Author + information
- Gregg W. Stone, MD, FACCA,*,
- Cindy L. Grines, MD, FACCB,
- Donald Rothbaum, MD, FACCC,
- Kevin F. Browne, MD, FACCD,
- James O’Keefe, MD, FACCE,
- Paul A. Overlie, MD, FACCF,
- Bryan C. Donohue, MD, FACCG,
- Noah Chelliah, MDH,
- Ronald Vlietstra, MD, FACCD,
- Tom CatlinB,
- William W. O’Neill, MD, FACCB,1,
- for the PAMI Trial Investigators
- ↵*Dr. Gregg W. Stone, The Cardiovascular Institute, 2660 Grant Road, Mountain View, California 94040.
Objectives. We sought to determine the relative cost and effectiveness of two different reperfusion modalities in patients with acute myocardial infarction (AMI).
Background. Recent studies have found superior clinical outcomes after reperfusion by primary percutaneous transluminal coronary angioplasty (PTCA) compared with thrombolytic therapy. The high up-front costs of cardiac catheterization may diminish the relative advantages of this invasive strategy.
Methods. Detailed in-hospital charge data were available from all 358 patients with AMI randomized to tissue-type plasminogen activator (t-PA) or primary PTCA in the United States from the Primary Angioplasty in Myocardial Infarction trial. Resource consumption during late follow-up was estimated by assessment of major clinical events and functional status.
Results. Compared with t-PA, primary PTCA resulted in reduced rates of in-hospital mortality (2.3% vs. 7.2%, p = 0.03), reinfarction (2.8% vs. 7.2%, p = 0.06), recurrent ischemia (11.3% vs. 28.7%, p < 0.0001) and stroke (0% vs. 3.9%, p = 0.02) and a shorter hospital stay (7.6 ± 3.3 days vs. 8.4 ± 4.7 days, p = 0.04). Despite the initial costs of cardiac catheterization in all patients with the invasive strategy, total mean (±SD) hospital charges were $3,436 lower per patient with PTCA than with t-PA ($23,468 ± $13,410 vs. $26,904 ± $18,246, p = 0.04), primarily due to the reduction in adverse in-hospital outcomes. However, professional fees were higher after primary PTCA ($4,185 ± $3,183 vs. $3,322 ± $2,728, p = 0.001), and thus total charges, although favoring PTCA, were not significantly different ($27,653 ± $13,709 vs. $30,227 ± 18,903, p = 0.21). At a mean follow-up time of 2.1 ± 0.7 years, no major differences in postdischarge events or New York Heart Association functional class were present between PTCA- and t-PA–treated patients, suggesting similar late resource consumption. Including in-hospital events, 83% of PTCA-treated patients were alive and free of reinfarction at late follow-up, compared with 74% of t-PA–treated patients (p = 0.06).
Conclusions. Compared with t-PA, reperfusion by primary PTCA improves clinical outcomes with similar or reduced costs. These findings have important clinical implications in an increasingly cost-conscious health care environment.
(J Am Coll Cardiol 1997;29:901–7)
© 1997 by the American College of Cardiology
Prospective, randomized studies comparing reperfusion by primary percutaneous transluminal coronary angioplasty (PTCA) with reperfusion by thrombolysis in patients with acute myocardial infarction (AMI) have documented superior clinical outcomes with the invasive approach, including reduced rates of death, reinfarction, recurrent ischemia and stroke ([1–4]). In an era in which the national health budget is experiencing reduced growth, any discussion of the relative efficacy of different treatments must take into account cost considerations. In this regard, concerns have been voiced that the high up-front costs of cardiac catheterization and PTCA may diminish the attractiveness of the primary PTCA approach to AMI. We therefore examined the costs and relative effectiveness of reperfusion by primary PTCA compared with thrombolysis with tissue-type plasminogen activator (t-PA) in the U.S. cohort of the Primary Angioplasty in Myocardial Infarction (PAMI) trial.
The methodology of the PAMI trial has been previously described (). In summary, 395 patients of various ages presenting at 12 centers with AMI of ≤12 h duration were randomized to treatment with t-PA or primary PTCA without antecedent thrombolytic therapy. Patients were excluded based on the absence of ST segment elevation or the presence of left bundle branch, cardiogenic shock, standard risk factors known to predispose to increased bleeding risk after thrombolytic therapy and the inability to give informed consent.
Patients assigned to the t-PA arm received 100 mg (or 1.25 mg/kg body weight for patients weighing <65 kg) of t-PA (Activase [Genentech]) over 3 h. After t-PA infusion, patients were treated conservatively according to phase 2B of the Thrombolysis in Myocardial Infarction (TIMI) trial (). Rescue PTCA was permitted, however. Patients assigned to the primary PTCA arm underwent emergency arteriography followed by PTCA if appropriate (performed in 90% of patients). Intravenous heparin was continued in all patients for 3 to 5 days. Radionuclide ventriculography was performed within 24 h of admission for acute assessment of left ventricular ejection fraction. According to the protocol, after initial treatment, unscheduled catheterization followed by subsequent revascularization with either PTCA or coronary artery bypass graft surgery was performed only for the in-hospital recurrence of unstable ischemia or a positive predischarge exercise thallium test.
1.1 Data collection and statistical analysis
Clinical data were collected prospectively at each site by a research nurse. After on-site confirmation by an independent study monitor, data were entered into a computerized data base. Three categories of cost were assessed: hospital charges from the index admission, professional cardiology (invasive plus noninvasive) and cardiac surgery fees from the index admission and postdischarge follow-up resource consumption. Hospital and physician bills were obtained from all 358 patients enrolled at the 11 U.S. sites and forwarded to the coordinating center. Cost data were not available from the 37 patients enrolled at one European site, and these patients were excluded from the analysis. Summary ledger forms (UB 92) and detailed itemized bills were available and reviewed from all patients. Mean hospital charges were subdivided into the following 18 categories: emergency room, coronary care unit room and board, noncoronary care unit room and board, clinical laboratory tests, medications and intravenous solutions, cardiac catheterization laboratory, radiology, electrocardiography, medical and surgical supplies, operating room, anesthesia, recovery room, surgical intensive care unit, respiratory therapy, exercise treadmill testing, nuclear cardiology, blood products and cardiac rehabilitation. In-hospital professional charges were also collected. Follow-up data were collected from examination of postdischarge clinic and hospital visits, telephone interviews and mailed questionnaires. Cost assessment during follow-up was not feasible given the large number of physicians, practice settings and hospitals involved. Late resource consumption was therefore approximated by tabulating hospital readmissions and major clinical events during the first 2 years after discharge.
Analysis was made on an intention-to-treat basis. Categoric variables were compared by chi-square analysis or the Fisher exact test. Continuous variables are presented as the mean value ± SD and were compared using the Student ttest or Mann-Whitney Utest. Median charges are also expressed, with 90% confidence intervals. Univariate correlates of increased hospital charges were determined from 28 variables (13 baseline clinical and hemodynamic variables [Table 1], 14 outcome variables [Table 2] and treatment assignment [t-PA vs. PTCA]). All variables with a univariate p value ≤0.10 were entered into a forward stepwise multiple regression analysis to determine the independent correlates of increased hospital charges. Three analyses were performed; the first involving only baseline demographic features, the second including the randomization arm and the third including all variables, including clinical events. The F ratio, reflecting the relative contribution of each variable to the univariate and multivariate model, is reported. A p value <0.05 was considered significant. Statistical analyses were performed using commercially available software (JMP v3.1, SAS Institute, and Statview 4.5, Abacus Concepts).
2.1 Baseline characteristics and in-hospital outcome
There were no significant differences in baseline demographic or clinical features on presentation between patients treated with t-PA and PTCA (Table 1). Compared with t-PA–treated patients, however, patients treated with primary PTCA had lower rates of in-hospital death, reinfarction, recurrent ischemia and postadmission unscheduled cardiac catheterization and PTCA and a shorter hospital stay (Table 2).
2.2 In-hospital charges
Per patient hospital charges (excluding professional fees) were significantly lower, by a mean of $3,436, in patients treated with PTCA compared with t-PA (Table 3). As shown in Fig. 1(left panel), most of the excess charges accrued after t-PA occurred in patients accumulating large hospital bills. Charges in low cost patients with an uncomplicated hospital course were similar after t-PA and PTCA, as reflected in the near identical lower end of the confidence intervals of the median hospital charges (Table 3).
Table 4shows the effect of treatment modality on hospital outcomes and charges in patients predefined as “high risk” (age >70 years, admission heart rate >100 beats/min or anterior infarct location) versus “non high risk,” as defined by the original TIMI investigators (). The greatest reduction in hospital charges in patients treated initially by PTCA rather than t-PA occurred in “non high risk” patients (mean savings of $4,365 per patient), in whom PTCA resulted in discharge 1.3 days earlier. In contrast, in “high risk” patients, PTCA resulted in markedly reduced in-hospital mortality rates and a lower rate of stroke, although with only an insignificant trend toward a reduction in hospital charges of $2,464 per patient.
By multivariate analysis, the only baseline variables that correlated with increased hospital charges were advanced age, previous myocardial infarction and previous heart failure. When the randomization arm was entered into the model, age, previous myocardial infarction and previous heart failure retained significance, but the randomization arm did not. The results of the global multivariate analysis in which baseline features, randomization arm and outcomes were included appear in Table 5. In this model, the primary determinants of hospital charges were adverse in-hospital events, including a prolonged hospital stay, need for intraaortic balloon counterpulsation, nonprotocol PTCA, intubation, stroke and bypass surgery. Angioplasty did not have a significant independent effect on costs.
2.3 Professional fees and total charges
In contrast to lower hospital charges, professional fees were on average $863 higher in patients treated with PTCA compared with t-PA ($4,185 ± $3,183 vs. $3,322 ± $2,728, p = 0.001). As a result, only an insignificant trend was present for a $2,574 per patient reduction in total hospital charges after primary PTCA compared with t-PA ($27,653 ± $13,709 vs. $30,227 ± $3,183, p = 0.21), this difference occurring primarily in patients with a complicated, expensive hospital course (Fig. 1, right panel).
2.4 Postdischarge clinical events and resource consumption
Follow-up data were available in 340 (99%) of 341 patients discharged alive. There was no difference in the mean follow-up duration in patients randomized to PTCA versus t-PA (2.2 ± 0.7 years vs. 2.1 ± 0.7 years, respectively, p = 0.27). Events during the follow-up period occurred with similar frequency in patients initially assigned to t-PA and PTCA (Table 6), although trends were present for a greater late incidence of nonelective hospitalization and late bypass surgery in PTCA-treated patients. Considering cumulative in-hospital and late events, 146 (82.5%) of 177 patients randomized to PTCA were alive and free of reinfarction at the end of the follow-up period, compared with 134 (74.4%) of 180 patients randomized to t-PA (p = 0.06).
An ideal therapeutic agent or intervention would result in improved clinical outcomes compared with the available strategies, while at the same time reducing health care resource consumption and costs. Such a combination is unusual in an era dominated by the explosive growth of expensive technology. The results of the PAMI trial suggest that primary PTCA at skilled centers, when compared with t-PA for reperfusion of AMI, approaches this ideal. Coronary angioplasty resulted in improved in-hospital and long-term outcomes, although total hospital charges, rather than being increased by the high up-front costs of cardiac catheterization necessary to perform primary PTCA, were actually similar or reduced.
3.1 Present study
In the PAMI trial, hospital charges were reduced with primary PTCA compared with t-PA followed by a watchful waiting approach. The higher radiology and cardiac catheterization laboratory charges with the invasive approach were more than offset by higher drug and solution charges, room charges and charges for electrocardiographic and clinical laboratory tests after thrombolysis. By multivariate analysis, however, the reperfusion modality (PTCA vs. t-PA) was no longer a significant correlate of cost. Rather, the primary determinants of cost were the development of adverse in-hospital events, similar to the findings from the Primary Angioplasty Registry (). Thus, it is not primary PTCA itself that reduces hospital costs compared with lytic reperfusion; rather, it is the favorable effects of PTCA in reducing the rate of recurrent ischemia compared with thrombolysis ([1–4, 7]), which results in a reduced need for predischarge catheterization and subsequent PTCA, as well as the lower rate of stroke from eliminating thrombolytic administration. As a consequence of this more stable hospital course, primary PTCA facilitates early discharge ([1–3, 7]), which was the strongest determinant of hospital charges in the present analysis.
As a corollary, and in contrast to what otherwise might be expected from the above considerations, the greatest absolute reduction in hospital charges by treatment with PTCA rather than t-PA was realized in patients defined as “non high risk.” Because recurrent ischemia after t-PA occurred just as frequently in high risk and non high risk patients, 60% of t-PA–treated patients who were not at high risk still required predischarge catheterization, and nearly 50% underwent predischarge revascularization, compared with only 8% and 12%, respectively, after PTCA. As stroke, intubation and need for intraaortic counterpulsation rarely occurred in non high risk patients, the clinical stability afforded by PTCA in this patient group resulted in a 1.3-day shorter hospital course and significant cost savings of $4,365 per patient. Thus, the major benefits of mechanical reperfusion compared with thrombolysis in high risk patients are improvements in infarct-free survival and freedom from stroke, whereas lower risk patients benefit from a more stable hospital course, less recurrent ischemia, a shorter hospital stay and a less expensive hospital stay ([1, 2, 8–10]).
The lower hospital charges after PTCA compared with t-PA were somewhat offset by increased professional fees with the invasive strategy. Furthermore, as a result of the wide range of charges and the modest study size, the mean $2,574 per patient reduction in total hospital charges after primary PTCA compared with t-PA did not reach statistical significance. Given the number of patients enrolled, the study had only 31% power to detect a difference in total hospital charges. With the differences observed, a p value <0.05 would have been reached if 99 more patients had been enrolled.
3.2 Previous studies comparing PTCA and thrombolysis
The smaller study by Gibbons et al. (), which compared t-PA with primary PTCA, found a trend toward a $4,589 reduction in estimated hospital plus professional costs after PTCA, also as a result of less recurrent ischemia and a shorter hospital stay. An additional significant savings of $2,258 per patient was realized in the first 6 months after discharge as PTCA-treated patients required fewer readmissions than t-PA–treated patients. In the randomized study from the Netherlands (), in which the less expensive agent streptokinase was used, total 12-month costs of primary PTCA and thrombolytic therapy were similar. Clinical outcomes were improved after reperfusion by PTCA compared with streptokinase, however, and thus despite these comparable costs, cost efficacy analysis showed that the average cost for an event-free survivorwas $25,431 for patients assigned to PTCA versus $36,798 for those assigned to thrombolytic therapy (p < 0.01) ().
3.3 Costs versus charges, and a “real world” economic analysis
The PAMI study is the largest published, randomized trial comparing thrombolytic therapy with primary PTCA. One limitation of the present analysis, however, is the substitution of charges for true costs. As a result of cost shifting to cover unpaid debts or underreimbursed fees, hospital charges are significantly greater than absolute costs ([6, 12, 13]). True costs, however, are difficult to measure and require assumptions and approximations that may also not be valid. Previous analyses of cost effectiveness from the randomized studies of PTCA and thrombolytic therapy have either used charge data (excluding noncardiac charges) (), assumed a fixed ratio between costs and charges () or assumed a fixed unit price per procedure (). To the extent that costs and charges generally track together (), the hospital-based costs of AMI management with t-PA are most likely somewhat higher than those for PTCA, although the absolute differences would be less than the $3,436 per patient found in this study.
To the hospital balance sheet, costs are only relevant in relation to reimbursements. In this regard, even if PTCA and t-PA have similar hospital costs, differing reimbursement may determine whether a profit or loss is realized. For example, as reported by Mark et al. in 1995 (), the Medicare diagnosis-related group (DRG) reimbursement for an uncomplicated myocardial infarction with or without cardiac catheterization (DRG 122) in North Carolina was $3,807. If PTCA was performed as part of the admission, reimbursement increased to $6,635 (DRG 112), and if bypass surgery was performed reimbursement was $19,092 (DRG 106). Based on data from the randomized PTCA–thrombolysis trials ([1–3]), in the primary PTCA group, PTCA alone is performed in 85% of patients, bypass surgery is performed with or without PTCA in 10% and 5% are treated with catheterization only. In the thrombolytic therapy group, 60% are treated with thrombolysis with or without catheterization, 30% undergo PTCA and 10% undergo bypass surgery. It can then be calculated based on the North Carolina reimbursement data that the average hospital reimbursement in a pure Medicare population (assuming other factors are equal) would be $7,739 per patient after a primary PTCA strategy versus $6,184 after thrombolytic therapy—a $1,555 per patient difference. The magnitude of this difference may be even greater in other states with higher relative reimbursement. In Michigan, for example, where the reimbursements for DRG 112 and 122 are $11,090 and $6,617, respectively, a primary PTCA approach would result in $2,732 more reimbursement per patient than thrombolytic therapy.
3.4 Strategies to further reduce AMI costs
Costs may further be reduced by earlier patient discharge. In 1991, the mean hospital stay after AMI in the United States was 9.5 days (). In comparison, the mean time to discharge was 7.5 days after PTCA compared with 8.4 days after thrombolysis in the PAMI trial (). Earlier discharge after thrombolysis is often precluded by the frequent and unpredictable occurrence of spontaneous recurrent ischemia within the first week after lytic-mediated reperfusion ([7, 18]). Previous studies have shown that discharge on day 3 or 4 may be feasible after thrombolytic therapy in ∼18% to 30% of patients, but their identification requires either routine cardiac catheterization or predischarge exercise testing ([19, 20]), the costs of which would tend to offset the savings from the early discharge. In contrast, in the PAMI-2 trial, in which primary PTCA was performed in 1,100 patients, ∼50% of the study group was prospectively identified from readily obtainable clinical and angiographic variables. These patients could be managed after PTCA without the coronary care unit, and a day 3 discharge strategy was proven to be safe without noninvasive predischarge studies, resulting in significant cost savings ().
3.5 Implications of the present study
The significance of these findings is likely to vary according to the perspective of the particular payor and payee. The reduced hospital charges and greater reimbursements associated with primary PTCA are likely to be attractive to hospital administrators who do not have to pay physician bills. Third-party purchasers of health care are generally presented hospital chargedata (not costs), from which payments are then negotiated. Depending on the particular insurance vehicle (private pay vs. third party vs. preferred physician organization [PPO] vs. health maintenance organization vs. DRG based), the patient’s bill may or may not be reduced to reflect the lower payor and hospital charges after PTCA. Professional fees are arbitrary and have little relation with reimbursement. Calculating true societal costs is extremely complex and must take into account not only in-hospital direct costs and induced late costs such as readmission and repeat catheterization, but also factors such as work status and productivity, which were not considered in the present study ().
Perhaps more important than these cost implications is the efficacy analysis. The data from this trial and the other randomized studies suggest that if patients with AMI present at centers with skilled PTCA operators, primary PTCA can be expected to save lives and lower the incidence of nonfatal reinfarction and stroke compared with treatment with thrombolytic therapy. As primary PTCA results in comparable or lower consumption of health care resources compared with thrombolytic reperfusion, PTCA is a therapy that society can afford and should prefer. The major issue that then arises is how to make this therapy more widely available in a cost-effective manner to patients presenting at hospitals without interventional facilities, whether by altering ambulance triage strategies or investing in new infrastructure.
- acute myocardial infarction
- diagnosis-related group
- Primary Angioplasty in Myocardial Infarction
- percutaneous transluminal coronary angioplasty
- tissue-type plasminogen activator
- Thrombolysis in Myocardial Infarction
- The American College of Cardiology
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- Grines CL,
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