How good is Repatha: It lowers heart disease by 20%, but at $14,000 a year is it worth it?

Drugs have both benefits and risks, something that has to be balanced by the individual taking the drug and the insurance company paying for it. Sometimes the risks are not side effects but rather are cost. Such is the case of Repatha, a new monoclonal antibody that uniquely can drive down LDL cholesterol when patients take injections of it either once or twice a month. In an industry-sponsored study that just came out, the use of Repatha in high risk people for cardiovascular disease (CVD) already on statin cholesterol medicines with LDL cholesterols above 70 decreased serious heart events by 20% compared to the use of statins alone.

But there is a catch. While the new drug had virtually no side effects, it costs $14,000 a year. So, while patients may be sanguine about the outcome, insurance companies need to assess if this benefit justifies the cost.

What are the actual numbers? In this study of 27,500 high-risk people over 2 years, out of 1000 people taking the drug, 15 had reduced heart attack or stroke, as the first BRCT shows. There was little mention of whether the strokes were disabling (most strokes are small and resolve quickly) or whether the heart attacks were clinically significant or fairly minor, information that would certainly help decide if the price tag is worth it. But regardless of those details, after 2 years, 985 people out of 1000 derived no additional benefit from this drug. In the next BRCT, it is shown that 0 people out of 1000 who used Repatha cut down their risk of death or of hospitalization for congestive heart failure of unstable angina. In other words, no lives were saved with this drug, and no hospitalizations beyond those for non-fatal strokes or heart attacks were averted. We do not know how long the hospital stays were for the strokes and heart attacks, and what the cost was of those events, since the details are omitted from the article.

The study’s authors are adamant that the positive impact of the monoclonal antibody derives from its effect of lowering LDL cholesterol, and they spend much of their conclusion stressing that point. But that is not something that has consensus among cardiovascular researchers. In fact, several drugs that lower LDL cholesterol do not improve outcome, and some, like torceptrapib (no longer available) dramatically lowered LDL cholesterol but increased the rate of death. The study’s authors point to a drug called Zetia to demonstrate that non-statin drugs that lower LDL can help heart disease since, as they state, Zetia “significantly reduced major cardiovascular events.”

In fact, early Zetia studies showed no improved outcome with its use, and a recent drug-company (Merk) sponsored study that compared Zetia with a statin to just a stain alone found that just 3/1000 people on the combination drug benefited, as the BRCT shows. Thus, lowering LDL is certainly not the primary mechanism in helping high risk heart patients live longer and avoid heart attacks.

It is important to realize that this is one study, it was conducted by Amgen, which is the company that makes the drug, and it is rare that subsequent studies verify results of early pharmaceutical-sponsored studies. Also, we do not know how this drug will impact people after two years; it may improve benefit further, or it could cause serious adverse effects. Finally, we do not know how well this drug may work in people not on statins, or how effective it is compared to statins alone. The benefit of reducing adverse outcomes among people with high risk heart disease who take statins alone is that approximately 50 people avoid serious adverse events out of 1000 people who take the drug compared to those not taking statins, as the BRCT shows.

And unlike with Repatha, statins do reduce the risk of death (12/1000) and are very inexpensive. However, they have side effects that need to be weighed against their benefits, side effects that lead to a fairly high rate of drug discontinuation. A recent blog we put on the AHIP website explains many of the risks and benefits of statin use, and for now those drugs remain the standard of care in people with CAD.

The role of Repatha needs to be assessed for each individual patient, and there may be instances when the high price tag pays for itself by reducing dangerous and expensive outcomes. But certainly we need more studies, more details about the severity of the heart attacks and strokes in the control group, and more time to assess if this drug is going to be worth its excessive price.