Prof. Gabriel Steg who was a discussant for the ELIXA trial at the hot line sessions today, called non-inferiority safety trials of diabetes drugs a waste of resources. Some of the panelists agreed. He also cautioned that showing no difference in efficacy between drugs in a non-inferiority safety-driven trial does not mean the test drug has no CV efficacy.
Dr Lopez Sendon the discussant for the SCOT trial said it won't change practice. Should still use celecoxib at lowest effective dose for shortest treatment duration in patients at low CV risk.
Dr Lars Wallentin a discussant for the OPTIDUAL trial was disappointed that it was stopped early. He called for Europe to do more independent, investigator-initiated trials leveraging the healthcare system. Citing the TASTE trial as a good example, he said that research should be part of usual care and incorporated into the healthcare infrastructure.
I went to an interesting session this afternoon on differences in approval for drugs and devices. The back and forth presentations alternated b/w US and European perspectives. Representatives from regulatory bodies, industry, and physicians each had a voice. US voices included Steve Nissen, Robert Califf, Chris Canon and Robert Scott (Amgen). EU voices included Hans Hillege (NL), CW Ham (DE) and Alan Fraser (UK).
Califf called for more conversation b/w FDA and EU regulators. He urged the two groups to learn from each other.
Nissen said wisdom is not geographical. He showed examples where the US and EU got it right and wrong--the US was wrong about metformin and the EU was wrong on renal denervation.
Scott complained about the burden of FDA advisory committees. He made a compelling case.
Cannon used the FDA's non-approval of dabigatran 110 to call attention to the goal of regulatory bodies: should regulators judge how much benefit to risk ratio is just right?
Hamm contrasted the pluses and minuses of CE mark. Bad -- renal denervation; Good -- Aortic valves.
Fraser lauded the FDA for its transparency and lamented the EMA for its lack of it.
OptiLink HF: Dr. Michael Bohm from Homburg Germany presented data on telemedicine alerts from patients whose volume status had "crossed fluid thresholds". Unfortunately there was no impact on all cause death or hospitalization at 18 months. HOWEVER, a large percentage of patients felt well and declined the offered intervention which likely impacted the primary endpoint.
I am at the ESC Hot-line press conference -- OPTILINK HF study showed no change in all cause death or cardiovascular-related hospitalization with telemedicine notification of rises in intra-thoracic rises in impedance. This is a big blow for Medtronic's OPTIVOL feature in ICDs.
This should have worked. The idea is that fluid overload precedes HF decompensation. OPTIVOL detects fluid overload pretty well. Why wouldn't the notification work? Dr. Bohn made the point that the active treatment arm did NOT include an audible alert to the patient. Instead it sent a notice only to the caregiver.
< I see this is as a serious weakness of the protocol. CHF patients must be engaged in their own care. The best CHF care is when patients are actively engaged with their own care.
The SERVE-HF trial presented today by Dr. Martin Cowie, London UK demonstrated a worsening of mortality when CENTRAL (not obstructive) sleep apneic patients with reduced LV systolic ejection fraction were treated with Adaptive Servo Ventilation for 5 hours per night/7 days per week. More questions remain than answers but the theories include possible issues with the autonomic nervous system/arrhythmia link that might explain the increase in sudden death. More study is certainly necessary to tease out the issues but it was enough information that Dr. Cowie feels that this therapy should not be applied in low EF patients with central sleep apnea for now.
The BENEFIT study: Presented by Dr. C. Morillo, Ontario: Treatment of CHAGAS disease (T. cruzi) induced cardiomyopathy with benznidazole treated the parasitic infection as measured by reduction in parasite DNA but a reduction in parasite activity did not impact clinical outcomes. Perhaps the treatment was induced too late? or the inflammatory process that was initiated early on should now be the target of therapy. Chagas is becoming more of a global issue with an increasing burden of heart failure in many parts of the world emphasizing the importance of producing more studies on the topic.
CUPID 2-Presented by Dr. Barry Greenberg from U of California San Diego: This is the largest gene therapy study to date in heart failure. Patients with the following characteristics were studied: Average LVEF of 24% with Class II-IV heart failure, both non-ischemic and ischemic cardiomyopathy patients were included,a requirement of either elevated BNP or HF admission in the last few months was necessary for enrollment. They then received intra-coronary infusion AAV1/SERCA2a preceded by NTG infusion. 250 patients were randomized to therapy or placebo. The therapy failed to reduce the primary endpoints of time to recurrent HF-related hospitalization, all cause death or need for transplant. It is back to the drawing board for Gene therapy in HF.
"One minute comments" from the presenters at this morning's Press conference: Clinical trials that don't confirm the hypothesis help us to design other clinical trials. They are building blocks and help future endeavors in management of heart failure. Regarding CHAGAS cardiomyopathy-5 million dollars was spent for 13 years to study 3K patients helped us to achieve a remarkable 99% follow up with patients. Regarding the central sleep apnea study: I'm hopeful now we have the network to move the study of sleep apnea along as well as the study of other processes. Dr. S. Yusuf who chaired the session: You learn more from a trial that DIDN'T tell you what you already knew. (That seemed to be the theme for the day)
More on ETOH-septal ablation for HOCM
Presentation by Dr. Josef Veselka (CZ) on the Euro-ASA registry. My comments: This is a registry, not a RCT. It's hard to make comparisons to septal myectomy or medical treatment. It's also open to selection bias as one doesn't get ETOH ablation unless there is suitable anatomy. And there's the caveat that this is a skill dependent procedure and experience of operator and centre is key.
5) Only 9% of patients had ICD!
4) At 10 years, 77% of patients were still alive
3) Dose of ETOH relates strongly to incidence of heart block. (Overall pacing rate only 12%. < Wow
2) Degree of LVOT reduction associated with symptom improvement and mortality
1) Annual post-procedure death rate is low at 2.4%
PLATFORM trial presented by Dr. Pamela Douglas, DUKE University, S.C. USA: Historically, over 50% of patients who undergo a coronary angiogram do NOT have fixed obstructive disease. This study included stable chest pain patients deemed at intermediate risk who underwent combined CT-FFR . This approach resulted in the cancelling of 61% of planned invasive angiograms. This study required 3D modeling of hyperemia with sophisticated algorithms . At up to 90 days there were NO adverse events in those patients in whom the angiogram was cancelled. This approach was deemed safe and improved patient selection for angiography.
ABSORB STEMI TROFI II trial: Dr. Patrick Serruys London UK: Nearly complete arterial healing was noted in STEMI patients who received everolimus coated bioabsorbable stents at 6 months. Non-inferiority was noted compared to drug coated metallic stents which included the primary endpoint , a score assessing stent coverage and restenosis of the target vessel as evaluated by optical coherence tomography imaging (OCT). Dr Serruys was asked if he felt this type of stent platform is the wave of the future. He answered, "I think metal will be in the minority in 2020" .
ABSORB JAPAN: Presented by Dr. Takeshi Kimura, Kyoto Japan. Published online today in the Euopean Heart Journal, this trial evaluated stable CAD patients who received either an Everolimus-eluting bioresorbable scaffolds or a. Xience cobalt chromium everolimus eluting metallic stent. AMI patients were excluded from this trial as well as patients with LVEF less than 30% or who had excessive tortuosity or calcification. At 12 months, bio-resorbable stents demonstrated a similar safety and clinical efficacy profile as the metal drug coated stent. Dr. Patrick Serruys commented on that trial that "The hope is that at 2-3 years we might see a benefit" but for now we only know that short term 6-12 months trials demonstrate similarity and non-inferiority.
One of the most interesting decisions in electrophysiology is the choice between CRT-P and CRT-D. The COMPANION trial (done more than a decade ago) was not designed as a head-to-head comparison of the two devices. Both devices compared favorably against medical therapy.
In the US, we implant mostly CRT-D.
But i believe CRT-P devices should be discussed with patients. As such, I was drawn to a presentation at ESC on the CerRiTuDe trial. This is a multicenter registry trial looking at patients implanted with CRT-P or CRT-D. It's not a randomized trial but it is real-world data. Patients implanted with CRT-P were older and had more advanced disease. It's no surprise then that mortality was higher in patients with CRT-P
But...and this is big: There was no difference in sudden death. That means the excess mortality in CRT-P group was do to advancing heart failure and other diseases.
Interesting take on CVD in women
You ever wonder why females rarely die during sport? @ssharmacardio presents new data on gender-specific adaptations to sport #esccongress
Dr Sigrun Halvorsen reports 800 drugs interact w warfarin. Hold the presses, #esscongress, I think that's a good thing. Forces monitoring!
My tweet out suggesting express DLR service for future meeting got a reponse! The power of social media
ESC 2015 Highlights Dr. Cecilia Linde:Stockholm chose her top picks for impactful studies:
Mantra AF" RFA ablation is superior to AAD to maintain sinus rhythm when given as first therapy, however the success of AF therapy depends upon lifestyle modification.
XANTUS: First large prospective study describing use of Rivaroxaban in a broad non-valvular AF patient population . Rates of stroke and major bleeding were low in routine clinical practice at 96% after one year. It was noted that adherence was 80% at one year and 75% were satisfied with therapy.
Leadless pacing: This is promising for VVIR pacing needs but also open up future possibiliites of more advanced pacing modes and combinations with sub q ICD.
The Environment: Household appliances are safe : i.e. hair dryers- provided proper grounding. Cellular phones- need 15 cm distance from device. Security systems-don't linger or lean on them. CERTITUDE registry: Could CRT Paced pts benefit from ICD? This was a 4-year follow up : The conclusion was that sudden cardiac death mortality was identiical between Paced patients and those with ICD's because heart failure and other non- CV causes were responsible for the majority of deaths.
ESC launches call to action on the environment targeting air and noise pollution and sustainable transport
"Not many people know about the link between pollution and CVD. The environment is not something individuals control. It is an issue that needs to be addressed by politicians and companies. Members of the public can play a role though, in lobbying for change,” said ESC Press Committee Chair, Prof Steen Kristensen, from Denmark in a press release.
ESC 2015 Highlights continued: Dr. Frank Ruschitzka-Zurich: With regard to ALBATROSS: "It used good old spironolactone in MI: The smoking gun: STEMI's benefited!! BUT....Is good old Spironolactone good enough? Companies have now developed new MRA's and one of them is Finerenone, a novel molecule that has greater receptor selectivity. in ARTS-HF: It did not meet the primary endpoint of reduction of BNP but the higher doses of Finerenone (a hypothesis generating finding) at 15-20 mg had lower clinical events", he concluded. His ending remarks: " We are a global congress,the biggest in the world!! So our brilliant south American colleagues will say this (next trial) is why I came to London! The BENEFIT trial is A REALLY NEAT study! Up to 7 million people could be treated with this drug Benznidazole but unfortunately there was NO benefit. We will see if they need a higher dose of the drug. The highlight of the entire meeting was in sleep disordered breathing in heart failure. This was a RUDE awakening!!! When your spouse is snoring and you have to change rooms, that's obstructive apnea but central apnea is Cheyne-Stokes breathing. Dr. Martin Cowie thought tackling it would be a slam dunk! BUT in SERVE-HF, the use of that little innocent device that seems to say' we'll help you' actually didn't. BUT in HF patients with EF of 30%, this was a RUDE awakening!! It not only doesn't help, it may even kill you! What are we going to do with that? Take your patients with heart failure and reduced EF's OFF this device!!...and come to Florence May 21-24 for heart failure congress 2015. You will see new treatments. For God's sake, we need to hold devices to the same standards as drugs!", he stated emphatically.
Dr. Byran Williams: London, UK. started with EUROASPIRE : "Only 35% of pts are treated for elevated blood pressure and clearly there is room for improvement! With regard to BP severe enough to require 3 drugs, the optimal treatment of this resistant hypertension remains undefined. In PATHWAY-2 we randomized spironolactone, doxazosin, bisoprolol and placebo in a random cycling order for six weeks with no washout periods. Spironolactone 25-50 mg was superior to placebo and to the other two drugs. It was also safe despite concerns regarding potassium but there were no withdrawals. Additionally, patients should NOT be defined as "resistant" unless they have been treated with A+B+C drugs AND spironolactone. In the next trial, we looked at diuretics: Thiazides traditionally have issues of glucose intolerance and potassium elevation so they asked, 'Can combining ameloride with thiazide be more effective and also metabolically neutral? The primary endpoint was the glucose tolerance test. There was an increase in glucose with HCTZ but a highly significant reduction in glucose with Amiloride. The combination of amiloride plus HCTZ was more effective at lowering BP. It's the only diuretic with superiority in outcomes trials (vs calcium channel blockers and beta blockade). Then there is the new LCZ696 Neprilysin inhibitor (ARNI) studied in isolated systolic hypertension. This compliments RAS blockage. In PARAMETER, the reduction of systolic BP and pulse pressure was impressive compared to Olmasartan. There was a superiority of central and peripheral systolic pressure reductions especially night time pressure which is known to be the more dangerous elevation. There was also a reduction in NT-proBNP and urinary cGMP. This was the first study to demonstrate these benefits of LCZ696.
Dr. Raphael Rosenhek of Vienna commented on trans catheter valves: The UK TAVI registry compared the trans-apical, direct aortic and subclavian access approaches that demonstrated subclavian access to be the most favorable non-femoral access . Pre-existing Afib predicted long term mortality and new onset a fib predicted CV events in the short term. With regard to Transcatheter MV implant : When extensive annual calcification is present it is often a cause for patients to be turned away. In this study, there were 13 cases of patients with severe annular calcification with good outcomes -1 patient died , 11 demonstrated substantial improvement in MR. With regard to the TRAMI-Registry-MITRA-CLIP: There was a 20% mortality after one year with predictors of mortality including those with severe symptoms, the presence of anemia, a history of prior aortic valve intervention, the presence of elevated creatinine, an EF < 30% and severe TR. Then there are some new Innovations: In degenerative MR, there were 75 pts with severe degenerative MR who were approached with a Neochord implantation who did well especially in those with isolated P2 lesions. We also saw 40 patients who had a femoral trans-septal approach using a Cardioband screwed around the annulus that led to a reduction in MR and certainly more is going to come in the future!!!
I'm signing off now! Check back with our HEARTWIRE journalists and my co-blogger Dr. John Mandrola who will have continued contributions from this meeting today and for several days to provide you with complete professional coverage of news and views from London. It was a pleasure and an honor to walk among some of the greatest minds in cardiology to gain impactful insight into the practice of cardiology. It was my pleasure to pass along those findings to you and ultimately to your patients. Best of luck to you in your implementation of this information! #ESCcongress@theheart.org.