To Cath or Not to Cath? Gender Is the Question
Abstract & Commentary
By Allan J. Wilke, MD, Residency Program Director, Associate Professor of Family Medicine, University of Alabama at Birmingham School of Medicine, Huntsville Regional Medical Campus, Huntsville. Dr. Wilke reports no financial relationship to this field of study.
Synopsis: Strategies to determine treatment of acute coronary syndromes need to take gender into account.
Source: O'Donoghue M, et al. Early invasive vs conservative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction: A meta-analysis. JAMA 2008;300:71-80.
This meta-analysis sought to answer two questions: Which approach to acute coronary syndrome (ACS), early catheterization and stenting or medical control, is better, and is there a difference between the sexes. Some trials have suggested no benefit and possibly harm to women who underwent early invasive treatment (INV)1; others have shown an advantage for women at high risk.2 A 2006 Cochrane review concluded that INV was preferable to medical therapy in unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI), provided the patient survived initial hospitalization.3
The authors searched Medline and Cochrane databases for articles focusing on invasive, conservative, or selective invasive strategies for ACS, NSTEMI, and UA and found eight that met their inclusion and exclusion criteria, all published between 1994 and 2005. They defined invasive strategy as one that referred all patients to coronary angiography and possibly revascularization. A conservative strategy emphasized medical therapy optimization with referral of only those patients who failed medical treatment or who had inducible ischemia. They went back to the authors and got gender-specific data, including creatine kinase MB (CK-MB), troponin, and ST-segment deviation on electrocardiogram (ECG). The eight trials enrolled 10,412 patients. The women were older than the men (64 years vs 61 years), and were significantly sicker (more diabetes mellitus, hypertension, and hyperlipidemia at baseline). On the other hand, the men were more likely to smoke and have a history of myocardial infarction (MI). The women's ECGs were more likely to show T-wave inversion, and the men's cardiac markers were more likely to be elevated.
The results of angiography in the men and women randomized to catheterization differed. Women were more likely to have little or no coronary artery disease (CAD) than were men (24% vs 8%). This was true even for women who had ST-segment deviation or elevated cardiac markers. Men were more likely to have three-vessel or left main disease (35% vs 23%).
At 12-month follow up, more patients in the conservative group (26% vs 21%) had reached the composite endpoint of death, nonfatal MI, or re-hospitalization with ACS. The odds ratios (OR) for the composite endpoint were 0.81 (95% confidence interval [CI], 0.65-1.01) in women and 0.73 (95% CI, 0.55-0.98) in men. When the individual elements of the endpoint were examined separately, only re-hospitalization was significant in women. INV had no significant effect on all-cause mortality, nonfatal MI, or a composite of death or MI. Both men and women had a nonsignificant increase in death or recurrent MI before hospital discharge (OR 1.37; 95% CI, 0.93-2.02). The odds ratio for the composite endpoint favored INV in patients with elevated cardiac markers or ST-segment deviation. This was true for men and women and to the same degree. There was a nonsignificant 35% higher OR for death or MI in women who did not have elevation of cardiac markers and who received INV (OR 1.35; 95% CI, 0.78-2.35). Women who required coronary artery bypass graft surgery by the end of follow up had higher odds of the composite endpoint than did men.
Commentary
On the basis of this meta-analysis, women at high-risk (i.e., they have elevated cardiac markers or ST-segment deviation) and all men benefit from an invasive strategy for UA or ACS. Woman not at high-risk may suffer from INV. These findings are in line with recent American College of Cardiology/American Heart Association guidelines.4 As the authors rightly point out, the results of this meta-analysis need to be addressed by larger prospective trials, especially since a lot has changed since 1994, including the use of medications to prevent stent occlusion and the development of drug-eluting stents, and many of the confidence intervals included 1.00, indicating nonsignificance.
Why do women differ from men in their treatment of ACS? The authors speculate that perhaps women "have a greater burden of microvascular disease or abnormal vasodilatory reserve ... resulting in subendocardial ischemia, coronary vasospasm, or possibly other acute disease states that mimic ACS secondary to obstructive CAD." They advance the argument that since women have less demonstrable CAD on angiography, they are less likely to be helped by an invasive strategy that by its design only treats epicardial disease. What is yet to be determined is how women at high risk differ from low-risk women. Tissue necrosis (as evidenced by its surrogates elevated cardiac markers and ST-segment deviation) is obviously not a good thing, but the data presented in this meta-analysis are not robust enough to be more specific about the differences.
My take-away message from this report is: Except for women at low risk (no elevation of cardiac markers or ST-segment deviation), anyone who arrives in an emergency department with ACS deserves a catheterization.
References
1. Clayton TC, et al. Do men benefit more than women from an interventional strategy in patients with unstable angina or non-ST-elevation myocardial infarction? The impact of gender in the RITA 3 trial. Eur Heart J 2004;25:1641-1650.
2. Glaser R, et al. Benefit of an early invasive management strategy in women with acute coronary syndromes. JAMA 2002;288:3124-3129.
3. Hoenig MR, et al. Early invasive versus conservative strategies for unstable angina & non-ST-elevation myocardial infarction in the stent era. Cochrane Database Syst Rev 2006;3:CD004815.
4. Anderson JL, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction. J Am Coll Cardiol 2007;50:e1-e157.
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