Gender-Based Differences in Long-Term Outcome After ST-Elevation Myocardial Infarction in Patients Treated with Percutaneous Coronary Intervention

Abstract

Background:

In the era of fibrinolysis, women suffered from higher early and late mortality rates than men after acute ST-elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention (PCI) has been determined to be the most effective therapy strategy in STEMI. It is not clear if female gender is an independent predictor of a worse long-term prognosis among patients who were systematically treated with PCI. We, therefore, examined the effect of PCI on long-term outcome between women and men.

Methods:

Between 1999 and 2001, 500 consecutive patients at the Wuppertal Heart Centre were treated with PCI after acute STEMI. A long-term follow-up (up to 7 years) was achieved in 97% of the patients.

Results:

In comparison to men, women were 7 years older (65 ± 12 vs. 58 ± 11) and had significantly more diabetes mellitus. The time between onset of symptoms and intervention tended to be longer in women than men. There was no difference in 30-day mortality (8.9% vs. 6.6%), cardiac late mortality (3.6% vs. 3.2%), and long-term cardiac overall mortality up to 7 years (12.1% vs. 9.6%). Stepwise regression analysis did not identify female gender as an independent predictor of late mortality. The quality of life was comparable.

Conclusions:

There was no gender-related difference in the long-term outcome if patients were sytematically treated with PCI in STEMI. PCI in STEMI has a long-lasting positive effect in women and should, therefore, be considered the treatment of choice for women with acute myocardial infarction.

Introduction

Gender-related differences in the outcome after acute ST-elevation myocardial infarctions (STEMI) have gained increasing attention over the past decade. Recently published results of a U.S. database with more than 78,000 STEMI patients in 420 U.S. hospitals revealed a worse in-hospital prognosis for women compared with men even after multivariable adjustment.¹ Percutaneous coronary intervention (PCI) or fibrinolysis had been used in these studies as reperfusion therapies. In the fibrinolysis era, studies showed that women have a worse outcome than men after STEMI.^2
–4 PCI is considered to be the gold standard in patients with acute myocardial infarction (MI). Current guidelines of national societies recommend PCI as the first-line therapy in STEMI when infrastructure is suitable and timelines are met.^5
–7 However, < 50% of patients undergo PCI for a variety of reasons.^1,8 If one looks at gender-specific rates of PCI, the percentage of women receiving this kind of therapy in acute MI is lower than the percentage of men. Possible reasons for this are that women are, on average, older and have more coexistent morbidities, a longer delay before medical treatment, and less effort in terms of both diagnosis and therapy than men.⁹

The influence of gender on late mortality after acute MI is still a matter of controversy in cardiology. Another problem with interpreting the findings is that most of the data derive from randomized, controlled trials, which often do not reflect the patients in a real world setting. Melhilli et al.¹⁰ showed that women treated predominantly with PCI after acute MI had a similar short-term prognosis to men. The aim of this study was to investigate if this effect in women is still apparent in terms of a long-term prognosis up to 7 years after treating women with PCI in acute MI compared with men, based on data of a real world setting in a prospective registry.

Materials and Methods

Patients

Between November 1999 and September 2001 in the Wuppertal Heart Centre, 500 consecutive patients were prospectively enrolled into the study. Inclusion criteria were at least two of the following: (1) prolonged typical chest pain > 30 minutes, (2) persistent significant electrocardiographic ST-elevations in two or more contiguous leads or a new left bundle branch block (LBBB) compatible with myocardial ischemia, and (3) an increase in serum creatine phosphokinase (CPK) with a significant muscle brain type (MB) band of > 7%. In addition, onset of symptoms and intervention should have been < 12 hours. Patients without subsequent intervention, that is, with no significant coronary stenosis in the target vessel, were excluded from the study.

PCI

The decision for a stent implantation was up to the examiner. Concomitant medication included acetylsalicylic acid 500 mg by intravenous application and unfractionated heparin by intracoronary application up to activated clotting time of > 300 seconds. Glycoprotein IIb/IIIa antagonists were used facultatively. Patients who had undergone pretreatment with fibrinolysis (facilitated PCI or rescue PCI) were excluded. Patients in cardiogenic shock underwent an extended medical drug therapy and a mechanical device, an intra-aortic balloon pump, was employed.

Follow-up to evaluate long-term outcome

A first clinical reevaluation of patients was performed after 30 days and repeated after 3.9 months. Mortality in the first 30 days and the need for revascularization with either PCI or bypass surgery (CABG) were evaluated. After 3–4 months, a control coronary angiography was planned and was performed in 73% of the patients. Patients were again reevaluated between 5 and 7 years after initial presentation by writing or a telephone interview of the patient or his general practitioner. Follow-up was achieved in 97% of the patients. We evaluated mortality, repeated coronary angiography, revascularization procedures, MI, and symptoms of angina pectoris.

Definitions

“Cardiac mortality” was defined in our study as death due to MI, documented or unexpected sudden cardiac death, or death due to heart failure. “Noncardiac mortality” implemented all other causes of death. The time between onset of symptoms and beginning of the intervention was compared in both groups. “Late mortality” was defined as mortality that occured between 30 days and 7 years after treatment. “Reinfarction” was defined as clinical non ST-elevation myocardial infarction (NSTEMI) or STEMI after the first infarction.

Statistics

A p value < 0.05 was considered statistically significant. Continuous variables are expressed as means ± standard deviation (SD). Differences among qualitative variables were analyzed with a Fisher's exact or chi-square test as appropriate. Quantitative variables were analyzed with either a Wilcoxon signed rank test or a Mann-Whitney U test. Comparison of continuous variables was performed using Student's t test. In a logistic regression analysis, several variables were analyzed to be independent predictors of mortality: age, gender, diabetes, smoking, hypertension, hyperlipoproteinemia, beginning of symptom time to intervention, degree of coronary artery disease (CAD), previous PCI or CABG, localization of the infarction.

Results

Characteristics of patients

Of the 500 patients included in the study, 124 were women (24.8%) and 376 were men (75.2%). Demographic data are shown in Table 1. Mean age for women and men was 65 ± 12 (31–87) and 58 ± 11 (23–94) years, respectively. There were significantly more smokers in the male group (p < 0.001), and a significantly higher percentage of women had diabetes (p < 0.001). The time between onset of symptoms and begin of intervention tended to be longer in women than in men.

Table 1.

Baseline Characteristics of Patients

Characteristic	Women (n = 124)	Men (n = 376)	p value
Age, years ± SD	65 ± 12	58 ± 11	< 0.001
Age > 70 years (%)	27.4	17.8	0.029
Diabetes mellitus (%)	24.2	11.2	< 0.001
Smoker (%)	40.3	67.3	< 0.001
Hypertension (%)	54.8	66.0	0.055
Hyperlipoproteinemia (%)	50.0	47.3	0.682
Family history of coronary disease (%)	17.7	14.9	0.538
Previous PCI (%)	4.0	5.6	0.658
Previous myocardial infarction (%)	8.9	11.7	0.479
Previous bypass surgery (%)	0.8	5.6	0.046
Time symptoms to reperfusion (min)	254 ± 168	230 ± 157	0.099
Less than 6 hours to reperfusion (%)	89.5	89.9	0.960

SD, standard deviation; PCI, percutaneous coronary intervention.

Short-term results

The extent of CAD with regard to affected vessels was similar in both groups (Table 2). The prevalence of cardiogenic shock was 11.3% in the female group and 10.1% in the male group (Table 3). The number of complicated courses after MI, such as cardiopulmonary resuscitation, ventilation, acute renal failure, or multiorgan failure, was similar in both groups and was associated with a diagnosis of cardiogenic shock (Table 3).

Table 2.

Angiographic and Clinical Characteristics

Characteristic	Women (n = 124)	Men (n = 376)	p value
1-vessel disease (%)	54.0	48.1	0.031
2-vessel disease (%)	24.2	27.7	0.523
3-vessel disease (%)	21.8	24.2	0.667
Anterior infarction (%)	41.9	33.2	0.100
TIMI III flow after recanalization (%)	91.9	91.5	0.957
TIMI I/II flow after recanalization (%)	2.4	2.4	0.747
Left ventricular function, acute (%)	59 ± 14	55 ± 14	0.03

TIMI III flow, fully restored flow in the coronary artery; TIMI I/II flow, impaired flow in the coronary artery.

Table 3.

Clinical Characteristics and Complications

Characteristic/complication	Women (n = 124)	Men (n = 376)	p value
Cardiogenic shock (%)	11.3	10.1	0.838
Cardiopulmonary resuscitation (%)	12.9	11.2	0.718
Respiration (%)	7.3	6.6	0.978
Renal failure (%)	1.6	1.3	0.835
Multiorgan failure (%)	0.8	0.5	0.744
Apoplexy (%)	0.0	0.3	0.559
False aneurysm at access site (%)	4.0	2.4	0.519
Hematoma access site (%)	10.5	5.9	0.121

A primary successful reperfusion of the affected target vessel was achieved in 91% of patients in both groups. In the remaining patients, either flow was reduced because of thrombotic clots in the vessel or the vessel could not be recanalized. There were no significant differences between the two groups after the intervention except for bleeding complications at the access site in women. The 30-day mortality clinical reevaluation was performed for all patients (100%), and the results were similar in women and men at 8.9% and 6.6%, respectively (p = 0.529) (Table 4 and Fig. 1).

FIG. 1.

Kaplan-Meier curves, 30-day mortality.

Table 4.

Short-Term and Long-Term Clinical Outcome

Outcome	Women (n = 124)	Men (n = 376)	p value
30-day mortality (%)	8.9	6.6	0.529
30-day mortality without shock (%)	2.4	2.4	0.747
Re-PCI any vessel (%)	27.3	28.8	0.869
Re-PCI infarct vessel (%)	20.9	22.9	0.751
Reinfarction (%)	5.5	7.3	0.701
Bypass surgery (%)	9.7	12.0	0.594
Late mortality (%)	9.7	6.9	0.417
Cardiac late mortality (%)	3.2	3.2	0.783
Cardiac overall mortality (%)	12.1	9.6	0.526

Long-term prognosis

Of the 464 patients who survived the first 30 days, 73% (n = 339) had an elective coronary angiography after 3.9 months. The rate of restenosis of the treated vessel defined as ≥ 50% was the same in both groups (women 36.5% vs. men 29.7%). Of the survivors (n = 464), a long-term follow-up study could be performed in 97% of the patients (n = 450); the follow-up range varied from 4 to 7 years (mean 5.6 years). Direct contact with the surviving patients was possible in 96% via telephone; in 4%, information was obtained via their general practitioners.

In the nonsurvivors, information on mortality was obtained from hospital charts and general practitioners. In both groups, the follow-up study was performed using a structured interview on long-term clinical outcome. A revascularization by PCI was necessary in 27.3% of the women and 28.8% of the men (PCI of infarct vessel, 20.9% of the women and 22.9% of the men). A similar percentage of patients suffered another MI in the follow-up period (women 5.5% vs. men 7.3%). CABG was performed in 9.7% of the women and 12.1% of the men.

Mortality was 9.7% in the group of women and 6.9% in the group of men (p = 0.417) (Table 4 and Fig. 2). Cardiac long-term mortality was not statistically different (p = 0.783) between the groups (women 3.2% vs. men 3.2%). After combining cardiac mortality of the first 30-days and the follow-up period, no difference was seen between the two groups. Using stepwise logistic regression analysis, diabetes mellitus was identified as an independent predictor of mortality (odds ratio [OR] 18.4993, 95% CI 10.02–34.13), but gender was not (OR 0.7716, 95% CI 0.40–1.48). Of the men, 57.5% were free of angina pectoris symptoms compared with 48.5% of the women in the long-term follow-up study (p = 0.756). Chest pain with mild physical activity was reported by 24.7% of the women and 23.6 % of the men, and dyspnea with mild physical activity was stated by 26.8% vs. 20%, respectively. No dyspnea was reported by 48.7% of the women and 44.3% of the men.

FIG. 2.

Kaplan-Meier curves, long-term mortality.

Discussion

This study demonstrates that women with an acute MI have a similar long-term prognosis to men if they are systematically treated by PCI without fibrinolysis as a reperfusion strategy. Total reopening of the infarct vessel was successful in > 90% of the patients. This is a similar percentage to those reported in other PCI studies^9,11,12 and leads to the low 30-day mortality in both groups with respect to gender. In patients without cardiogenic shock, 30-day mortality was 2.5% in both groups and rose to 8.9% in women and 6.6% in men if patients with cardiogenic shock were included. These mortality rates are similar to those in other studies reported in the literature.^10,11,13

Mean follow-up of patients was 5.6 years (4–7 years). In our study, long-term follow-up of the patients could be achieved in 97% of all patients.

The late cardiac mortality rate was low and similar in both groups (women 3.6% vs. men 3.2%). Although the female cohort in the study had a higher proportion of diabetes mellitus and were on average older than men, they appeared to benefit to the same extent as men from PCI after MI. The need for further revascularization either by re-PCI or CABG was the same in both groups. Stepwise logistic regression analysis did not identify female gender as an independent predictor of mortality.

Data from the prefibrinolysis era, such as the Framingham Heart Study, showed a higher short-term and long-term mortality for women.¹⁴ Tofler et al.¹⁵ reported a cumulative mortality rate 48 months after MI of 36% in women and 21% in men. In the era of fibrinolysis, women suffered from a higher early and late mortality rate than men.^16
–18 The GUSTO I study¹⁷ additionally revealed a higher reinfarction rate in women after fibrinolysis. The worse prognosis in women has been explained by older age and more coexistent comorbidities.^19

–24 Additionally, findings from large database studies have indicated that women with acute MI tend to undergo less aggressive hospital management than men; for example, revascularization procedure rates are lower for women than for men, which seems to account for excess mortality.^25
–27

In 2002, Melhilli et al.¹⁰ showed that despite their more advanced age and greater prevalence of diabetes or hypertension, women had similar short-term outcomes 1 year after intervention compared with men if they were treated predominantly by PCI. Our study confirms these findings, and it is especially worth noting that our results suggest that a long-lasting effect of this treatment strategy in terms of comparable late outcome in women and men can be seen.

Several limitations should be acknowledged. The data derive from the experience of a single center and need to be replicated in other centers with the same treatment strategy. The relatively small sample size reduces the power of subset analyses. This observational study reflects only the strategy of the use of primary PCI in patients with STEMI.

Conclusions

We conclude that the systematic use of PCI in STEMI has a long-lasting positive effect in women and should, therefore, be the treatment of choice for women with acute MI.

Footnotes

Disclosure Statement

The authors have no conflicts of interest to report.

References

Jneid

, Fonarow

, Cannon

et al. Sex differences in medical care and early death after acute myocardial infarction. Circulation, 2008; 118:2803–2810.

Woodfield

, Lundergan

, Reiner

. Gender and acute myocardial infarction: Is there a different response to thrombolysis? J Am Coll Cardiol, 1997; 29:35–42.

Weaver

, White

IID

, Wilcox

. Comparisons of characteristics and outcomes among women and men with acute myocardial infarction treated with thrombolytic therapy. JAMA, 1996; 275:777–782.

Maynard

, Every

, Martin

et al. Association of gender and survival in patients with acute myocardial infarction. Arch Intern Med, 1997; 157:1379–1384.

ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction—Executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation, 2004; 110:588–636.

2007 Focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction. A reprort of the ACC/AHA Task Force on Practice Guidelines. Circulation, 2008; 117:296–329.

Task Force on Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation. Eur Heart J, 2008; 29:2909–2945.

Rogers

, Canto

, Lambrew

et al. Temporal trends in the treatment of over 1.5 million patients with myocardial infarction in the U.S. from 1990 through 1999: The National Registry of Myocardial Infarction 1,2 and 3. J Am Coll Cardiol, 2000; 36:2056–2063.

Lansky

, Pietras

, Costa

et al. Gender differences in outcomes after primary angioplasty versus primary stenting with and without abciximab for acute myocardial infarction: Results of the CADILLAC trial. Circulation, 2005; 111:1611–1618.

10.

Mehilli

, Kastrati

, Dirschinger

et al. Sex-based analysis of outcome in patients with acute myocardial infarction treated predominantly with percutaneous coronary intervention. JAMA, 2002; 287:210–215.

11.

Cheng-I

, Kuo-Ho

, Hsueh-Wen

et al. Comparison of baseline characteristics, clinical features, angiographic results, and early outcomes in men vs women with acute myocardial infarction undergoing primary coronary intervention. Chest, 2004; 126:47–53.

12.

Keeley

, Boura

, Grines

. Primary angioplasty versus thrombolytic therapie for acute myocardial infarction: A quantitative review of 23 randomised trials. Lancet, 2003; 361:13–20.

13.

Hannan

, Racz

, Arani

et al. Short- and long-term mortality for patients undergoing primary angioplasty for acute myocardial infarction. J Am Coll Cardiol, 2000; 36:1194–1201.

14.

Kannel

, Sorlie

, McNamara

. Prognosis after myocardial infarction: The Framingham Study. Am J Cardiol, 1979; 44:53–59.

15.

Tofler

, Stone

, Miller

et al. Effect of gender and race on prognosis after myocardial infarction: Adverse prognosis for women, particularly black women. J Am Coll Cardiol, 1987; 9:473–482.

16.

Becker

, Terrin

, Ross

et al. Comparison of clinical outcomes for women and men after acute myocardial infarction. Ann Intern Med, 1994; 120:638–645.

17.

Weaver

, Simes

, Betriu

et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: A quantitative review. JAMA, 1997; 278:2093–2098.

18.

Woodfield

, Lundergan

, Reiner

et al.

Gender and acute myocardial infarction: Is there a different response to thrombolysis?

J Am Coll Cardiol, 1997; 29:35–42.

19.

Dittrich

, Gilpin

, Nicod

et al. Acute myocardial infarction in women: Influence of gender on mortality and prognostic variables. Am J Cardiol, 1988; 62:1–7.

20.

Marx

, Feinstein

. Methodologic sources of inconsistent prognoses for postacute myocardial infarction. Am J Med, 1995; 98:537–550.

21.

Pan

, Cedres

, Liu

et al. Relationship of clinical diabetes and asymptomatic hyperglycemia to risk of coronary heart disease mortality in men and women. Am J Epidemiol, 1986; 123:504–516.

22.

Puletti

, Sorlie

, Curione

et al. Acute myocardial infarction: Sex-related differences in prognosis. Am Heart J, 1984; 108:63–66.

23.

Smith

, Marcus

, Serokman

. Prognosis of patients with diabetes mellitus after acute myocardial infarction. Am J Cardiol, 1984; 54:718–721.

24.

Vaccarino

, Krumholz

, Beckmann

. Sex differences in mortality after myocardial infarction: Is there evidence for increased risk for women? Circulation, 1995; 91:1861–1871.

25.

Landberg

, Wikstrom

, Bostrom

et al. Exploring sex differences in case fatality in acute myocardial infarction or coronary death events in the northern Sweden MONICA Project. J Intern Med, 2002; 251:235–244.

26.

Barakat

, Wilkinson

, Suliman

et al. Acute myocardial infarction in women: Contribution of treatment variables to adverse outcome. Am Heart J, 2000; 140:740–746.

27.

Heer

, Schiele

, Schneider

et al.

Gender differences in acute myocardial infarction in the era of reperfusion (the MITRA Registry)

Am J Cardiol, 2002; 89:511–517.