Statins are so ubiquitous that people
sometimes joke about putting them in the drinking water (which, of
course, is absurd and dangerous). Nevertheless, this facetious
suggestion—that everyone should get access to these drugs—hints at a
disagreement over the efficacy of statin therapy among patients with no
previous history of heart disease.
Before we unmoor into the waves of
controversy regarding statin use, let’s first look at November 2018
recommendations from a joint task force of the American College of
Cardiology and the American Heart Association, which reconcile the
renewed importance of LDL-cholesterol (LDL-C) levels as a biomarker and
actual risk of cardiovascular disease.
Changing recommendations
Originally in 2013, the joint task force stressed treating the risk
of developing heart disease, and taking the focus off target lipid
levels and lipid management. This approach made for a sea-change in how
clinicians viewed statins and heart disease. In the intervening years,
though, researchers have once again drifted back to the importance of
LDL-C levels, as reflected in the update to task force guidance
regarding statin use.
“The 2018 guideline emphasizes reducing risk of atherosclerotic
cardiovascular disease (ASCVD) through lipid management,” wrote members
of the task force. “It updates the 2013 guideline and emphasizes a more
intensive approach based on recent controlled studies and expert
consensus.”
Here are the 10 most important takeaways from the
2018 ACC/AHA Multisociety Guideline on the Management of Blood Cholesterol:
- In all individuals, emphasize a heart-healthy lifestyle across the life course.
- In patients with clinical ASCVD, reduce LDL-C with high-intensity statins or maximally tolerated statins to decrease ASCVD risk.
- In very high-risk ASCVD, use an LDL-C threshold of 70 mg/dL (1.8 mmol/L) to consider the addition of nonstatins to statins.
- In patients with severe primary hypercholesterolemia (LDL-C level ≥
190 mg/dL [≥4.9 mmol/L]) without calculating 10-year ASCVD risk, begin
high-intensity statin therapy.
- In patients 40 to 75 years of age with diabetes and an LDL-C level
of ≥ 70 mg/dL, start moderate-intensity statins without calculating
10-year ASCVD risk.
- In adults 40 to 75 years of age evaluated for primary ASCVD
prevention, have a clinician-patient risk discussion before starting
statin therapy.
- In adults 40 to 75 years of age without diabetes and with LDL-C
levels ≥ 70 mg/dL (≥ 1.8 mmol/L), at a 10-year ASCVD risk of ≥ 7.5%,
start a moderate-intensity statin if a discussion of treatment options
favors statin therapy.
- In adults 40 to 75 years of age without diabetes and 10-year risk of
5% to 19.9%, risk-enhancing factors favor initiation of statin therapy.
- In adults 40 to 75 years of age without diabetes and with LDL-C
levels ≥ 70 mg/dL to 89 mg/dL (≥ 1.8–4.9 mmol/L), at a 10-year ASCVD
risk of ≥ 7.5% to 19.9%, if a decision about statin therapy is
uncertain, consider measuring coronary artery calcium.
- Assess adherence and percentage response to LDL-C–lowering
medications and lifestyle changes with repeat lipid measurement 4 to 12
weeks after statin initiation or dose adjustment, repeated every 3 to 12
months as needed.
Of note, risk calculations are based on the
ASCVD Risk Estimator Plus.
Statin wars
So, what exactly happened over the past few years to divert focus of
the medical community away from the importance of LDL-C levels when
prescribing statins only then to renew interest in the importance of
lipid levels? This curious shift is allegorized by a “statins war” waged
between the
BMJ and
Lancet, with both publications accusing the other of threatening public health with harmful statin information.
The
BMJ launched the opening salvo with a 2013
review,
led by Harvard researcher John D. Abramson, MD, MSc, lecturer,
Department of Health Care Policy, Harvard Medical School. In a review of
statins for the primary prevention of cardiovascular disease, Dr.
Abramson and coauthors concluded the following:
“Our calculations using data presented in the 2012 [Cholesterol
Treatment Trialists’ Collaboration] patient level meta-analysis show
that statin therapy prevents one serious cardiovascular event per 140
low-risk people (five-year risk < 10%) treated for five years. Statin
therapy in low risk people does not reduce all-cause mortality or
serious illness and has about an 18% risk of causing side effects that
range from minor and reversible to serious and irreversible. Broadening
the recommendations in cholesterol lowering guidelines to include statin
therapy for low risk individuals will unnecessarily increase the
incidence of adverse effects without providing overall health benefit.”
Specifically, Dr. Abramson and colleagues noted that, based on their
analysis, the excess myopathy risk related to statins is 0.5 occurrences
per 1,000 patients, which translates to a ‘number needed to harm’ of
2,000. With respect to diabetes, there was a 10% increase in relative
risk while on statin therapy, or more than 5 new occurrences per 1,000
patients treated for 5 years.
In 2016, the
Lancet took its shot with the publication of a
review
in which researchers concluded that, as secondary prevention, statins
offered a 10% absolute benefit vs a 5% absolute benefit for primary
prevention. In other words, in 10,000 patients taking statins for 5
years, 1,000 fewer patients who had a history of heart disease
experienced heart attack and stroke (ie, secondary prevention), and 500
fewer patients without a history of heart disease experienced first
heart attack and stroke (ie, primary prevention). Furthermore, they
wrote that concerns about adverse effects were overblown and figured
into absolute benefit of the drugs.
The
Lancet article also noted that previous research decrying risk and minimizing benefit (ie, the
BMJ study) had a major limitation in that it used observational studies.
In an accompanying
editorial, Dr. Richard Horton, the editor-in-chief of the
Lancet, wrote:
“Controversy over the safety and efficacy of statins has harmed the
health of potentially thousands of people in the UK. After publication
of disputed research and tendentious opinions about statin use among
people at low risk of cardiovascular disease in 2013, patients already
taking statins were more likely to stop their medication both for
primary prevention (an 11% increased risk of stopping treatment) and
secondary prevention (a 12% increased risk).”
In turn, Dr. Abramson, defended the validity of his study, and
addressed the prospect of his findings contributing to statin
nonadherence in a 2017
Lancet editorial:
“The only fault with our
BMJ article was the interpretation
of a retrospective cohort study: our article stated that 18% of people
stopped statins because of statin-related events, whereas the correct
number was 9%.”
Of note, this correction was made to the original article by Dr. Abramson et al after calls for a retraction of two
BMJ articles questioning the value of statins in low-risk individuals were made and subsequently reviewed by the
BMJ.
Interestingly, the calls for retraction were made by the head of the
Cholesterol Treatment Trialists’ Collaboration—Sir Rory Collins, FRS,
FMedSci, professor of medicine and epidemiology, University of
Oxford—whose data were analyzed in the paper by Dr. Abramson et al.
The debate culminated when the editor-in-chief of the
BMJ, Dr. Fiona Godlee, wrote the following in a
Lancet correspondence:
“Independent third party scrutiny of the statins trial data remains
an essential next step if this increasingly bitter and unproductive
dispute is to be resolved. I have now written to England’s chief medical
officer, Sally Davies, asking her to call for and fund an independent
review of the evidence on statins.”
More recently, researchers have highlighted a paucity of statin
prescriptions among those who are candidates. For instance, according to
survey results from a
2019 study published in the
Journal of the American Heart Association,
more than half of those eligible for statins reported not being offered
the drugs, with many patients claiming that they would consider such
treatment advised. Finally, in those that refused statin therapy,
adverse effects were a major concern.
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A 'bitter and unproductive dispute' has occurred over statin therapy.