AFTER EIGHTY

After-EightsBesides being one of the better study names around, this Norwegian RCT in the Lancet also shifted my prejudice. I was really thinking invasive vs conservative treatment for those over 80 with NSTEMI/UAP would show little difference. Maybe even a win for conservative treatment. But the scales tipped quite heavily in favour of invasive treatment.

Intro
This excerpt from the intro of a comment in the Lancet covering the After Eighty study sums up the negative attitude towards the very elderly NSTEMI patients:

Management of NSTE-acute coronary syndrome has many challenges in very elderly patients, who often present later, have atypical symptoms, and are a more heterogeneous cohort than younger patients. These patients are also more likely to have comorbidities, cognitive decline, physical frailty, polypharmacy, and more complex coronary artery disease with greater ischaemic burden.1 These factors could be perceived to diminish the benefits and increase the risk of complications from invasive treatment. Consequently the management of very elderly patients has traditionally been more conservative than guidelines recommend, with suboptimum access to early angiography and optimum revascularisation and medical treatment.

Evidence from registry studies have pointed towards benefit also in the very elderly: “Following presentation with high-risk NSTE-ACS, an evidence-based approach to management was noted less frequently with advancing patient age. Angiography, in particular, was less likely to be undertaken. Revascularization, however, when performed, was associated with significant benefits at 6 months, independent of age, and did not increase risk of stroke” , but many (including myself) have been sceptical.

The Study

Of over 4000 eligable patients, only about 10% were included. Over half due to exlusion criteria (especially short life-expectancy and clinical unstability), showing that selecting the right octogenarian for invasive procedure is probably important. These 450 pts were randomised to either invasive or conservative treatment (which included anti-platlet therapy).

The primary outcome was the composite (ugh!) of a new MI, need for urgent revascularisation, stroke or death.

Results
The composite endpoint was reached in only 40% of invasive patients vs 60%. Quite a big win for the invasive group! Decomposing the composite into individual endpoints is not neccessarily reflective of the actual endpoints reached, as only the first endpoint to be invoked was recorded. So if a patient had a new MI, event recording was stopped, and dying a week after that new MI was not recorded for the study.

With that in mind, the big differences in outcome was were we’d expect PCI to help: it lowered the risk of reinfarction and need for urgent revascularisation. There was also a tendency for reduced risk of stroke, but too small numbers. Death from any cause wasn’t much different. The invasive group vs conservative was 25% vs 27%, and not statistically different.

Looking at the data on the patients >90 years old, the results were less clear-cut.

For decision-making, it was also relieving to see that bleeding complications were not different between the groups.

Discussion
Since these very elderly patients with NSTEMI/UAP will often have quite widespread calcification of their (coronary) arteries, it’s a bit surprising that stenting one or a few individual lesions would help much in the long run. We already know that the most stenotic part of the coronaries is not neccessarily the culprit of their next cardiac event.

The need for urgent revascualrisation is not that surprising, but on the other hand it’s not neccessarily a useful or important endpoint.

The trend towards a lower incidence of stroke is a bit surprising, but might be a chance finding and is not statistically significant.

In earlier, similar studies of invasive vs conservative management of NSTEMI/UAP in not so old patients, the overall mortality has been between 2.5-5%, in the After Eighty study overall mortality is around the 25% mark.

The high overall mortality is of course due to the high “natural” risk of death in this group even when disregarding their current NSTEMI/UAP, as well as their “frailty”, and this high background numbers would go a long way to mask any mortality difference between the two study groups due to the interventions themselves. You’d need much higher number of patients to see if there is a real difference in survival.

Also, the high “natural” background mortality in this age group might make the focus on “well-being” outcomes more important than focusing on postponing death at any cost. And remember the study was done on clinically stable patients without signs of ischemia at the time of inclusion, so it’s not given that these results are valid for more emergent settings were revascularisation is considered.

Conclusion
Invasive treatment of NSTEMI/UAP is effective, even in the very elderly >80 years old. Mainly by reducing the risk of a recurrent MI by 50% compared with the best medical treatment alone, and also reduces the need for urgent revascularisation. The effect is less clear when patients reach 90. Still, for me, this study shifts my attitude towards invasive treatment of the very elderly.

Invasive versus conservative strategy in patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris (After Eighty study): an open-label randomised controlled trial, Lancet, 2016.

Management and 6-month outcomes in elderly and very elderly patients with high-risk non-ST-elevation acute coronary syndromes: The Global Registry of Acute Coronary Events, Eur Heart J, 2008

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