Modern Cardiology May Change Next Sunday
First of all, Happy April Fools day. I thought about writing a fake-trial post. But thought the better of it.
I normally tell you about a single study on Monday.
This week, I want to alert you to the potential bigness of next weekend, when the American College of Cardiology meets in Atlanta. Sunday is an especially important day, as we will hear the results of three clinical trials—each of which could change cardiology in major ways.
The most interesting one is TACT 2—a trial of…sit down for this…chelation.
Ten years ago, Dr. Gervasio Lamas presented results of the placebo-controlled TACT 1 trial, which showed that chelation of heavy metals reduced major cardiac adverse events. The hazard ratio was 0.82, and the upper bound of the 95% confidence interval hovered below one at 0.99. A significant result! What’s more, a subgroup of patients with diabetes seemed to benefit even more.
The medical establishment went nuts. JAMA published the study, but the editors-in-chief had to write an explanatory letter as to why they would publish a “positive” study. A prominent trialist wrote an accompanying editorial expressing concern about the reliability of the trial.
Dr Lamas was not deterred. He went back to NIH for funding. His plan was to restudy chelation in patients with diabetes—the group that looked to benefit most.
Sunday he tells us the results of this confirmatory trial. I am excited.
Think about the consequences of a positive chelation trial: a) humility comes to the medical establishment; b) a new disease-modifying therapy for diabetes is found; c) heavy metals emerge as an important cause of atherosclerosis—opening a new chapter of preventive cardiology; d) Lamas shows the scientific world how to deal with a positive subgroup: that is, don’t over-call it, test it in another trial.
If TACT 2 is non-significant, we all learn the most common thing about medical science: new discoveries are hard.
In the same session, Jacob Eifer Møller, MD, PhD, from Odense University in Denmark, will present the results of the DanGer-Shock trial. I rank this trial—of the Impella ventricular assist device in patients with cardiogenic shock—as one of the most important trials of this decade.
Doctors have implanted tens of thousands of these devices, for 18 years since its FDA approval. The device looks great in drawings. It pulls blood from a failing left ventricle and mechanically pumps it into the aorta. It should work.
The device is invasive and expensive. In 18 years since its approval, no randomized controlled trial has convincingly shown it benefits patients. Recently, the FDA has noted serious safety issues, which the NYT covered last week.
DanGer-Shock aims to be a properly powered trial. Meaning that it should have enough patients to sort out benefit.
Such a trial could not be done in the US. US doctors believe the device works—despite the lack of evidence. The makers of the device heavily market it. Unlike chelation, Impella has many proponents.
The consequences of a negative DanGer shock are massive. Imagine if this device has been used for 18 years and a proper trial shows no benefit. If that happens, the FDA should hold an emergency meeting about how medical devices are approved.
If it is positive, well, then, the observations of the clinicians who actually use the device will be proven correct.
The worst-case scenario would be if the results are inconclusive. I really hope the confidence intervals of the treatment effect are narrow enough to make a reliable conclusion.
Also in that same Sunday morning session, yet another trial testing one of cardiology’s strongest dogmas faces the test of the randomized trial.
Starting a patient who survives an MI on a beta-blocker has reached knee-jerk status. In fact, if you don’t do this, you get dinged for practicing poor quality medicine.
Yet the studies that reported benefit from beta-blockers were done in the 1980s-1990s, well before we opened arteries with stents.
Swedish investigators will test beta-blockers in post-MI patients who have normal ventricular function. REDUCE AMI has two groups: beta-blocker or no beta-blocker. The primary outcome is major adverse cardiac events.
I predict no benefit. If that happens, cardiology is changed.
And we will have learned the important concept that seminal trials should have an expiration date.
Bottom-line: pay attention next weekend. We will have much to discuss in the coming weeks. It’s like a Super-Bowl weekend for cardiology.
Why aren’t ALL doctors in ALL specialties not demanding emergency hearings on the WPATH files? A huge scandal. I know it is not the topic of this great essay, but I could not help but be struck by the call for emergency FDA hearings if the device turns out to not show benefit in spite of 18 yrs of cardiology “ believing “ it works.
The WPATH files are much more devastating and effects young people . Surely the industry of gender affirming troubled kids with outright lies and no informed consent deserves emergency action.
This is NOT about legal protection for trans adult which is just. WPATH( world professional assoc of trans health) has knowingly violated every norm standard and ethic that has been the bedrock of the doctor patient relationship. It is way beyond malpractice which is about accountability for errors.. Sterilizing kids first with hormonal manipulation and then with aggressive surgical interventions($$$$$ for those who do these interventions) without any evidence( but lying and claiming evidence) and without informed consent is a travesty ( There is no word to that captures the enormity of what these WPATH practitioners are doing still) and every doctors’ business. This is not an error on their part. It is however a grave error on the medical profession if we fail to stand for what we KNOW is right and protect these ever growing number of confused troubled kids.
Thanks for the previews of these various trials. I'll be interested to hear about the results.
I wonder if you could talk to someone at the conference about improving the ACC's risk calculator for developing ASCVD, which has absurdly nonsmooth properties which undermine its credibility. According to a calculator, a 52 year old Caucasian male, total cholesterol 179, LDL 110, HDL 50 , BP 110/70, nonsmoking, no diabetes/meds has a lifetime risk of 5% (light blue bar below):
https://tools.acc.org/ascvd-risk-estimator-plus/#!/calculate/estimate/
If you increase total cholesterol from 179 to 180 (a negligible increase) and leave the other values the same, lifetime risk jumps from 5% to 36% !?!?! It's just not plausible that such a tiny increase in total cholesterol should lead to such a giant jump in lifetime risk. The ACC can do better than this. Millions and millions of people are being advised about whether to take a statin, whether to change their diet and lifestyle, etc, in part based on this calculator. Since it's available to anyone online, it's easy enough for numerically-inclined skeptical patients to find it online, play around with it, discover its ridiculously nonsmooth behavior and lose some confidence in the medical system.
There are thousands and thousands of data scientists out there who would love the chance to collaborate with the ACC on improving that calculator. The current calculator can't possible be based on rigorous methodology if it jumps from 5% to 36% when total cholesterol goes from 179 to 180.