COMMENTARY

Feb 19, 2021 This Week in Cardiology Podcast

John M. Mandrola, MD

Disclosures

February 19, 2021

Please note that the text below is not a full transcript and has not been copyedited. For more insight and commentary on these stories, subscribe to the This Week in Cardiology podcast.

In This Week’s Podcast

For the week ending February 19, 2021, John Mandrola, MD comments on the following news and features stories.

COVID

Cases declined from last week, the slope of decline has too.

Plus, millions are receiving highly effective vaccines. We are seeing observational data on vaccines that look quite similar to study efficacy. I think we are coming out of this mess.

My question—how will society deal with a virus that will so obviously become endemic as have many other respiratory viruses?

Even with effective vaccines, and degrees of herd immunity, SARS-CoV2, like influenza, will likely stay with us, and cause infection and death, especially in vulnerable people, for years to come.

Bernard Lown

While there is nearly always a bit of sadness in death, which young person would not sign up for this story.

  • A life of nearly 100 years.

  • Death in your home rather than the hospital.

  • A marriage of over 60 years.

  • The adulation of colleagues.

  • Discovery of a truly life-saving device—the external defibrillator.

  • A Nobel Peace prize.

  • And perhaps his greatest achievement a career defined by an utterly contrarian view of CAD—which, now, has proven to be correct.

In 1981 – the year I graduated high school, and long before statins, Lown was the senior author of NEJM paper describing 212 patients who had profound ST segment depression on a stress test. They followed these patients for 5 years and reported an annual incidence of 1.4%. Only 9 had CABG.

They concluded that such severe ST-segment depression is not associated with a poor prognosis. There is rarely a need to resort to cardiac surgery; medical management is highly successful and associated with a low mortality.

Lown tried to teach us about CAD, but we didn’t listen. To this day, I often think of Dr Lown when I walk by our white board listing the names of people getting nuclear stress studies, which so often lead to caths, and caths find CAD, and this leads to PCI or CABG.

It may take two generations to undo the clogged-pipe frame of CAD.

--a personal note:

I never met Dr Lown, but he too changed my career trajectory.

Years ago, I got involved in the Lown Institute and through that made connections with like-minded people.

From these connections I learned about evaluating evidence, understanding research, and really, most of the meager academic contributions I have made, trace back to the connections I made through Lown.

The Lown Institute called this group the right care alliance.

Right Care sounds banal, but it is not. It is the essence of good doctoring: simple things like sitting down next to the patient, listening, removing their fears, and helping patients understand the true nature of atherosclerosis and heart disease.

Lown railed against fearful phrases. He felt grim scenarios achieved the objective of gaining the patient’s compliance without the need for reasoned and time-consuming explanations.

Type 2 MI

JACC published a large observational study led by James Januzi, looking at type 1 vs type 2 MI with the Nationwide Readmissions Database.

The study included over 200k patients with type 1 MI and about 37k with type 2 MI.

Recall that a type I MI is one due to a plaque rupture and acute coronary occlusion. It is a highly specific syndrome and it is usually easy to tell when someone is having a type 1 MI. You often do not need a troponin—there is pain and acute ST changes.

A type 2 MI occurs when there is acute myocardial ischemia due to a mismatch in myocardial oxygen supply and demand.

Type 2 MI differs from acute and chronic myocardial injury in that the myocyte damage is NOT due to ischemia, say from post-ablation, or a shock, or acidosis, or CKD, or myocarditis.

The main finding of the new study is that patients with type 2 MI have a unique cardiovascular phenotype when compared with type 1 MI, and are managed in a heterogenous manner.

  • Patients with Type 2 MI were older, more often female, had more HF, CKD, and AF.

  • Patients with Type 2 MI less often had cath, PCI, and bypass.

  • Patients with Type 2 MI had lower risks of in-hosp mortality and readmissions at 30 days.

This reiterates the important therapy distinction: type 1 Mi therapy is to open the artery—fast. Type 2 MI therapy is most often to correct the underlying cause.

You can have STEMI or NSTEMI in both type 1 and type 2 Mis. For example, a coronary dissection is not due to plaque rupture and acute thrombosis, but it could present with ST elevation or ST depression.

The study findings surely support an improvement in coding, which should better align with the fourth Universal Definition of MI. Final comment:

This is a good observational study because its descriptive—the authors don’t make causal inference. And since MI is an inpatient condition it makes sense to use the Nationwide Readmissions Database. Too often inpatient databases are used to report on procedures that are often done in patients that are outpatients.

COVID19 and Early AC

Now for a bad observational study.

The BMJ published the study done on about 4300 patients admitted early in the pandemic to VA hospitals.

The main question was whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death at 30 days among patients admitted to hospital with COVID

Thus, there were 2 groups—non-randomized, of course:

84% of the patients received prophylactic anticoagulation within 24 hours of admission, almost always SQ heparin or enoxaparin and a second group of 16% of patients did not receive early anticoagulation.

  • 30-day death rates were 14.3% in those who got anticoagulation and 18.7% in those who did not.

  • No differences in bleeding.

The main problem with this paper is seen in the Kaplan Meier curves. They split immediately and then do not differ. The difference in morality is the same on day 3 as it is on day 26.

Are you telling me that 2 early doses of SQ prophylactic anticoagulation immediately reduces mortality? Of course, it does not.

During that time in the pandemic people were deathly scared of clots in COVID19. And it is well known that patients sick enough to be hospitalized on IM services should receive VTE prevention—this is usually with SQ enoxaparin.

So, a clinician who decided to withhold early anticoagulaiton had to do it for a reason – and this is likely the reason the curves split immediately. Sicker patients did not receive the early anticoagulation.

These findings DO NOT provide any evidence to support anything. They are too confounded.

Sacubitril/Valsartan and HFpEF

FDA approved an expanded indication for sacubitril/valsartan (Entresto). The package insert now reads: to reduce the risk of CV death and HHF in patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal.

The labeling cautions that "LVEF is a variable measure, so use clinical judgment in deciding whom to treat."

In the package insert they cite the findings of PARAGON-HF which I have discussed many times – in short, it compared sacubitril/valsartan vs valsartan in HFpEF with a primary endpoint HF hospitalization and CV death.

The 95% CI of the relative risk reduction ranged from a 25% reduction to a 1% increase in events. There was no significant difference in CV death. The benefit in the composite was driven by HF hospitalizations.

The FDA ad committee was persuaded by two observations

  • the subgroup finding in PARAGON where the reduction in the PEP in patients with EF less than 57%

  • and a meta-analysis combining PARADIGM (s/v vs E) and PARAGON; this analysis found a graded benefit based on EF.

Subgroup findings in trials with nonsignificant primary endpoint are very susceptible to bias, and combining the two trials is dodgy since they used different comparator drugs (medium dose enalapril and valsartan).

Doctors will have to use judgment. Health care is super-expensive. This drug will add lots more cost to an already unjust and unequal system.

My argument therefore would be to force another trial. Let the sponsors pick the subgroup of HFpEF they think the drug will work. If it shows benefit, then we can readily adopt it.

Look at the SGLT2i class for instance – there are almost too many trials to count.

Comments

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