Analysis of Current Treatment Options in Atrial Fibrillation - Thesis Example

?Introduction This literature review will study about the recent development of the treatment for atrial fibrillation. This will include the current mortality rate in America and how these advancements can alleviate the death rate of humans suffering with this disease. We will also take a strong point on the issues associated with the current treatment options to treat atrial fibrillation. Collectively this review will have twenty journals, five websites and five articles that covers the advancement in treatment, current status of this ailment, medical assessment in the hospitals, the medicines that are prescribe and the limit of dosage. We will also incorporate certain drug prescription in anticoagulants and anti-arrhythmic drugs that are available in the market. These include its affectivity and rate of recovery. Background of the study 1. Nature of Atrial fibrillation Atrial fibrillation (AF) is one of the types of cardiac arrhythmia wherein the normal electrical impulses were plagued by incompetent electrical impulses that lead to abnormal conduction of impulses in the sinoatrial node. As to its consequences, it leads irregular conduction of impulses to the ventricle that is responsible for heartbeat. Currently, this is the most common arrhythmia in U.S. affecting more than 2.2 million Americans with higher tendency in the elderly (American Hearts association, 2004). As researched by Hart, R.G., et al 2007, 1% of the affected citizen is 60 years old and increase by twofold as it reaches the age 70. The heart pumps the blood to the rest of the body. As the heart beats two upper chamber of the atrium contract, followed by the two ventricles. The electrical impulse begins in the sinoatrial node, located in the right atrium. This adjusts the rate of impulses depending on the work of the body. When the sinoatrial node directs an electrical impulse, it spreads downwards through the right and left atria. As they receive the signal, they contract as it forces the blood inside the ventricle (Cleaveland Clinic, 2012). During the atrial fibrillation, electrical signals come from several areas thus forming a wham to the entire heart. This would destroy the regular rhythm of the heart affecting further the rate and the blood flow. Symptoms in most cases are chest pains or angina, rapid and irregular heartbeat with palpitations, dizziness, lightheadedness, anxiety, reduced exercise capacity, symptoms of hyperthyroidism such as weight loss and diarrhea, and symptoms of lung cancer are also situated therein (Mathew, J.P., 2004). However, one-third of the patients show no obvious symptoms therefore becoming unaware of the abnormal heartbeat thus having post detection (Schmidt, C., 2011, Fuster, V., 2006). Management to this treatment is focusing in three points: thromboembolism or the anti-coagulation therapy, re-establishing and maintaining sinus rhythm and controlling ventricular rate with atrioventricular node blocking agents. These three hold a series of discussions and effectivity which will be discussed later. Options for management of the disease include anti-coagulants, anti-arrhythmic drugs and cardiac ablation (Collier, J., 2006). Collectively, the treatment aims to prevent the clotting of the blood thus reducing the risk of stroke; control how often the ventricle contracts that will result a normal circulation and proper distribution of oxygen in the body; return the normal relationship of atria and ventricle making them work together normally; and treat any underlying disorder that may cause or raise the risk of atrial fibrillation for example, hyperthyroidism. Rate of the heart is attained with medications that reduce the blockage at the level atrioventricular node. This would effectively decrease the number of impulses that conduct into the ventricles. Rhythm on the other hand focuses in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) that is mainly used for early detected atrial fibrillation where it is believed that in this time range the heart is not behaving at its worst conduction. However, disputes and statistics show that rhythm management has higher levels of mortality (Collier, J., 2006). 2. Recent developments on Pathology of Atrial fibrillation A study of Packer D.L., 2012 shows that 30% of patients with an acute stroke have underlying atrial fibrillation. Comparing the tests, mortality risks is elevated to 20% notch in atrial fibrillation patients with underlying acute stroke than with atrial fibrillation alone. In the Framingham studies, underlying diseases such as hyperthyroidism and acute stroke triggers the mortality of patients with atrial fibrillation (Kannel B., et al, 1998). These studies were supported by Fuster, V., 2006 that Diabetes, hypertension, transient ischematic attack and ventricular dysfunction can trigger the atrial fibrillation. Thromboembolism or the blockage of the veins due to the blood clotting have been a factor that affect atrial fibrillation patients (Howard S.C., 2011). Researches tried to work on the drugs that will secure the treatment for thromboembolism without affecting atrial fibrillation. Anti-coagulants have been used to help patients recover from thrombosis. Wafarin and aspirin had been used as anti-coagulatory remedy for thromboembolosis. Warfarin was more often used for adults and aspirin for the younger ones due to the degree of atrial fibrillation (Sega, J.B., 2011, King, D.E, 2002). Discussion for the disputes regarding the use of the medicine for treatment will be elaborated later in this review. Antiarrhythmic medications help return the heart to its normal sinus rhythm or maintain normal sinus rhythm. There are several types of rhythm control medications, including: procainamide (Pronestyl); disopyramide (Norpace); flecainide acetate (Tambocor); propafenone (Rythmol); sotalol (Betapace); dofetilide (Tikosyn) and amiodarone (Cleveland clinic, 2012). Rate control medications, such as digoxin (Lanoxin), beta-blockers [metoprolol (Toprol, Lopressor)], and calcium channel blockers such as verapamil (Calan) or diltiazem (Cardizem), are used to help slow the heart rate during atrial fibrillation. These medications do not control the heart rhythm, but do prevent the ventricles from beating too rapidly. Anticoagulant or antiplatelet therapy medications reduce the possibility of blood clot and eventually stroke, consequently it does not remove the risk. Regular blood tests are required when taking these medications to see how well they are working. Talk to your doctor about the anticoagulant medication that is right for you (Webmed.com, 2012) Rate control strategy was applied to older patients and wt people with coronary artery disease. They have seen that atrial fibrillation have contratindications with anti-arrhythmic drugs so they have to be careful because mortality had been rising since rate control therapy is used with patients using anti-arrhythmic drugs. Rate control patients were treated with a list of medication approved by the pathologists. This includes beta-blockers, calcium channel blockers (verapamil and diltiazem), and digoxin. The goal of rate control to stabilize the heart rate at 80 beats per minute and slight exercise be at the range of 110 beats per minute (Collier, J., 2006). Rhythm control has been on issues since it has shown more mortality than that of rate control. Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) was of less effect than to rate control drugs that are available in the market. Upstream therapy pertains to the utilization of non-antiarrhythmic drugs that adjust the atrial substrate- or target-specific mechanisms of AF to prevent the recurrence of the arrhythmia (Savelieva, I., et al, 2011). Such agents include angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), statins, n-3 (?-3) polyunsaturated fatty acids, and possibly corticosteroids (Murray K.T., et al 2001). Recent studies application of upstream theraphy was applied to animals have persuasively confirmed the defending effect of these agents against electrical and structural atrial remodeling in association with atrial fibrillation. The key targets of this upstream therapy were structural changes in the atria, such as fibrosis, hypertrophy, inflammation, and oxidative stress, but direct and indirect effects on atrial ion channels, gap junctions, and calcium handling were being applied. Upstream therapy is anticipated to reduce the left atrial size, thereby restricting the number of functional reentrant circuits. Although there have been no formal randomized controlled studies in the primary prevention setting, retrospective analyses and reports from the studies in which atrial fibrillation was a pre-specified secondary endpoint have shown a sustained reduction in new-onset atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with significant underlying heart disease. 3. Management, arguments and issues on atrial fibrillation treatment This argument will focus on the three factors on the society: clinically including mortality, comparison of treatments and medications; epidemiologically in terms of the statistics of the current patients around the world, collection and comparing of data, effect of treatments and outbreak investigations; and economically in requisites of the work done by the government to alleviate the problem in the hospitals including the billing and expenses. Kannel B., et al, 1998 showed a remarkable two fold increase in total and cardiovascular mortality on atrial fibrillation patients. Though this is has not been a life threatening ailment, such increase is denoted by Framingham heart study data as one of the growing arrhythmia in the world. Twenty-fold scale is expected until 2050 if the remedy will not come as soon as this matters increase. Factors that may elevate the mortality of patients with atrial fibrillation include the advanced age, mitral stenosis, aortic valve disease, coronary artery disease, hypertension, and congestive heart failure. Supported by Benjamin, E.J., a damatic increase of mortality is directly proportional to the advancement of age as they surveyed the data and gathered a 1.9% increase in the mortality thereof. Causes that would trigger the increased mortality of atrial fibrillation that would be included here would circle with the researches included stroke, thromboembolism, tachycardia-induced cardiomyopathy Noted by Friberg J., et al (2003) that hospital admissions for atrial fibrillation had increased noticeably by 66%. This is due to the rising of the aged boom babies having a chronic heart disease. Hospitalization due to atrial fibrillation had been a financial burden to America, United Kingdom and other countries (Le Heuzey, J.Y., 2004, Khoo, C.W., 2009). Even though there are improvements in healthcare, the prognosis related to atrial fibrillation does not seem to progress. In connection, a study made by Wattigney, W.A., et al (2002) that mortality rate rose up from 8.3% in 1980 to 11.6% in 1998. Another one showed that hospital discharges due to atrial fibrillation decreases from 75% to 60% (Miyasaka et al, 2007). This shows that more cases got worse from 80’s to 20th century making them stay at hospitals and more specifically in emergency unit. As an indication, enlarged hospitalizations are noted by some researches for the past 25 years (Miyasaka, Y., et al, 2008, Stewart, S., 2001) this can be attributed to the elevated incidence due to the ageing population and morbidity of atrial fibrillation. Therefore, this made the patients settle to be associated with higher healthcare cost that is provided by the government and longer inpatient stays (Khoo K.W., et al, 2009). The mortality and morbidity associated with atrial fibrillation are not uniform when looking into consideration related co-morbidities, complications, and treatment strategies. The group bearing the lowest risk would be the so called “lone AF”, which is essentially a diagnosis of exclusion, where AF is associated with no obvious pre-disposing factor or underlying diseases mentioned in the symptoms and on thorough clinical history and examination, with a structurally normal heart on echocardiography, normal ECG, normal blood tests, and normal chest X-ray (Taggar, J.S., et al, 2008). As we recently highlighted, some series even report an increased mortality with lone AF patients. This may replicate how hard we look for connections for co-morbidities, and furthermore, as patients get older, new co-morbidities will interfere. Researchers focus therefore on the underlying treatments and how it has affected the epidemiology of atrial fibrillation. The first concern of the treatment of atrial fibrillation is the prevention of thromboembolic events or stroke which is associated with the ailment. Atrial fibrillation is one of the most triggered factors for stroke in the aging patients (Chung, M.K., 2003). As researched by Wolf, P.A., et al (2003), the risk of stroke for patients with non-valvular atrial fibrillation increases with age and cardiovascular diseases. Patients with atrial fibrillation showed an approximately two-fold to six-fold increase in the risk of stroke (Albers, G.W., et al, 2001). Supported by a research of Thibault, B., (2000), among the 403 patients examined, 81.9% of which had at least one risk factor for stroke. 60% of them are on warfarin medication. 2.2% had thromboembolic attacks, all having a risk factor for stroke. Six of them happened in patients who were either not anti-coagulated. Eight of the patients were in sinus rhythm as well. This has proven that anticoagulants were underused in atrial fibrillation patients at risk of stroke. Thromboembolic events are most often associated with suboptimal levels of anticoagulation and they occur despite the appearance of sinus rhythm maintenance. In the Framingham Heart Study, the annual stroke rate is 4.2%, and has shown the connection of risk of stroke with the presence of atrial fibrillation. Other diseases like coronary artery disease, hypertension and congestive heart failure increase the presence of atrial fibrillation among the people. Age has very big factor for atrial fibrillation. A study showed that it is less for a person, 60 years old and below to have atrial fibrillation. This is due to the presence of hypertension for the elderly. A meta-analysis of prevention trials for stroke in patient had estimated that the incidence of stroke that can happen for individuals of below 65 years old is approximately 1% per year. Risk factor increases as the age reached from 70 to 85 (Hart, R.G.,2007). Anti-coagulation has been shown to decrease ischemic stroke in atrial fibrillation. However, the disputes regarding the safety and efficacy were on process. Patients that are older than 70 years of age were the most affected because the atrial fibrillation patients are most concentrated in this year bracket. A research was done to evaluate the decreased mortality in patients with atrial fibrillation. This has shown that dosage of warfarin has significantly decreased the mortality rates by fifteen percent notches. Major bleeding was decreased from 10% to 7% when warfarin was induced in the patients (Roy, B., et al, 2012). Warfarin is the most common and effective anti-coagulating drug as of today. From 28044 patients and 29 trials made by the group of doctors (Hart, G.H., 2007), adjusted dosage of warfarin and antiplatelet agents reduce stroke by approximately 60% and 20% respectively, in patients with atrial fibrillation. This has concluded that warfarin is more effective than antiplatelet agents. Significantly, the absolute increase in extracranial hemorrhage was 0.3% which denotes safety for warfarin. Another study conducted between the adjusted doses of warfarin versus aspirin (Hart, R.C., et al, 2007) shows helps in the thromboembolism. Risk factors have been seen in induced-warfarin for ages 60 and below. New anti-coagulant is now under research and development in the form of Vitamin K antagonists. These are still on process because it carry out some issues regarding its unwieldy usage because it exhibits multiple interactions with food and drugs (Schmidt, C., 2011, Fuster, V., 2006). Warfarin has gathered a better rate of combined primary outcome compared with aspirin. It is mostly seen among the patients at the age of 85 and above. As compared, it was in younger patients and was also more effective when examining patient subgroups based on gender, previous history of stroke, or baseline risk of stroke. At the same time, warfarin was not more effective than aspirin in the prevention of non-stroke vascular events or overall mortality rates. A surprising finding was that there was no significant increase in the risk of major hemorrhage with warfarin versus aspirin therapy. However, the confidence intervals in this finding were wide; suggesting that a larger patient cohort or greater adherence to randomized therapy could have demonstrated a significant difference between treatments. The researchers also note that their target INR was lower than in previous studies, which could also account for lower rates of hemorrhage among participants receiving warfarin. Reducing the risk of stroke is one of the most important aspects of caring for patients with atrial fibrillation, and improvements in therapy beyond anticoagulation or antiplatelet therapy may have lessened the risk for stroke over the last decade (circulation, 2006). The annual rate of stroke among patients with at least a moderate baseline risk was 3.3%, which compared favorably with a predicted rate of 9.9% based on previous reports. In addition, a recent trial of clopidogrel plus aspirin versus warfarin for stroke prevention among patients with atrial fibrillation and at least 1 other risk factor for stroke also found a lower than expected rate of vascular events, with an annual rate of stroke of 3.93% in the warfarin arm of the trial. This trial was stopped early because of the apparent superiority of warfarin compared with aspirin plus clopidogrel in vascular outcomes. In general, antithrombic therapy between aspirin and warfarin are summarized as follow, Warfarin is induced by patients at the age of 75 above, and younger age atrial fibrillation patients are encouraged to take aspirin or heparin (circulation, 2006). Younger patients without risk factors had a low rate of stroke when treated with aspirin. 4. Future studies on atrial fibrillation Research and development on the treatment and prevention of atrial fibrillation have been in the laboratories looking for the future advancements. They focus on decreasing the risk rate and the control of the underlying diseases. Management of the anti-coagulant medicine will be managed and will try to make it more affordable. The future of atrial fibrillation cure will lie on the genetics side for atrial fibrillation. They would do try to improve the statistics regarding the mortality and the morbidity that is associated with atrial fibrillation (Thompson, M, 2008). The meta-analysis showed a significant reduction in the rate of cardiovascular hospitalization or death in patients receiving dronedarone. This drug have been analyze for the future study to prevent and eventually cure or alleviate the positive impact on patient’s survival. Genetic improvement with the quality of the medicine was under process of researching. The scientists have been looking for the possibilities of the genetic make up for the cure for atrial fibrillation (Calkins, H., 2009). a greater understanding of the genetics of atrial fibrillation should yield insights into novel pathways, therapeutic targets, and diagnostic testing for this common arrhythmia (Ellinor, P.T., 2008). The search for new oral anti-coagulant drugs that are effective, safe and convenient to use has focused primarily on direct thrombin inhibitors. (Schmidt, C., 2011). Further researches on the novel-ion chanel targets and anti-arrhythmic gene therapy preventing substrate were currently being established, evaluated and experimented in clinical experimentation to animal and human sample to optimize the treatment for more complex form of arrhythmia (Schmidt, C., 2011) Conclusions For better illustration, it is better to list the conclusion in this review. 1. Atrial fibrillation predisposes to thromboembolism. If ischemic stroke or systemic thromboembolism occurs, early diagnosis and treatment can improve outcomes. 2. Patients with continuous atrial fibrillation should have additional lesions to ablate atrial macroreentry. 3. Both rate-control and rhythm-control strategies are reasonable primary approaches. Rate control has been favorable in atrial fibrillation patients as compared with the rhythm control therapy. 4. Effectivity of the atrial fibrillation treatment still remains not on the acceptable degree of significance in terms of epidemiological and clinical relevance. 5. Current anti-arrhythmic drugs display reduced efficiency and limited safety due to the prevailing risk factors. 6. Treatment for atrial fibrillation still has a high hospitalization and maintenance cost. This is due to the on going research and trial s for the new medicine. Soon, other drugs such as the emerging Vitamin K antagonist might be available in the market. 7. Underlying diseases trigger to more mortality rate for atrial fibrillation patients. There should be proper allotment of medication for these diseases so that this will not interfere the medication for atrial fibrillation. References Albers GW, Dalen JE, Laupacis A, et al. Antithrombotic therapy in atrial fibrillation. Chest 2001; 119(suppl):194S–206S. American Heart Association. 2004 Heart and Stroke Statistical Update, American Heart Association. 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