Literature Review

The World Health Organization (WHO) predicts that cardiovascular diseases will be the leading causes of mortality and morbidity in developing countries by the year 2020. In Saudi Arabia, cardiovascular diseases alone result in 42% of mortality in the general population compared to 33% in a developed country such as Canada. Rapid urbanization in the last 3 decades has resulted in increased calorie intake and low rates of regular exercise, with subsequent increased rates of overweight/obesity and diabetes mellitus compared with the developed countries. The major dreadful and feared complication of these illnesses is coronary artery disease, with acute myocardial infarction (AMI) representing the main cause of morbidity and mortality. The AMI patients who have complete and sudden occlusion of one of their coronary arteries will suffer from ST-elevation myocardial infarction (STEMI) and would be at high risk of death and/or heart failure if their occluded coronary artery does not get opened promptly in a timely fashion (i.e: reperfusion). Currently, there are 3 main internationally-accepted strategies for opening the occluded artery in STEMI patients:

1- Fibrinolytic Therapy (FT): dissolving the clot with these medications is the most widely used strategy world-wide. However, the success rate of this strategy is only around 70-80%, unless FT is given in the ambulance at the pre-hospital level which increases its efficacy dramatically but it requires a very competent Emergency Medical System (EMS).

2- Primary PCI (PPCI): mechanically opening the blocked coronary artery by taking the patient directly to the catheterization laboratory (Cath. Lab.) - without prior FT – and inflating a balloon then deploying a stent in the blocked area. When done properly and efficiently (Door-to-Balloon time less than 90 minutes), this method has been shown to be superior to the FT strategy with a success rate of more than 95% and results in saving lives. However, only few cardiac centers worldwide could offer such a strategy on a 24-hour basis and in all days of the year (i.e: 24/7 PPCI Program) because of the requirement of several essential elements for its success and long-term sustainability, including well-trained interventional cardiologists and Cath Lab staff, very competent EMS, efficient transportation infrastructure in the city, and financial re-imbursement for the performance of such an emergency and high-risk procedure that carries also increased radiation exposure to the operators. Several quality improvement initiatives lead by international scientific cardiac societies have called for adopting such a strategy, such as the Stent for Life (SFL) initiative by the European Society of Cardiology and the Door to Balloon (D2B) initiative by the American College of Cardiology.

3- Pharmaco-Invasive (PI) or “Drip and Ship”: This is a hybrid approach that combines the “good” of both of the above strategies. Following FT with appropriate conjunctive anticoagulant and antiplatelet therapy; the patient will categorised into either one of those 2 tracks:

1- Unsuccessfully Reperfusion: defined as <50% resolution of the ST elevation in the worst ECG lead at 90 minutes post FT, hemodynamic instability, or refractory ventricular arrhythmia. The patient in that scenario will be transferred immediately to a Cath Lab facility to open the occluded coronary artery (Rescue PCI).

2- Successful Reperfusion: in the absence of the above criteria the patient is considered stable and should be scheduled within 6-24 hours following FT for coronary angiography and possible PCI (Elective Cath +/- PCI).

This approach is a scientifically-valid and very pragmatic approach in most of the countries worldwide, particularly in very busy and crowded cities, rural areas, and in regions with under-developed EMS. In fact, Armstrong PW et al (NEJM, 2013) have demonstrated recently that the PI strategy has been associated with similar outcomes (30-day all-cause death, shock, congestive heart failure, or re-infarction) to timely PPCI in STEMI patients presenting within 3 hours of symptom onset. Furthermore, in a very well established STEMI program (Vital Heart Response) in Edmonton and Northern Alberta in Canada, the PI strategy has been used in 40% while PPCI in only 44%, with an overall in-hospital mortality of 5.9% (personal communication, Prof. Robert Welsh). However, this approach still requires establishment of a very well organised system of clearly-defined critical pathways for patients’ triaging among Cath Lab and non-Cath Lab hospitals in every city.

International examples of STEMI quality-improvement initiatives

1. Canada

Vital Heart Response (VHR) is a regional reperfusion protocol for treatment of patients with STEMI within Northern and Central Alberta. There are five centers in metropolitan Edmonton with 2 primary PCI centers. The estimated catchment area for the population in this study is about 440,000 km2 serving 1.8 million inhabitants and approximately 44% of the study population lives in a non-metropolitan region. The VHR system is activated by Emergency Medical Services from the ambulance or Emergency physicians from the emergency departments, when the clinical history and 12-lead electrocardiogram (ECG) are compatible with a STEMI. For pre-hospital patients, the 12-lead ECG is electronically transmitted to the VHR physician who confirms the diagnosis and reviews the clinical history with the on-site practitioner and then decides on one of the two reperfusion strategies in the protocol (PPCI or fibrinolysis) depending on patient’s characteristics and the estimated temporal factors. For in-hospital STEMI patients, on-site clinicians review the patient’s characteristics and investigations and determine the reperfusion strategy with the potential to activate the VHR process of care described for pre-hospital patients. Practicing clinicians typically follow the American College of Cardiology and American Heart Association STEMI guidelines.

2. France

One of the most impressive examples of how improvement of STEMI health care system over the years has resulted in improvement in mortality rates and other important hard clinical outcomes is the French experience (Puymirat E et al; JAMA. 27 Aug, 2012). That was a four 1-month French nationwide registries, conducted 5 years apart (between 1995, 2000, 2005, 2010), and included a total of 6707 STEMI patients admitted to intensive care or coronary care units. The main findings of this study are that 30-day STEMI mortality decreased by approximately 9% (13.7% in 1995 to 4.4% in 2010), a decrease of 68% in 15 years, and although this reduction parallels improvements in care, such as greater use of primary PCI, and adjunctive therapies, it was also associated with a substantial change in the patient risk profile (increased rates of smoking particularly among young women, implicating also the need for major health care preventive policy measures).

3. United Kingdom

The National Infarct Angioplasty Project (NIAP) is another unique example and was sponsored by the UK government to examine the introduction of PPCI in a variety of urban, rural and mixed communities. The UK Prime Minister’s Development Unit and the Department of Health (DoH) agreed to support the NIAP in association with the British Cardiovascular Society (BCS) and the British Cardiovascular Intervention Society (BCIS). The project has resulted in a rapid change and by 2012/13 over 95% of eligible patients received PPCI. Survival of patients with STEMI has improved over time (30-day mortality has decreased from approximately 12% in 2003/04 to 9% in 2012), and length of stay in hospital halved (de Belder MA et al; EuroIntervention. 2014; 10-T96-T104).

4. India

The Kovai Erode Pilot STEMI Study was the first attempt to develop a system of care combining PPCI with the PI strategy of reperfusion. This was important since Cath Labs are located in urban areas, where PPCI is feasible, while more than 70% of STEMI cases are in rural and semi-urban areas where only thrombolysis is possible. This study showed that: (1) it is possible to develop a hub and spoke model combining primary PCI with a PI approach, (2) awareness and reasonably early access to medical care are possible even in rural communities, and (3) a good ambulance system significantly reduces travel times (median time from symptom onset to presentation decreased from the 360 minutes reported in a previous registry called “CREATE” to 165 minutes). Based on the experience from the Kovai Erode Pilot STEMI Study, STEMI INDIA – a non-profit organisation working to develop STEMI systems of care – has proposed a model known as the STEMI INDIA model. STEMI management in India will adopt the dual approach of combining PPCI with a PI strategy of reperfusion to produce a coherent framework for developing a system of care (Kaifoszova Z et al. EuroIntervention. 2014;10-T87-T95).

STEMI care in Saudi Arabia: Current Situation

We and others have initiated and lead major “snap-shot” cardiac registries in Saudi Arabia and the Arabian Gulf countries (Saudi Project for Assessment of Coronary Events “SPACE” and Gulf Registry of Acute Coronary Events “Gulf RACE”) in the last decade. These studies have demonstrated that patients with STEMI present at relatively young age (5-10 years younger than those in the developed countries), which is related to the high prevalence of coronary artery disease risk factors (particularly diabetes mellitus). More than a third present late (after 12 hours of symptoms onset), and most of the STEMI patients get treated by FT rather than the optimal and more effective strategy of PPCI (≤ 1 in 10 patients undergo PPCI). This very low rate of PPCI has been demonstrated recently (Figure 1) in comparison with other European and Mediterranean countries (Kristensen et al; EHJ. Jan 2014). Although there are more than 42 Cath Labs in Saudi Arabia, only few governmental Cath Lab-hospitals in Saudi Arabia that have a 24/7 PPCI program (4 in Riyadh, 1 in Qassim, 1 in Madina, 1 in Hafouf, 1 in Khamis Mushayt, none in Jeddah or other cities!). There are few other private hospitals with 24/7 PPCI Cath Labs but their volume of STEMI cases is low and their outcomes is unknown. In addition, the Northern and Southern regions of Saudi Arabia are greatly under-served and in urgent need for more cardiac centers with Cath Lab facilities and to have more comprehensive STEMI programs. Even in those who get treated by FT or PPCI, only a third receives such a therapy in the standard timeline (i.e: Door-to-needle time ˂ 30 minutes and Door-to-balloon time ˂ 90 minutes). Furthermore, a minority of these patients (≤ 1 in 5 patients) arrive to the hospital by the emergency medical system (Saudi Red Crescent Authority “SRCA”) either due to lack of awareness or low trust in such services. Thus, they get assessed first in a primary and/or secondary hospital before being transferred to a tertiary care hospital with a Cath Lab facility. This results in major delays in saving the patient’s heart muscle from the damage particularly when the FT fails to dissolve the clot and unblock the occluded coronary artery. However, the overall usage rate of the evidence-based oral medications (i.e: antiplatelets, ACE-I/ARB, statins, and beta-blockers) is reasonable. We have demonstrated in the Gulf RACE-2 that the overall in-hospital, 30-day, and 1-year mortality rates of STEMI patients in Saudi Arabia were 4.58%, 7.56%, and 10.36%; respectively. Although these mortality figures might seem similar and even lower than those reported in many of the contemporary European and North American registries, direct comparison is not valid scientifically because of different study designs and health care systems, variable proportions of certain treatment strategies, unmeasured clinical variables, and more importantly the major difference in the average age of presentation and DM prevalence in our STEMI population.

The PI strategy is being used sporadically and there are rare examples of a well-designed STEMI Network with a PI strategy in the country (such as that of Madina Cardiac Center and surrounding referring hospitals). A similar strategy has been also used during the Hajj season which has resulted in an impressive 50% reduction in mortality, and the project has won Prof. Mohammad AlFagih Research Award at the Saudi Heart Association conference few years ago.

The presence of several health care providers and absence of a universal health care is one of the major challenges to access health care in a timely fashion and thus major delays occur in the treatment of such a cardiac emergency. Last but not the least, around 1 in 5 of STEMI patients is an expatriate and many of these patients are “blue-collar” workers whose health care coverage is insufficient to get them treated with costly invasive procedures such as PPCI. Although there is a Royal Decree that all emergency patients should be treated for free in any hospital, the reality is most of the major cardiac centers do not accept the ambulance transfer for the purpose of PCI in the expatriate patients, unless these patients end up “landing” in their emergency departments. We have seen it in our daily clinical practice and also in our national SPACE registry that there is a clear disparity of health care between expatriates and Saudi patients with STEMI. Not surprisingly, expatriates have worse hospital outcomes likely due to unequal health coverage and limited access to care issues (AlFaleh H. et al, in press).

In short, there are “pockets” of success stories around the country but there are several challenges and unanswered questions as of date regarding the optimal health care planning for the management of STEMI patients in Saudi Arabia:

1- What is the absolute number of STEMI patients every year?. We have taken an informal survey of key-opinion leaders from different health care sectors around the country in this regard and the answers were either “not sure” or in the realm of being extremely high or extremely low numbers!.

2- What are the long-term morbidity and mortality rates in STEMI patients?, and is there a geographical variation in this regard?.

3- How accurate is the WHO reports about the cardiovascular health care and its outcomes in Saudi Arabia?, and even how accurate are the “snap-shot” cardiac registries we have undertaken in the last decade?.

4-What is the optimal strategy for treating STEMI patients in Saudi Arabia?.

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