The first late breacking clinical trial presentations from ACC 2015 will be PROMISE:, A Randomized Comparison of Anatomic versus Functional Diagnostic Testing Strategies in Symptomatic Patients with Suspected Coronary Artery Disease and PEGASUS: Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin. Stay tuned for topline findings...
ACC President Patrick O'Gara kicked off the opening session after an intro video that looked and sounded like a trailer for the latest Hollywood blockbuster.
ACC President Patrick O'Gara on EHR in opening session, "Pearls of wisdom cannot be measured in a single drop- down menu". Are we compromising patient care to improve billing and archiving?
Dr. Pamela Douglas presenting the results of the PROMISE trial during the late-breaking clinical trials session at ACC 2015. In the US, more than 4 million stress tests ordered each year for patients with chest pain but there is little data to show which test is preferable.
In today's opening session of the ACC 2015: Dr. Abraham Verghese-Infectious disease specialist, gave a lecture entitled, "I Carry Your Heart". "The electronic medical record are a waste of words. They are about billing. They have nothing to do with the patient's heart. My problem isn’t that it isn’t just fiction. I like fiction, I read fiction and I write fiction for God’s sake. Does the word 'electronic' medical record just grate on you? My problem is what it does with the actual words we would get to spend with the patient.. In the coming days, you will be discussing the metaphorical heart, but the real heart awaits you the next time you see a patient. It will come with the other heart for which you have tracings and other kinds of data. When you listen and touch with skill your own heart, then your head and your heart will be fulfilled, ....it will be a kind of poetry. You will have said without words, "I carry your heart. I carry you in my heart”. Real advice for real practitioners with real patients. He is an oracle for the ages.
Over 2 years, coronary CT angiography did not reduce hard clinical events compared with functional testing, PROMISE showed. Low event rate in both treatment arms, around 3.1%, which is likely the result of patients being well treated with cardiovascular medications.
In the functional testing arm of PROMISE, 67% received a stress nuclear test, 23% received stress echo, and 10% underwent exercise ECG testing.
Dr. Jennifer Mieres on PROMISE: 50% were women in this cohort ! Congratulations!
Bob Harrington on PEGASYS (Tigagrelor 90 mg vs. 60 mg vs. placebo with history of remote MI): "It’s nice to to see the North American results going along with the rest of the trials!! (audience laughter) . "Now that we’ve seen the DAPT trial results on stented patients, it seems pretty clear there is not a time you should EVER come off the dual platelet therapy. If you were treated with 90-mg bid up front, when you get to a year should we down titrate? Presenter Dr. Mark Sabatine's Answer: Our treatment spanned from a minimum of 16 mo. to 4-years, ¼ were a half decade out from their qualifying MI and it looks like the curves continue to diverge. The 90-mg dose performed exceedingly well in the acute setting. In terms of platelet inhibition patients may require something different 2 -hours vs. 2- years out. I think the question about titrating should be a topic of future study . I think I’d start at 90-mg (acutely) and at one-year downward titrate to 60 mg bid.
Melissa holds the PROMISE investigators' feet to the fire at the press conference!
It's been a several hours since the keynote by Abraham Vergehse on the impact that the business of medicine especially the electronic health record has had on the sacred and extraordinary relationship doctors have with their patient.
I can't help but acknowledge all that has been lost and regret that much of the "healing arts" has been lost and SOME of it is physicians fault. But we are increasingly becoming employed physicians (As i walk around seeing friends from residency and fellowship almost all are now employed by the dominant medical gorilla in their market)
It will be increasingly difficult to change back to these subjective healing experiences in a RVU and meaningful use dominated world.
In the "Debating the Optimal Pharmacology for PCI in ACS" session-BallRoom ACC 2015: 3-hour Post PCI infusion of Bivaliruden in AMI eliminates the SAT issue, (effectively reducing bleeding and therefore reducing mortality). Excellent review oF Bivalirudin by Dr. Greg Stone.
More from "Debating Optimal Pharmacology in ACS". Per Dr. Greg Stone, " Finally, in the last few minutes we have the real world NCDR-Cath PCI registry. If you do the procedure with Bivalirudin and use a femoral closure device, bleeding is reduced. (Even in patients with radial access? YES!!! ) "Bivalirudin still substantially reduced major bleeding" because "major NON-access bleeding is GI bleeding which drives mortality. Bivalirudin reduces both." In the words of the late Mr. Spock, "FASCINATING". No exclamation point ..... of course.
Beta Blockers under attack at session here today question their use in uncomplicated post MI with changes in guideline recommendations being highlighted.
To kick it off the new smart phone audience response system was used and 75% of the audience only use oral beta blockers prior to discharge in uncomplicated MI - therefore do not use beta blockers early or IV
Arguing for Beta Blockers in MI Robert DiDomenico
The physiologic effects and anti-ischemic effects and potential antiatherosclerotic effects are rationale for their protective effects of beta blockers - There are 1685 trial of beta blockers over the last 5 years
First trial published 50 years ago this year => Lancet 1965;2:551-3 Propranolol reduced mortality by 50%. (patient's were hospitalized for 28 days post MI)
In BHAT trial JAMA 1982;247:1707-14 reduced mortality 9.8 to 7.2% at 3 years ARR=2.6%
ISIS-1 used early IV and then 7 days of beta blocker with atenolol - only 7 days had benefit that extended to 20 months
There are 7 large trials of > 1000 patients which show benefit - meta analysis are challenging to interpret since they include some beta blocker trials which included non FDA approved beta blockers
He says that even if mortality benefit is challenged the reinfarction data for beta blockers is wrong and rivals the reinfarction benefits seen in DAPT trials
In addition cardiac biomarker changes have changed the definition of MI - early trials 1965-80 used transaminases for MI Dx, from 1980 - 2000 we used CPK and now are using trepan which "picks up" smaller MI
2. 50 yrs of evidence
3. data arguing for reduced role have limitations
Douglas Jennings argues against
arguing that beta blocker use should stop =. "COMMIT to other drug therapies"
COMMIT trial (2005) of MI patients NOT treated with PCI had IV metoprolol early and then orally at 200 mg for 28 days had no benefit of death, reinfarction or cardiac arrest. There was significantly more hazard from CHF, hypotension and cardiogenic shock in beta blocker treated patients. Characteristics of shock patients were age > 70, HR > 110, SBP < 120 and patient with Fillip 3 were all had high risk for shock with beta blockers. In the lowest risk patients the likelihood of shock was neutral but he medium and high shock index patients were at significantly higher risk. The takeaway was that the overall effect was neutral but there is a significant risk of shock in these patients that DID NOT receive PCI
COMMIT led to ACC/AHA guideline change for STEMI care in 2008 and maintained in 2014 STEMI guidelines making IV Beta Blockers a Class III recommendation (may be harmed)
Most contemporary dat in MI is for anti platelet trials, DES, strategies of PPCI like thrombectomy and the beta blocker data is mostly before 2980 (except for COMMIT). Beta blockers were beneficial in reperfussion era but in meta analysis in repercussion era showed increased CHF and shock but decrease angina and recurrent MI.
CHARISMA shows no benefit of beta blockers on mortality. REACH showed no survival benefit of beta blockers
"Stick with aspirin and statin"
1. Avoid IV Beta blocker
2. Reconsider routine use of oral beta blockers post MI - the destruction of myocytes that beta blockers provided in older era is no longer an issue because of mechanical revascularization with primary PCI
3. Avoid routine use in stable CAD
Joe Alpert (moderator) says the therapy should be individualized - beta blocker should be used on a case by case basis e.g. hypertension. Avoid them in patients with bradycardia
What to look forward to on Sunday at ACC15
Late-Breaking Clinical Trial Session II features:
OSLER: Effect of the PCSK9 Inhibitor Evolocumab on Cardiovascular Outcomes
EMBRACE STEMI: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety, Tolerability and Efficacy of Intravenous Bendavia™ on Reperfusion Injury in Patients Treated with Standard Therapy Including Primary PCI and Stenting for ST-segment Elevation Myocardial Infarction
REG1: A Randomized, Open-Label, Multi-Center, Active-Controlled, Parallel Group Study To Determine the Efficacy and Safety of the REG1 Anticoagulation System Compared to Bivalirudin in Patients Undergoing Percutaneous Coronary Intervention
SCOT-HEART: Computed Tomography Coronary Angiography In Patients With Suspected Angina Due To Coronary Heart Disease
Late-Breaking Clinical Trial Session III features:
PARTNER 1: Five-Year Outcomes after Randomization to Transcatheter or Surgical Aortic Valve Replacement: Final Results of the PARTNER 1 Trial
A Randomized Comparison of Self-expanding Transcatheter and Surgical Aortic Valve Replacement in Patients with Severe Aortic Stenosis Deemed at Increased Risk for Surgery 2-Year Outcomes
SAPIEN 3: Early Clinical and Echocardiographic Outcomes with the SAPIEN 3 Transcatheter Aortic Valve Replacement System in Inoperable, High-Risk and Intermediate-Risk Aortic Stenosis Patients
DEFLECT III: A Prospective Randomized Evaluation of The TriGuardTM HDH Embolic DEFLECTion Device During Transcatheter Aortic Valve Replacement
Outcomes of the Initial Experience with Commercial Transcatheter Mitral Valve Repair in the United States
BEST TREATMENTS FOR PPCI
Roxanne Mehran Bivalrudin vs Heparin in STEMI. She takes the Bivalrudin is best position
Heparin has several limitations - it's unpredictable and causes platelet activation and ha a longer half life
Bivalrudin inhibits platelet activation and is a specific inhibitor of Factor X
In REPLACE, ACUITY, HORIZON there was mortality benefit and less transfusion
In HORIZON 3 yr MI 5.1% vs 2.9% (Bivalrudin compared to heparin + GPI)
In Euromax Bivalrudin had lower mortality than Heparin plus routine or bailout GPI
BRIGHT had 1/3 heparin monotherapy 1/3 bivalrudin 1/3 heparin + GPI with no mortality benefit but less bleeding with bivarudin
HEAT showed 30 day MACE Bivalrudin 8.7% vs Heparin 5.7% but criticized because bilvalrudin had stent thrombosis of 2.7% - this was also found in met analysis
Expect to get results from Angio-MATRIX of 7500 patients expected on Monday here at ACC
1. Consistent benefit of NACE
2. Will rely on ANGIO-MATRIX to validate or refute HEAT findings especially stent thrombosis
Upstream therapy for STEMI
Excess stent thrombosis with bivalrudin seen in meta analysis with a benefit on bleeding Lancet 2014;384:599-606
In ATOLL trial there was a trend toward benefit in per protocol MACE was at 1 month using enoxapirin 0.5 mg IV and lower bleeding compared to heparin. Also similar benefit of LMWH in FINESSE and ACOS and FAST-MI
1. Shorter acting agents (bivalrudin and LMWH) are safer for bivalrudin and more effective fro LMWH compared to UFH
2. Moderate anticoagulation is needed after primary PCI
Robert Harrington - Optimal Upstream platelet inhibition
STEMI guidelines DAPT is a Class 1 indication for primary PCI; US guidelines do not distinguish between clopidogrel and new agents but European guidelines recommend new agents over clopidogrel because in bothPLATO & TRITON there was a significant benefit in STEMI or PPCI populations compared to clopidogrel
In ATLANTIC for NSEMI showed no benefit using ticagrelor early Stent thrombosis at 50 days 1.2 vs 0,2% favoring early treatment
In STEMI, Clopidogrel absorption is worse than in health volunteers making its use more problematic. Morphine may also effect bioavailability
Cangrelor (an IV ADP inhibitor) is rapid on and rapid off and might be attractive in STEMI been shown to have lower stent thrombosis tan clopidogrel
My take home from best practices in STEMI patients receiving PCI (PPCI)
1. The trials don't address exactly what many programs do: patients are given heparin in the field by EMS or in the ER and come to the lab with that on board. Once access is gained (for us almost always radially) the option is to check an ACT and give additional dose as needed or begin bivalrudin)
2. Patients have all received aspirin either in the field usually (or by themselves at home)
3. Adding the second agent for DAPT is the standard protocol with different institutions choosing diffrenet agents (ticagrelor or prasugrel) before the patient comes to the lab
4. The unanswered question for me is - can we wait to give the P2Y12 inhibitor until the angiogram is complete in case the patient needs emergency coronary bypass surgery? Is it worth the hazard of not giving it to the 95% who will get PCI and possibly benefit by it vs the hazard/ inconvenience of having to wait four days for surgical revasculalrization for the < 5%.
We are now cranking up the live Blog from the floor of the ACC 2015 Sunday Morning Late Breaking Joint Session of the American College of Cardiology/Jama. It is chaired by Eric Peterson and Jeffrey Kuvin. Panelists: Chris Cannon, George Dangas, Judith Hochman, James McClurken, and Sortirios Tsimikas. ,Presenters: Marc Sabatine, Michael Gibson, Roxana Mehran, David Newby and Daniel Mark. Topics: PCSK9 inhibitors, EMBRACE (Bendavia), REG1 anticoagulation, and two topics on CTA. Stay tuned!
The data from OSLER looks particularly impressive with massive LDL-cholesterol lowering. The median decline in the trial was from 120 mg/dL to 48 mg/dL. The study even hinted at a decline in cardiovascular events, although this analysis was just exploratory. The one-year trial was not powered for hard endpoints. Still, as Dr. Seth Bilazarian told the heartwire reporters, this is probably the last real look at the PCSK9 inhibitor data before a possible FDA approval.
Yes! great information on PCSK9 inhibitor sub q injection EVOLOCUMAB : “The curves diverged early and continued to separate over time", said Dr. Marc Sabatine. The therapy was safe and well tolerated but neurocognitive events : confusion, delirium and forgetfulness included in this ‘grab bag’ of adverse events occurred in .9% on therapy vs. 0.3% on standard therapy. We look forward to the FOURIER trial in which formal neurocognitive testing will be performed -to be reported in 2017. FOURIER will include primary and much desired HARD endpoints of CV death, MI, hospitalization for Unstable Angina, stroke and revascularization.
Eric Peterson to Dr. Michael Gibson: “Congratulations for joining the ranks of those who have studied drugs that work well in animals but not so well in humans”; commenting on the EMBRACE trial. The compound BENDAVIA was studied and it’s effect on Re-perfusion injury on patients treated with standard therapy including primary PCI for STEMI. The study was not powered to detect an impact on reperfusion arrhythmias.
Dr. David Newby on CCTA patients with suspected angina: (Prior to the study), "We were doing an awfully lot of unnecessary angiograms. We had a lot of skeptics across Scotland. For me, it's that clarification of the diagnosis. We stopped a lot of statins and anti-anginals. These are treatments that would have been given for life. We need to do the economic evaluation which is a work in progress. There are two issues: Early outcomes that are driven by revascularization and long term outcomes...to see if statins perhaps over a 5-year period of time will make a difference".
Now in the press conference for the late-breaking clinical trials, with Dr. Sabatine chatting about the OSLER study. I'm covering the SCOT-HEART study, which is a trial of coronary CT angiography. As Dr. Walton-Shirley stated, the researchers are reporting they improved the certainty of diagnosing angina due to coronary artery disease but also reduced unnecessary interventions, such as coronary angiograms.
The CSPPT study, which included almost 21,000 adults in China, showed that 10 mg enalapril plus 0.8 mg folic acid reduced the risk of first stroke in those with no prior history of MI vs enalapril alone (its primary outcome). No significant between-group differences in frequency of treatment-related adverse events. Presenter Dr. Huo Yong: "We believe these findings are universal and not only for China populations but also for populations throughout the world, including the United States."
The MitraClip may shine a little brighter, at least in its perceived prowess: Its CMS-mandated postmarket study, presented at a late-breaker today by Dr Paul Sorajja (Minneapolis Heart Institute) found more pronounced mitral valve functional improvement than had been observed in the pre-approval randomized trials. Why? Could be any of a number of factors, he told me, but one possibility: freed of having to comply with study eligibility criteria in the real word experience, operators may have taken on patients with more severe MV impairment in the first place. The worse the valve function initially, often, the greater the improvement with intervention. My story is coming soon.
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In the “Ulnar Artery Intervention Non-inferiority to radial approach" talk today, Dr. Rajendra Gokhroo” dispelled the myth that ulnar access is inferior to transradial approach. Chalking up the prior poor results to inexperience, he looked at ulnar cannulation performed only by operators who had performed at least 50 ulnar cannulations. CABG and shock patients were excluded . 2400 patients were randomized to ulnar or the radial approach. The primary endpoint was a composite of MACE, major cardiovascular events, hematoma and cross over. The primary endpoint was comparable in both groups with radial cases have a surprisingly but not statistically significant increase in vasospasm. Dr. Gokhroo concluded that “if you have expertise in ulnar cannulation, 75% of femoral artery cannulations can be avoided” and “If both arteries are palpable, I’ll go for ulnar. We are doing all palpable ulnar arteries first at our center”. Very very Interesting.
Antonio Columbo - update on bifurcation tips and tricks
1. If side branch disease is more than 5 mm beyond the ostium don't treat it as bifurcation - put in 2 stents
2. For sidebranch rewiring avoid hydrophillic wire for recrossing
3. DK-crush is preferred to culotte because yoou dont have to give up the parent wire
4. Almost always do post dilation and finish with IVUS with goal of > 7 mm2 final CSA
5. When crossing to 2 stent strategy from provisional approach use TAP: T and protrusion
6. In planned 2 stent technique use DK Crush or culotte
7. Ostial diagonal lesions are particularly challenging - use medical therapy until the patient matures the LAD lesion. The hazard of ostial diagonal lesion treatment alone is significant for LAD compromise. Less is more.
Dr. Jung-Min Ahn from South Korea presented the 5-year follow up results from the Pre-COMBAT study. These were Unprotected left main patients comparing PCI to standard surgery. At 1 year, PCI was non-inferior. After two years, ischemic TVR rates were higher in the PCI group at 9% vs. 4.2%. 5-year follow up data demonstrated that only 70% of PCI patients were still on standard anti- platelet therapy. Though the rate of MACCE as well as the rate of death, MI or stroke was not significantly different between patients assigned to PCI with a CYPHER stent compared to those who underwent CABG, there was an increased incidence of ischemia driven TVR of 17% in those with Left Main and 3v vessel disease who underwent a PCI vs. 4% in those who underwent CABG. An audience question: Would newer stent platforms have preformed better? My question: Especially in CYPHER patients if more than 70% had remained on standard anti-platelet therapy, would that have significantly impacted outcomes?
Commenting on the GARY Registry, the LARGE high-risk all-comer population of German cohorts of 15,964 TAVR patients Dr. Thomas Walther presented outcomes of a severe vital complication rate plus cross-over rates remaining at 4%, stable sternotomy requirements of 1.2% and decreasing complication rates over the years. At the conclusion of his presentation, he was asked, “Do you plan to go on recording every single procedure?” He replied, “We can’t go on forever capturing every single procedure. It costs some money”. He later added, “We need some more time for valve durability studies”, so I guess that really is a “yes”.
The DAPT data was described today by a commenter as “An amazing study not likely to be duplicated”. This study randomized 11K ACS and non-ACS patients post PCI remaining on thienopyridine therapy for 12 months to now 18 months. While ACS patients had greater risks for ischemic events, the treatment benefit of continuing thienopyridine therapy was beneficial for both and bleeding risks were similar. When Dr. Robert Yeh, the presenter of the DAPT data was asked ‘what is the future?’, he replied, “We have an NIH grant to develop clinical tools to identify a population of patients in whom it’s exceedingly necessary to continue therapy. He also pointed out that the majority who developed adverse events were due to repeat revascularization, oddly enough, not bleeding. There was a numerical imbalance as well with cancer rates that was explained by a cancer diagnosis at the time of randomization.
BEST trial of teh ABbot Xience DES vs CABG in multivessel CAD, showed that MACE was higher with PCI 17% vs. 12% CABG at 5 yrs, mostly driven by revascuaization with no signifiant digffenece in death (but trends against PCI.
>CABG still "best" for MVD esp daibetes