A Cost-Effective Analysis of Primary Coronary Angioplasty Versus Thrombolysis for

Acute Myocardial Infarction Menko Jan de Boer, MD, Ben A. van Hout, PhD, Ay Lee Liem, MD,

Harry Suryapranata, MD, Jan C.A. Hoorntje, MD, and Felix Ziilstra, MD

I n the Zwolle trial, patients with acute myocardial in- farction were randomly assigned to undergo primary coronary angioplasty or to receive intravenous strepto- kinase. A higher patency rate of the infarct-related ves- sel, smaller infarct size, preserved left ventricular func- tion, less recurrent ischemia, and a reduction in hospital mortality were observed in patients assigned to angio- plasty compared with those treated with intravenous streptokinase.1-3 Another multicenter trial conlirmed these findings.4 However, facilities for primary coronary angioplasty are restricted or not widely available, and the costs of the initial procedure are considerably higher than for thrombolytic therapy. Still, the higher initial costs may be acceptable when balanced against the addition- al benefits and when account is taken of the potential savings. The present study addresses the balance be- tween costs and effects during the first year after initial treatment. The calculation of costs is based on total med- ical costs, including all hospital admissions, additional procedures, and other medical events. Effects are defined as survival without recurrent myocardial infarction, stroke, or additional revascularization procedures.

. . . The study included 301 patients aged ~76 years with

signs of acute myocardial infarction, without contra- indications for thrombolysis, and who presented within 6 hours after onset of symptoms. If there were signs of ongoing ischemia, patients could be included up to 24 hours. After patients gave informed consent, they were randomly assigned to undergo primary angioplasty or to receive treatment with streptokinase, 1.5 million units intravenously in 1 hour. Patients assigned to coronary an- gioplasty were immediately transported to the catheter- ization laboratory and underwent coronary angiography. If the coronary anatomy was deemed suitable for angio- plasty, this procedure was performed immediately using standard techniques.

The question of efficiency was addressed by way of a cost-effectiveness ratio, the difference in costs in the numerator, and the difference in effects in the denomi- nator. The estimates of costs concern the direct medical costs. They were estimated by multiplying volumes with estimates of unit costs. The volumes concern hospital days (distinguishing between normal, coronary, and post- operative intensive care), procedures, and medication

From the Department of Cardiology, Ziekenhuis de Weezenlanden, Zwolle, the Netherlands, and the Institute for Medical Technoloav Assessment, Erasmus University, Rotterdam, the Netherlands. Dr. & Boers address is: Deoartment of Cardioloav. The Weezenlanden Hospital, Groot Wezehland 20, 801 1 JW ?&olle, The Netherlands. Manuscript received February 16, 1995; revised manuscript received and accepted July 14, 1995.

830 THE AMERICAN JOURNAL OF CARDIOLOGY@ VOL. 76

(including the thrombolytic drugs given). All volumes were registered during the initial admission, during read- missions, and during visits to the outpatient clinic. By general survey of patients (mostly by telephone inter- view) and of the referring physicians, readmissions to other hospitals could be traced and these data were added to the database. All patients were scheduled for follow- up angiography after 3 months, and the costs of this pro- cedure were included in the calculations. Data were col- lected for 12 to 14 months of follow-up after the index myocardial infarction. Effects were measured in terms of event-free survival after 1 year. Events in survivors include recurrent myocardial infarction and stroke. Coro- nary angioplasty or coronary bypass surgery during fol- low-up were included because of their effects on the cost- effectiveness ratio. Information about mortality, mor- bidity, and functional status was gathered during visits to our outpatient clinic and by telephone interview with referring physicians.

Functional status was defined as follows: class 1, no symptoms like dyspnea or angina during daily life or with exercise; class 2, symptoms only with strenuous exercise; class 3, symptoms with moderate exercise; and

TABLE I Follow-Up Data at One Year

Angioplasty Streptokinase (n = 152) (n = 149) p Value

F yctional status (class) 120 (79) 93 (62)

2 23 (151 34 (23)

3+4 2 (11 9 I61 Deceased 7 (51 13 A 0.15

Trend analysis 0.0026* Days olive (all patients) 353 335 0.51

Anterior wall infarct 339 321 0.61 Nonanterior wall infarct 365 345 0.50

Medication at 1 year n= 145 n- 136 Aspirin 121 (83) 109 (80) 0.47 Warforin 16 (1 1) 23 (17) 0.15 Nitrates 12 PI 25 (18) 0.012* p blocker 34 (23) 37 (27) 0.47 Calcium blocker 42 (29) 32 (24) 0.30 Diuretics 13 (91 22 (16) 0.067 Angiotensinconverting 32 (21) 42 (31) 0.09

enzyme inhibitors Antiarrhythmic drugs 9 (61 12 (91 0.40 Cholesterol-lowering drugs 4 (31 5 (4) 0.74

Medication (aspirin excluded) 0 52 (36) 32 (24) 1 61 (42) 49 (36) r2 32 (22) 55 (40)

Trend analysis 0.001*

*Significant. See text for definition of functional status. Values are expressed OJ number of patients w).

OCTOBER 15, 1995

class 4, inability to perform any exer- cise without symptoms or symptoms at rest.

Unit costs for procedures and hos- pital days were calculated on the basis of hospital administration data of 1992. They included the professional charges and were corrected for the costs of pro- cedures during the night or the week- end. All costs are expressed in US dol- lars using the 1992 exchange rate for Dutch guilders (Dfl). Costs applied for diagnostic catheterization were Dfl 1,500 ($945), for angioplasty Dfl8,OOO ($5,040), for coronary bypass surgery Dfl 18,000 ($11,340), for 1 day in the coronary care unit Dfl 1,550 ($980), for 1 day in the postoperative intensive care unit Dfl2,250 ($1,420), and for 1 day on a general ward Dfl500 ($315).5 Costs for streptokinase and tissue plasminogen activator were $250 and $1,260, respectively. Coronary angiog- raphy was considered part of the an- gioplasty procedure only if it was per- formed in the same session. All costs were recorded and analyzed according to the intention-to-treat principle.

r TABLE II Total Costs During the First Year Angioplasty Streptokinase (n = 152) (n = 149) p Value

Days in CCU (first admission) 3 (2-4) 3 (3-5)

I 2ocm ltmo 1

us

<

p

0,

nrobabilitv that the inner ellinse includes the true mar-

1m

14ocm

loo00 I First admission 3 4 5 6 7 8 9 10 11 12 Montn

12ooO

-o- Angioplasty

- - + - Streptokinase <

FIGURE 1. Total cumulative costs during the first patient, in&din in-hospital costs and costs of

ear per

treatment in bo 18 J armacologic

treatment arms.

lower for patients assigned to angioplasty, namely $659.60 versus $854.30 for the streptokinase patients (p = 0.01).

In-hospital costs and costs during follow-up are list- ed in Table II together with the procedures performed. In Figure 1, the cumulative costs (in-hospital costs and costs of medication) during the tirst year are depicted. After 1 year the total costs per patient in both treatment groups are almost the same (Table II). The efficiency of both treatment modalities can be addressed by putting forward the average costs per event-free survivor. The cost-effectiveness ratios were $25,431 for patients assigned to angioplasty treatment and $36,798 for those assigned to streptokinase therapy. The marginal cost- effectiveness ratio (defined as additional costs per addi- tional event-free survivor) was estimated at $3,010. The reliability of this estimate is indicated in Figure 2 where change in costs and change in effects are depicted as a bivariate normal distribution. This figure shows that the

ginal co&effectiveness ratio is 5%, whereas the proba- bility that it lies within the outer ellipse is 95%. Since the 95% confidence ellipse lies completely below the line indicating the cost-effectiveness ratio of streptokinase therapy, it may be concluded that the probability that treatment with primary angioplasty is more cost-effec- tive than treatment with streptokinase is >95% (calcula- tions show that this probability is even >99%, thus rep- resenting a p value ~0.01). Furthermore, changing all unit cost estimates with 20% did not affect the baseline conclusion that treatment with angioplasty is more cost- effective than treatment with streptokinase.

. . . Previously, it was demonstrated that the combination

of thrombolytic therapy and immediate coronary angio- plasty has no additional clinical benefit above stand- alone thrombolytic therapy. 7*8 Until recently, however, it was unclear if coronary angioplasty would be effective as a stand-alone procedure. Furthermore, the cost-effec- tiveness of this therapy was only a subject for debate in _ 1 report, concluding mat angioplasty was not more ex- pensive than thrombolytic therapy? In this study, we ex- amined resource consumption, the actual costs, and func- tional status in 301 patients admitted for acute myo- cardial infarction, randomly assigned to treatment with primary coronary angioplasty or intravenous streptoki- nase during the first year. Knowledge of coronary anato- my, obtained early in the angioplasty-assigned patient group, will certainly influence the number of revascu- larization procedures during the in-hospital stay. How- ever, it may also shorten the in-hospital stay consider- ably, although in our study this was rather long in both patient groups (partly due to study purposes). On the oth- er hand, if recurrent ischemia is encountered more fre- quently in thrombolysis-treated patients, this will in- crease the incidence of readmissions and revasculariza- tion procedures in this group during follow-up.

The better functional status of the angioplasty- assigned patients in the present study, together with low-

Primary Angioplasty vs Streptokinase differences in costs and effects

loooo PTCA less PTCAmors 8000 1 effective and effactive but

v) more more 3i

8000 ) 8

4000 I expensive expensive 1 c 2000 1 .- E

0' + p10.95

t? -2000

g 4000 PTCA less PTCAmora / fi -8000, bTsf;;g

effective

-8000 ' costs and saving

-10000 1

COStS

-100% -80% 80% 40% -20% 0% 20% 40% 80% 80% 100%

Difference in event-free survival

FIGURE 2. Bivariate normal distrib- ution of costs and effects compar- ing primary coronary angioplasty and streptokinase treatment for acute myocardial infarction. A 95% confidence ellipse (i.e., a simultane- ous confidence region for both costs and effects) is calculated. Dif- ferences in effects b-axis] and costs (y-axis) are presented. The line indicated by the arrow represents the cosbdfectiveness ratio (C/E- ratio) line of streptokinase therap PTCA = percutaneous translumina T coronary angioplasty.

832 THE AMERICAN JOURNAL OF CARDIOLOGY@ VOL. 76 OCTOBER 15, 1995

er consumption of pharmacologic and other sources, compensated for the higher costs on first admission asso- ciated with primary angioplasty. Because of the better clinical status at 1 year and the better left ventricular function and coronary anatomy than that in patients treat- ed with intravenous streptokinase, it may be expected that primary coronary angioplasty will have a more pro- nounced beneficial effect on health care costs in the fol- lowing years, in favor of the angioplasty-treated patients.

Our study was conducted in a hospital in the Nether- lands with the preexisting infrastructure for interven- tional cardiology (including a 24-hour cardiosurgical covering). It is unrealistic to assume that all patients pre- senting with myocardial infarction can be treated with primary coronary angioplasty because of limited avail- ability and the enormous logistic burden for hospitals, doctors, and ancillary personnel. Furthermore, these data are not necessarily transferable to community hospitals without these facilities or to other countries with differ- ent health care systems. The results of this study may help to encourage introduction of primary coronary an- gioplasty as a treatment modality for patients with acute myocardial infarction in hospitals with existing inter- ventional cardiology programs.

The present study indicates that primary coro- nary angioplasty is effective with regard to mortali- ty, morbidity, and functional status in patients with acute myocardial infarction. The concern that this new approach is far more expensive than conser- vative thrombolytic therapy was not confirmed.

Acknowledgment: We are indebted to Professor Maarten L. Simoons, Thoraxcenter, Rotterdam, for his valuable advice and support during the completion of this study.

1. Zijlstra F, de Boer MJ, Hoomtje JCA, Reiffers S, Reiber JHC, Suryapranata H. A comparison of immediate comnaty angioplasty with intravenous streptokinase in acute myccardial infarction. N Engl J Med 1993;328:680-684. 2. de Boer MJ, Hoomtje JCA, Otterwnger JP, Reiffers S, Suryapranata H, Zijlstra F. Immediate coronary angioplasty versus intravenous streptokinase in acute myo- cardial infarction: left ventricular ejection fraction, hospital mortality and reinfarc- tion. JAm Coil Cardiol 1994;23:1~1008. 3. de Boer MJ, Suryapranata H, Hoomtje JCA. Reiffers S, Liem AL, Miedema K, Hermens WT, van den Brand MJBM, Zijlstra F. Limitation of infarct size and preservation of left ventricular function after primary coronary angioplasty com- pared with intravenous streptokinase in acute myocardial infarction. Circulation 1994;90:753-761. 4. Gtines CL, Browne KF, Marco J, Rothbaum D, Stone GW, OKeefe J, Overlie P, Donahue B, Chelliah N, Timmis GC, Vlietstra RE, Strzelecki M, Fuchrowicz- Ochocki S, ONeill WW, for the Primary Angioplasty in Myocardial Infarction Study group. A comparison of immediate angioplasty with thmmbolytic therapy for acute myocardial infarction. N Engl J Med 1993;328:673-679, 5. Hilgeman CN, Koopmanschap MA, Rutten FFH. Kosten van intensieve zorg in Nederland. Ned Tijdschr Geneeskd 1994;138:2252-2256. 6. van Hoot BA, Al MJ, Gordon GS, Rotten FFH. Costs, effects and C/E-ratios alongside a clinical trial. Health Econ 1994:3:309-319. 7. Simoons ML, Arnold AER, Betriu A, de Bono DP, Co1 J, Dougherty FC, Von Essen R, Lambertz H, Lubsen J, Meier B, Michel PL, Raynaud P, Rutsch W, Sanz GA, Schmidt W, Sermys PW, Thery C, Uebis R, Vahanian A, van de Werf F. Willems GM, Wood D, Verstraete M. Thrombolysis with tissue plasminogen acti- vator in acute myocardial infarction: no additional benefit from immediate percu- taneous coronary angioplasty. Lancer 1988;1:197-203. 8. TIMI Research Group. Immediate vs delayed catheterization and angioplasty fol- lowing thrombolytic therapy for acute myocardial infarction. TIMI 2A results. JAMA 1988;260:2849-2858. 9. Gibbons RJ, Holmes DR, Reeder GS, Bayley KR. Hopfenspirger MR, Gersh BJ. Immediate angioplasty compared with the administration of a thrombolytic agent followed by conservative treatment for myocardial infarction. N Engl .I Med 1993; 328:685-691.

Role of lransthoracic, lranseso ha lransgastric Two-Dimensional an % f

eal, and Co or Doppler

Echocardiography in the Evaluation of Mechanical Complications of Acute Myocardial Infarction

Fabio Chirillo, MD, Antonio Cavarzerani, MD, Paolo Ius, MD, Oscar Totis, MD, Andrea Bruni, MD, Carlo Valfr6, MD, and Paolo Stritoni, MD

1111 echanical complications of acute myocardial in- farction (AMI) include acute mitral regurgitation and myocardial rupture. Ruptures of the free ventricular wall, ventricular septum, and papillary muscles are usu- ally catastrophic and require prompt recognition and sur- gical repair. Acute free wail rupture is usually lethal, except when rupture is contained by the pericardium with pseudoaneurysm formation. However, pseudoaneurysms have a greater tendency than true aneurysms to rupture? making the differential diagnosis essential for adequate management of patients. 3,4 Transthoracic echocardiog- raphy is considered the first choice for a bedside diag- nosis in all mechanical complications of AMI.5-8 In crit-

From the Department of Cardiology and Cardiovascular Sur Regional Hospital, Treviso, Italy. Dr. Chirillos address is: Car cl

cry, 1010

gia, Ospedale Regionale, 3 1 100 Treviso, Italy. Manuscript received March 9, 1995; revised manuscript received and accepted July 13, 1995.

ically ill patients, acquisition of optimal precordial im- ages is often disturbed by mechanical ventilation, obe- sity, inability to roll to the left lateral decubitus, chest, or abdominal tubes. Transesophageal echocardiography (TEE) may circumvent the technical limitations of trans- thoracic echocardiography and may provide superior im- age quality. This study evaluates the utility of TEE in prompt recognition and adequate management of pa- tients with mechanical complications of AMI.

. . . The study group consisted of 22 consecutive patients

(17 men and 5 women; mean age 64 f 7 years) with mechanical complications of AMI. Thirteen patients had inferior, 7 had posterolateral, and 2 apical AMI. The clin- ical presentation of mechanical complications occurred within 72 hours of AM1 in 13 patients (6 cardiogenic shock, 5 pulmonary edema, and 2 syncope); and from 4 to 15 days in 9 patients (congestive heart failure). All

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