Both sexes should be treated equally: sex difference in patients with ischemic heart failure undergoing surgical revascularization

We read with the interest the work of Piña et al. (1). STICH trial (2) is the first and for long time remains only randomized trial to compare CABG plus medical therapy for heart failure (HF) versus medical therapy for HF only in patients with severe left ventricular dysfunction (EF ≤35%, for inclusion criteria see below). Data for this randomised trial is collected from 99 centers of 22 countries, which means on average one expects 12 patients collected from every center, and on average 55 patients from every country. This makes us think that there should be some wide range of variability when it concerns quality of the data collection, protocol application, practical application of inclusion and exclusion criteria. It is well known that coronary artery disease (CAD) is a leading cause of death and HF is the leading cause of hospitalisation in woman >65 years old (3,4).

After 2,000’s female patients (with a mean age of 70) counted for only 2% of total world population (around 140 million; The World Bank Data interactive site: https://data.worldbank.org/). Fifteen million in Europe (5) and 6 million (6) in the United States only have HF, with most common cause is a CAD (7) and complications from it, HF when come to example.

From the landmark clinical trials’ results that from starting 70’s it is recommended to perform CABG for relieving symptoms of angina, particularly among high risk patients (8) but excluded patients with severe left ventricular dysfunction by that time. The STICH trial (2) addressed this problem few years ago and concluded for ‘no significant difference between groups with respect of primary end point (rate of death for any cause); rate for cardiovascular death or hospitalisation was lower in CABG group’. However, the authors did not underline the sex differences in that original paper. Female sex, as matter of fact, considered as a risk factor for CABG and poor prognostic variable for perioperative risk evaluation scores, for example EuroSCORE [mainly used in Europe (9,10)] and many others [for example STS Score (Society of Thoracic Surgeons site: http://riskcalc.sts.org/stswebriskcalc/#) (11)].

Piña et al. (1) conducted study using STICH trial data with longer follow up (median around 10 years). Authors selected two groups dividing them by gender. By the original trail design the inclusion criteria were (12):

• man;
• women not of childbearing potential;
• age ≥18 years old;
• LVEF ≤0.35 measured by means of contrast magnetic resonance ventriculography, gated SPECT ventriculography, echocardiography, or contrast ventriculography within 3 months of trial entry;
• CAD suitable for revascularization.

It is not difficult to point out that there could be some bias on female patients inclusion in to this trial. In fact, authors elaborate on their limitations section underline that probably the design of STICH trial could have made the investigations to enroll less ‘sick’ women and left out more symptomatics out from the inclusion to trial. Ignoring this bias Piña et al. (1) analysed the data without using valid statistical technique (e.g., propensity score matching) in order to loosen the bias although it is not possible to remove after all. Even after considering all the limitations still this paper and analysis of the contemporary data is valuable. Take home message here is that the sex should not be the bias for addressing female patients to CABG. Moreover, it seems that even when female patients clinically are worse candidate are over-performing in the follow up having less all-cause and cardiovascular mortality. In our opinion for the future elaboration on this topic with available data should be analysed in more statistically complex and appropriate manner.

Acknowledgements

None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

References

1. Piña IL, Zheng Q, She L, et al. Sex Difference in Patients With Ischemic Heart Failure Undergoing Surgical Revascularization: Results From the STICH Trial (Surgical Treatment for Ischemic Heart Failure). Circulation 2018;137:771-80. [Crossref] [PubMed]
2. Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med 2011;364:1607-16. [Crossref] [PubMed]
3. Koelling TM, Chen RS, Lubwama RN, et al. The expanding national burden of heart failure in the United States: the influence of heart failure in women. Am Heart J 2004;147:74-8. [Crossref] [PubMed]
4. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation 2015;131:e29-322. Erratum in: Circulation 2016;133:e417. Circulation 2015;131:e535. [Crossref] [PubMed]
5. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008;29:2388-442. Erratum in: Eur Heart J 2010;12:416. Eur Heart J 2010;31:624. [Crossref] [PubMed]
6. Lloyd-Jones D, Adams RJ, Brown TM, et al. Executive summary: heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation 2010;121:948-54. Erratum in: Circulation 2010;121:e259. [Crossref] [PubMed]
7. Gheorghiade M, Sopko G, De Luca L, et al. Navigating the crossroads of coronary artery disease and heart failure. Circulation 2006;114:1202-13. [Crossref] [PubMed]
8. Varnauskas E. Twelve-year follow-up of survival in the randomized European Coronary Surgery Study. N Engl J Med 1988;319:332-7. [Crossref] [PubMed]
9. Nashef SA, Roques F, Sharples LD, et al. EuroSCORE II. Eur J Cardiothorac Surg 2012;41:734-44; discussion 744-5. [Crossref] [PubMed]
10. Nashef SA, Roques F, Michel P, et al. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999;16:9-13. [Crossref] [PubMed]
11. Hannan EL, Wu C, Bennett EV, et al. Risk stratification of in-hospital mortality for coronary artery bypass graft surgery. J Am Coll Cardiol 2006;47:661-8. [Crossref] [PubMed]
12. Velazquez EJ, Lee KL, O'Connor CM, et al. The rationale and design of the Surgical Treatment for Ischemic Heart Failure (STICH) trial. J Thorac Cardiovasc Surg 2007;134:1540-7. [Crossref] [PubMed]