Nov 022016

In patients with COPD with exertional hypoxemia, long-term supplemental oxygen did not improve survival or quality of life in a multicenter randomized trial published in the New England Journal of Medicine. The NIH-funded study calls into question the current practice of routinely treating moderately hypoxemic COPD patients with supplemental oxygen, and the billions spent for it yearly by Medicare and private insurers.

Long-term oxygen is known to help people live longer and feel better when their oxygen levels are very low at rest. Supplemental oxygen has typically also been provided to the far larger group of people with normal resting oxygen levels that fall during exertion, but any benefits of this have never been established.

What They Did

The trial was originally designed to test the time until death among patients newly diagnosed with mild resting hypoxemia, but almost no patients could be enrolled. (Maybe they took issue with the 50% chance of being randomized to receive no oxygen for months or years.) Investigators then called an audible and redesigned the trial.

Patients at 42 centers (n=738) with COPD who had either a) resting oxygen saturations of 89-93% or b) normal resting oxygen saturations that fell to the 80-90% range during a 6-minute walk test were randomized to receive either supplemental oxygen or no oxygen. The study was unblinded. Those with resting hypoxemia were prescribed 24-hour oxygen. Those with exertional hypoxemia were prescribed oxygen only with exertion and sleep. They were followed for up to 6 years (median 1.5 years). To juice up the statistical power, the time to first hospitalization was added to time to death after diagnosis into a new composite primary outcome.

What They Found

Those patients receiving oxygen had no improvement in the primary outcome (rate of hospitalization or time to death after diagnosis, hazard ratio 0.94), nor in quality of life or exercise capacity, compared to patients not receiving oxygen.

What It Means

Authors concluded, "Among patients with COPD who have a resting SpO2 of more than 88%, long-term supplemental oxygen therapy does not result in longer survival than no long-term supplemental oxygen therapy, regardless of whether the patients have exercise-induced desaturation."

Whoa: then why are Medicare and private insurance companies spending more than $2 billion a year for it? More on that in a moment.

Doctors caring for patients with COPD vary widely in their approaches to testing for ambulatory hypoxemia in patients with COPD. Some test ambulatory oximetry (6 minute walk distance) in all patients; others in a more select group. Are the tens of thousands of these walk tests performed annually necessary or helpful at all? For the majority, this study suggests possibly not.

(The new LOTT trial in no way calls into question the established benefits of 24-hour supplemental oxygen in patients with resting SpO2 ≤ 88% or Pao2 ≤ 55 mm Hg, or ≤ 59 mm Hg with signs of right-sided heart strain or polycythemia.)

Dr Magnus Ekstrom, the New England editorialist, went on record against routinely providing long-term oxygen therapy for people with COPD with mild or moderate hypoxemia at rest or during exercise. But he hedges, as most physicians likely will, adding, "A trial of oxygen use might still be appropriate in selected patients with moderate exertional hypoxemia and intractable breathlessness despite appropriate evidence-based treatment."

The challenge with that approach is the prevalence and power of the placebo effect. Patients living with a chronic respiratory illness often feel better having oxygen on hand to use as needed -- even when told there's no medical benefit and they don't "qualify". Even NFL players and other pro athletes think oxygen helps them (it doesn't). Give breathless people oxygen with subjective benefit as the criterion, and it's very hard to take it away.

For these delicate situations, Dr Ekstrom proposes an interesting n-of-1 trial with patients acting as their own controls:

I think that the oxygen treatment should be evaluated by means of blinded exercise tests while the patient is breathing ambient air or oxygen and discontinued if the patient perceives no benefit during the test or within a day or two after it. If there is benefit, these selected patients should be prescribed oxygen, and I think that this treatment should be covered by insurance payers.

This kind of mind game has been tried in clinical trials, but it's another thing entirely to widely implement it as an acid test for oxygen eligibility among consumerist Americans, who will bristle at being tricked out of their coverage for a desired medical therapy. How would this test work? An arbitrary difference in dyspnea scores between blinded administration of room air or oxygen? It's possible, but seems cumbersome and infeasible in the foreseeable future.

About a million U.S. citizens are using supplemental oxygen for moderate hypoxemia due to COPD, but for how much longer is hard to predict. NIH tamped down any fear of mass revocation of oxygen on its FAQ page:

Medicare current coverage policy for home oxygen therapy is flexible enough to cover patients with moderate COPD who may have hypoxia-related symptoms or findings that might be expected to improve with oxygen therapy, if providers and patients make that decision.

But the truth is, the $28 million LOTT study was commissioned and financed by CMS, specifically to determine whether its billions spent on oxygen therapy are improving health of Medicare beneficiaries. The answer it got from LOTT is "no."

The next step is for statisticians and physiologists of the world to dissect the results of the trial and ask whether its findings -- from 738 patients and 1.5 years median follow up -- are robust enough to be believed. Another question is whether there are other benefits of oxygen therapy (or certain patient populations) that were not adequately tested or captured by the new LOTT trial.

So what now? Medicare and insurers will likely reconsider current policy in response to this study. But how health care dollars get spent is ultimately a political decision. If CMS threatens the great oxygen pipeline, Congress might intervene in response to pressure from angry constituents, or from lobbying by DME giants Apria and Lincare.

Medicare and "Obamacare" would take most of the heat as the bad guys in any doomsday scenario. But physicians wouldn't be held blameless, and as the possessors of the nearest throats to choke, would be in for some tough conversations with patients who have become used to this expensive and -- in this trial, at least -- unhelpful treatment.

Read more: A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation. N Engl J Med 2016; 375:1617-1627. October 27, 2016. [PubMed]

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Long-term oxygen brought no benefits for moderate hypoxemia in COPD