PodMed Double T is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week. A transcript of the podcast is below the summary.
This week’s topics include harms related to medical treatment, when to start a common Parkinson’s disease drug, factors related to living to 90, and a diabetes drug and prevention of heart disease.
0:38 Using a diabetes drug to prevent heart disease
1:36 Midway change in the trial
2:26 Which diabetes drug is best?
3:20 Harms of medical treatment
4:20 Rate decreased over 21%
5:20 Help focus in on places to intervene
6:27 When to start medicine for Parkinson’s disease
7:27 No difference in when levodopa is started
8:25 Viral component?
9:00 Factors related to living to 90
10:10 Men had linear association with physical activity
Elizabeth Tracey: What’s going on with harms related to medical treatment?
Rick Lange, MD: Treating diabetes to prevent heart disease.
Elizabeth: What are the impacts on longevity for men and women?
Rick: And when to start therapy for Parkinson’s disease.
Elizabeth: That’s what we’re talking about this week on PodMed TT, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a medical journalist at Johns Hopkins, and this will be posted on January 25th, 2019.
Rick: And I’m Rick Lange, President of the Texas Tech University Health Sciences Center in El Paso, where I’m also Dean of the Paul L. Foster School of Medicine.
Elizabeth: Rick, I’m going to pitch the ball right to you and ask you to talk about using a diabetes drug to prevent heart disease.
Rick: There are many new therapies for type 2 diabetes, one of which is called the sodium glucose cotransporter 2, or SGC2. Now we know that that’s effective in lowering sugar, but the question is can it help prevent heart disease in those that are at risk? There are some studies that suggested in those that already have advanced atherosclerosis or have heart disease it can actually prevent heart failure, but what about those that are simply at risk for it?
So these investigators did a really large trial. This is over 17,000 individuals. About 7,000 of them had existing heart disease, but 10,000 of them did not. They were just at risk. They were placed on dapagliflozin or placebo and followed for 4 years. The major outcome was did this agent prevent major adverse cardiac events? And the answer was it did not. But interestingly enough, midway through the trial, some information came out that suggested these agents could, in fact, prevent heart failure.
What they did was they modified the outcomes of this trial in the middle of it. They got FDA approval, and what they discovered was it reduced the risk of heart failure by about 25%. By the way, it slowed the progression of kidney disease by about 25%. This is great news. This is what I’m going to call a two-for drug. This is a drug that helps lower sugar for diabetes and also helps prevent heart failure hospitalizations for individuals at risk for heart disease.
Elizabeth: And of course, the kidney failure outcome is also really important. We didn’t mention or I didn’t mention that this is in the New England Journal of Medicine. I think that these kinds of studies are informative because there are so many agents out there that target different aspects of the glucose metabolic pathway, and we really need to understand which of these is best.
Rick: Elizabeth, we talked before about the importance of not using glucose as the primary outcome because you can lower sugar, but if you actually don’t prevent some of the vascular complications or some of the complications of diabetes, then you really haven’t received much of a benefit. Now what this study will do is they’ll go on next to say, “What about people that already have existing heart failure? Can this medication in diabetics prevent recurrent hospitalization for heart failure?” So we’ll report that to our listeners when that information becomes available.
Elizabeth: My understanding is that the FDA is changing its focus with regard to diabetes drugs in that they’re not just saying, “Hey, it’s got to lower sugar,” but it also has to have some impact on some of these other outcomes.
Rick: And that’s why this trial is important. It was approved by the FDA, and to get that kind of data requires a large number of patients. In this particular case, over 17,000 patients followed for 4 years, so this is very robust.
Elizabeth: Let’s turn from here to JAMA Network Open. I thought this one was rather interesting. What about adverse effects of medical treatment and mortality in the United States? As we’re both aware, lo these many years ago, there was a focus on, “Wow, how many people are experiencing adverse events when they interact with the medical system, sometimes resulting in death?” And that was more than 20 years ago. The Harvard Medical Practice Study provided the first estimate of that. Now, of course, people are estimating it and attempting to intervene in lots of different ways.
In this particular study, they took a look at data from 1990 to 2016 on mortality that’s due to these adverse events related to medical treatment. They discerned that there were 120,000+ deaths that occurred during that time period, and although there was an increase in the absolute number of those deaths over time, the rate actually decreased by over 21%. So that’s really good news. Also, men and women had similar rates of death related to these types of events. This is not surprising. Age 70 or older had mortality rates that were nearly 20 times higher compared with those in the age group 15 to 49 years.
Interestingly, they also saw a geographic variation with California having the lowest death rate relative to medical treatment and Mississippi having the highest death rate. Unsurprisingly, surgical and perioperative events were the most common types of interventions that resulted in mortality.
Rick: I’m disturbed by the geographic variation. Why should this event rate be twice as high in Mississippi as it is in California? When you drill down a little bit and you say, “What causes these?” About 9% were due to adverse drug events. About 64% were due to surgery and perioperative adverse events. About 9% due to misadventure and about 14% associated with medical management. So this will help us focus in. If two-thirds of these are due to adverse events related to surgery or perioperative care, we can focus on those particular events. That’s obviously, as you mentioned, more likely in the elderly because they’re the ones that are most likely to have surgical procedures.
Elizabeth: Yeah, I think this definitely provides evidence for very targeted interventions specifically around operative and perioperative times.
Rick: So Elizabeth, have you given it any thought as to why the geographic variation is so high?
Elizabeth: I would like to see some examination of patient characteristics with regard to that, because as we know, there’s a good deal more obesity, diabetes, existing cardiovascular disease in that southern belt of the United States, and we’ve talked about that data before. I suspect that’s got something to do with it.
Rick: I suspect, too. You’re right. Health care utilization may be a part of the reason. There are state regulatory efforts that differ among the different states. The patient, the clinician characteristics could be different, staffing patterns — so a lot of different things, but this gives us at least a baseline so we can begin to work on those areas that haven’t seen as much of a decline.
Elizabeth: Very good. Let’s turn to your second one, back to the New England Journal of Medicine, this really important issue of, “Gosh, when do we start using levodopa in people who have Parkinson’s disease?”
Rick: And initially, there was some concern that the use of this could actually progress Parkinson’s disease at a faster rate. Some previous studies done about 14 years ago suggested that wasn’t the case and actually hinted the therapy may actually be a disease-modifying therapy. Perhaps it could slow the progression of Parkinson’s disease. So based upon that, these investigators took a total of 445 patients that had early-stage Parkinson’s disease, and they randomized this entire group to receive 80 weeks of therapy. Half of those individuals received 80 weeks of levodopa. The other half received 40 weeks of placebo and then 40 weeks of levodopa, and they examined [them] at the end of 80 weeks to see whether their symptoms were the same or whether those that had been on the levodopa for a longer period of time had less symptoms.
Well, I’m sorry to report that after the end of 80 weeks there was really no difference in terms of the clinical symptoms between the groups. So where does that leave us? It leaves us saying that first of all, there’s no reason to delay therapy. This suggests that the decisions should be based upon the clinical need, and that what we should do is use the lowest dose available to minimize the side effects.
Elizabeth: And of course, it also points to just this dire need for something that’s more effective than levodopa, especially over the long term.
Rick: In fact, previous studies have looked at not just the clinical symptoms, but actually the neurologic changes that occur based upon MRI. We know the particular area of the brain where there’s degeneration of the neurons, and to modify this disease, we actually need to have some therapy that slows the loss of those neurons. We do know there’s a lot of heterogeneity in the disease. There’s some genetic factors as well, and perhaps in the future we can target these.
Elizabeth: Well, I would say that one thing that I’ve been very tantalized by is the idea that somehow there could be a viral component to this, and that it’s a retrograde transmission from neurons that are in the stomach that go into the CNS into the brain and that may ultimately precipitate movement disorders. So I’m hoping that some of this is going to come to fruition and we’re going to be able to say, “Hey, maybe a vaccine will take care of this.”
Rick: That would be lovely. It’s an interesting hypothesis. As you know, it’s heterogeneous so there are probably a number of different things that cause these particular neurons to degenerate and ultimately cause the symptoms, so stay tuned.
Elizabeth: Let’s turn finally, then, to the British Medical Journal, a study taking a look at a big cohort from the Netherlands. Of course, we are so fond of these because they gather such robust datasets relative to all of this. In this case, what they were looking at are what are the factors that impact on whether someone is going to reach 90 years of age? So they had participants born between 1916 and 1917, so they had almost 8,000 of those who completed a questionnaire in 1986. And then they followed these folks up. Almost 5,500 of them were then included in this analysis. They wanted to take a look at what are the things that make a difference in terms of whether you’re going to make it to be 90.
It turns out that height is really an interesting factor, and since you and I are both tall, we’re sort of happy, I’m sure, [LAUGHTER] to hear that that’s something that’s positively associated. In women, it turns out that 60 minutes of physical activity per day was probably a sweet spot with regard to their ability to live longer. In men, it was a positive linear association between non-occupational physical activity and reaching 90 years of age. The other factor that was really important in women was how has your body mass index changed since you were 20 years old? Those in whom weight gain was noted were more at risk for mortality, so evidence that it’s good if you can hang on to that weight you were when you were 20, as long as that was also a reasonable BMI.
Rick: In both genders, physical activity not related to your occupation ended up being associated with survival. I like the way they did the study. They asked people that were 70 or just about 70 their characteristics and what was likely to predict you to be 90 years of age. Not only do you want to live to be 90, but you want to be a healthy 90, so it’s nice to know that physical activity did influence overall survival. And as you mentioned, the presence of obesity influenced survival in women, but not in men, which I found a little bit surprising.
The height thing is also kind of interesting. I was saying, “Why would height make a difference?” But height is a surrogate for nutrition in childhood. How do you live to be 90? You exercise, you probably eat right, if you’re a woman, you watch your weight, and you enjoy good health.
Elizabeth: I’m going to say, “All right, this is a good way to sum all of this up, but I think men still need to watch their weight.”
Rick: And you could argue that you feel better, but in this particular study, it didn’t seem to improve mortality. It was less important in men than it was in women.
Elizabeth: More on this, unquestionably. On that note, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.
Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.