Our rant from this series is about the drug Vioxx's scandal from the early 2000s, a drug that has been implicated as contributing to hundreds of thousands of deaths and disabilities, and one in which Merck prioritized profits over Americans' health outcomes.
Ethan: I want to talk about a couple of examples of how direct to consumer advertising, especially with the allowance of these companies to send consumers to a secondary source or location to get all of the required information legally, including safety data, efficacy data, contraindication, side effects, all that other jazz. One of them we will dive into much deeper detail in a subsequent episode. But in 1996, Purdue Pharmaceutical released Oxycodone. They essentially misrepresented [00:01:00] data, manipulated graphs about how long oxycodone would last in the system, when its concentrations would peak, and made a lot of claims based on a lack of data. They had a very aggressive, dishonest, immoral marketing campaign, specifically initially targeting the region of Appalachia, where myself and Michael are from. And they are widely believed to have played a major role in instigating the opioid and the drug epidemic that we find ourselves in now, with over a hundred thousand overdose deaths per year and having one in five world overdose deaths.
The other example is Vioxx, or Rofecoxib, an NSAID, or Non-Steroidal Anti-Inflammatory Drug, similar to something like Ibuprofen (Advil) or Naproxen (Aleve).[00:02:00] Merck spent 160 million in 1999 on direct to consumer advertising for Vioxx. Vioxx was out for four or five years and, in hindsight, has been implicated as causing 140,000 heart attacks and strokes, and around 45,000 deaths. Merck used an internal study called the VIGOR Study, the VIoxx Gi Outcomes Research Study that showed a much reduced risk of stomach bleeding, which is a common side effect of NSAIDs. For that reason, they claimed it would be a more effective and a safer medication (than other NSAIDs). However, their 2000 VIGOR study, it showed a four to five times increased risk of heart attack [00:03:00] with Vioxx compared to the standard of care at the time, Naproxen.
Vioxx came out in 1999. In 2000, they released the VIGOR study, showing a four to five times increased risk of heart attack. And in 2001, the Arthritis Drugs Advisory Committee, an FDA subsidiary, met to discuss the VIGOR study. A Merck representative said that the finding of four- to five-time increased risk of heart attack was actually due to naproxen’s cardio-protective effect. The next day, on February 8th, 2001, after the Arthritis Drugs Advisory Committee of the FDA met, Merck sent a bulletin to its entire Vioxx sales force, over 3000 representatives, ordering in all caps: DO NOT INITIATE DISCUSSIONS ON THE FDA ARTHRITIS ADVISORY COMMITTEE OR THE RESULTS OF THE VIGOR STUDY. [00:04:00]. And, they actually created this cardiovascular card, a pamphlet that was produced by their marketing department, indicating that Vioxx was associated with one eighth of the mortality from cardiovascular causes of that found with any other anti-inflammatory drugs. They produced these results by pooling data from other studies using low-dose Vioxx for a short period of time, studies that were not designed to assess cardiovascular safety.
After the fact, in congressional hearings (in 2004), Merck was forced to turn over a lot of this internal data. It gets so much worse. Not only did their VIGOR study find an increased risk of heart attack and stroke, Merck apparently designed the study specifically to [00:05:00] exclude those at risk of heart attack, and they still had a huge increased risk of heart attack. So who knows what the actual increased risk was, it may have been 8 or 10 times increased risk.
Eric Topol (a Cleveland Clinic cardiologist) and two of his colleagues published a paper in JAMA, the Journal of the American Medical Association, arguing that the VIGOR study most likely showed that Vioxx raised the risk of heart attacks and warned doctors to be wary of prescribing it to patients at risk of heart attack. He first sent the paper to a colleague at Merck, which then quickly triggered a visit from Alise Reicin, a senior Merck scientist, who told him that he had gotten it wrong and basically threatened him that he would be embarrassed if he published a paper on it. So, many years later, Eric Topol testifies in front of Congress that Merck had done [00:06:00] this. On top of that, I reached out to Eric Topol to see if he had any interest in commenting on this or giving us his firsthand account. And, it was really disheartening, the response basically said that he could not go back to that period of time in his life, that it was a very difficult time for him and his family.
This guy got demonized. He tried to get discredited by Merck because he was trying to sound the alarm and This is a guy who is just trying to do what is right for his patients. At the end of all this, Vioxx is recalled in 2004, five years after it was released and analysts estimate that Vioxx accounted for about 1.2 billion of Merck's 6.6 billion net income in 2003 alone. They did pay out almost 5 billion in settlement money,[00:07:00] but this is one of the most egregious examples of how unchecked marketing and advertising within a healthcare company or a pharmaceutical company can lead to really bad outcomes for us Americans, for us patients.
Michael: Especially when you have essentially a disconnect between what the science and the clinical data says versus what the messaging is. There are selective and non-selective anti-inflammatory medications. What they were trying to do is find one that was, as you mentioned, less destructive. So you can decrease inflammation by blocking this Cox2, helps with inflammation across the body, but then also Cox1 is associated with the lining of the gut. And so a medication to decrease inflammation across the body generally also can affect the lining of the gut. And that's where you get a lot of the gastric irritation or ulcers and GI bleeds. So the goal of [00:08:00] these was to go to something that's more Cox2 selective and you think, oh, we get all the benefits across the body inflammation while avoiding the adverse effects. But the problem is, as Dr. Topal would talk about, is you are now saying we're gonna be more selective for decreasing inflammation, but blood vessels need inflammation to increase perfusion, and you clamp down on a vessel, now you're talking about vascular events, ischemia and things like that. So the science of it makes sense and somebody like him looked at this and said, just thinking about it, you're doubling down on this one mechanism. Now we're thinking hypertension, we're thinking strokes, but that goes against the marketing, which is, ‘no, this should be better for the stomach’. And that's part of the issue. Other medications that came along like it, such as Bextra (Valdecoxib), the same thing, is when you double down on this mechanism, that's a problem. The hubris to say we're going to ignore the fact that scientifically this seems valid, but because we have a narrative. We want to say that this is a safer drug we [00:09:00] move toward and Naproxen, my goodness, oh yeah, Naproxen has actually benefits cardiovascularly, it's funny that this drug that's been out for decades, and suddenly has that ability. Naproxen seems to be about one of the best ones of these newer medications for the heart, but to use that and say, oh no, it's to blame Naproxen for skewing the data.
Ethan: And it's not that Naproxen is cardioprotective. Naproxen is not as cardiotoxic.
Michael: Yeah. The manufacturers of Aleve petitioned the fda right around, 2016. And they said can we say that we have a cardioprotective effect? And the FDA said, ‘no, you can't say that. ‘
Ethan: And Eric Topol, when Merck came back to him, and said, ‘No, no, no. You're misinterpreting this,’ basically what we call ‘gas-lighting’ today, right?
Michael: Yep.
Ethan: ‘No, you've got this thing wrong. This older naproxen is cardio-protective. That's what's skewing the data.’ And Eric Topal says, ‘what the fuck are you talking about? I've been [00:10:00] a cardiologist for many years, learning medicine, going to medical school, going to residency, passing all kinds of standardized tests about these issues, and I've never once heard that Naproxen is cardio-protective. It's so obviously pushing a narrative. These examples are so egregious they really just piss me off. I understand the drive for profit. But it's like, your back is against the wall, you have been caught red-handed, it is clear that your drug is causing more harm than good, and like you said, they continue to double down. They continue to fight the system and say, ‘no, it wasn't me. I didn't do it,’ even at the expense of Americans’ health.