Dr Eva Swahn

"At last women are treated the same as men, but now I'm turning things upside down," Swahn said. However, she warned that the number of women in the study was small—they had planned to recruit 1600 women but were able to enroll only 184—"so we could not definitively answer the question; the study was underpowered, and the findings will require confirmation in a larger trial."

Asked during the press conference why they had been unable to recruit more women for the study, Swahn noted that OASIS-5 was a worldwide study, including 11 countries, but in the end only Poland and Sweden enrolled significant numbers of women. She said the only assumption she could make was that doctors had not wanted to treat women differently from men and so had been reluctant to enroll them in a trial that would do exactly that. "But, hopefully, when people see the results, we will get enough women for another study. Women should be equally treated, but we must have enough power in the studies to know that we are treating women in the best way for women," she commented.

Discussant for the trial, Dr Annika Rosengren (Sahlgrenska University Hospital, Goteborg, Sweden), said there were many possible reasons that women might not benefit as much as men from a routine invasive strategy, such as differences in anatomy and pathophysiology or the fact that they tend to be older when they get sick and therefore have more comorbidities. "Any of these things may tip the balance from a benefit to either no effect or an adverse effect in women," she noted. She cautioned, however, that it is premature to say that a routine invasive strategy is dangerous in women based on this study alone but concluded that much more gender-specific research is needed.

Swahn explained that a number of previous studies, including FRISC II, RITA-3, and TACTICS-TIMI-18, have shown a benefit of a routine invasive strategy in men with non-ST-elevation acute coronary syndrome, but that the results of these same studies in women "were contradictory."

OASIS-5 randomized 20 078 non-ST-elevation ACS patients within 24 hours to fondaparinux (2.5 mg sc once daily) or enoxaparin (1 mg/kg twice daily) for two to eight days, followed by angiography and intervention where appropriate. The results showed similar efficacy of the two drugs in reducing cardiac events but a significant reduction in bleeding with fondaparinux.

In the women's substudy, 184 patients received either fondaparinux or enoxaparin and then were further randomized, with 92 receiving a routine early invasive strategy (cath followed by PCI/CABG within seven days) and 92 receiving a selective invasive strategy, whereby they received coronary angiography only if symptoms or signs of angina occurred. The primary outcomes over two years of follow-up were death/MI/stroke and death/MI/stroke/refractory ischemia. Bleeding was also assessed.

In the early invasive group, 58% underwent PCI/CABG compared with 31% in the selective invasive group. There was no significant difference in either of the primary end points, but there were more deaths among the routine invasive group—eight (all cardiovascular deaths) compared with only one in the selective group, which was due to bleeding (hazard ratio 4.65 for death in routine vs selective groups; trend to significance). Bleeding was also more frequent in the early invasive group (HR 6.90).

"Patients randomized to a routine early invasive strategy had a higher mortality rate. With these alarming results in this very small trial, we need to conduct a large randomized trial to determine the safety and efficacy of an early invasive approach in women," Swahn said.

Because of the small number of women recruited into this substudy, Swahn and her colleagues performed a meta-analysis of death in the routine invasive vs selective invasive arms among women in FRISC II, RITA-3, TACTICS-TIMI-18, and OASIS-5. The odds ratio for death was 1.5 for the routine invasive strategy (p=0.07).

"The results [of OASIS-5] taken together with the results of previous larger trials suggest that the results from men do not necessarily apply to women and that large-scale randomized trials in women are needed to determine the optimal strategy in NSTE-ACS," Swahn said.

Also, she told heartwire, doctors need to take into account female gender and body weight when dosing medications used in ACS, she said. For example, in FRISC I, she noticed a higher bleeding rate among women taking either heparin or low-molecular-weight heparin and so adjusted the doses accordingly, taking into account both body weight and female gender. But generally there is an indiscriminate approach to dosing in women, she said.