by: Hanis Sophia
Practically every day this spring, New York University cardiologist
Aakriti Gupta, MD, MS, has received a phone call from friends or relatives in
India who have COVID-19. They want to know whether they should start taking
statins, which are cheap and available without a prescription in Gupta’s
COVID-19–ravaged homeland.
A history of myocardial infarction, congestive heart failure, and
hyperlipidemia have all been associated with an increased risk of in-hospital
mortality from COVD-19. Observational studies by Gupta and others have
suggested that taking statins might not only lower blood cholesterol levels but
also reduce the risk of dying from COVID-19.
Statins do more than lower cholesterol, Gupta noted in an interview.
They have both anti-inflammatory and antithrombotic properties, which could
make them an attractive class of drugs for treating COVID-19, Gupta and her
coauthors suggested in a May 2020 article.
Preclinical studies indicate that statins could worsen COVID-19 or at
least increase the chances of infection, Italian researchers pointed out in a
recent JAMA Internal Medicine article. That’s because statins,
along with several other classes of drugs used to treat atherosclerotic heart
disease and its risk factors, upregulate angiotensin-converting enzyme 2 (ACE2)
receptors, which happen to be SARS-CoV-2’s gateway into cells. Yet theoretically,
the authors noted, the same drugs may improve the clinical course of COVID-19
by reducing vasoconstriction, inflammation, and oxidation.
Mixed Findings
So far, most studies examining whether statins might benefit people with
COVID-19 have been retrospective analyses of hospitalized patients. To try to
mimic randomized controlled clinical trials, researchers have matched patients
who’d been taking statins with those who had not on the basis of such factors
as vital signs, laboratory values, and body mass index—a method called
propensity-score matching.
Their findings haven’t consistently linked the drugs with a lower
short-term risk of dying after contracting COVID-19. These observational
studies found an association between statin use and lower mortality among
patients with COVID-19:
- In
an article published earlier this year, Gupta and her colleagues found
that among 1296 New York City patients hospitalized with COVID-19, 26.5%
of patients who hadn’t been taking statins died within 30 days of hospital
admission compared with 14.8% of patients who used the drugs.
- Wayne
State University researchers found that in a cohort of 466
patients hospitalized with COVID-19, those who had been taking moderate or
high doses of statins, but not low doses, had a significantly reduced risk
of dying compared with those who had not been taking statins. The study did
not find a significant association between statin use and intensive care
unit (ICU) admission or the need for mechanical ventilation.
- A study of
1179 patients with COVID-19 in Massachusetts General Hospital that has not
yet been peer-reviewed found that statin use during hospitalization, newly
initiated or not, was associated with improved 28-day mortality for
patients older than 65 years but not for patients 65 years or younger.
- In
a study of nearly 14 000 patients hospitalized with COVID-19 in
Hubei Province, China, 5.2% of statin users compared with 9.4% of matched
statin nonusers died of any cause.
On the other hand, some studies have found no association between statin
use and lower COVID-19 death rates:
- A meta-analysis of
9 studies conducted in the US, China, and elsewhere concluded that statin
use was not associated with reduced severity or death among patients
hospitalized with COVID-19.
- Using
data from Danish nationwide registries, researchers found no
difference in all-cause mortality between statin users and nonusers among
people with COVID-19, regardless of whether they were hospitalized.
- The
aforementioned Italian study in JAMA Internal Medicine analysed
data from about 4000 patients with confirmed COVID-19 in Lombardy, Italy,
ICUs. Long-term treatment with statins, ACE inhibitors, diuretics,
β-blockers, angiotensin II receptor blockers, antiplatelet drugs, and
anticoagulants before admission was associated with higher mortality but
only in an unadjusted analysis. Unmeasured confounders, as opposed to the
drugs themselves, could explain that observation, the authors noted.
Don’t Start, Don’t Stop
Given a lack of randomized clinical trial data to support such a
recommendation, no one is yet advising that people for whom statins aren’t
indicated start taking the drugs to lower their risk of dying from COVID-19.
Guidelines from the National Institutes of Health go only as far as
advising that patients with COVID-19 who were already taking statins continue
to do so. Massachusetts General Hospital advises that if patients with
COVID-19 aren’t already taking statins, only those who have an indication for the
drugs and no contraindications should start taking them.
Unanswered Questions
Because observational studies have focused on hospitalized patients, the
generalizability of their results to people with COVID-19 who aren’t
hospitalized is limited, the Wayne State researchers pointed out. They also
noted that patients who take statins might generally be more health-conscious
than nonusers and, therefore, manage their comorbidities better and seek care
earlier in the course of COVID-19.
As Gupta and others have emphasized, only randomized controlled trials
could show whether statin use itself or other characteristics of statin users
might contribute to a lower risk of death from COVID-19.
Preliminary results from one such study, for which Gupta serves on the
steering committee, were presented May 16 at a late-breaking clinical
research section at the American College of Cardiology (ACC) meeting.
The trial involved ICU patients with COVID-19 in Iran. It was
designed to answer 2 primary questions: whether a higher anticoagulant dose or
a newly prescribed statin could reduce the risk of dying within 30 days of
hospital admission. Patients were randomized to a higher dose or standard dose
of anticoagulant therapy, and then each of those groups was randomized to 20 mg
per day of atorvastatin or a placebo.
The higher anticoagulant dose did not reduce mortality, the author
reported recently in JAMA. Because the statin vs placebo arm of the
trial excluded people who’d already been taking statins, more patients had to
be enrolled to reach a goal of 600 needed to adequately power that arm, and it
was unblinded only in early May, principal investigator Behnood Bikdeli, MD,
MS, said in an interview.
At the ACC meeting, Bikdeli reported findings from the study’s
statin group that were similar to the anticoagulant group findings. Twenty
milligrams per day of atorvastatin did not reduce 30-day mortality compared
with the placebo, said Bikdeli, a physician-investigator in cardiovascular
medicine at the Brigham and Women’s Hospital who is originally from Iran.
Still, Bikdeli said, he holds out hope for statins’ usefulness in
treating some patients with COVID-19. A subgroup analysis of his data found
fewer deaths and blood clots in 1 group: those who were admitted to the ICU
within 7 days of their first symptoms. “This is not sufficient to change
practice,” he said, “but I think it’s very important to pursue in future
studies.”
In addition, Bikdeli said, the trial results don’t rule out the
possibility that initiating statin therapy might help patients with COVID-19
who don’t require ICU care, including people with long COVID who have
persistent symptoms. Or, perhaps, doubling the atorvastatin dose would be
effective in the ICU, Bikdeli said, adding that he is considering a trial to
answer that question.
“It’s not early in the pandemic anymore,” he said. “We need data to
guide management.”
The Upshot
For now, when friends and family with COVID-19 ask whether they should
start taking statins, Gupta said, “I would suggest it only if there was an
indication.” In other words, she wouldn’t advise otherwise healthy 30-year-olds
with COVID-19 to take statins, but many of her callers from India are older and
overweight and, likely, have unfavourable blood lipid profiles.
“Just take statins,” she tells them. “You probably should already be on
them.”
