Tuesday, August 16, 2011

All In For Crestor

The American Heart Association will be holding its annual meeting this November.  Cardiobrief.org just posted the announced "late-breaking" clinical trials. These are the big name trials that usually grab a lot of headlines. One of the trials is the AIM-HIGH trial which showed that Niacian didn't really do much in patients whose bad cholesterol or LDL was controlled with a statin (see my post What to do about Niacin? )
Another very important study will also be presented that same November 15th, 2011: Comparison of the Progression of Coronary Atherosclerosis for Two High Efficacy Statin Regimens with Different HDL Effects: SATURN Study Results.  The SATURN study is the Astra Zeneca (makers of Crestor) study comparing high dose Crestor (40mg) with high dose Lipitor (80mg).

Patients in the SATURN study will have known cardiac disease as indicated by a need for coronary angiography (angiogram) and angiographic evidence of coronary disease.  The main end point is  is IVUS-assessed change in the percent atheroma volume in a >40-mm segment of a single coronary artery; which is a "doctor" way of saying they are going to look for plaque build up in the artery.  This is the same end point used in the famous (or infamous) ENHANCE trial which showed that adding Zetia to simvastatin (zetia + simvastatin = Vytorin) did absolutely nothing to plaque build up ( Vytorin and Zetia: What to do now? )

What's interesting about SATURN is that the LDL lowering properties of the highest doses of Crestor and Lipitor are about the same.  However, at those doses Crestor raises the HDL or good cholesterol by about 8% where Lipitor only raises HDL by 3%.  Other studies have shown that plaque build up in the arteries (atherosclerosis) that causes heart attacks and strokes, is not just about LDL, but also about HDL.  Other studies looking at high doses of Crestor when compared to placebo show that it can prevent plaque build up and possibly even lead to regression.  The Lipitor data on this is less robust.

The timing of the results at the AHA is particularly interesting, since it will coincide with Lipitor going generic.  Zocor or simvastatin has been generic for a while, and works well in many patients.  However, patients requiring more aggressive reduction in their cholesterol will not meet their goals on simvastatin and high dose simvastatin is associated with side effects, which prompted a recent FDA warning. (See Don't Take High Dose Simvastatin). Thus, the need for a generic potent statin like Lipitor is huge.  However, this could mean that insurers will make it very, very difficult for patients to get Crestor.  UNLESS......... SATURN proves that high dose Crestor compared to high dose Lipitor significant reduces plaque build up in high risk patients.
Therefore, the SATURN trial is really a huge gamble for Astra Zeneca.  When Merck's ENHANCE trial showed that Vytorin didn't really do more than the generic statin, prescribing rates dropped precipitously. Crestor likely faces the same fate is SATURN turns out to be a negative study.

Thursday, August 4, 2011

Why OTC Lipitor is a Bad Idea

As reported by the Wall Street Journal, Pfizer, the maker of one the best selling drugs ever, is trying to get the FDA to approve an Over the Counter (OTC) version of their blockbuster Lipitor, not coincidentally on the eve of Lipitor going generic.
Readers of this blog know that I am a big proponent of cholesterol lowering medications like Lipitor (statins) for patients at moderate to high risk of cardiovascular disease.  In particular, I am a fan of the more potent statins like Lipitor and Crestor, because of their increased efficacy with fewer side effects (see Don't Take High Dose Simvastatin).  Finally having a generic version available of Lipitor will be a great thing for many patients.

That said, making Lipitor OTC is a bad move. First, there is a difference between medications like Prilosec and Claritin that have gone over the counter and Lipitor.  Diagnosis for GERD and allergic rhinitis for which those medications respectively treat are made mostly on symptoms alone.  Patients don't need to go to medical school to suspect that they may suffer from heart burn or allergies. Starting treatment without seeing a physician is actually medically sound because more often then not the medications will relieve symptoms avoiding a physician office visit.  In contrast, starting a patient on a statin is much more tricky.  Patients need to know their individual risk for cardiovascular disease.  Though there are tools available online to determine this (I use the NIH's risk calculator daily in my clinic), determining individual risk of disease, benefit of taking a medication and weighing this against potential side effects is best decided by a discussion between a doctor and patient. Secondly, before starting a statin medication, one needs to know their cholesterol levels.  Though there are other methods (health fairs, work screenings) of determining cholesterol levels, getting a blood test usually requires a visit to the doctor's office. In addition, follow up blood work (checking for medication efficacy, liver side effects) is warranted after starting treatment. Thus, the benefit of having a medication OTC is negated.  Finally, Claritin and Prilosec are very safe.  They are as safe or safer then other OTC medications.  Lipitor is also very safe, but is associated with rare, but serious side effects.  Taking Lipitor OTC without consultation with a physician creates the risks of patients developing these side effects without proper warnings and therefore potentially worse outcomes if attention is not sought.

The second main reason that OTC Lipitor is a bad idea is that it will hurt more patients than it will help.  The reason for this is that when a medication goes OTC, insurance companies usually will not pay for them.  Now that Allegra is over the counter, it is virtually impossible for any of my patients to get a prescription version antihistamine.  Though they can easily get this OTC, not having a prescription means they need to pay for it out of pocket.  The cost of an OTC medication, even if the generic OTC version is used, is generally more than the co-pay for a generic prescription.  It is unlikely that generic Lipitor will make the $4 Walmart or Target list, but after six month, the co-pay for generic Lipitor would still likely cost a lot less for most patients then paying for OTC Lipitor out-of-pocket. 

Bottom Line: The reason why Pfizer wants Lipitor OTC is for one reason: to make more money.  They can argue that cardiovascular disease is the number one killer in the US, and by having Lipitor OTC, it will be available to more patients.  However, because statins require blood work and medical consultations, the risk of harm to patients outweighs the potential benefits of greater availability.  In addition, this will result in cost-shifting to patients in order to boost Pfizer's profits. Hopefully, the FDA will say what they said when Merk tried to pull this off: "No."