–But the benefits may be substantially diminished when patient preferences are considered.

A new analysis provides staunch support for the use of statins for the primary prevention of cardiovascular disease. But the same analysis also emphasizes that this support varies dramatically based on the values and concerns of individual patients.

Kirsten Bibbins-Domingo (UCSF) led a group of researchers who estimated the effect of a broad range of primary prevention strategies.

In their paper, published online in Circulation, the researchers compared three different strategies:

  • The ATP III guideline, in which all people with a 10-year Framingham CHD risk of 20% or more receive statins, along with those at lower risk but with elevated LDL levels.
  • The current ACC-AHA guideline, in which all people with LDL levels over 190 mg/dL and people with lower LDL levels with a 10-year CVD risk of 7.5% or more, receive statins.
  • A universal treatment strategy in which all adults (men 45-74 and women 55-74) take statins, regardless of their LDL level or risk status.

 

The authors estimate that 13.9 million men (45-75) and women (55-75) now take statins for primary prevention, representing 22% of this population.

  • Full implementation of ATP III would increase the number by 23% to 22.7 million, based on new statin treatment in 7.6 million and intensification of treatment in 1.2 million.
  • Full implementation of the ACC-AHA guideline would lead to 55% of the population taking statins, an increase of 12.3 million over the ATP III.
  • The universal treatment strategy would lead to nearly 50 million additional people on statins compared to the status quo.

 

In all the scenarios treatment costs increased along with the number of patients receiving statins, but the total costs, which include drug costs and toxicity in addition to savings from avoiding CV events and chronic treatment costs of CV disease, dropped as more people received treatment.

The authors calculated that the ATP III model would result in the prevention of 341,000 CHD events and 42,300 lives saved, the ACC-AHA model in the prevention of 578,000 events and 86,000 lives saved, and the universal strategy would result in the prevention of 999,000 events and 135,000 lives saved.

The benefits of broader statin strategies was more evident in men than in women. “All statin strategies were cost-saving for men relative to the next-broadest strategy, such that ACC-AHA dominated ATP III and the age/sex-based strategy dominated ACC-AHA in turn.” But this pattern did not hold in women, for whom the ACC-AHA strategy “was not cost-saving relative to the ATP III strategy.”

At first glance the results present an overwhelmingly positive view of statins for primary prevention. But when the patient perspective is taken into account the view is far more nuanced and complex. The ACC-AHA guideline places a big emphasis on patient-physician shared decision making, and recent studies have found that, as the authors write, “daily medication use causes a non-trivial disutility for many individuals (also called ‘pill burden’).” When the authors incorporated the patient perspective into the analysis they found that “an individual patient’s degree of benefit from long-term statin use depends strongly on their personal tolerance for pill burden and some on projected side effects.”

The benefits of statins were substantially diminished when the authors accounted “for even modest estimates of the potential pill burden associated with statins.” When the authors assumed “a pill disutility equivalent to two weeks’ lost perfect health over a decade” they found that both the ACC/AHA guideline and the universal strategy “may result in net harm in the population relative to the status quo.”

I asked Bibbins-Domingo to discuss the implications of her study. She started by noting that “statins are effective at CVD prevention, which is the rationale for broadening indication for their use. Our study confirms that even with broader use of statins these medications result in net benefit and are cost saving.”

But the problem begins because of course not everyone who takes a statin will benefit from it. “The chance that any given person taking statins will experience the benefit from these drugs is low (and even lower if we consider lower risk individuals for treatment),” said Bibbins-Domingo. “And it turns out that an individual’s preference/tolerance for taking a daily pill is actually an important factor in the determination of likely net benefit for that individual. Clinicians should- of course- always discuss patient preference for treatments we recommend, but this is particularly important for lower risk individuals where the likelihood of benefit is lower and may be offset if a patient perceives a high burden/annoyance /reluctance to taking a daily medication for prevention.”

Bibbins-Domingo also talked about the effect of adverse effects in the decision equation. “The trials and CTT tell us that statins are generally well tolerated but there are known side effects though rare and we need more information particularly in less well studied groups like older adults.”

But even if critics are right and the adverse event rate is higher than reported, Bibbins-Domingo said that her “analysis suggests that on the population level the benefits of statins are robust” even with “assumptions of far greater rates of adverse reactions than currently described.”

Asked to comment on the concept of “pill disutility,” Steve Nissen (Cleveland Clinic) said that he found “incredulous the claim that ‘pill disutility’ somehow negates the net benefit of statins. No reasonable public health advocate would equate the burdens of taking a single pill daily to the benefits of avoiding a myocardial infarction, coronary intervention or stroke.”

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9 Comments

  1. I think Nissen is misunderstanding “pill disutility” concept. It’s not the authors who have pill disutility. It’s the people who would be asked to take statins, some of them. I have met many people over the years who just hate taking a daily pill.

    1. “A” daily pill? How many of them are also on the BP pill, the PPI, the Alendronic acid and all the other polypharmacy that accompanies ageing? Including pills for the side effects of the other pills?

      The true disutility is to the drug companies whenever anyone stops their meds.

      And let’s not even mention the “diet disutility” that necessitates the drugs . . .

  2. ‘he found “incredulous the claim that ‘pill disutility’ somehow negates the net benefit of statins….” ‘

    Perhaps he meant “incredible”. If widespread misuse of that word makes it unsuitable, the answer is not to misuse ‘incredulous’. Maybe he meant ‘absurd’ but I suppose we’ll never know.

  3. This should silence the statin heretics, but I have an uneasy feeling this may be wishful thinking. Nothing is beneath them, even a forensic examination of ‘facts’ and true interpretation of the data! And woe to the researchers if these pesky critics dare to question the Lipid Hypothesis !!!

  4. I fail to see why a paperr that states “We used the Cardiovascular Disease (CVD) Policy Model to estimate the cost-effectiveness of …” would silence any critical thinker. Perhaps you could explain?

  5. We must remember that this is an “analysis”, not a randomized controlled trial. So, every conclusion arrived at depends on a raft of trials from the 1960s till recently – some of which were done reasonably well for the time, some not.

    How often is an intolerable side-effect labelled, by a cardiologist with bias (We all have our own biases), as “pill disutility”? Obfuscating euphemism.

  6. “… the universal strategy would result in the prevention of 999,000 events and 135,000 lives saved.”

    This assumes no changes in weight, diet, stress, pollution, exercise etc?

    Why ignore these lifestyle changes?

    If these have been incorporated into the study then, assuming a lowering of cholesterol in at least 50% of cases why only about 1% success rate?

    Why is it never considered why statins don’t work in the majority of cases?

    If estimates (lifestyle) can be wrong how do you know there is ANY statin effect at all?

    1. Because blind Belief in the efficacy of statins is a matter of faith, not Facts. Too many $ and Reputations at stake in my humble opinion, to allow stepping down from this position…
      Diet / Lifestyle has far more potential to prevent CVD, and does a power of good afterwards, many Scientists would go further…

    2. Because if you don’t ignore lifestyle changes you can’t tease out the effect attributable to the drug itself. This is an analysis of the potential population effects of changing the drug treatment recommendations, not of individual ideal treatment or population effects of effective lifestyle interventions. If you have a way to get the whole population to improve its dietary and exercise habits, I’m sure thousands of frustrated cardiologists would love to hear it, though.

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