In the setting of acute myocardial infarction and sinus rhythm, the heart rate (HR) has been demonstrated to correlate closely with mortality. In patients presenting with acute myocardial infarction and atrial fibrillation (AF) on admission, however, the prognostic relevance of the HR has not yet been systematically addressed. A post hoc subgroup analysis of the data from the OMEGA trial was conducted to analyze whether the admission HR determines the 1-year mortality in patients presenting with AF in the setting of acute myocardial infarction. Of 3,851 patients enrolled in the OMEGA study, 211 (6%) presented with AF on admission. This subgroup was dichotomized according to the admission HR (cutoff 95 beats/min). Multiple regression analysis revealed that an admission HR of ≥95 beats/min independently determined the 1-year mortality in patients with AF (odds ratio 4.69, 95% confidence interval 1.47 to 15.01; p = 0.01). In conclusion, this is the first study demonstrating that a high HR (≥95 beats/min) on admission in patients with AF and acute myocardial infarction is associated with an almost fivefold mortality risk.
The heart rate (HR) is one of the most fundamental and yet simplest diagnostic tools in medicine. A high HR reflects increased sympathetic activity; however, far from being a mere indicator of underlying illness, it has been proposed as an independent cardiovascular risk factor. In fact, a high HR has been strongly associated with increased mortality in the general population, notably in the elderly, in hypertensive subjects, and in patients with coronary artery disease. In acute myocardial infarction (AMI), an elevated HR portends a poor prognosis in terms of early and long-term mortality, at least in patients with sinus rhythm. Atrial fibrillation (AF) is encountered in 2% to 22% of patients with AMI and is generally not perceived by clinicians as a critical event in the peri-infarction period, unlike heart failure or ventricular tachyarrhythmias. Nevertheless, the presence of AF in the context of acute coronary syndrome correlates with increased mortality. However, the prognostic relevance of admission HR in patients with AMI presenting with AF has not yet been explored. This was the rationale for the present subgroup analysis within the scope of the OMEGA trial.
Methods
The OMEGA trial was a prospective, randomized, double-blind, controlled trial investigating the effect of omega-3 fatty acid supplementation on the rate of sudden cardiac death in survivors of AMI. The study protocol was previously published in detail. In brief, the patients were enrolled within 3 to 14 days after ST-segment elevation myocardial infarction (STEMI) or non–ST-elevation myocardial infarction (NSTEMI) and followed up for a 12-month period. The participants received the study drug (omega-3 acid ethyl esters-90 vs placebo) in addition to modern guideline-adjusted therapy. The latter included revascularization measures and current guideline-driven medication. Death from any cause was a secondary end point in the OMEGA trial. Because of its advantage of being the “hardest” and most reliable end point, total mortality was chosen for the present substudy. In-hospital mortality was excluded from the analysis. All patients gave written informed consent. The study protocol complied with the Declaration of Helsinki and was approved by the local ethics committees.
The data management procedures and general statistical methods applied to the OMEGA data set have been previously described in detail. The study population was dichotomized according to the HR on admission. The cutoff of 95 beats/min resulted in 2 groups of almost equal size. Continuous variables are presented as the median with quartiles and categorical variables as percentages. To test the differences between the 2 HR groups, we applied Wilcoxon’s rank sum test to the continuous and Pearson’s chi-square test to the dichotomous variables. All p values refer to 2-sided hypotheses. Analyses were performed using SAS, version 9.2 (SAS Institute, Cary, North Carolina).
Results
Of 3,818 patients recruited for the OMEGA trial from October 2003 to June 2007, 214 presented with AF on their admission electrocardiogram. Two of them had no documentation of the hospital stay, and the HR of 1 patient had not been indicated. Thus, the baseline data from 211 patients (6%) with AF on admission were available for analysis. The baseline characteristics and in-hospital treatment, including early revascularization measures and medical management of the patient cohorts, dichotomized according to the HR on admission (cutoff at 95 beats/min) are listed in Table 1 . The secondary end points of the study are summarized in Table 2 . The percentage of patients with AF who were treated with omega-3 fatty acids versus placebo was almost evenly distributed (53% vs 47%). One patient with AF was lost to follow-up.
| Variable | HR (beats/min) | p Value | |
|---|---|---|---|
| ≥95 (n = 107) | ≤94 (n = 104) | ||
| Age (yrs) | 72 (64–78) | 73 (67–80) | 0.21 |
| Age >70 yrs | 57 (53%) | 65 (63%) | 0.17 |
| Women | 43 (40%) | 28 (27%) | <0.05 |
| Killip class ≥II | 37 (35%) | 25 (24%) | 0.09 |
| Arterial hypertension | 81 (76%) | 87 (84%) | 0.15 |
| Diabetes mellitus | 35 (33%) | 44 (42%) | 0.15 |
| Creatinine >2 mg/dl | 4 (4%) | 3 (3%) | 0.73 |
| Heart rate (beats/min) | 120 (105–135) | 77 (63–87) | <0.01 |
| Anterior wall myocardial infarction | 18 (17%) | 22 (21%) | 0.42 |
| Left ventricular ejection fraction <40% | 29 (32%) | 37 (37%) | 0.40 |
| Left ventricular ejection fraction (%) | 50 (40–59) | 48 (38–57) | 0.57 |
| Primary percutaneous coronary intervention | 56 (52%) | 76 (73%) | <0.01 |
| Medication at discharge | |||
| Acetylsalicylic acid | 88 (83%) | 82 (79%) | 0.44 |
| Clopidogrel | 76 (72%) | 82 (79%) | 0.23 |
| Vitamin K antagonist | 26 (25%) | 28 (27%) | 0.69 |
| β Blocker | 99 (93%) | 93 (89%) | 0.30 |
| Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker | 98 (93%) | 95 (91%) | 0.77 |
| Statin | 99 (93%) | 92 (89%) | 0.21 |
| Digitalis | 21 (20%) | 18 (17%) | 0.64 |
| Variable | HR (beats/min) | p Value | |
|---|---|---|---|
| ≥95 | ≤94 | ||
| Total mortality | 16/106 (15%) | 8/104 (8%) | 0.09 |
| Revascularization: primary coronary intervention and/or coronary artery bypass graft | 17/76 (22%) | 19/83 (23%) | 0.94 |
| Rehospitalization | 49/81 (61%) | 55/89 (62%) | 0.86 |
| Bleeding requiring transfusion | 2/80 (3%) | 2/88 (2%) | 0.92 |
The median age of the OMEGA subgroup with AF on admission was 72 years (lower and upper quartile 65 and 78, respectively), and 34% were women. The total AF cohort presented with a median HR of 95 beats/min (range 77 to 120). The anthropometric variables were evenly distributed between groups ( Table 1 ). The distribution of major cardiovascular risk factors (arterial hypertension, hypercholesterolemia, diabetes mellitus, current smoker, family history of coronary artery disease) was also similar. No differences were found with regard to the prevalence of bundle branch block. The percentage of STEMI and NSTEMI was 36% and 64% for a HR of ≥95 beats/min and 49% and 51% for a HR of ≤94 beats/min (both p = 0.06), with 70% and 71% of these being first events, respectively. In the whole AF cohort, left ventricular function was mildly reduced, the median left ventricular ejection fraction was 49% (range 40% to 58%). Medical therapy at discharge complied with current standard guidelines ( Table 1 ).
Total mortality after 1 year was 11% in the patients with AF. Multivariate analysis revealed that a HR of ≥95 beats/min was strongly associated with all-cause mortality after adjustment for age >70 years, female gender, Killip class ≥II, diabetes mellitus, arterial hypertension, moderately or severely reduced LV function, chronic obstructive pulmonary disease, renal insufficiency (defined as creatinine >2 mg/dl), peripheral artery disease, previous stroke, anterior myocardial infarction, percutaneous coronary intervention, and medical management (β blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor type 1 receptor blockers) of the study patients (odds ratio [OR] 4.69, 95% confidence interval [CI] 1.47 to 15.01, p = 0.01; Figure 1 ). Female gender was a strong predictor of a high HR, and advanced age and diabetes were predictive of a lower HR (p <0.05; Figure 2 ).
The study population represented a particular subgroup of patients managing the issue of triple oral antithrombotic therapy (i.e. concomitant use of dual antiplatelet therapy [acetylsalicylic acid plus clopidogrel] and an oral anticoagulant). The distribution of subjects receiving triple therapy was homogeneous in the patients with AF, and the frequency of major bleeding complications (defined as bleeding requiring transfusion) was similar between the groups ( Table 2 ). The rate of revascularization procedures and rehospitalization did not differ significantly among the survivors ( Table 2 ).
Results
Of 3,818 patients recruited for the OMEGA trial from October 2003 to June 2007, 214 presented with AF on their admission electrocardiogram. Two of them had no documentation of the hospital stay, and the HR of 1 patient had not been indicated. Thus, the baseline data from 211 patients (6%) with AF on admission were available for analysis. The baseline characteristics and in-hospital treatment, including early revascularization measures and medical management of the patient cohorts, dichotomized according to the HR on admission (cutoff at 95 beats/min) are listed in Table 1 . The secondary end points of the study are summarized in Table 2 . The percentage of patients with AF who were treated with omega-3 fatty acids versus placebo was almost evenly distributed (53% vs 47%). One patient with AF was lost to follow-up.
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