Beta Blockers After Myocardial Infarction
The acute care nurse practitioner on the cardiology service treats a 67 year-old-male admitted after recovering from an acute ST-Elevation Myocardial Infarction (STEMI). His risk factors include obesity, Type II diabetes mellitus, and family history. Upon exam the patient asks why he has not been started on a beta blocker yet. He explains further that when his brother had a “heart attack” in 2005, he was immediately placed on a beta blocker because the cardiologist reported how beta blockers reduce mortality after myocardial infarction (MI). The patient wants to know if a beta blocker would reduce his chance of mortality? Using the Patient-Intervention-Comparator-Outcome (PICO) format we formulated the following question. In a 67-year-old male with multiple co-morbidities with MI (P), does treatment with a beta blocker (I), compared with no beta blocker or placebo (O), reduce mortality rate (O)? Risk Factors, Incidence and Prevalence of Disease
•US incidence rates of cardiovascular disease, including MI, are seen in men more than women (Alexander et al., 2007). This trend is also true in Utah (“Impact of heart,” 2007). •The incidence rates of cardiovascular disease increase with age (Alexander et al., 2007). •Risk factors for cardiovascular disease include not eating enough fruits and vegetables, lack of physical exercise, smoking cigarettes and the co-morbidities of diabetes, hypertension, hyperlipidemia, and obesity (“CDC national heart,” 2010). •The clinical scenario patient was at high MI risk being male, over 65, diabetic and obese. Article Critiques
•The following primary article critiques were based on the CONSORT statement (2010). Primary Article One
Article selection and evidence.
•The article by Chen et al. (2005) was selected because it was the only current randomized control trial we could find addressing the use of a beta blocker to treat an acute MI. •This article was an individual randomized control trial reporting findings in narrow confidence intervals, thus earning a level of evidence of 1b when applying the CEBM scale (“Oxford
•The title and abstract were identified this article as a randomized controlled trial. •Abstract and introduction were organized well, stressing purpose, methods and results. •Randomized and controlled design with a metoprolol group and a control placebo group. Patients were blinded, but there was no mention of blinding researchers. •Inclusion, exclusion, and study settings were described. •Experimental and control groups were treated the same.
•Low numbers were lost to follow-up, although about 10% of those studied were excluded because they were not compliant with medication in an outpatient setting. •Results show the groups had no significant differences in mortality. •Subjects receiving metoprolol had fewer adverse events of ventricular fibrillation and reinfarction groups, but this was offset by an increase in cardiogenic shock episodes. Clinical scenario relevance.
•This study applies to our clinical question by showing no significant difference in mortality after MI in those treated with or without metoprolol. Primary Article Two
Article selection and evidence.
•The article by Wienbergen et al. (2007) was selected because it was specific our PICO question in evaluating beta blocker use during MI episodes and evaluating the outcomes. •This was a progressive cohort study, evaluating the therapies physicians selected when treating patients during STEMI event, and the subsequent outcomes. The level of evidence is 2b when applying the CEBM scale (“Oxford centre,” 2009).
•Abstract and introduction were organized well, stressing purpose, methods and results. •Inclusion, exclusion, and study settings were described. •Progressive cohort study design. One acute STEMI group received aspirin, ACE-Inhibitor and a beta blocker, while the other only received aspirin and ACE-Inhibitor. •Assignment of intervention group was not controlled by the
researcher, resulting in the beta blocker group being much larger in size than the non-beta blocker group. •Treatment groups not treated the same. For example, more participants from the beta blocker group received a percutaneous coronary intervention (PCI). •Significantly less mortality seen in the beta blocker group, 4.9% compared to 10.8%.
Clinical scenario relevance.
•This information could be applied to the STEMI patient in our scenario, but with caution. This is because the level of evidence could have been stronger, there was room for confounding factors and groups were not treated equally. Primary Article Three
Article selection and evidence.
•The article by Halkin et al. (2004) was selected because the subject matter was specific to giving a beta blocker during an MI episode and evaluating the outcomes. •This was a progressive cohort study, evaluating the effects of outcomes in acute MI groups did or did not receive a beta blocker based on the physician’s choice. The level of evidence is 2b when applying the CEBM scale (“Oxford centre,” 2009).
•Abstract and introduction were organized well, stressing purpose, methods and results. •Inclusion, exclusion, and study settings were not described well. Instead, they referred the reader to another article to learn of these items in more detail. •The research design was a progressive cohort study, so beta blocker use as an intervention was determined by the doctors independent of researcher influence. •Clinically unstable patients often did not receive beta blockers before PCI. •Significantly reduced mortality 30 days after PCI for MI were seen when beta blockers were used. Mortality values were reported as percentages, and not actual case numbers. Clinical scenario relevance.
•This observation study design lends itself to confounding factors. For example, the patients who did not receive a beta blocker were generally less stable. It is possible that the initial stability of a patient influenced
their mortality rates, not the use beta blockers. •The value of this article for the clinical scenario is questionable. The evidence would have been stronger if the design was a randomized controlled trial, controlled better for confounding factors, and without omission of any study methods information. Primary Article Four
Article selection and evidence.
•Although outdated, we selected the article by by Herlitz, Karlson, and Hjalmarson (1985) because many articles we surveyed made reference to this article and the content sounded like it could be relevant to our clinical question. •This was an individual randomized control trial with wide confidence intervals, earning a level of evidence of 2b when applied to the CEBM scale (“Oxford centre,” 2009).
•Abstract and introduction were organized well, stressing purpose, methods and results. •A randomized, double-blinded design, comparing metoprolol experimental outcomes to a placebo controlled group. •Participant inclusion, exclusion, and clinical setting data were detailed. •Both groups were treated equally with usual care and follow-up. •The confidence interval for mortality differences between groups contained the value zero, supporting no statistical difference in mortality between groups. •142/2901 deaths seen in the control group, and 123/2877 deaths in the metoprolol group, making for comparable CER and EER rates, 0.049 and 0.043 respectively. With this small difference the NNT value would be of little worth. •Information about adverse effects seen with metoprolol vs. placebo were not discussed, so we could not calculate the NNH.
Clinical scenario relevance.
•The difference between placebo and intervention were not statistically significant, and can be applied to our clinical scenario to suggest no benefit for beta blocker use. Primary Article Five
Article selection and evidence.
•Although outdated, we selected the article by Roberts et al. (1991) because many articles we surveyed made reference to this article and the content
sounded like it could be relevant to our clinical question. •This article is an individual randomized control trial. Confidence intervals were not reported. This earned a level of evidence of 2b when applying it CEBM scale because the information needed to be a higher level was not reported. (“Oxford centre,” 2009).
•The phrase “randomized control trial” was not mentioned in the title. It can be deduced from the abstract but is not clearly written there either. •The abstract highlighted key information but the format was not broken into categories, making it more difficult to read and interpret. •Research objectives and rationale were clearly explained in the introduction. •Randomized research design with beta blocker groups assigned to receive immediate administration or delayed administration. Research included multiple hypotheses not involving beta blockers, resulting in subgroups and multiple intervention combinations. •Did not report blinding of test subjects or researchers. •Participants in groups were not treated equally, with metoprolol being titrated in some cases based on patient response (lower dose when hypotension, etc.). •> 20% of subjects in groups were lost to follow-up.
•It was reported that there was no overall difference in long-term death outcomes based on the time when an MI patient received metoprolol.
Clinical scenario relevance.
•This paper showed that it doesn’t matter if our patient receives a beta blocker quickly or if it is delayed in terms of long-term outcomes. However, we would not use the information in this paper. It was not presented clearly, there was no mention of researcher or participant blinding, there was poor follow-up, participants were not treated equally, their study was not focused and they did not answer our specific clinical question. Systematic Review
Reason for Selection.
The article selected as a systematic review was written by Perez, Musini and Wright (2010). Perez et al. (2010) objectives were to determine the
immediate, short-term and long- term effects of anti-hypertensive mortality after a cardiovascular event. This applies to our PICO question and clinical scenario. The following was based on evaluation of systematic reviews by Ciliska, Cullum, and Marks (2001) and the QUORUM statement by Moher, Cook, Eastwood, Olkin, Rennie, and Stroup (1999).
•The Cochrane Review selected for the systematic review addresses all effects of anti-hypertensive medication following a cardiovascular event. It specifically addresses the effects of beta blockers after MI. •Systematic review included randomized control trials with parallel design comparing anti-hypertensive drug with placebo or no treatment in patients with MI. •Perez et al. (2010) identified their search methods, which included electronic searches of databases and detail of their search strategy. •Two reviewers independently decided what trials were included for analysis. Interventions included any anti-hypertensive medication administered within 24 hours after a cardiovascular event and a control group that received a placebo or no anti-hypertensive. Otherwise the same medical treatment as the intervention group.
•Adverse effects to treatment with beta blockers were not reported in this analysis and therefore the data for calculating the numbers needed to harm were not available. •This review is broad but will apply to our patient and clinical question as it addresses mortality rates between beta blocker group and control group.
Results and Interpretation.
•Six trials reported mortality at two days, 10 days and 30 days for all groups. Results varied between the six trials, two favored the control group, three favored the intervention, and one was statistically insignificant. •Perez et al. (2010) reports in Figure 9 that beta-blockers were not associated with a significant reduction in mortality at day two. All six trials reported mortality at 10 days, where three trials favored the
control group, one was not estimable, one was not significant, and one favored the beta blocker group. •Results from study population (N= 72,600) at day two, including 20 eligible trials, may be generalized to our patient, scenario, and practice setting. •Using Figure 9 (Perez et al., 2010), calculation of rates of mortality between the beta blocker and control groups at day two, are as follow: •Treatment group rate of 0.0162 from 552 incidences in the 34,019 study participants. •Control group rate of 0.017 from 580 incidences in the 33,998 study participants. •The absolute risk reduction was then calculated as 0.17 – 0.162 = 0.008. •The relative risk reduction was calculated as (0.017 – 0.0162) / 0.017 = 0.047. •The number needed to treat was calculated as 1 / 0.008 = 125. •Perez et al. (2010) report beta blockers were not associated with a statistically significant reduction in mortality at day 2, 10, and greater than 30 days. •Confidence intervals for each study were reviewed and total results were plotted. The total for each group crossed zero on the forest plot verifying no statistical significance existed between the beta blocker groups and control groups (Perez et al., 2010). Guideline Addressing Clinical Issue
The clinical guideline selected was written by Antman et al. (2007), which addressed STEMI management and treatment. The following critique was based on Hadorn, Baker, Hodges, and Hicks, (1996) system of rating clinical practice guidelines.
•Writing committee members, tasks force members, and organizations were listed. •The ACC/AHA guidelines were developed with a review of the current evidence and by weighing the quality of evidence and the grade of recommendations. •Criteria for inclusion of data included publication in a peer-reviewed journal, large randomized placebo control trials, strengths and weakness of research methodology, and number of previous trials showing consistent results. •Table 1 indicates clearly and concisely the level of evidence and grade for the recommendation using a class and level system (Antman et al., 2007). •The results were peer-reviewed and provision of future review by the task force is given.
•Potential conflicts of interest and search methods were not listed. •Guidelines were based on meta-analysis of trials from the pre-fibronolytic era. Dramatic decreases in post MI mortality rates occurred after the implementation of fibrnolytics which may challenge the benefits of reviewing beta blocker use from the earlier studies. •Guidelines cite patients who received beta blockers showed a 14% relative risk reduction in mortality through seven days (Antman et al., 2007).
Results and interpretation.
•According to the 2004 practice guidelines, oral beta blockers should be administered promptly to acute MI patients without contraindication, and this is of Class I level A evidence (Antman et al., 2004). •2007 updated recommendations state that oral beta blocker therapy should be initiated in the first 24 hours of MI for patients who do not have contraindications, but the level of evidence was reduced to Class I level B evidence (Antman et al., 2007). •Antman et al. (2007) define Class I level B evidence as a recommendation that treatment is useful or effective but limited evidence comes from single randomized control trial or nonrandomized studies and the results were not made readily available. •We may not be able to apply these guidelines to our clinical scenario because important data about the studies selected in the guideline were not included (clinical settings, selection parameters, demographics, etc.). Evidence-Based Answer to Clinical Question
In 2004, the ACC/AHA published clinical guidelines for STEMI management recommending with Class I Level A evidence that beta blockers should be given promptly after MI as long as there are no contraindications (Antman et al., 2004). However, in 2007, the level of evidence was reduced to a Class I Level B recommendation when advising to give a beta blocker within the first 24 hours after MI (Antman et al., 2007).
Reduced mortality with beta blocker use during acute MI were reported in two primary observational studies we reviewed, but the beta blocker groups were not treated equally and confounding factors were not controlled. The best
articles in the primary review supported no statistical difference between beta blockers and placebo with improving mortality rates (Chen et al., 2005) (Herlitz et al., 1985). The systematic review article reviewed also found no statistical significance in mortality rates at 2, 10, and greater than 30 days between groups receiving beta blockers after MI and those that did not receive a beta blocker (Musini & Wright, 2010).
Therefore, to answer our PICO question, we would advise our patient that although there were strong recommendations in 2004 for beta blocker use after MI to reduce mortality rates, those recommendations have changed. Current guidelines recommend treatment with beta blockers after MI, but this evidence does not come from research of the highest quality (Antman et al., 2007). For every 125 patients who are treated with a beta blocker there will be one additional patient who lives, compared to patients in the control group who received a placebo. However, there are risks of side effects to treatment with a beta blocker and those must be weighed against the benefits of treatment. Unfortunately, the articles we reviewed did not list specific adverse effects data for treatment with beta blockers and we were unable to calculate the number needed to harm. Without the information to present risk versus the benefit of treatment with beta blocker, we would not advise treatment with a beta blocker in addition or over the current standard of care after MI.
Alexander, K.P., Newby, K., Armstrong, P.W., Cannon, C.P., & Gibler, W.B., Rich, M.W., . . . Ohman, E. M. (2007). Acute coronary care in the elderly, part ii: ST-segment-elevation myocardial infarction: a scientific statement for healthcare professionals from the american heart association council on clinical cardiology: In collaboration with the society of geriatric cardiology. Circulation, 115(19), 2570-2589. Antman, E. M., Hand, M., Armstrong, P. W., Bates, E. R., Green, L. A., Halasyamani, L. K., Hochman, J. S., . . . Smith, S. C. Jr. (2007) focused update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Writing Group to Review New
Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction). Journal of the American College of Cardiology, 51, 210 – 247. Antman, E. M., Anbe, D. T., Armstrong, P. W., Bates, E. R., Green, L. A.., Hand, M., . . . Ornato, J. P. (2004). Acc/aha guidelines for the management of patients with st-elevation myocardial infarction—executive summary a report of the american college of cardiology/american heart association task force on practice guidelines. Circulation, 110, 588 – 636. CDC national heart disease and stroke prevention program: Utah basic implementation. (2010). Retrieved from http://www.cdc.gov/dhdsp/programs/nhdsp_program/ut.htm Ciliska, D, Cullum, N, & Marks, S. (2001). Evaluation of systematic reviews of treatment or prevention interventions. Evidenced Based Nursing, 4. doi: 10.1136/ebn.4.4.100
Chen, Z. M., Pan, H. C., Chen, Y. P., Peto, R., Collins, R., Jiang, L. X., & Xie, L. S. (2005). Early intravenous then oral metoprolol in 45852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet, 366(9497), 1622 – 1632. The CONSORT statement. (2010). Retrieved from http://www.consort-statement.org/consort-statement/overview0/ Hadorn, DC, Baker, D, Hodges, JS, & Hicks, N. (1996). Rating the quality of evidence for clinical practice guidelines. Journal of Clnical Epidemiology, 49(7) Halkin, A., Grines, C. L., Cox, D. A., Garcia, E., Mehran, R., Tcheng, J. E., . . . Stone, G. W. (2004). Impact of intravenous beta blockade before primary angioplasty on survival in patients undergoing mechanical reperfusion therapy for acute myocardial infarction. Journal of the American College of Cardiology, 43(10), 1780-1787. Herlitz, J., Karlson, B. W., & Hjalmarson, A. (1985). Metoprolol in acute myocardial infarction (MIAMI). A randomised placebo-controlled international trial. European Heart Journal, 6(3), 199 – 226. Impact of heart disease and stroke in Utah, 2007. (2007). Retrieved from http://health.utah.gov/hearthighway/pdfs/BurdenReport2007.pdf Moher, D, Cook, DJ, Eastwood, S, Olkin, I, Rennie, D. & Stroup , DF. (1999). Improving the quality of reports of meta-analyses of randomised controlled trials: the quorom statement. quality of reporting of meta-analyses. Lancet, 354(9193) Oxford centre for evidence-based medicine – levels of evidence (2009). Centre for Evidenced Based Medicine, University of Oxford, Oxford,
United Kingdom. Retrieved from http://www.cebm.net/index.aspx?o=1025 Perez, M. I., Musini, V. M., & Wright, J. M. (2010). Effect of early treatment with anti-hypertensive drugs on short and long-term mortality in patients with an acute cardiovascular event. Cocharane Database of Systematic Reviews, 2009(4), CD006743. Roberts, R., Rogers, W. J., Mueller, H. S., Lambrew, C. T., Diver, D. J., Smith, H. C., . . . Passamini, E. (1991). Immediate versus deferred beta blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) II-B study. Circulation, 83, 422 – 437. Wienbergen, H., Zeymer, U., Gitt, A. K., Juenger, C., Schiele, R., Heer, T., . . . Senges, J. (2007). Prognostic impact of acute beta blocker therapy on top of aspirin and angiotensin-converting enzyme inhibitor therapy in Consecutive patients with ST-elevation acute myocardial infarction. The American Journal of Cardiology, 99(9), 1208 – 1211.