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Optimization of the Medical Treatment
of Acute Myocardial Infarction

Iraola, Marcos; Valladares, Francisco;
Alvarez, Frank; Nadal, Jose; Rodriguez, Belkys.

University Hospital "Dr. Gustavo Aldereguía Lima". Cienfuegos. Cuba

SUMMARY
Introduction: Thrombolytic and other drug treatments have greatly reduced hospital mortality following acute myocardial infarction (MI). Despite the proven efficacy of these treatments shown in control studies, their use among doctors is not uniform.
Objectives: To determine the impact that information and education of doctors on the pharmacological therapeutic options for the treatment of MI have on their use of these treatments, and on hospital mortality.
Methods: 267 patients admitted to our Intensive Care Unit (ICU) with MI in 1999 were studied. Use among doctors of drug therapy available for these patients (Aspirin [ASA], beta-blocker agents [BBA], streptokinase, nitrates and calcium channel blockers), and related patient mortality, were assessed before and after information and education provision.
Results: Increased use of ASA, BBA and nitrates, and decreased use of streptokinase and nitrates were found after informative and educative intervention. This was associated with a significant reduction in patient mortality (p<0.05). Table 1.


Discussion: A gap exists between the emergence of new, evidence-based, medical treatments and their implementation in clinical practice. Several factors can account for this; notably the long way from initial presentation of results from a clinical trial, through preparation in attractive form for publication in a peer reviewed journal, to final clinical application. Limited accessibility to new information can make this gap wider, preventing patients from benefiting from these new treatments. This is manifest in the use of available drugs for the treatment of heart ischaemia, where under-use, without obvious contraindication, of ASA, BBA and nitrates, and routine use of streptokinase and calcium channel blockers is shown.
Conclusions: Information and education on the available proven pharmacological options for the treatment of patients with MI resulted in the optimization of their medical treatment and in a reduction in mortality.

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INTRODUCTION
   Acute Myocardial Infarction (AMI) is the non-transmissible disease that motivates the greatest number of admissions to Intensive Care Units (ICU). Both in the world and in our country, AMI is one of the main causes of morbility and mortality, even though the latter has decreased during the last three decades.(1) The creation and development of coronary care units with the possibility of detection and effective treatment of malignant ventricular arrhythmias, the introduction of trombolythic therapeutics, as well as the early use of other pharmacological agents and the availability of interventionist procedures in some centers, have had impact to a higher or lesser degree upon intra-hospital lethality by AMI.(2,3)

   Despite the thorough information provided by large controlled international studies which give an account of the proven efficacy of these interventions in patients who undergo an AMI, there is not yet uniformity in their use, specially in regards to some drugs of proven efficacy such as acetilsalicylic acid (ASA) and adrenergic beta blocker agents (BBA) in the different centers.(4)

OBJECTIVES
   Motivated by the continuous improvement of the quality of the care given to AMI patients in our hospital, we decided to carry out this study in order to determine the behavior of certain pharmacological options such as ASA, BBA, recombinant streptokinase (RE), nitrates and calcium channel blocker, as well as intra-hospital lethality before and after an informative-educational intervention (talk) given to the doctors at the ICU.

MATERIALS AND METHODS
   Setting: ICU at the "Dr. Gustavo Aldereguía Lima" University Hospital in Cienfuegos, Cuba.
Patients: All those admitted to the ICU diagnosed with AMI from January 1st to December 31st 1999.
Study design: Case studies, before and after, in order to assess the impact of an informative-educational intervention (talk) given to the doctors at the ICU in relation to the use of certain pharmacological strategies of proven efficacy for patients with AMI.(5) This information was widely discussed during the last week of June 1999 (intervention). The patients in the first group were those admitted to the ICU during the first semester in 1999 (before the intervention), and those in the second group were the ones admitted in the second semester (after the intervention).

   Some of the variables included in our study were: age, sex, electrocardiographic location of the AMI, comorbilities, medication usage (specifically ASA, BBA, RE, nitrates and calcium channel blocker), causes that motivated the non-use of the first three drugs, as well as the patient's condition upon discharge from the ICU in order to estimate the disease lethality. The variables studied in the first group were taken retrospectively from the clinical files of the patients already discharged from hospital; and in the second group, the information was taken prospectively during the patient's hospitalization. In the case of ASA, BBA and nitrates, we think that their use was early when they were administered in the first 12 hours of the initiation of symptoms.

   Statistical analysis: A database was created in the Epi Info program, version 6.0, where all the variables taken were introduced. For the analysis of the data, they were divided into two categories: before and after the intervention. In this way, the differences between both groups were compared, using absolute numbers, percentages, means, differences in means and proportions.

RESULTS
   During the year 1999, 267 patients were admitted to the ICU with a diagnosis of AMI; 147 (55%) during the first semester (group prior to the intervention) and 120 (45%) in the second semester (group after the intervention). Both groups were comparable with regards to age and sex. In relation to registered comorbilities, the antecedents of diabetes mellitus and hypertension were similar in both groups. It was not the case of previous myocardial infarction and non-coronary vascular disease, which were more frequent in the first group (Table 1A and Table 1B).

   The use of ASA, BBA (p=0.00003) and nitrates was greater in the second group, that is, it increased after the intervention. The use of trombolythics (RE) was high in both groups and only decreased slightly in the second group; in addition calcium channel blocker were used very scarcely in both groups. Intra-hospital lethality decreased in an statistically significant way in the second group (p=0.01126) (Table 2).

   Among the causes that motivated not to use the drugs of proven efficacy in the early management of AMI were: gastric intolerance to ASA, cardiac insufficiency and bradiarrhythmias for BBAs, and prolongued cardiopulmonary resuscitation for RE (Table 3A and Table 3B).

DISCUSSION
   By the end of the XX Century, the panorama of ischaemic cardiopathy offers positive elements such as better knowledge of its pathogenesis and the availability of new strategies both preventive and therapeutical, but it also offers negative elements in relation with its elevated prevalence and the failure to achieve homogeneous practical application of all the information available which is accepted to have great value.(6)

   Clinical management of ischaemic cardiopathy in all its clinical forms, but specially AMI, requires a bigger change, and today there exists an important gap between what we know and our actions. This is influenced upon by the oversimplification of algorithms with practical aims (where ethiopathogenic aspects in particular are ignored), the emergence of new risk factors, the lack of application of all the current knowledge and the distance that seems to exist between the presentation of the results of a clinical trial in a great event, its attractive appearance in a scientific publication and its practical application at the sick man's bed.(7)

   The use of anti-ischaemic drugs in the peri-infarct period, in particular the early use of ASA, trombolythics, BBA, nitrates and calcium channel blocker is an example of this problem; both in the sense of underusage (in the case of the first three drugs) without a clear counterindication, and in the use of oral nitrates and calcium channel blocker in a routinary way.

   In our study, after the intervention, there was an increase in the early use (<12 hours of symptom initiation) of ASA and BBA. Similar results were obtained by the authors of a Canadian multicentric study which had a design much like ours.(4)
antiplatelets, ASA in particular, are useful both in the early management and in the secondary prevention of AMI.(5) Platelets and trombosis play an important role in the genesis of acute coronary syndromes, aspect which is widely reviewed in the publications of the American Heart Association and the American College of Cardiology.(8,9) The ISIS 2 study demonstrated the efficacy of ASA both alone and associated to streptokinase in the reduction of mortality after 35 days (23% and 42% reduction respectively).(10)

   In the same way, BBA agents have proved to be effective in the early management of AMI.(8-10) This disease is associated to a reflex adrenergic shock which is theoretically, at least responsible for the genesis of fatal ventricular arrhythmias and for the progression of the ischaemic process, due to the increase of the consumption of myocardial oxygen. The adrenergic beta block diminishes this sequence of facts and besides, while prolonguing diastole it improves myocardial perfussion, particularly in the subendocardium. Several clinical trials during the 80's have already shown benefits in regards to mortality decrease with the early use of these drugs,(11,12) not always in such a convincing way, and this has been corroborated in other more recent studies as, for example, a clinical trial with carvedilol (in fact a mixed alpha beta blocker).13 Anyway, these agents are still underused, particularly in certain groups of patients such as elderly adults.(14)

   In relation to the use of trombolythic agents, after our intervention, the percentage of treated patients decreased, but only slightly. As percentages come from the total number of patients in each group and not from the eligible ones, this could bias these results. In fact, trombolysis is not underused in our environment judging from the results obtained in 1999 (69.1%) and comparing them with the percentage of inclusion in the National Infarct Registration of the United States (39%).15 This constitutes an achievement due to all the efforts carried out in our hospital in order to improve the quality of care to the AMI patient. The impact of the use of fibrinolythic agents in the reduction of the mortality of patients with AMI is universally accepted, as demonstrated in a metaanalysis of nine research papers on trombolythic therapy.(16) The most frequent motives of non-usage after the intervention in our study were the time factor (more than 12 hours after symptom initiation) (41%); prolongued cardiopulmonary resuscitation (25.6%) and the risk of bleeding (12.8%). At an international level, the time factor is also a frequent cause of exclusion, accepting that approximately half the patients with AMI are admitted to hospital too late to benefit from lythic therapy.(2) Fortunately, in our environment age does not constitute a motive for exclusion, unlike in other countries.(15)

   The early use of nitrates increased after the intervention. Independently from the fact that one very patient received nitrates through more than one way, we can say that most patients in each group used sublingual nitroglycerin in the first hours, something logical because except counterindications, its usefulness is widely acknowledged.(5) Oral nitrates were used in a non-despicable number of patients in both groups and even though we do not discriminate whether they were prescribed, it must be insisted on the fact that they do not constitute a routinary indication in the early management of AMI.(5,7) The efficacy of the use of nitrates in AMI, according to international studies, has resulted to be confusing depending on the design of the study and on the selection of patients. Thus, for instance, in the pre-trombolythic era, sublingual nitroglycerin within the initial four hours proved to be very effective, but in patients with cardiac insufficiency (ejection fraction under 40%).(18) Already in the post-trombolythic era, the GISSI-3 and ISIS-4 megatrials did not report benefits,(18,19) but in groups that included low-risk patients, then we must assume that the benefit of nitrates depends on the existence of a base physiopathological disorder, upon which they can influence favorably.(7)

   Finally, intra-hospital lethality was significantly lower among the patients in the post-intervention group. The design of our study does not permit to infer why this decrease occurred, issue that was not included among the proposed objectives. We cannot justify it only by the increase of the early use of BBA. It must be remembered that among the patients in the first group, the percentage of sick people with previous myocardial infarction and non-coronary vascular disease was larger. Besides, the most frequent exclusion motive not to use RE was prolongued cardiopulmonary resuscitation, that is, patients who were already classified as high-risk ones on admission.

CONCLUSION
   The informative-educational intervention in relation to the use of drugs of proven efficacy in the treatment of patients with AMI, favored the optimization of the treatment and was associated to a reduction in mortality.

REFERENCES

1. Salomaa V, Rosamond W, Mahonen M. Decreasing mortality from acute myocardial infarction: effect of incidence and prognosis. J Cardiovasc Risk 1999; 6: 69-75.

2. Tavazzi L. Clinical epidemiology of acute myocardial infarction. Am Heart J 1999; 138: 48-54.

3. Stomel RJ, Rasak KM, Bates ER. Treatment strategies for acute myocardial infarction complicated. Chest 1994; 105: 997-1002.

4. The Clinical Quality Improvement Network (CQIN) investigators. Influence of a critical path managemant tool in the treatment of acute myocardial infarction. Am J Man Care 1998; 4: 1243-51.

5. Ryan TJ, Anderson JL, Antman EM, Braniff BA, Brooks NH, Califf RM, et al. ACC/AHA. Guidelines for the Management of Patients with Acute Myocardial Infarction. JACC 1996; 28: 1328-428.

6. Braunwald E. Introduction. A symposium: New Insights Into the Pathogenesis and Management of Coronary Artery Disease . Am J Cardiol 1998; 82(suppl): 1H.

7. Opie LH. Review of Trials in the Treatment of Coronary Artery Disease: theoretical expectations versus lack of practical success. How can we explain the differences? Am J Cardiol 1998; 82 (suppl):15H-20H.

8. Fuster V, Dyken ML, Vokonas PS, Hennekens C. Aspirin as therapeutic agent in cardiovascular disease . Circulation 1993; 87: 659-75.

9. Fourth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy. Chest 1995; 108(suppl): 225S-522S.

10. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised Trial of intravenous streptokinase, oral aspirin, both, or neither among 17187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; 2: 349-360.

11. First International Study of Infarct Survival Collaborative Group. Randomised trial of intravenous atenolol among 16027 cases of suspected acute myocardial infarction: ISIS-1. Lancet 1986; 2: 57-66.

12. The MIAMI Trial Research Group. Metoprolol in acute myocardial infarction: patient population. Am J Cardiol 1985; 56: 1G-57G.

13. Basus S, Senior R, Raval U, Van der Does R, Bruckner T, Lahiri. Beneficial effects of intravenous and oral carvedilol treatment in acute myocardial infarction. A placebo-controlled, randomized trial. Circulation 1997; 96: 183-91.

14. Soumerai SB, Mclaughlin TJ, Spiegelman D, Hertzmark E, Thibault G, Goldman L. Adverse outcomes of underuse of beta-blockers in elderly survivors of acute myocardial infarction. JAMA 1997; 277: 115-21.

15. National Heart, Lung, and Blood Institute. 9-1-1: Rapid identification and treatment of acute myocardial infarction. Bethesda, Md: US Department of Health and Human Services, Public Health Service, National Institutes of Health; May 1994. NIH Publication 94-3302.

16. Fibrinolytic Therapy Trialists (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overwiew of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 1994; 343: 311-322.

17. Jugdutt BL, Wamica JW. Intravenous nitrogliceryn therapy to limit myocardial infarct size, expansion and complications. Effect of timing, dosage and infarct location. Circulation 1988; 78: 906-919.

18. GISSI-3 Study. GISSI-3: effects of lisinopril and trasdermal trinitrate single and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet 1994; 343: 1115-1122.

19. ISIS-4 Collaborative Group. A randomised factorial trial assessing early oral captopril, oral mononitrate and intravenous magnesium in 58 050 patients with a suspected acute myocardial infarction. Lancet 1995; 345: 669-685.

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2nd Virtual Congress of Cardiology

Dr. Florencio Garófalo
Steering Committee
President
Dr. Raúl Bretal
Scientific Committee
President
Dr. Armando Pacher
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President
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