2
The Classic Scenario
I arrive in the emergency department and read the patient summary; 79 year old man with type 2 diabetes mellitus who has had chest pain for over an hour’. Shortly after my arrival in the emergency department, the patient was brought in, clearly in pain, by the paramedic crew. The paramedic electrocardiograph (ECG) demonstrates inferior ST segment elevation. I proceed to undertake my focused assessment and consent for the PPCI we need to perform as an emergency. The patient agrees to the procedure after a discussion. All the loading medications (dual anti-platelets) are given and the patient is taken up to the catheter laboratory, where the rest of the team have assembled, including the Interventional Cardiology Consultant.
Shortly after, right radial artery access is obtained and the angiogram is performed and it shows the right coronary artery (as expected) is blocked. However, our angiogram has also shown a severe stenosis in the proximal left anterior descending artery. This gentleman has multi-vessel coronary artery disease. The gentleman is haemodynamically stable. We now face one of the biggest challenges in modern interventional cardiology; do we tackle the culprit (right coronary artery) only or both the significant narrowings identified (right coronary artery and the left anterior descending artery)?
The Size of the Problem
Multi-vessel disease is present in 40% to 65% of patients presenting with a STEMI.3,4 Given the aging The group of people being studied. Populations may be defined by any characteristics e.g. where they live, age group, certain diseases. and more complex co-morbidities, this frequency is likely to increase. The multi-vessel coronary artery disease in the context of a STEMI is a significant finding for the patient as the rates of one year death, non-fatal infarction and need for revascularisation are higher.5-7 On limited evidence, the recommendation from the American College of Cardiology /American Heart A relationship between two characteristics, such that as one changes, the other changes in a predictable way. For example, statistics demonstrate that there is an association between smoking and lung cancer. In a positive association, one quantity increases as the other one increases (as with smoking and lung cancer). In a negative association, an increase in one quantity corresponds to a decrease in the other. Association does not necessarily mean that one thing causes the other. (ACC/AHA) and the European Society of Cardiology (ESC)8 was to tackle the culprit only lesion at the time of the STEMI. A multi-vessel approach is favoured in STEMI with cardiogenic shock.
As I stand in the catheter laboratory next to my consultant I ponder the challenge we face; do we just tackle the culprit blockage and leave the other narrowing alone? That may mean a procedure later in that admission or should we tackle the other lesions in the same sitting? What difference does this actually make to the patient? Can we cause harm by leaving or intervening on the bystander disease now? What about the implications on the service? (If we are doing a prolonged procedure and another STEMI occurs we cannot take them straight in to the catheter lab). What are the potential procedural risks of either approach?
A Change in Tone
Following several high profile randomised A trial in which a group (the ‘intervention group’) is given a intervention being tested (for example a drug, surgery, or exercise) is compared with a group which does not receive the intervention (the ‘control group’). (CvLPRIT 20159; DANAMI-3-PRIMULTI 201510 and more) a benefit was reported in taking a multi-vessel approach to revascularisation at the time of PPCI. The international guidance was subsequently updated to reflect this new evidence and recommend complete revascularisation in STEMI patients who are stable.11,12 However the AHA/ACC/ESC recognise the limited evidence in this area and only provide the recommendation to tackle non-culprit disease at the time of the STEMI in haemodynamically stable patients as a IIb recommendation (not strongly favoured!).11,12
The Core of the Problem
It still isn’t clear what the best strategy for the individual patient is when they present with a STEMI and have multi-vessel disease. For my patient should we tackle the culprit vessel and leave the other critical lesions, or tackle everything?
The Cochrane Review
Several observational and randomised controlled Clinical trials are research studies involving people who use healthcare services. They often compare a new or different treatment with the best treatment currently available. This is to test whether the new or different treatment is safe, effective and any better than what is currently used. No matter how promising a new treatment may appear during tests in a laboratory, it must go through clinical trials before its benefits and risks can really be known. over the last two decades have set out to answer this question. Bravo et al,13 recently published a Cochrane Reviews are systematic reviews. In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. on Complete versus culprit-only revascularisation in ST elevation myocardial infarction with multi-vessel disease. The The use of statistical techniques in a systematic review to combine the results of included studies. Sometimes misused as a synonym for systematic reviews, where the review includes a meta-analysis. is the most comprehensive on this topic to date. The inclusion criteria were sensible and real world; randomised controlled trials in STEMI patients with multi-vessel disease (full text, abstracts and unpublished Data is the information collected through research.). Nine randomised controlled trials with 2633 patients enrolled were included in the analysis that compared complete (n=1381) vs culprit-only (n=1252) revascularisation in STEMI patients with multi-vessel disease. The primary objectives were long-term outcomes over 1 year (all-cause mortality, cardiovascular death, non-fatal myocardial infarctions and adverse events). Secondary outcomes were set over shorter time periods.
The studies included were varying in size and in the amount of data reported. The number of centres in each An investigation of a healthcare problem. There are different types of studies used to answer research questions, for example randomised controlled trials or observational studies. varied and in some included studies the number of centres were not reported. Only 4 studies reported their drop-out The speed or frequency of occurrence of an event, usually expressed with respect to time. For instance, a mortality rate might be the number of deaths per year, per 100,000 people.. The complete revascularisation procedure was a staged procedure (performed later in the admission) in six studies, whereas in three other studies it was undertaken at the time of the index procedure. I cannot quite square how these trials can be truly comparable as they are different strategies (staged revascularisation versus index revascularisation). The patient will be at different stages in the pathological process and realistically this has to affect outcomes.
Randomization is the process of randomly dividing into groups the people taking part in a trial. One group (the intervention group) will be given the intervention being tested (for example a drug, surgery, or exercise) and compared with a group which does not receive the intervention (the control group). to revascularisation strategy occurred at the time of the index angiogram, therefore Blinding is the process of preventing those involved in a trial from knowing to which comparison group a particular participant belongs. was not possible. This is acceptable in my opinion, as practically, how should this choice be made without making an informed decision (non-blinded)? Impressively many of the studies blinded the outcome monitors, to minimise detection and performance Any factor, recognised or not, that distorts the findings of a study. For example, reporting bias is a type of bias that occurs when researchers, or others (e.g. drug companies) choose not report or publish the results of a study, or do not provide full information about a study.. Significant non-culprit disease was defined differently between each study, potentially influencing the actual decision to intervene in the real world. Undeniably the study designs did significantly vary between the comparable studies reflecting a limitation of the evidence in this field.
The populations were predominantly European with the exception of one Chinese study. Across the study the majority of participants were male and had a mean age in their sixties. A way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. factors for coronary artery disease were reported by some (but not all studies). For those that reported An aspect of a person's condition, lifestyle or environment that affects the chance of them getting a disease. For example, cigarette smoking is a risk factor for lung cancer. frequencies in their populations the prevalences reported were similar , except for Diabetes Mellitus (5.0%-41.2%).13 Application of the study data to individual patients depends on exactly who comes off the back of the ambulance.
The techniques and materials used reflect the broad history of angioplasty during the period in which the included studies were published (2004-2015), with changes in the types of stents and the techniques used. This would be an obvious source of variation between each study. From a quality perspective, it is concerning that several studies did not report any of this information.
So, what was found?
Overall the included trials demonstrated that the multi-vessel complete revascularisation strategy in stable STEMI patients has lower long-term rates of all-cause mortality, cardiovascular death and non-fatal myocardial infarctions. The occurrence of adverse events was no different between either strategy in both the short and long term. The results of this Cochrane Review are similar to other meta-analyses that have been performed in recent years.14,15
How relevant and reliable is this evidence?
Bravo et al13 provide the most comprehensive analysis of the evidence to date and this is mandated reading for all interventional cardiologists in my opinion. I agree the more recent randomised controlled trials suffer from some weaknesses, but overall they overcome these limitations in the context of this difficult area of research. However, the evidence was rated as low quality for the issues we have discussed earlier. It strengthens the case for more definitive evidence to be undertaken.
One of the major limitations of the evidence is the population of patients that have actually been studied. The studies to date have been predominantly male and Caucasian (presumably as all but one study is from northern Europe), which means basing decisions on these datasets for females and/or non-Caucasian patients is not backed up completely by the available evidence. Caution would have to applied at this time.
What about the second person that comes in?
Part of my problem is complete revascularisation strategies take time and therefore have implications for service provision. Most centres (in the UK) I know of have only one emergency catheter laboratory team on-call. This means only one emergency out-of-hours procedure can be performed at a time. A complete revascularisation approach as the standard of care will involve the emergency team working on one patient for longer. I foresee implications of this strategy given the current service in the UK. If another emergency comes in, and needs to go to the catheter laboratory, that patient will not be able to go immediately and this will impact on the potential benefit of a PPCI for the patient. A balance would need to be struck if complete revascularisation becomes the standard of care.
Where does this leave us?
The decision of which revasculariation strategy is best remains hotly debated and very current. The broad concensus is the evidence reflects the need to adopt a multi-vessel revascularisation strategy in stable patients presenting with STEMIs. Many questions still remain regarding the exact strategy to use (staged vs indexed) and who will exactly benefit. Certainly the AHA/ACC and ESC have altered their recommendations in their latest version of guidance respectively. The concensus is more definitive evidence is needed to answer the question. However, my concern is in the UK what will the impact be on wider society if the PPCI service is engaged for longer during on-call periods.
The decision we took for my patient in the lab was to tackle the culprit artery at the time, as we were not yet convinced by the evidence (completely) and there was another STEMI on the way. Another busy night!
Chris McAloon has nothing to disclose.
References may be found here.