Mandrola's Top 10 Cardiology Stories 2015

John Mandrola, MD


December 17, 2015

1. PCSK9 Inhibitors Released Into the Real World

This year, the FDA approved the injectable monoclonal antibodies evolocumab[1] and alirocumab[2], which induce dramatic drops in LDL cholesterol. The problem is we do not know whether that translates to fewer heart attacks, strokes, or death. We also don't know whether the drugs are safe over the long term. The longest follow-up in a clinical trial was less than 2 years; LDL-lowering is a lifelong proposal. I'm not saying the drugs are unsafe; I'm merely saying we don't know.

Without outcomes data, we can’t know anything about cost-effectiveness. We have made a big gamble. If the outcomes trial (FOURIER) due out in 2017 shows minimal to no benefit, we will have wasted a lot of money—and waste is something the US healthcare system needs less of. A caveat: patients with familial hypercholesterolemia who have high LDL-C levels uncontrolled with statin drugs might want to take a chance on these drugs.

2. SPRINT Delivers, but Not Without Trade-offs

Blood-pressure control is important, but we don't know the ideal target. SPRINT[3] compared lowering blood pressure to 120 mm Hg against a more lenient goal of 140 mm Hg in high-risk older adults. The data safety monitoring board stopped the trial early because of an increased number of cardiac events in the lenient-BP arm. Efficacy of intense BP control came at a cost: more drugs were required, and more subjects in the intense-BP arm experienced syncope, acute kidney injury, and electrolyte abnormalities.

SPRINT was a positive trial; the challenge will come in applying the results to real-world practice. Do not downplay the pill-burden issue. In a hypothetical study, many people would trade dying earlier[4] to avoid daily medications.

3. Coffee and Fat Are Back

Nothing is more basic to health than what we eat. This year, we relearned that not a single randomized controlled clinical trial backed the 1970s-era advice to cut fat consumption to less than 30% and saturated fat to less than 10%.[5] This revelation led an expert panel to release new recommendations to the US government.[6] In the 570-page report, many of the basics remained, such as eat more fruits, vegetables, whole grains, nuts, and fatty fish and fewer refined sugars and trans fats. Two major reversals included the allowance of moderate caffeine intake and removal of limits on dietary cholesterol. In 2015, a consensus grew that refined sugars promote illness—and momentum grew for using nudges, such as taxes, to reduce their consumption.

4. The Basics Make a Comeback in AF Treatment

There were three discoveries in atrial fibrillation (AF) this year. First, the STAR-AF 2 trial[7] surprised many because it found that additional ablation beyond pulmonary-vein isolation in patients with advanced forms of AF did not improve outcomes. Second, the LEGACY trial[8] and CARDIO-FIT trials[9] showed that weight loss and gains in fitness delivered potent antiarrhythmic effects. Finally, the ARREST-AF Substrate study,[10] which won a Young Investigators Award at the AHA meeting, showed that risk-factor modification worked by improving electrical and structural properties of human atria.

The big difference in 2015 is that thought leaders now speak and write about risk-factor modification. They say, yes, it's hard to achieve, but it is central to the care of patients with atrial fibrillation.

5. SGLT-2 Inhibitors Impress, but Concerns Remain

Medical meetings are conservative affairs. The fact that Dr Silvio Inzucchi (Yale University, New Haven, CT) received a round of applause during his presentation of the EMPA-REG Outcome trial[11] at a European diabetes meeting warrants mention. Patients with type 2 diabetes and established cardiovascular disease receiving empagliflozin (Jardiance, Boehringer Ingelheim/Lilly), a sodium glucose cotransporter-2 (SGLT-2) inhibitor, were less likely to die than those taking placebo. Experts called this a landmark trial because it's the first time a drug for diabetes has lowered death rates.

Two notes of caution: One is that no one understands how the drugs reduce mortality. Another is that the FDA issued warnings about ketoacidosis and bone fractures with these drugs.

6. NOAC Reversal Agents Soothe Our Worrying Minds

More than 70,000 patients were enrolled in the clinical trials comparing the new oral anticoagulant drugs against warfarin. All the trials reported fewer deaths in the NOAC groups. Yet, in the risk-averse human mind, the what-if bleeding scenario weighs heavily.

This year brought relief. The dabigatran reversal agent idarucizumab[12] (Praxbind, Boehringer Ingelheim) received FDA approval in October. And in a New England Journal of Medicine[13] paper released online in November, the factor Xa reversal agent andexanet alfa safely reversed the anticoagulant effect of apixaban and rivaroxaban in older volunteers. FDA approval for andexanet will likely come soon.

7. Cutting the Cord in Pacing

The Achilles' heel of cardiac pacing devices is the lead. This year began the wireless revolution in cardiac pacing. Both the NanoStim LP[14] leadless pacemaker (St Jude Medical) and the Micra TPS[15] (Medtronic) performed well. Both devices have earned CE Mark in Europe, and FDA approval is likely.

One way to look at these devices is that the impact will be small because single-chamber ventricular pacing accounts for a small proportion of devices. That's true; but this is the first of many (wireless) disruptions to come in cardiac pacing.

Two more thoughts: a leadless pacemaker is placed through a femoral sheath. That means any cardiologist can implant it. Look for a rise in the number of single-chamber device implants. Second, think forward 5 years. It's likely that a leadless pacemaker will be combined with a subcutaneous ICD generator to make a leadless ICD.

8. Interventional Breakthrough Not in the Heart but in the Brain

Five clinical trials[16,17,18,19,20] demonstrated clear benefit for the use of endovascular treatments alone or as an add-on to tPA in patients who present with acute stroke. The numbers needed to prevent major long-term disability were consistently less than 10.

Previous studies of endovascular therapy in patients with acute stroke had not shown benefit. The difference in the newer studies: faster interventions, newer-generation retrievable stents, and inclusion of patients with documented occlusion of a major vessel.

There's also a Watchman-like lesson embedded in this story. The first of these trials, MR CLEAN,[16] enrolled 500 patients from a small country of only 16.8 million people. In an editorial[21] in the New England Journal of Medicine, Dr Werner Hacke (University Hospital Heidelberg, Germany) gave the Dutch government credit for this feat. He said enrollment was that good because the device was only reimbursed when used in a clinical trial. He added this timely quote: "This policy may be difficult to implement in other healthcare systems, but imagine what progress the medical-device field would see if this strategy were the rule."

9. For Most Patients, Say No to Bridging

The rationale for periprocedural bridging in patients taking anticoagulants is that exposing them to a higher risk of bleeding will be offset by fewer thrombotic events. That never made sense to me. Math dictates that the daily risk of coming off anticoagulants before and after an intervention is tiny. And many nonrandomized observational trials had failed to show a net benefit for bridging.

This year, two studies, one observational[22] and one a large randomized clinical trial[23] (BRIDGE), demonstrated that bridging resulted in higher bleeding rates and no lowering in thrombotic events. In the observational trial, bleeding was 17 times higher with bridging. A big caveat: investigators from the BRIDGE trial excluded high-risk patients with mechanical valves and previous stroke. So we don't know the answer for these patients. For most, though, less is clearly more.

10. MOC, Still in the ICU, but Off Pressors

Multiple authors, mostly Robert Lowes from Medscape Medical News, wrote stories this year on the American Board of Internal Medicine (ABIM) maintenance of certification (MOC) process. Each story garnered hundreds of comments—most of them negative toward the ABIM.

First there was the "we-got-it-wrong" apology from Dr Richard Baron. Then came the announcement of a rival certifying group. Investigative reporter Kurt Eichenwald upped the rhetoric in his "Civil War in Medicine" story in Newsweek. Later in the year, an analysis published in Circulation[24] showed board certification was not a strong predictor of PCI outcomes.

By the end of the year, ABIM's concessions—allowing specialists to recertify only in their specialty, loosening of MOC requirements, and talk of changing the 10-year exam—seems to have dampened criticisms. What certification looks like in the coming years is unknown.

That's it for 2015. I want to thank you for the support. I'm grateful for your comments, even when in disagreement. See you next year.




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