Mortality of women with ST-segment elevation myocardial infarction and cardiogenic shock – results from the PL-ACS registry

Introduction

Cardiogenic shock (CS) complicates approximately 4.2–7.7% of ST-segment elevation myocardial infarctions (STEMI) and results in a very high in-hospital mortality rate ranging from 47% to 70%. The STEMI patients aged 65 or more, with left ventricular ejection fraction (EF) < 35%, elevated creatinine kinase activity, diabetes or impaired fasting glucose, a history of prior myocardial infarction or multivessel coronary artery disease are prone to CS development. The risk of shock is also higher in female patients with history of stroke, heart failure and atherosclerosis of lower extremities [1]. The history of cardiac arrest and neurological defects as well as no reperfusion therapy also affect the prognosis. The main cause of CS in the early hours of STEMI is acute left ventricular failure resulting from a massive necrosis or some combination of a moderate necrosis and muscle freezing in the adjacent areas. Mechanical complications of MI as well as other rare cause are also reported [2]. The SHOCK trial clearly showed benefits from the use of an early revascularization strategy. This effect was observed only in patients below 75 years of age [3, 4]. It has become a source of controversy over the optimal treatment of elderly patients. Dzavik et al. reported that in patients over 75 years the in-hospital mortality was 48% in those who underwent early revascularization vs. 81% in the conservative treatment group (p = 0.003) [5]. Dauerman et al. reported lower mortality in patients treated invasively compared to those treated conservatively, but this effect also affected patients aged 75 years or more [6, 7]. Similar conclusions were drawn from the Polish Registry of Acute Coronary Syndromes (PL-ACS). The mortality was lower in patients with CS treated with percutaneous coronary intervention (PCI) versus conservative treatment (54.6% vs. 69.9%, p < 0.001) [8]. In addition, between 2003 and 2009 the improvement in STEMI patients’ prognosis resulted from the extent of revascularization techniques, improved logistics, and the efficiency of drug therapy [9], especially abciximab [10]. The SHOCK trial showed that survival was not related to gender, diabetes, ST-segment elevation index, right heart catheterization, pulmonary capillary wedge pressure, use of intraaortic balloon pump (IABP), thrombolysis, the use of glycoprotein IIb/IIIa inhibitors, inotropes and vasopressors, or a history of prior MI, PCI and coronary artery bypass grafting (CABG) [11]. Gender-related differences are well elucidated in STEMI patients, but data on patients with CS are scarce and do not indicate the cause-effect relationship. There have been no proposals on the improvement in prognosis in women with CS complicating STEMI. In the present study gender- and age-related issues in the management of cardiogenic shock were studied and possible improvement in prognosis in the female group is discussed.

Material and methods

Data were derived from the Polish Registry of Acute Coronary Syndromes (PL-ACS). The basic principles of our registry have been reported previously and are available on-line [8]. Briefly, this is an ongoing, nationwide, multicenter, prospective, observational study of all patients with acute coronary syndromes. The study group was extracted from a population of 57 400 consecutive STEMI patients included between May 2005 and November 2008 and followed up until January 2010. A total of 3589 (6.3%) patients were included in the final analysis. The inclusion criteria were STEMI and CS defined as a systolic blood pressure of less than 90 mm Hg for at least 30 min secondary to myocardial dysfunction.

Statistical analysis

The continuous parameters are expressed as mean ± standard deviation or median and interquartile range, depending on the normality of data distribution. The significance of differences between means was tested using Student’s t test or unpaired ANOVA rank test, Kruskal-Wallis and Mann-Whitney or 2 test as appropriate. Mortality was analyzed using the Kaplan-Meier method, and the log-rank test. Multivariate analysis of factors influencing mortality was performed by the Cox proportional hazard method. A p-value ≤ 0.05 was considered significant (two-sided). Calculations and statistical analyses were performed using Statistica PL version 6.1 (StatSoft, Inc.).

Results

Baseline characteristics

Women were older than men, more of them were over 65 years of age, and more women than men had arterial hypertension, diabetes and obesity. Women less frequently than men had a history of myocardial infarction, coronary angioplasty and smoking. Initial cardiac arrest affected more men than women, while it occurred more commonly during the in-hospital course in the female group. Women more frequently had atrial fibrillation. Fewer women than men were admitted during the first 2 h of the chest pain, and more women than men were admitted to hospital after 12 h from the symptom onset (Table 1).

Treatment strategy

Women were treated conservatively more frequently than men. Coronary angiography, PCI and CABG were performed less frequently in women. In women the revascularization strategy was applied after 12 h more often (p = 0.046). Fewer women received IABP. There were no differences in in-hospital complications. Women received less glycoprotein IIb/IIIa inhibitors and clopidogrel. The increased use of insulin in women was observed (Table 2). There were no differences in the invasive treatment according to age groups except in women older than 80 (Table 3).

Mortality

In-hospital, 30-day, and 12-month mortality was higher in women with CS than in men with CS (Table 4). In age subgroups there were no differences in mortality between males and females (Table 5). In the multivariable analysis adjusted for age and cardiovascular risk factors female sex did not influence mortality (Table 6).

Discussion

The gender-related differences in coronary heart disease are undeniable. They include age (women are older), risk factors (diabetes, oral contraceptives and hormone replacement therapy) [12], symptoms [13, 14], delay in medical interventions including revascularization [15], more frequent complications [16], occurrence of CS, increased mortality associated with angioplasty [17], worse long-term results of late revascularization [18–20] and worse clinical outcomes of CABG [17]. These differences can also be seen in the etiology, course and prognosis of women with STEMI complicated by CS [21]. In ongoing studies in recent decades gender-related issues in prognosis and treatment strategies were analyzed, but with no comment on CS [22–25]. Many studies have shown that poor clinical outcomes in women are related to suboptimal treatment [26–29]. Conversely, several lines of evidence indicate that guidelines-compliant treatment in women and men results in significant improvements in outcomes [30]. It is known that a delay in the application of invasive treatment significantly worsens the prognosis of patients with STEMI [31]. All studies cited above, and the study of (S)MASH, confirmed the effectiveness of invasive therapy and the improvement in prognosis of patients with STEMI [32]. The complications profile was similar to other reports [33]. In the present study women were less likely to undergo PCI, and significantly fewer women underwent coronary stenting during PCI. There were also noted more than 2 h PCI delay and significantly less frequent administration of GP IIb/IIIa inhibitors and clopidogrel in the female group. It may be hypothesized that the discrepancy observed resulted in worse prognosis in the female group. In younger patients who underwent a similar therapeutic approach, the outcomes in women were better and were similar to those in men, even though the rate of bleeding complications was higher in the female group.

Conclusions

Women with cardiogenic shock were less likely to receive optimal therapy when compared to men, which resulted in a poor clinical outcome. This should encourage medical professionals to apply advanced therapeutic strategies without gender bias. Only if there are no gender-related discrepancies in the management of patients with cardiogenic shock may the beneficial impact of invasive treatment be fairly assessed and the hypothesis that more guideline-adherent treatment of women results in better outcomes be validated.

Conflict of interest

The authors declare no conflict of interest.

References

1. Goldberg R, Samad N, Yarzebski J, Gurwitz J, Bigelow C, Gore JM. Temporal trends in cardiogenic shock complicating acute myocardial infarction. N Engl J Med 1999; 340: 1162-8.
2. Zachura M, Piątek Ł, Kurzawski J, Janion M. Coronary embolism causing acute myocardial infarction. Review of the literature. Medical Studies 2016; 32: 131-5.
3. Jeger RV, Harkness SM, Ramanathan K, Buller CE, Pfisterer ME, Sleeper LA, Hochman JS. Emergency revascularization in patients with cardiogenic shock on admission: a report from the SHOCK trial and registry. Eur Heart J 2006; 27: 664-70.
4. Webb JG, Sanborn T.A, Sleeper LA, Carere RG, Buller CE, Slater JN, Baran KW, Koller PT, Talley JD, Porway M, Hochman JS. Percutaneous coronary interventions for cardiogenic shock in the SHOCK Trial Registry. Am Heart J 2001; 6: 964-70.
5. Dzavik V, Sleeper LA, Cocke TP, Moscucci M, Saucedo J, Hosat S. Early revascularization is associated with improved survival in elderly patients with acute myocardial infarction complicated by cardiogenic shock, a report from the SHOCK Trail Registry. Eur Heart J 2003; 24: 828-37.
6. Dauerman HL, Goldberg LJ, White K, Gore JM, Sadiq I, Gurfinkel E, Budaj A, Lopez DS, Lopez-Sendom J. Revascularization stenting and outcomes of patients with acute myocardial infarction complicated by cardiogenic shock. Am J Cardiol 2002; 90: 838-42.
7. Avezum A, Makdisse M, Spencer F, Gore JM, Fox KA, Montalescot G, Eagle KA, White K, Mehta RH. Impact of age on management and outcome of acute coronary syndrome; observations from the Global Registry of Acute Coronary Events (GRACE). Am Heart J 2005; 149: 67-73.
8. Poloński L, Gąsior M, Gierlotka M, Kalarus Z, Cieśliński A, Dubiel JS, Gil RJ, Rużyłło W, Trusz-Gluza M, Zembala M, Opolski G. Polish Registry of cute Coronary Syndromes (PL-ACS). Clinical characteristic, treatment and prognosis in patients with acute coronary syndromes in Poland. Kardiol Pol 2007; 65: 861-72.
9. Poloński L, Gąsior M, Gierlotka M, Wilczek K, Kalarus Z, Dubiel J, Rużyłło W, Banasiak W, Opolski G, Zembala M. What has changed in the treatment of ST-segment elevation myocardial infarction in Poland in 2003-2009? Data from the Polish Registry of Acute Coronary Syndromes (PL-ACS). Kardiol Pol 2011; 69: 1109-18.
10. Chan AW, Chew DP, Bhatt DL, Moliterno DJ, Topol EJ, Ellis SG. Long term mortality benefit with the combination of stents and abciximab for cardiogenic shock complicating acute myocardial infarction. Am J Cardiol 2002; 89: 132-6.
11. Webb JG, Sanborn TA, Sleeper LA, Lowe AM, White HD, Carere RG, Buller CE, Wong SC, Boland J, Dzavik V, Porway M, Pate G, Bergman G, Hochman JS. Percutaneous coronary intervention for cardiogenic shock in the SHOCK Trial Registry. Am Heart J 2001; 141: 964-70.
12. Gabet A, Chatignoux E, Ducimetière P, Danchin N, Olié V.Differential trends in myocardial infarction mortality over 1975-2010 in France according to gender: an age-period-cohort analysis. Int J Cardiol 2016; 223: 660-4.
13. Janion-Sadowska A, Sadowski M, Janion M. A female pattern of ischaemic heart disease – a new look at an old problem. Przegl Lek 2012; 69: 76-9.
14. Harshida P, Rosengren A, Ekman I. Symptoms in acute coronary syndromes: does sex make a difference? Am Heart J 2004; 148: 27-33.
15. Sadowski M, Janion-Sadowska A, Kurzawski J, Sielski J, Zandecki J, Janion M, Poloński L. Is the time between onset of pain and restoration of patency of infarct-related artery shortened in patients with myocardial infarction? The effects of the Kielce Region System for Optimal Management of Acute Myocardial Infarction. Studia Medyczne 2014; 30: 135-40.
16. Janion M, Polewczyk A, Sielski J, Szczukocka A. Genderrelated differences in the course of coronary heart disease in women. Kardiol Pol 2006; 64: 628-36.
17. Janion M. Underestimated coronary risk in young women. Kardiol Pol 2010; 68: 1038-9.
18. Reynolds HR, Łoboz-Grudzień K, Rużyłło W, Forman SA, Tamis-Holland JE, Steg PG, Mark DB, Pearte CA, Carvalho AC, Sapko G, Liu L, Lamas GA, Kruk M, Hochman JS. Relationships of female sex to outcomes after myocardial infarction with persistent total occlusion of the infarct artery: analysis of Occluded Artery Trial(OAT). Am Heart J 2012; 163: 462-9.
19. Janion M, Polewczyk A, Gąsior M, Poloński L. Progress in the management of ST-segment elevation myocardial infarction during economic transition in Poland between 1992 and 2006. Int J Cardiol 2009; 135: 253-65.
20. Sadowski M, Gąsior M, Gierlotka M, Janion M, Poloński L. Clinical characteristics of Polish women with ST-segment elevation myocardial infarction. Kardiol Pol 2010; 68: 627-34.
21. Łoboz-Grudzień K, Jaroch J. Women with acute coronary syndromes have worse prognosis: why? The need to reduce treatment-seeking delay. Cardiol J 2011; 18: 219-21.
22. Sadowski M, Gąsior M, Gierlotka M, Janion M, Poloński L. Gender-related differences in mortality after ST-segment elevation myocardial infarction: a large multicentre national registry. EuroIntervention 2011; 6: 1068-72.
23. Rosengren A, Wallentin L, Gitt AK, Behar S, Battler A, Hasdai D. Sex, age and clinical presentation of acute coronary syndrome. Eur Heart J 2004; 25: 663-70.
24. Sederholm Lawesson S, Stenestrand U, Lagerqvist B, Wallentin L, Swahn E. Gender prospective on risk factors, coronary lesions and long-term outcome in young patients with ST-elevation myocardial infarction. Heart 2010; 96: 453-9.
25. Rosengren A, Spetz CL, Kӧster M, Hammar N, Albrektsson L, Rosen M. Sex differences in survival after myocardial infarction in Sweden. Data from the Swedish National Acute Myocardial Infarction register. N Engl J Med 2001; 22: 314-22.
26. Heer T, Gitt AK, Juenger C, Schiele R, Wienbergen H, Towae F, Gottwitz M, Zahn R, Zeymer U, Senges J; ACOS Investigators. Gender differences in acute non-ST segment elevation myocardial infarction. Am J Cardiol 2006; 98: 160-6.
27. Moriel M, Tzivoni D, Behar S, Zahger D, Hod H, Hasdai D, Sandach A. Contemporary treatment and adherence to guidelines in women and men with acute coronary syndromes. Int J Cardiol 2008; 131: 97-104.
28. Simon T, Krause MM, Combou JP, Hanania G, Gueret P, Lablanche JM, Blanchard D, Genes N, Danchin N. Impact of age and gender on in-hospital and late mortality after acute myocardial infarction: increased early risk in younger women: results from French nation-wide USIC registries. Eur Heart J 2006; 27: 1282-8.
29. Carruthers KF, Dabbous OH, Flatcher MD, Starkey I, Jacob A, MacLead D, Fox KAA. Contemporary management of acute coronary syndromes: does the practice match the evidence? The Global Registry of Acute Coronary Events (GRACE). Heart 2005; 91: 290-8.
30. Kawecki D, Tomasik AR, Nowalany-Kozielska E, Morawiec B, Jacheć W, Wojciechowska C, Rybczyk R, Milejski W, Świtalska-Janiczek I, Przywara-Chowaniec B. Analysis of myocardial infarction time course in women compared with men in Upper Silesia population in 30-days follow-up. Int Heart J 2009; 9: 711-9.
31. Brodie BR, Hansen C, Stuckey TD, Richter S, Versteeg DS, Gupta N, Downey WE, Pulsipher M. Door-to-balloon time with primary percutaneous coronary intervention for acute myocardial infarction: impact late cardiac mortality in high-risk patients and patients presenting early after the onset of symptoms. J Am Coll Cardiol 2006; 47: 289-93.
32. Argulian E, Patel AD, Abramson JL, Kulkarni A, Champney K, Palmer S, Wientraub B, Wenger NK, Vaccarino V. Gender differences in short-term cardiovascular outcomes after percutaneous coronary interventions. Am J Cardiol 2006; 98: 48-53.
33. Lindholm MG, Kober L, Boesgaard S, Torp-Pedersen C, Ardershvile J. Cardiogenic shock complicating acute myocardial infarction: prognostic impact of early and late shock development. Eur Heart J 2003; 24: 258-65.

Addresss for correspondence:

Marcin Sadowski MD
Department of Interventional Cardiology
Świętokrzyskie Cardiology Centre
ul. Grunwaldzka 45, 25-736 Kielce, Poland
Phone: +48 606 906 454
E-mail: emsad@o2.pl