THROMBINS2 Is the New MONA

Cardiovascular disease and its sequalae remain one of the largest health care problems in the United States. Each year there are approximately 620,000 new cases of acute coronary syndrome (ACS) and 295,000 recurrent ACS events.⁷ ACS can be subdivided into three different categories: unstable angina (UA), non ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). The generalized definition of ACS is a condition in which there is sudden reduction of blood flow to the heart.⁴ Out of the three categories of ACS, approximately 70% are NSTEMI.

During the treatment of acute coronary syndrome (ACS) or other coronary events, the mnemonic MONA (morphine, oxygen, nitroglycerin, aspirin) has been used by prehospital providers, emergency room personnel, and educators for years. Evidence-based medicine (EBM) now shows that MONA is no longer as beneficial to the cardiac patient as was once believed. In a review by Kline, Conti, and Winchester (2015), they listed recent information that could be used to deter providers from using MONA on a routine basis.⁵ Morphine had been found to potentially mask ischemic symptoms and its clinical benefits were questioned. Even though oxygen is recommended for the patient with pulmonary edema, judicious use of supplemental oxygen for other patients was encouraged. In the DETOX2X-AMI study, oxygen was not found to make a difference in the normoxic patient with suspected acute myocardial function.² In a Cochrane review discussed by Gouda, Bainey, and Welsh (2016), oxygen could have paradoxical effects of increased coronary vascular resistance and reperfusion injury toxic oxygen free radicals.³ Glycerol nitrate (nitroglycerine) might cause endothelial dysfunction and toxic pro-oxidant effects along with masking symptoms which could delay activation of the emergency response system.³ Aspirin is the only piece of the MONA mnemonic that still proves to have a significant medical effect and has been supported by strong evidence. In 1990, it was given a Class 1 recommendation for almost all patients with myocardial infarction,⁵ and those recommendations are still in place today.

As practitioners move away from using MONA medical mnemonic as an easy way to remember what to do for ACS events, another mnemonic has taken its place.

THROMBINS₂

THROMBINS₂ is the cue to help guide care when treatment for ACS is quickly needed.

Thienopyridines are a class of adenosine diphosphate (ADP) receptor antagonists that include drugs like prasugrel and clopidogrel. Other non-thienopyridine drugs that also inhibit the P2Y12 receptor are cangrelor and ticagrelor. Platelet activation is inhibited differently than aspirin by all these drugs, which then provides a dual-antiplatelet blockade. Even though there is an increase in bleeding, the modest decrease in cardiac events warrants their use for routine patient management.⁵

Anticoagulation and antiplatelet therapy are recommended for ACS treatment. There are multiple options available for anticoagulation, but Unfractionated Heparin (UFH) is still commonly used. Heparin remains popular because of its low cost and reversibility.⁵ Other Heparin-based options are the low-molecular-weight heparins (LMWH), like enoxaparin. These drugs have a greater specificity for factor Xa than UFH, but their long duration of action puts them at odds for patients who may be undergoing percutaneous coronary intervention (PCI) or cardiac bypass surgery.⁵

Renin-Angiotensin-Aldosterone System (RAS) blockade is accomplished through either using angiotensin converting enzyme inhibitors, or angiotensin receptor blockers. These classifications of drugs inhibit steps along the RAS and attenuate ventricular remodeling after acute MI, which provides benefits regarding mortality.⁵

Oxygen has been in use for all cardiac patients for many years. The prevailing thought has been supplemental oxygen provides improved oxygen delivery to cardiac tissue, which then decreases the size of infarcted myocardium and ischemic injury. Despite that information, there are definite risks with using oxygen routinely with every cardiac patient. Moradkhan and Sinoway (2010) stated hyperoxygenation could lead to vasoconstriction through several mechanisms.⁶ A prospective, randomized study in 2015 reported that supplemental oxygenation was associated with statistically significant elevations in creatinine kinase levels, recurrent MI, arrhythmias, and elevated infarct size by cardiac MRI compared to those without supplemental oxygen.⁵ Finally, Burrell (2017) reported the DETO2X-AMI study showed the routine use of supplemental oxygen in patients with suspected MI who did not have hypoxemia was not found to reduce one-year all-cause mortality, and that oxygen does not make any difference to outcomes in normoxic patients with suspected AMI.²

Morphine is commonly used for pain control and relief of symptoms in patients with ACS. Despite its ability to decrease oxygen demand on the myocardium through anxiolysis, venodilation, and decreased blood pressure and heart rate through increased vagal tone, no large randomized trials have shown an improvement in outcomes.⁵

Beta-blockers (BB) reduce heart rate and myocardial oxygen consumption, improving outcomes in patients diagnosed with acute MI. Current recommendations state that BB should be started within 24 hours of MI if there is no evidence of heart failure, shock, or heart block.⁵ Hauk (2014) also lists other contraindications as a PR interval greater than 0.24 seconds, second- or third-degree heart block in patients without a pacemaker, asthma, and reactive airway disease.

Invasive cardiac interventions should be considered with all patients with ACS. For providers practicing in facilities without this option, a clear and reliable referral system should be in place long before a patient is seen who is presenting with ACS symptoms. Patients with non-ST elevation ACS who have refractory angina or hemodynamic or electrical instability may require immediate treatment via an invasive strategy.⁴ An early revascularization strategy relatively reduces the risk of mortality at two years by 25%.¹

Nitroglycerin acts as a venodilator to decrease venous return to the heart, which then decreases left ventricular workload and myocardial oxygen demand. At the same time, the coronary artery dilatory effects help deliver oxygen to ischemic areas in the myocardium. Even with these pro-cardiac properties, nitrates have not shown to have a significant effect on mortality.⁵

New cholesterol guidelines suggest a high-intensity statin for patients aged 75 and under, and moderate-intensity statin therapy for patients over 75 with coronary artery disease.¹ Statins work through inhibition of hydroxymethyl glutaryl-coenzyme A reductase, an enzyme necessary for cholesterol production.⁵ The long-term benefit appears to happen after two years, with a 25% relative risk reduction in death after that point.

Aspirin continues to be a mainstay option for the medical treatment of acute coronary syndrome. Immediate aspirin therapy is standard due to the corresponding benefits observed with decades of trials in patients with suspected acute MI.³ The ISIS-2 trial showed that aspirin reduced death in STEMI by 23% at five weeks in comparison to placebo.⁵ Aspirin is an irreversible inhibitor of the COX-1 receptor, reducing thromboxane A2 and platelet aggregation. Aspirin is the only drug in the original MONA mnemonic that proves to be a good option for most patients with CAD.

Many studies and treatment modalities have been discovered since MONA was put into clinical practice. THROMBINS₂ is a modern approach for clinicians to use to treat their patients with ACS and it summarizes and complements current ACCF/AHA guidelines.⁵

References

• Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE. 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American college of cardiology foundation/American heart association task force on practice guidelines. Circulation. 2013. 127, 663-828.
• Burrell A. DETO2X-AMI. The Bottom Line. September 22, 2017. Retrieved from: https://www.thebottomline.org.uk/summaries/icm/deto2x-ami/.
• Gouda P, Bainey K, Welsh R. The demise of morphine oxygen nitroglycerin aspirin (MONA). Canadian Journal of Cardiology. 2016. 32. Retrieved from: https://www.onlinecjc.ca/article/S0828-282X(15)01566-4/fulltext.
• Hauk L. Management of the non-ST elevation acute coronary syndrome: A guide from the AHA and ACC. American Family Physician. 2014. 92(2), 151-153.
• Kline KP, Conti CR, Winchester DE. Historical perspective and contemporary management of acute coronary syndromes: from MONA to THROMBINS₂. Postgraduate Medicine. 2015. 127(8), 855-862.
• Moradkhan R, Sinoway LI. Revisiting the role of oxygen therapy in cardiac patients. Journal of American College of Cardiology. 2010. 56, 1013-1016.
• Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Helt JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB. Executive summary: Heart disease and stroke statistics-2012 update. Circulation. 2014. 129, 399-410.