Whiplash warning! Readers brace for possible neck injury as competing claims on statins hit the headlines

Woman Reading Letter After Receiving Neck InjuryYou’ve felt that pain before. Red wine is good for you. Red wine is bad for you. One day chocolate=bad; the next, it’s good for you. Scanners and surfers of health and medical news are accustomed to being jerked back and forth by competing Twitteresque soundbites.

Readers worried about their cholesterol could be getting whiplash this week as news headlines poured out saying either the entire population should be put on a statin, or statins are so toxic that nearly half the people who take them have muscle pain and other problems.

Cardiology conference generates the news

The event that radiated such statin-laden headlines was the American College of Cardiology’s annual conference in Chicago. The pro-statin message arrived with pieces I perused in CNN, CBC and NBC focusing on the HOPE-3 trial, a 12,000-patient trial looking at the benefits of statins mixed with various antihypertensives.

CNN: Global study lays groundwork for daily statin usage to prevent heart disease

CBC: ‘Simple’ treatments to prevent heart attacks and strokes: McMaster study

NBC: Study finds cholesterol-lowering statins cut heart disease risk

Published this week in the New England Journal of Medicine and funded by the Canadian government and drugmaker Astra Zeneca, it essentially found that 10 mg per day of rosuvastatin (Crestor) added to some blood pressure meds resulted in a lower risk of cardiovascular events than placebo. The study authors concluded that: “The results of HOPE-3 and other trials of statins collectively provide an extensive body of evidence of a significant clinical benefit in a broad group of persons of diverse ethnic backgrounds. In particular, trials of low-dose statins, such as HOPE-3, suggest that the risks associated with such therapy are low.”

Absolute numbers needed for context

Generally if you only read the headlines you’ll be revisiting the “statins should be in the water” hypothesis that has been circulating for years. Though if you took the time to dive into the stories you’d find helpful and context-rich criticisms of that theory. Matthew Herper, writing in Forbes, agreed that taken on the surface, HOPE-3 might stoke interest in wider statin prescribing, yet he also brought us to succinct reality with the absolute numbers of people who had a heart attack, stroke or heart-related effect (3.7% on statins versus 4.8% on placebo) as well as the absolute numbers of adverse effects of rosuvastatin including increased risk of cataracts (3.8% of patients on statins had cataract surgery, versus 3.1% on placebo) and muscle pain (5.8% on the drug versus 4.7% on placebo).

His was one of the few mentioning that HOPE-3 might have dealt a fatal blow to the much overhyped and illogical polypill hypothesis which proposes mixing a bunch of possibly helpful drugs into a single pill. In this study, despite the high numbers of enrolled patients, the researchers found no added benefit of adding antihypertensives to low-dose statins. CNN’s piece also went out of its way to give some context to the controversies around statin treatment and to quote outside sources not connected to the study.

John Abramson, MD, a health policy expert from Harvard Medical School, told me that he thought the media hype around HOPE-3 was “absurd.” He wrote to me in an email, critical of the study and what wasn’t reported: “There’s no breakdown by subgroup. No significant mortality benefit, and (unbelievably) incidence of serious adverse events are not reported.” For him, “the bottom line is that 91 people have to be treated with a statin for 5.6 years in order to prevent 1 non-fatal heart attack or stroke.”

Study finds alarming adverse effects — who funded it?

Contrasting the hyped message of the benefits of statins were another set of stories found in CBS, Forbes, Time and the Washington Post, which veered in another direction, reporting an incredibly high level of statin adverse effects. The take-home message of the GAUSS-3 study –funded by Amgen, which makes the injectable LDL-lowering drug evolocumab (Repatha) — is that statin adverse effects are really, really bad.


Evolocumab is in a new class of drugs known as PCSK9 inhibitors (the bad reporting on which we’ve reported in the past) and enrolled patients suffering muscle effects of atorvastatin. Randomizing these “statin intolerant” patients to either revolocumab or ezetimibe, it found that 43% of patients taking atorvastatin had muscle side effects (versus about 27% taking placebo). As for what to take away from that study, John Abramson told me that “Gauss-3 proves nothing about benefit because there are no long-term studies of PCSK9 inhibitors’ effect on cardiovascular outcomes.” In other words, the drug might lower LDL, but so what? None of the media reports seemed to remind readers that surrogate outcomes are just that, and we’ve been fooled before chasing surrogates that turn out not to reflect benefits on the outcomes we care about, like heart attacks.  (See our explainer on surrogate markers if this is new to you.) And surprisingly, none of the media reports captured the obvious: that this trial was all about building a market for a new and expensive LDL-lowering drug, and to do that you needed to show that MANY people suffer the adverse effects of statins and hence needed something else.

Stories didn’t dig on author conflicts of interest

A lot of the reporting mentioned the funding sources for both of these studies but none of them covered the conflicts of interest disclosures, (such as these associated with the HOPE-3 trial). For example, lead author Salim Yusuf indicates he has received grants, fees and research support from at least six drug manufacturers, and his coauthors also have many conflicts of interest with the manufacturers of statins and antihypertensive drugs. Clearly these authors may have an incentive to put their results in the best possible light given the source of funding.

Last word has to go to a cheeky report found in The Health Care Blog by Saurabh Jha, a fellow HealthNewsReview.org reviewer, who brought some levity to the discussion. His somewhat comical zingers about HOPE-3 include writing that “the Number Needed to Treat (NNT) conscripts a village to save an individual but no one in the village knows who has been saved.” HOPE-3 has an NNT that is almost 100 and he saucily adds: “It might not have escaped your attention that ‘NNT minus 1’ is the number who did not need to be treated.”

At the end of the day, headlines mislead and if you only read those, you’re likely to be feeling a little whiplashed this week.

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Comments (3)

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Matthew Herper

April 5, 2016 at 4:48 pm

Thanks for the kind words! I think you’re missing the point on Gauss-3, which I’m seeing I could have described better. What was interesting was that the patients included in the study had muscle aches while on atorvastatin but not on placebo. (It was a crossover design.) Yes, people also had muscle aches on placebo, but not atorvastatin, but we can at least say that statin intolerance was higher while on atorva, and that the group who had it while on atorvan, but not placebo, was enriched for truly statin intolerant patients.

I found it pretty striking that even with evolocumab, a lot (20%!) of these people still couldn’t take a cholesterol medicine. Anyway, I thought this was a pretty striking finding demonstrating that statin intolerance is not just in people’s heads and really does exist. Does a rare rate of muscle aches mean you should never try a statin? Of course not, especially if the aches are reversible! But deciding when the risk exceeds the benefit is a personal decision. There are cases that seem clear to me (you’re at high risk of CV disease) and cases that are less so (is it worth taking a statin for 20 years to try and further reduce your risk?). At the end of the day, these are decisions about ones own values…

    Alan Cassels

    April 5, 2016 at 9:43 pm

    Mathew, thanks for the comments and the clarification. I’ll just focus on one thing and that is the muscle ache issue. Is it not surprising that the rate of these in the HOPE-3 trial was about 1% but in the GAUSS-3 it was over 20% (compared to placebo)? There is certainly an issue about the under, and mis-reporting of adverse effects found in statin trials and in one relatively robust review the rates of statin adverse effects are between 10 and 20%. Others have pegged it higher. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849981/
    Suffice to say if people at higher risk of heart disease are unable to walk or exercise due to even a mild rate of muscle weakness and discomfort then maybe the statins are preventing them from doing the one thing we know reduces risks of future events: exercise. Obviously the patient values are a critical part, but my research has shown that the patient preferences speak loud and clear: compliance on statins beyond 2 years is only about 30-40%, which is to say, there could be as many as 70% of ‘real world’ patients stopping their statin within 2 years of being put on them, speaking to a pretty high rate of intolerability in the world outside of a randomized trial.

Naomi Price

April 5, 2016 at 4:58 pm

The other number(s): How many people have heart attacks or strokes despite taking statins. Not trivial.