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.
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.
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.