God and Statins

flying cadeuciiOf life’s two certainties, death and cataracts, it seems statins defer one and prompt the other, although not necessarily in the same person. If you blindly love life you may be blinded by your love for life.

In the HOPE-3 trial, ethnically diverse people without cardiovascular disease were randomized to 10 mg of rosuvastatin daily and placebo. The treatment group had fewer primary events – death from myocardial infarction (MI), non-fatal myocardial infarctions, and non-fatal stroke. For roughly ten MIs averted there were seven excess cataracts. Peter may be blinded without being saved. Paul may be saved without being blinded. And then there is Rajeev who may be blinded and saved. But the very nature of primary prevention is that you don’t know you’re Peter, Paul or Rajeev. So everyone is grateful to statins. Not even God of the Old Testament had such unconditional deference.

Once you’re taking statins there is no way to disprove that any and every breath you draw is because of statins. Statins enjoy the metaphysical carapace, the immunity from falsification, which not even God enjoys. At least you can experiment with God. Don’t pray for a week and see if you’re still alive- you know if God really cares about prayer-adherence. Even if you die at age 55 on statins, you can never disprove that you wouldn’t have died sooner if you weren’t taking statins.

HOPE-3 will have a different impact in different countries. In the US it is a step closer to mixing statins with water. In some circles, statins have become proof of matrimonial commitment. I attended a birthday party of an Indian physician recently. It was a remorselessly boring event which was briefly animated by a discussion of what investments they were making. One physician said, looking at his wife dotingly, “my only investment is a statin. It keeps my wife safe.” His wife looked back at him lovingly in that LDL-induced hypnotic gaze.

It is the overburdened British GPs I feel sorry for. They will sink deeper into the rabbit hole of shared decision making. They will be obliged to yank people, who are well and minding their own business, from the streets and tell them in a non-judgmental tone: a) you may benefit from statins, b) there are no guarantees you will benefit from statins, c) you may develop a cataract, d) there are no guarantees you will develop a cataract, e) you may be blown up by ISIS and all of this may be an utter waste of your time.

While some will use decision aids, flash cards, a clever app, the fact remains that GPs will be diverted from dealing with the presently ill to those who might be ill in twenty years. Primary prevention is like financial planning. GPs are expected to be like that professional who simultaneously manages bankruptcies and hedge funds.

HOPE is a Canadian-led politically correct trial funded by the Canadian Institutes of Health Research and AstraZeneca. Since Canadians are nicer people and are not motivated by money, we have been mercifully spared of protracted discussions of financial conflicts of interest (COI) with pharma. Obsession with COI just detracts from a fundamental truth, which is that there are many ways death can be marginally deferred probabilistically, which evidence-based medicine (EBM) will uncover.

If you still think EBM will reduce healthcare costs you may as well believe in the tooth fairy. There are two legitimate reasons not to be on statins – you can’t be bothered to take them (which I suspect speaks for vast swathes of mankind), or the healthcare system can’t afford them. There is no shame in admitting the latter, but I suspect nobody will. But let us end the notion though that statins for primary prevention are unscientific.

The science of statins is an odd science though. It is predicated on the numbers needed to treat (NNT). The NNT is a clever extension of absolute risk reduction, a bulwark against the therapeutic optimism of relative risk reduction. Some of Dr. Oz’s remedies have an NNT of infinity. A little shy of hundred, HOPE’s NNT is impressive. It might not have escaped your attention that “NNT-1” is the number who did not need to be treated.

The NNT conscripts a village to save an individual but no one in the village knows who has been saved. Primary prevention is like winning a lottery every day but never seeing the money. Were I God, I’d be jealous of statins. Perhaps the statin is Vishnu’s tenth reincarnation.

Saurabh Jha is a radiologist and contributing editor to Healthcare Blog. He used to be skeptical. Now he is even more skeptical.

He can be reached on Twitter @RogueRad

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9 replies »

  1. Dr Jha, this is so good I wish I’d written it. You may very well be the most entertaining radiologist writing today. As a patient, I love your take on primary prevention (“…like winning a lottery every day but never seeing the money), the niceness of us Canadians, the “rabbit hole of shared decision making”, and of course the “LDL-induced hypnotic gaze.” I’m still laughing out loud at that one…

  2. Dr. Hadler questions such as this are quite perplexing and the mental gymnastics we go through to come to a decision leave me exhausted especially when the one’s providing much of the data are interested parties.

    In the Scientific American article you write: “Consider Pill A, which reduces a blood chemical known to predispose to heart damage. The “best case” science says that if 100 adults take the pill for 5 years, perhaps 2 will be spared non-fatal heart damage and 10 will suffer muscle pain. However there is no suggestion that anyone will be spared death before their time. Would you take Pill A?”

    Based upon only the factors above I can’t see why one wouldn’t take the Statin. Eventually we all die mostly from cancer or heart disease. If we don’t die of cancer then we are left with heart disease that kills us years past the 5 years mentioned above. Would not that non fatal heart attack have an effect on us later in life? Is 5 years enough to draw a conclusion that the benefits above are not compounded with age? Just because the adverse effect is so much more common than the positive effect of the Statin should that adverse effect be utilized in this type of argument? Those ten that suffer muscle pain that is 5 X the number helped can all stop the Statin virtually eliminating the problem.

    Of course there is more at play than the above, but I was using your construct as is to prevent even more mental gymnastics before proceeding onward with a question that has no definitive answer.

  3. Three critical points, Matthew:
    1. Which single malt whiskey is causing “muscle pain and mental fogginess”? Based on N=1 data, your experience may be quite idiosyncratic.
    2. The Washington Post published an interview in 2012 where I made it clear that I would not let anyone check my cholesterol or my PSA for good reasons:
    3. You say, “And of course we’re all gambling that we’re the 99 not the 1.” I call that the “lottery mentality.” It does not pertain to a RCT. The appropriate question relates to the likelihood of being an outlier on crestor v not, i.e. what’s the chance of winning the lottery if I don’t buy the ticket.

  4. I’m one of the “too lazy to take statins” crowd even though I haven’t seen a PCP in about 5 years mostly to avoid that awkward conversation. It’s also worth pointing out that plenty of those on statins feel that they have both muscle pain and mental fogginess….but then I get both of those frequently too. Single Malt whisky causes both yet is not reimbursed by my health plan.

    And of course we’re all gambling that we’re the 99 not the 1…

  5. Dear Dr Jha,

    I am unable to imagine rosuvastatin (Crestor) as a divine glory of Vishnu. I am able to envision HOPE-3 as an even more egregious example of a marketing trial than JUPITER, the trial that created the mythology that hs-CRP quantification alone marks a population that should be treated with Crestor despite normal cholesterol levels. The JUPITER trial leaves legacies of medicalization, of increased equity for Astra-Zeneca, and of a high bar for data torturing. I made these points when JUPITER first appeared in the NEJM ( and used the trial as an object lesson in Citizen Patient (

    Along comes HOPE-3, the same exercise in data torturing but now targeting people declared to have “intermediate risk”. Some 13,000 people were recruited in 228 centers in 21 countries. Statisticians and epidemiologists were hired to tease a tiny reduction in clinical outcomes out of all this heterogeneity in a RCT conducted over the course of 5+ years. We are offered an exercise in “small effectology” that would boggle even the ñāṇa of Vishnu. Look at the main outcomes in TABLE 2.

    There is NO DIFFERENCE between those treated with Crestor and those on placebo in ANY component of the primary and secondary outcomes. The way a 1% difference was massaged out of these data was to combine the components.

    I’m just a hard-working clinician striving to do better by my patients. If a patient asks me what benefit to expect if they swallow a Crestor daily for 5 years, how am I to answer?

  6. Really good meds have NNT of less than one, e.g. .5. Then, a person can forget his meds every other day and still be saved. ;=)

  7. Don’t forget all the other side effects of statins as well, like, um, diabetes? And I believe this trial included only people who were clearly indicated for statins based on the label, not for some broad swath of humanity over age 55, right?

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