Inflammation, Ablation, Fats, LDL, etc .. My review of ESC 2017

The European Cardiology Congress, ESC as it is called, has grown into the largest medical meeting in the world. This year, more than 31,000 attendees from 153 countries came to Barcelona.

I was busy. Here is an update of the big stories:

Inflammation: 

Experts agree that inflammation associates with heart disease. One of the keys to showing inflammation causes heart disease would be to show a reduction of cardiac events with a drug that blocks inflammation.

The CANTOS trial tested the ability of a drug called canukinumab, which is already approved for rare causes of inflammatory diseases, to reduce cardiac events. Canukinumab exerts its anti-inflammation action by blocking a key signaling chemical in the inflammation cascade.

CANTOS turned out positive–well, sort of. Patients who took canukinumab had a 15% reduction of cardiac events. That sounds like a lot but translates to an absolute reduction of 0.64%. Researchers noted two other important observations: one was that blocking inflammation led to a small rise in fatal infections. The other nifty observation was that patients on canukinumab died from cancer at a lower rate than those on placebo. This anti-cancer effect will be explored further.

My post on CANTOS is here: Quick Thoughts on the CANTOS Trial

AF Ablation: 

The CASTLE-AF trial studied the effect of AF ablation in patients with advanced heart failure–patients had low ejection fraction and ICDs. Does ablation in these patients reduce death rates or hospital admissions? The preliminary answer was yes. (Preliminary because the trial has not yet been published.)

Investigators reported a lowering of death rate by 47%. That’s massive. Many drugs and ICDs have been shown to lower death rates in patients with heart failure, but the reductions range from 15-35%.

The published results of this trial will be novel and could change the view of AF ablation. Novel because, to date, AF ablation has only been shown to improve quality of life–not outcomes. One strong warning is that patients included in CASTLE-AF were highly selected, most had previously failed antiarrhythmic drugs and the centers doing the ablation were highly experienced. I worry that irrational exuberance at the time of trial publication will add to the overuse of AF ablation that already exists.

My Post on Castle AF is here:  CASTLE-AF: Does It Change the World of AF Ablation?

New Use of Rivaroxaban (Xarelto):

The drug rivaroxaban (Xarelto) has become well-established for prevention of stroke in patients with AF. At ESC, a huge trial called COMPASS tested lower doses of rivaroxaban for the prevention of cardiac events (heart attack, stroke, death) in patients with established heart disease. We call this secondary prevention.

Showing improvement in secondary prevention in 2017 is hard because we have so many good treatments already.

The COMPASS trial showed that the combination of low-dose rivaroxaban (2.5 mg twice daily) plus aspirin lowered the event rate by a mere 1.3%. And this gain was countered by a 1.2% rise in major bleeding. Though this sounds like a wash, experts from around mainstream cardiology lauded the results. The king of cardiology, Dr. Eugene Braunwald, from Harvard, provided the discussion in the main auditorium after the trial was presented. He embraced the results as a breakthrough.

I was not so embracing. My post on COMPASS is here: The COMPASS Trial: Time for Clear Heads, Not Celebration

Extremely Low Cholesterol Levels:

You may have heard about the new cholesterol-lowering drugs called proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor drugs. These 14,000$ per year injections cause dramatic drops in LDL–the bad cholesterol. In the previously published FOURIER trial, patients on PCSK9i drugs had a lower rate of cardiac events, but surprisingly, the reduction in nonfatal events did not translate to improved death rates.

At ESC, the authors of FOURIER presented a sub-analysis of the results looking specifically at the association of LDL and cardiac events as well as safety. (Extremely low levels of cholesterol raise concern about other bodily functions.)

Three findings emerged: one is that many patients in the trial achieved crazy-low LDL levels, some in the single digits! The second finding was that the lower the LDL, the lower the event rate. The third finding was that despite crazy-low levels of LDL, the investigators noted no safety issues.

One popular narrative from these observations is that LDL in the blood is toxic and should be removed. In my post, titled, FOURIER: Very Low LDL-C Post Hoc Analysis Doesn’t Move the Needle, I make the case that this evidence is not enough to change our thinking about these expensive drugs. And, since the trial was truncated after only 2 years, it’s hard to say much about safety. Remember, people don’t take cholesterol-drugs for only two years.

The Healthiest Diet? 

The debate on which diet and which percentage of nutrients, say fat, carbohydrates, plants, etc rages on. At ESC, results of massive observational study of more than 130,000 people across Earth, found that carbohydrates to be a villain, and fat intake, even saturated fat, associated with better outcomes. The PURE study, which included not one but three papers, was published in the Lancet.

One aspect of PURE is that it flies in the face of recommendations from our American Heart Association. My colleague Sue Hughes has great coverage of this story here: PURE Shakes Up Nutritional Field: Finds High Fat Intake Beneficial

Sue’s story includes this beautiful quote from senior researcher Dr. Salim Yusuf:

My hope is that our results will stop the whole population from feeling guilty if they eat fat in moderation. While very high fat intake—when it accounts for 40% or more of your dietary intake—may be bad, the average fat intake is about 30% and that’s okay. We’re all afraid of saturated fat, but actually we shouldn’t be. Saturated fat in moderation actually appears good for you.

Miscellaneous: 

I recapped these stories in my weekly podcast called This Week in Cardiology. 

I also gave my Watchman debate. I think I did pretty well as the antagonist. My opponent, Prof Horst Sievert was strong. He made mention that my case against Watchman came from a blog–but I countered that it has, in fact, been peer-reviewed and accepted for publication in a major journal. Stay tuned for more. Readers … stay suspicious of left atrial appendage closure.

Only a week after the terror tragedy, Barcelona felt like the safest city I have been in. If anything, given the tone at the meeting and on the streets, the terror event seemed to create greater cohesiveness of the people.

JMM

3 comments

  1. Does CASTLE-AF modify your view of the placebo effect being the explanation of ablation’s effectiveness?

    1. I don’t think I said AF ablation was placebo effect. I think I said it’s possible, and the evidence thus far has not refuted that possibility.

      The preliminary results of this trial does not/will not change that view, namely because there was no sham arm.

  2. Dr. John: Please help me understand something, re: the heart and inflammation. In a phrase, I have come to believe that exercise good, inflammation bad. Athletes are known to possess enlarged hearts as a result of exercise (inflammation?). Can this be explained as a good outcome – healthy? If so, can one deduce that there are two types of inflammation as far as muscles are concerned – the good exercise related inflammation, and the bad couch potato inflammation? Thanks.

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