BRIEF REPORTS

Underutilization of Thrombolytic Therapy in Eligible Women with Acute Myocardial Infarction Charles Maynard, phi& Ralph Althouse, MD, MPH, Manuel Cerqueira, MD, Michele Olsufka, RN, and J. Ward Kennedy, MD

N ew methods for the management of coronary artery disease are almost always evaluated in male patients or in groups of patients who are

predominantly male. l This bias is in part due to the fact that men develop coronary artery disease more frequent- ly and at an earlier age than do women.2 This problem is compounded by the usual practice of excluding elderly patients from therapeutic trials. Most trials of thrombo- lytic therapy for acute myocardial infarction (AMI) have an upper age limit of 70 or 75 years, as was the case in our own triak3 Because thrombolytic therapy has been largely evaluated in men, we have been concerned that once this therapy was demonstrated to be effective, it might be preferentially applied. In this analysis, we at- tempt to specify the role of gender in the eligibility for and use of thrombolytic therapy.

As part of the Western Washington emergency de- partment recombinant tissue plasminogen activator trial, all patients with documented AMI in 8 hospitals in the Seattle-Tacoma metropolitan area were identi- jied.3 From the medical record, patient age, sex, in- clusion and exclusion criteria for the trial, and the use of thrombolytic therapy in general were determined. Information on cardiac catheterization, coronary an- gioplasty and coronary artery surgery was also col-

From the Departments of Medicine and Radiology, University of Washington, Seattle, Washington. Dr. Maynard’s address is: Division of Cardiology, RG-22, University of Washington, Seattle, Washington 98195. Manuscript received February 19, 1991; revised manuscript received and accepted April 12, 1991.

TABLE I Eligibility of Women and Men with Acute Myocardial Infarction for Thrombolytic Therapy

Women (%) Men (%) All (%I (n = 353) (n = 675) (n = 1,078) pValue

Age > 75 years 39 19 26 <0.0001 Nondiagnostic 59 53 55 0.09

electro- cardiogram

Presented 30 27 18 0.71 > 6 hours

Medical contra- 33 32 33 0.78 indication

Eligible for throm- 16 25 22 0.0008 bolytic therapy

Eligible patients 55 78 72 0.0006 receiving throm- bolytic therapy (no. of eligible 55 166 221 pts.)

lected. Exclusion criteria, including age >75 years, time from symptom onset to hospital arrival >6 hours, nondiagnostic electrocardiographic changes, and medical contraindications to thrombolytic thera- py were reviewed in detail as was vital status at the time of hospital discharge. We also attempted to de- termine from the medical record why eligible patients did not receive thrombolytic therapy. In all, 1,028 patients with AMI, including I40 enrolled in the clini- cal trial, comprised the population for this analysis.

Between January 1987 and January 1988, 675 (66%) men and 353 (34%) women with AMI were admitted to the 8 participating hospitals. A higher proportion of women were >75 years; women were also older than men (72 f 9 us 65 f 12 years, p <O.OOOl) (Table I). Of the 221 (21%) patients who were eligible for thrombolytic therapy, men were more often eligible than women. Men and women differed in the reasons for ineligibility (Table I). Multiple rea- sons for ineligibility were noted more often in women than in men (65 us 55%, p = 0.02).

Eligible men received thrombolytic therapy as part of the clinical trial more often (Table I); i.e., only 55% of 55 eligible women received the drug, whereas 78% of 166 eligible men did. It was difficult to determine from the medical record why eligible patients did not receive thrombolytic therapy, since this information was unknown for 41% of these 61 patients. Similar proportions of men and women either refused or were not offered thrombolytic therapy by their physicians. An additional 3 men and 5 women, who were eligible, received thrombolytic therapy outside the trial. In addition, 9 men and 2 women, who were ineligible by study criteria, also had thrombolytic therapy.

The use of diagnostic and reperfusion procedures was also examined. Only 5 angioplasties and 4 surgi- cal revascularizations were performed in the 265 pa-

TABLE II Procedures, Treatments and Hospital Mortality for Patients Aged 5 75 Years

Women (%) Men (%) Event (n = 353) (n = 548) p Value

Cardiac catheterization 39 46 0.08 Thrombolytic therapy 17 26 0.01 Coronary angioplasty 9 8 0.46 Coronary artery surgery 11 13 0.53 Hospital death 10 11 0.89

BRIEF REPORTS 529

tients aged >75 years. Only I patient >75 years was given thrombolytic therapy. Table II displays the use of these procedures inpatients 17.5 years. Although a higher proportion of men underwent cardiac catheter- ization, the difference between men and women was not statistically significant. However, 26% of all men received thrombolytic therapy, whereas only 17% of all women did. Hospital mortality was similar in all men and women (13.3 us 14.2%, p = 0.88) and in men and women aged >7.5 (25.2 us 20.3%,p = 0.34). After adjustment for age, hospital mortality in men and women of all ages remained similar.

It is difficult to explain the underutilization of throm- bolytic therapy in women. It is possible that eligible women were closer in age to the upper limit of 75 years and thus were considered ineligible. However, eligible men and women not treated within the trial had the same mean age of 62 years. It is also plausible that women were treated less aggressively by predominantly male cardiologists. This is unlikely, since similar proportions of men and women underwent cardiac catheterization, cor- onary angioplasty and bypass surgery. Of course, the differential use of thrombolytic therapy may have been due to chance or to confounding variables. This is a

possibility, since we are unaware of other studies that report the underutilization of thrombolytic therapy in women.4,5 However, databases of trials of thrombolytic therapy should be examined to determine if there are gender differences in the use of thrombolytic therapy. Nevertheless, in this study, women were more often ineli- gible for thrombolytic therapy and were less often treated with thrombolytic agents even though eligible for treat- ment.

1. Douglas PS. Gender, cardiology, and optimal medical care. Circulation 1986;74:917-919. 2. Cunningham MA, Lee TH, Cook EF, Brand DA, Rouan GW, Weisberg MC, Goldman L. The effect of gender on the probability of myocardial infarction among emergency department patients with acute chest pain: a report from The Multicenter Chest Pain Study Group. J Gen Infern Med 1989;4:392-398. 3. Althouse R, Maynard C, Cerqueira MD, Olsutlm M, Ritchie JL, Kennedy JW. The Western Washington myocardial infarction registry and emergency depart- ment tissue plasminogen activator treatment trial. Am J Cardiol 1990;66: 1298-1303. 4. Lee TH, Weisberg MC, Brand DA, Rouan GW, Goldman L. Candidates for thrombolysis among emergency room patients with acute cheat pain. Ann Intern Med 1989;110:957-962. 5. Karlson BW, Herlitz J, Edvardsson N, Emanuelsson H, Sjolin M, Hjalmarson A. Eligibility for intravenous thrombolysis in suspected acute myocardial infarc- tion. Circularion 1990;82:1140-1146.

Effects of Luminal Eccentricity on Spontaneous Coronary Vasoconstriction After Successful Percutaneous Transluminal Coronary Angioplasty Tim A. Fischell, MD, and Kurt N. Bausback, MD

0 ver the past several years there has been increas- ing recognition that spontaneous coronary ar- tery vasoconstriction, or spasm, can occur in the

dilated coronary segment after percutaneous translumin- al coronary angioplasty (PTCA). This vasoconstriction after PTCA has been quantitated in clinical studies,‘v2 and has been well described in clinical series and in case reports.3-6 Although the etiology of vasoconstriction af- ter PTCA is not fully understood, several mechanisms have been postulated, including the release of vasoactive substances from aggregating platelets at the site of endo- thelial injury and the release of endothelium-derived constricting factor(s) after balloon trauma.7 Coronary spasm has been demonstrated to be one possible mecha- nism of acute vessel closure after successful PTCA.5y6 Furthermore, clinical studies have suggested a significant correlation between spontaneous or provoked vasospasm From the Division of Cardiovascular Medicine, Stanford University Medical Center, 300 Pasteur Drive, Stanford, California 94305. This report was supported in part by a Clinical Investigator Award (T.A.F.), and grant 1 KO8 HL-02001-01 from the National Institutes of Health, Bethesda, Maryland. Manuscript received March 25, 1991; revised manuscript received and accepted April 25, 199 1.

in the dilated coronary segment with increased restenosis rates after PTCA.8

It has been demonstrated that lesion eccentricity may be a risk factor for acute coronary closure after PTCA.9 The observations that eccentric lesions may have a great- er potential for dynamic changes in caliber in response to vasoactive stimuli1o has led to speculation that vasospasm may be more pronounced after PTCA in eccentric com- pared with concentric lesions, leading to a greater inci- dence of acute closure, and possibly late restenosis. l l,i2 This study was designed to examine whether there is any relationship between angiographically determined lesion eccentricity and the severity of spontaneous vasoconstric- tion early after PTCA in the dilated coronary segment.

Sixteen patients scheduled for elective 1 -vessel PTCA of focal stenoses were prospectively entered into the study after informed consent for both PTCA and the study was obtained. Three of these 16patients had been entered into a previously reported study’ of vasomotion after PTCA. Exclusion criteria included concurrent nitroglycerin therapy, recent myocardial infarction (<2 weeks), length of lesion to be dilated

530 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 68 AUGUST 15, 1991