Rheumatoid arthritis patients receive less frequent acute reperfusion and secondary prevention therapy after myocardial infarction compared with the general population

We obtained from each hospital a de-identified list of all patients with a discharge diagnosis of acute MI (International Classification of Diseases (ICD) 9-CM (Aust v2) code 410.xx or ICD 10-AM code I21.xx) between 1 July 1995 and 30 June 2005 (hereafter referred to as "MI admission"). The 15,278 individuals had received a discharge diagnosis of acute MI from one of the three participating hospitals between 1 July 1995 and 30 June 2005. We identified RA patients as those who had also received a discharge diagnosis code for RA (ICD 9-CM (Aust v2) code 714.xx or ICD 10-AM codes M05.xx, M06.xx, or M08.0) during the MI admission or any previous admission. Within the cohort of 15,278 acute MI cases, 133 individuals had also received a discharge diagnosis of RA and were classified as RA cases. The remaining 15,145 patients were classified as non-RA. The medical charts of the 133 RA patients were requested for formal review. Forty-three (32%) of the RA cases were not able to be included in the study: nine (7%) of the charts were unavailable or incomplete, 20 (16%) did not meet criteria for RA, and 14 (11%) did not meet criteria for definite MI. The remaining 90 RA patients (50, Alfred Hospital; 25, Royal Melbourne Hospital; 15, Epworth Hospital) were included in the study. The chart review of the control patients was performed in a similar manner. Thirty-four (38%) of the 90 matched controls initially selected were not able to be included in the study: 18 (20%) charts were unavailable or incomplete, and 16 (18%) patients did not meet criteria for definite MI. In these instances, a second matched control was selected from the de-identified list.

The diagnosis of RA was considered to be correct if a doctor had documented the diagnosis of RA in the chart during the MI admission or during any previous hospital encounter. We chose this definition of RA because comprehensive documentation of RA diagnostic criteria is frequently omitted in hospital medical notes, especially if the patient has been admitted with a nonrheumatologic medical condition (such as MI). We predicted that the use of more-stringent diagnostic criteria would result in the exclusion of many patients who truly had RA, because of an absence of detailed medical notes, rather than any doubt about the diagnosis. For each patient who met our definition of RA, we recorded additional information supporting the diagnosis of RA, including whether the patient fulfilled American College of Rheumatology (ACR) diagnostic criteria [11] or was being treated with disease-modifying antirheumatic drug (DMARD) therapy or both.

Myocardial infarction was defined according to the 2003 American Heart Association Scientific Statement [12] and was categorized as either ST-elevation MI (STEMI) or non-STEMI. We included only patients who were classified as "definite" MI. We defined "acute reperfusion" as the administration of thrombolysis or PCI within 12 hours of the first symptom of MI. Preexisting cardiovascular risk factors and comorbidities were recorded if they were documented in the medical chart or if the patient was receiving treatment for the condition during the MI admission. The documentation of a medical condition in the chart was largely due to patient self-report; however, results of prior investigations (for example, angiography, surgical procedures) or prior hospital admissions or both were also taken into consideration. Medications that we considered indicative of a medical condition included lipid-lowering agents (for hypercholesterolemia) and oral hypoglycemic agents or insulin (for diabetes mellitus).

The RA patients' charts were first reviewed for confirmation of the diagnoses of RA and MI, as defined earlier. If the diagnoses of RA and MI were not confirmed, the patient was excluded from the study. If the diagnoses of RA and MI were confirmed, the patient was included in the study, and a full review of the chart was performed, as described later. For each RA patient in the study, a non-RA control matched for age at time of MI (± 1 year), gender, treating hospital, and year of MI (± 1 year) was selected from the de-identified list. The control patients' charts were reviewed for a diagnosis of MI, as defined earlier. If the diagnosis of MI was not confirmed, the patient was excluded from the study, and another control was selected from the de-identified list. If the diagnosis of MI was confirmed, the patient was included in the study, and a full review of the chart was performed.

Chart abstraction and data collection were performed by a trained research assistant using a structured audit form. The accuracy of the chart abstraction was verified by independent audit of 5% of the charts by a second investigator (SV). The RA patients' charts were reviewed for RA-related characteristics, including ACR diagnostic criteria [11], disease duration, extraarticular disease, and DMARD treatment in the past and at the time of the MI admission. The charts of all patients (RA and non-RA) were reviewed for: confirmation of MI and type of MI, conventional cardiovascular risk factors and other comorbidities (including prior MI), medications taken at time of MI admission, administration and timing of reperfusion therapy (thrombolysis or PCI), and post-MI events such as in-hospital death and coronary artery bypass graft surgery. The clinical setting of the MI was classified into one of three categories: (a) "community based," the MI occurred outside a hospital with no acute medical illness immediately preceding it; (b) "after medical illness," the patient was already an inpatient for a medical illness and experienced the MI as a complication during that hospital admission; or (c) "after surgical event," the patient was already an inpatient and had undergone a surgical procedure and experienced the MI as a complication during that hospital admission. Urgent reperfusion is not necessarily indicated in all cases of MI; however, in the event of STEMI, early thrombolysis or PCI is considered the standard of care [13]. In those patients who experienced an STEMI and did not receive acute reperfusion, the reason for lack of acute reperfusion was determined from extensive review of the chart and was categorized as either (a) delayed diagnosis due to late presentation; (b) delayed diagnosis due to diagnostic uncertainty; (c) presence of a contraindication; or (d) unable to ascertain the reason. We also recorded whether treatment with secondary prevention medications (specifically aspirin, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, lipid-lowering agents, or a combination of these) was commenced during the hospital stay for each patient. If a patient had an allergy or other condition precluding the use of these medications, or if the patient was previously taking the medication and it was continued during the MI admission, the treatment was considered to have been provided.

The primary end point was the proportion of patients who received acute reperfusion after MI. In performing our sample-size calculation, we used data from our previous study, in which we found that RA patients were treated with PCI half as often as non-RA patients. Assuming acute reperfusion rates of 50% in the control patients and 25% in the RA patients, with power = 0.9 and alpha = 0.05, we calculated that a sample of 85 participants per group would be required. Descriptive data were summarized by using population means and standard deviation or percentages, as appropriate. Baseline characteristics and treatment with secondary prevention medications of the RA and control patients were compared by using the McNemar test for categoric variables and the paired t test for continuous variables. Treatment with cardiac interventions such as acute reperfusion, thrombolysis, and PCI in the RA and control patients was compared with the McNemar test (unadjusted analysis) and with conditional logistic regression adjusted for clinical setting of MI, type of MI, and prior MI. Our study covered a 10-year period during which the treatment of acute coronary syndromes evolved considerably. We therefore performed a post hoc analysis in which we compared treatment with acute reperfusion and secondary prevention pharmacotherapy between RA and controls over three time periods: prior to 1999, 1999 to 2002 inclusive, and after 2002. Analyses were performed with the use of Stata software version 10.0 (StataCorp, College Station, TX, USA).

Table 2 shows the treatment received by the RA and control patients after acute MI. No difference was noted between hospitals in the proportion of patients who received acute reperfusion (data not shown), so we present combined hospital data. In the unadjusted analysis, the RA patients were significantly less likely to receive acute reperfusion compared with the controls (16% versus 37%, respectively; OR, 0.27; 95% CI, 0.10 to 0.64). Thrombolysis was performed in 9% of the RA patients compared with 24% of the controls (OR, 0.3; 95% CI, 0.1 to 0.77); PCI was performed in 11% of the RA patients compared with 33% of the controls (OR, 0.2; 95% CI, 0.06 to 0.53); and coronary angiography was performed in 43% of the RA patients compared with 58% of the controls (OR, 0.41; 95% CI, 0.16 to 0.92). Coronary artery bypass surgery was performed more frequently in the controls; however, this variance did not reach statistical significance.

The presence of a medical or surgical illness immediately before the MI was substantially more common in the RA patients than in the controls (31% versus 16%, respectively: OR, 2.5; 95% CI, 1.2 to 5.5). The clinical setting of the MI, the type of MI, and the past history of MI could potentially have affected the likelihood that acute reperfusion was provided. Therefore, we performed an analysis by using conditional logistic regression, with adjustment for these variables (Table 2). In the adjusted analysis, RA patients remained significantly less likely to be treated with acute reperfusion, thrombolysis, and PCI, suggesting that acute concurrent conditions or prior MI or both were not responsible for the observed differential treatment of RA patients.

From our total study cohort of 180 patients, 29 of the RA patients and 39 of the controls were diagnosed with STEMI. Acute reperfusion was administered in 48% of the RA-STEMI patients versus 74% of the control-STEMI patients (P = 0.027 with the χ² test). In those STEMI patients who did not receive acute reperfusion (n = 25), delayed diagnosis of MI was the most common reason for failure to provide acute reperfusion: six (40%) of RA patients and five (50%) of controls. It was previously demonstrated that RA patients experience a higher rate of silent MI than does the general population, and this may also contribute to a delay in presentation to hospital [9, 14]. In our study, 39% of the RA patients did not experience chest pain during the MI compared with 22% of the control patients (OR, 0.5; 95% CI, 0.3 to 0.9). A contraindication to acute reperfusion was present in five (33%) of the RA patients, whereas none of the controls had a contraindication. In four (27%) of the RA patients and five (50%) of the controls, no clear reason was found for not providing acute reperfusion after careful review of the medical chart.

The numbers were too small in this subgroup of 25 patients to make any meaningful statistical comparisons; however, the difference in the prevalence of contraindication to acute reperfusion between the RA and control groups was of interest. Five RA patients had a contraindication to acute reperfusion; one had peptic ulcer disease (bleeding risk), one had a recent intracerebral bleed, and three patients had undergone major surgery in the previous 5 days. This was consistent with our finding that an antecedent medical illness or surgical event was more common in the RA subjects.

Table 3 shows the number of RA and control patients who received treatment with selected secondary prevention medications. The RA patients received less-frequent treatment with beta blockers (71% versus 83%: OR, 0.42 (95% CI, 0.18 to 0.96)) and lipid-lowering agents (40% versus 70%: OR, 0.21 (95% CI, 0.09 to 0.46)).

Ten of the RA patients and 11 of the controls had experienced MI before the study "MI admission." Table 4 shows the numbers of these patients who were already taking selected secondary prevention medications at the time of the study MI. The RA patients had lower rates of treatment with aspirin, beta blockers, and lipid-lowering agents at the time of their recurrent MI. These data mirror our findings in the analysis of the entire cohort and serve to validate the results of the present study.

Table 5 shows the frequency of selected post-MI treatments in RA and control patients for three time periods within our study period: prior to 1999, 1999 through 2002, inclusive, and 2003 and onward. For virtually all interventions, in each of the time periods, the RA patients received less-frequent treatment than did the controls. Within the subgroup of STEMI patients, a suggestion of higher rates of acute reperfusion was found in the most recent time period (small numbers limit this result); however, in all time periods, the RA patients received less-frequent acute reperfusion than did the controls. Treatment with lipid-lowering agents increased progressively over time for all patients; however, in each time period, RA patients again received less-frequent treatment with lipid-lowering agents than did controls.