This transcript has been edited for clarity.
Hi, my name is Mamas Mamas. I'm professor of cardiology at Keele University, and welcome to Medscape. Today we're going to talk about the top trials of 2019. Which trials in my view have made an impact on clinical practice?
These aren't really in any particular order, but rather just the order that I chose to talk about them in.
DAPA-HF
So the first one I want to talk about is the DAPA-HF trial, one of the real landmark trials in heart failure.
So we know that SGLT2 inhibitors in randomised controlled trials in patients with cardiovascular disease have been shown to reduce heart failure admissions. So the premise of this trial was to look at whether patients with heart failure have better outcomes with dapagliflozin (Forxiga, AstraZeneca).
This was a randomised controlled trial in 4500 patients with heart failure and an NT pro-BNP of greater than 600. The patients were randomised either to standard heart failure regimes or to the SGLT2 inhibitor dapagliflozin. The inclusion criterion was a reduced ejection fraction of less than 40%.
The primary outcome was worsening heart failure or death from cardiovascular diseases. And this was reduced by 25% in the dapagliflozin arm.
Now, this is a really important trial. Why? These patients were optimally managed with state-of-the-art medications, 10% had Entreso (Novartis), over 95% of these patients were on beta-blockers, and 60-70% were on ACE inhibitors.
So this was a well-managed cohort, and dapagliflozin reduced the primary outcome, both in diabetic and in non-diabetic patients. Actually, there was no difference in outcome irrespective of diabetes status. Why is this important? Well, we know that heart failure admission is associated with poor prognosis and patients with heart failure have worse outcomes than many patients with cancer.
This trial shows that this medication, dapagliflozin, even in patients with optimal management, has a marked benefit on prognosis and will really change how we think about the management of heart failure.
I think it also will raise questions on who should start these medications. Dapagliflozin is a diabetic drug, but we seem to see efficacy in non-diabetic patients. I think this really is an important trial.
PARTNER 3
The second trial I want to talk about is the PARTNER 3 trial. Patients are becoming increasingly elderly. We see this in clinical practice all the time, and among the commonest valvular heart disease is severe aortic stenosis. TAVR (transcatheter aortic valve replacement) has been used initially in patients who were inoperable, then in high-risk then intermediate risk patients. So PARTNER 3 was asking the question whether patients at low-risk, according to Society of Thoracic Surgeons risk score predicted mortality of less than 4%, would benefit from TAVR compared with surgical aortic valve replacement (SAVR).
This was a non-inferiority trial, 950 patients were randomised either to SAVR or to TAVR, and the primary endpoint was death, stroke or all-cause hospitalisation. Initially this was randomised as a non-inferiority trial, but as a secondary endpoint, they assessed for superiority.
And this was really quite an interesting trial. Why? Because TAVR proved to be both non-inferior and superior to surgical AVR. So the primary endpoint in TAVR at 12 months was 8.5%, in the surgical arm it was almost double that at 15%. In the endpoints, there was significant reduction in bleeding, length of stay, stroke, and atrial fibrillation in the TAVR arm. Whereas, unfortunately, there was an increase in permanent pacemaker and moderate and mild paravalvular leak in the TAVR arm. Why is this trial interesting? Well, I think for the first time, it really makes us question what is the optimal management of patients with severe aortic stenosis who are low-risk.
This trial shows superiority for TAVR over surgery. I think we have to bear some things in mind, however. First and foremost, this trial only recruited patients where TAVR was possible through the transfemoral route. And we know that this is not always the case in patients with severe peripheral vascular disease. The average age of the patients was 73. And so I think, certainly for younger patients, there is a lot of questions to be asked.
And I think the most important discussion that has to be had about this trial is that we only saw 1 year endpoints. There isn't really a lot of good data around the much longer-term outcomes of this population. We know that these low-risk young populations have very aggressive valvular degeneration. And so 5, 10 years down the line, we simply don't know whether the outcomes of TAVR are going to be similar to surgical AVR or whether the event rates will cross over in favour of the surgical AVR arm.
Certainly, from my practice, I probably would undertake TAVR in more elderly patients. But I think in younger patients in my view, surgical AVR is very much the standard of care until we have longer follow up data in this group of patients with TAVR.
ISCHEMIA
The third trial that I wanted to talk about was the ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches). The ISCHEMIA trial was presented at the American Heart Association and this is the trial that everybody's talking about.
This was a trial of over 5000 patients from 320 sites from across the world. And it asked the question of whether patients with moderate to severe ischemia on stress imaging or exercise tolerance tests were better managed either with optimal medical therapy or optimal medical therapy and an invasive therapy.
Initially patients had a coronary CT to exclude left main disease and if they excluded left main disease they were randomised to either optimal therapy or invasive PCI.
The primary endpoint was cardiovascular death, MI, hospitalisation for heart failure, unstable angina, or cardiac arrest. The median follow-up was 3.3 years, and the primary endpoint was met in 13.3% in those managed invasively and 15% in those managed with optimal medical therapy.
So there was no difference in outcomes. Why is this important? Well, I think it really answers the question in patients with stable coronary artery disease that have a high burden of ischaemia that actually these patients have very good outcomes with medical management. There is no difference in hard clinical end points between undertaking PCI and medical management.
One thing that the trial did show was better symptom relief at 1 year with PCI and it certainly will help our discussions with patients that PCI, even in contemporary practice, won't make patients live any longer, won't reduce their event rates, but may help reduce their symptoms at 1 year.
I think the other thing that the ISCHEMIA trial really brings out is whether stress tests are necessary. After all, identifying ischaemia in these patients, [whether] moderate [or] severe, if you're not going to do anything about it, if you're not going to do PCI in these patients or use this as a means or as a target for revascularisation, then why do it? So I think certainly, in the coming couple of years, we should see a reduction in stress testing for ischaemia, particularly if now we're saying that in patients with severe ischaemia, there's no real indication to do PCI unless for symptomatic benefit.
Other Highlights
So thank you for joining me for my top three trials of 2019. There have been several other trials: COMPLETE, ISAR-REACT 5, AUGUSTUS, but I thought that these three trials were the broadest and have the greatest impact on clinical practice. So thank you for joining me over 2019. I wish you and your families a very Happy Christmas and happy holidays. I wish you all the very best for 2020 and hope that you will join us in discussing trials and other interesting things on Medscape UK.
More:
Top 3 Cardiology Trials of 2019 - Medscape
- Best 30 Cardiology in Secaucus, NJ with Reviews - YP.com - April 12th, 2018 [April 12th, 2018]
- Cardiology | Weill Cornell Medicine - April 14th, 2018 [April 14th, 2018]
- Cardiology Conferences 2018 | Cardiology Meetings 2018 ... - April 26th, 2018 [April 26th, 2018]
- Dr. Anil Goel, MD - Birmingham, MI - Cardiology & Clinical ... - April 26th, 2018 [April 26th, 2018]
- Clinical Physiology (Cardiology) MSc/PGDip | Middlesex ... - May 15th, 2018 [May 15th, 2018]
- Cardiology Conferences 2018 | Upcoming Cardiology ... - May 16th, 2018 [May 16th, 2018]
- Clinical Cardiology Section | Cleveland Clinic - May 27th, 2018 [May 27th, 2018]
- Journal of Clinical and Experimental Cardiology - Open ... - June 6th, 2018 [June 6th, 2018]
- Cardiology Summit 2018 | Cardiology Conferences | Heart ... - June 23rd, 2018 [June 23rd, 2018]
- Cardiology Clinical and Research Faculty Members ... - June 26th, 2018 [June 26th, 2018]
- Cardiology Conferences 2018 | Cardiology Congress 2018 ... - June 26th, 2018 [June 26th, 2018]
- About Us - New Jersey Cardiology Associates - July 8th, 2018 [July 8th, 2018]
- About Us - Ventura Clinical Trials - August 16th, 2018 [August 16th, 2018]
- Clinical Cardiology Made Ridiculously Simple: Michael A ... - August 22nd, 2018 [August 22nd, 2018]
- Clinical Cardiology - American Society of Preventive Cardiology - October 2nd, 2018 [October 2nd, 2018]
- Heart Surgery Hospital in india | Cardiology Treatment ... - October 7th, 2018 [October 7th, 2018]
- Clinical Cardiology - American Society of Preventive ... - December 3rd, 2018 [December 3rd, 2018]
- Guideline Clinical App - American College of Cardiology - December 7th, 2018 [December 7th, 2018]
- Journal of Clinical and Experimental Cardiology- Open ... - December 12th, 2018 [December 12th, 2018]
- Clinical Cardiology - Baptist Health - December 30th, 2018 [December 30th, 2018]
- Cardiology at Cancun: Topics in Clinical Cardiology - February 5th, 2019 [February 5th, 2019]
- Department of Cardiovascular Medicine, KU School of Medicine - March 10th, 2019 [March 10th, 2019]
- Towards Health Equality: Improving the Management of Cardiovascular Diseases in Women - International Atomic Energy Agency - September 21st, 2019 [September 21st, 2019]
- Lifetime Risk of PAD Varies by Race, but All Are Vulnerable to Traditional Risk Factors - TCTMD - September 21st, 2019 [September 21st, 2019]
- DEFINE-HF: Dapagliflozin Improves Function and QoL, but Not Biomarkers, in HFrEF - TCTMD - September 21st, 2019 [September 21st, 2019]
- Combining Nature and Technology, Luye Medical and Cleveland Clinic Join to Build a Future Hospital in Shanghai - Yahoo Finance - September 21st, 2019 [September 21st, 2019]
- Will Renal Denervation for Hypertension Rise Again? - Medscape - September 21st, 2019 [September 21st, 2019]
- Obstructive Sleep Apnea, Sleep Symptoms, and their Association with Cardiovascular Disease - DocWire News - September 21st, 2019 [September 21st, 2019]
- CNE expands pulmonary, sleep services with Brigham & Women's physicians - Warwick Beacon - September 21st, 2019 [September 21st, 2019]
- What I Am Most Looking Forward to at TCT 2019 - TCTMD - September 21st, 2019 [September 21st, 2019]
- Serelaxin Not Linked to CV Mortality Reduction in Patients Hospitalized for Acute HF - The Cardiology Advisor - September 21st, 2019 [September 21st, 2019]
- Sacubitril-Valsartan Not Linked to Lower Hospitalization Risk, CV Death in HFpEF - The Cardiology Advisor - September 21st, 2019 [September 21st, 2019]
- FDA clears multiuse angiography systems from Siemens Healthineers - DOTmed HealthCare Business News - September 21st, 2019 [September 21st, 2019]
- Balloon Pulmonary Angioplasty Effective for Chronic Thromboembolic PH - The Cardiology Advisor - September 21st, 2019 [September 21st, 2019]
- RWJBarnabas Health, St. Luke's University Health launch clinical affiliation - FierceHealthcare - September 21st, 2019 [September 21st, 2019]
- Bilirubin: A Novel Indicator of Infective Endocarditis Adverse Outcomes - The Cardiology Advisor - September 21st, 2019 [September 21st, 2019]
- Major Bleeding Mostly Early, Not Severe With Rivaroxaban Plus Aspirin in COMPASS - TCTMD - September 21st, 2019 [September 21st, 2019]
- Community-based Care Model Reduces CVD Risk - Managed Healthcare Executive - September 21st, 2019 [September 21st, 2019]
- American College of Cardiology Steps Up: Equal Pay, Opportunities for All - TCTMD - September 21st, 2019 [September 21st, 2019]
- FDA Approves Novo Nordisk's Oral Semaglutide, First GLP-1 in Pill Form - AJMC.com Managed Markets Network - September 21st, 2019 [September 21st, 2019]
- A New Drug for HF? DEFINE-HF Bolsters Dapagliflozin Cardio Cred - Medscape - September 21st, 2019 [September 21st, 2019]
- Seeking Synergy: Bringing Cardiology into Your Enterprise Imaging Strategy - Health Imaging - September 21st, 2019 [September 21st, 2019]
- TCT 2019 Day Two: Transcatheter Valves, New and Old - TCTMD - September 30th, 2019 [September 30th, 2019]
- Transcatheter Options Best for Tricuspid Regurgitation in Matched Registry Analysis - TCTMD - September 30th, 2019 [September 30th, 2019]
- Bypass Surgery and Coronary Stenting Yield Comparable 10-Year Survival - Diagnostic and Interventional Cardiology - September 30th, 2019 [September 30th, 2019]
- TAVR Improves Health Status Over Surgery in Low-Risk Patients at 1 Year: PARTNER 3 - TCTMD - September 30th, 2019 [September 30th, 2019]
- Eidos Therapeutics to Present Interim Analysis of the Ongoing Phase 2 Open-Label Extension Study of AG10 in Patients with TTR Amyloid Cardiomyopathy... - September 30th, 2019 [September 30th, 2019]
- Off Script: The New Gatekeepers of Procedural Education - TCTMD - September 30th, 2019 [September 30th, 2019]
- Study Shows Safety and Efficacy of Near Infrared Spectroscopy (NIRS) Imaging to Identify Patients and Plaques at an Increased Risk for MACE - BioSpace - September 30th, 2019 [September 30th, 2019]
- The Heart of the Matter: Cardiovascular Fitness in Horses - United States Eventing Association - September 30th, 2019 [September 30th, 2019]
- Google parent Alphabet hires former FDA head Robert Califf to lead health strategy and policy - FierceHealthcare - September 30th, 2019 [September 30th, 2019]
- Inclisiran Benefits Patients With Familial Hypercholesterolemia and ASCVD - The Cardiology Advisor - September 30th, 2019 [September 30th, 2019]
- AUGUSTUS: Best Benefit With Apixaban, P2Y12 Inhibitor Dual Therapy - Medscape - September 30th, 2019 [September 30th, 2019]
- New TAVR System Safe and Effective for High-Risk Surgical Patients with Severe Aortic Stenosis - Newswise - September 30th, 2019 [September 30th, 2019]
- Dapagliflozin Improves Heart Failure-Related Health Status in HFrEF - The Cardiology Advisor - September 30th, 2019 [September 30th, 2019]
- Remote Ischemic Conditioning Did Not Improve 12 Month Clinical Outcomes After STEMI - The Cardiology Advisor - September 30th, 2019 [September 30th, 2019]
- Insights from the European Society of Cardiology congress | Speaking of Medicine - PLoS Blogs - September 30th, 2019 [September 30th, 2019]
- Smokers Have More Pulmonary Emboli, Leading to Higher Hospital Readmission Rates | - Diagnostic and Interventional Cardiology - October 22nd, 2019 [October 22nd, 2019]
- AZ's Farxiga gets heart failure prevention okay from FDA - PMLiVE - October 22nd, 2019 [October 22nd, 2019]
- Bayer Announces Recipients of the Pulmonary Hypertension Accelerated Bayer (PHAB) Awards at CHEST Annual Meeting 2019 - BioSpace - October 22nd, 2019 [October 22nd, 2019]
- The Epidemic Of The Metabolic Syndrome Among The Palestinians In The G | DMSO - Dove Medical Press - October 22nd, 2019 [October 22nd, 2019]
- Optina Diagnostics and the Montreal Heart Institute Partner to Develop a New Biomarker for Atherosclerosis - PRNewswire - October 22nd, 2019 [October 22nd, 2019]
- Even With Same Diagnosis, Women Get Half the Heart Attack Treatments as Men - AJMC.com Managed Markets Network - October 22nd, 2019 [October 22nd, 2019]
- Eva Dickerman, Andrew Weil - The New York Times - October 22nd, 2019 [October 22nd, 2019]
- EHR vendor Veradigm and partners creating new shared data tools for researchers - Healthcare IT News - October 22nd, 2019 [October 22nd, 2019]
- Evolocumab Well-tolerated as Add-on for Hypercholesterolemia Therapy - DocWire News - October 22nd, 2019 [October 22nd, 2019]
- Deborah Heart and Lung Center announces affiliation with Cleveland Clinic Heart & Vascular Institute - Health Essentials from Cleveland Clinic - October 22nd, 2019 [October 22nd, 2019]
- New Registry to Provide Insight into STEMI Occurrence, Treatment in North India | - Diagnostic and Interventional Cardiology - October 22nd, 2019 [October 22nd, 2019]
- Finding Your Best Fit in Cardiology - TCTMD - October 22nd, 2019 [October 22nd, 2019]
- Cardiology team expands to meet community need - The Union of Grass Valley - October 22nd, 2019 [October 22nd, 2019]
- Deaths After Ablation of Atrial Fibrillation 'Concerning' in Real-World Analysis - TCTMD - November 1st, 2019 [November 1st, 2019]
- Cutler Family gifts $15 million to University Hospitals to transform mens health care - Newswise - November 1st, 2019 [November 1st, 2019]
- Troponin Increases After Elective PCI Tied to Complexity, Extent of CAD - TCTMD - November 1st, 2019 [November 1st, 2019]
- Caregiving and the Soul of Medicine - Medscape - November 1st, 2019 [November 1st, 2019]
- STEMI Mortality Unaffected by Weekend, Weeknight, or Holiday Admission in France - TCTMD - November 1st, 2019 [November 1st, 2019]
- Cardiva Medical publishes positive results from the AMBULATE pivotal study Cardiology2.0 - Cardiology2.0 - November 1st, 2019 [November 1st, 2019]
- Gaps in Access to TAVR and SAVR: 'Something Needs to Be Done' - TCTMD - November 1st, 2019 [November 1st, 2019]
- Cardiva Medical Announces Publication of Data From the AMBULATE Pivotal Study in the Journal of the American College of Cardiology: Clinical... - November 1st, 2019 [November 1st, 2019]
- Raymond James 4 Analyst Favorite Health Care Picks With Huge Upside Potential - 24/7 Wall St. - November 7th, 2019 [November 7th, 2019]
- Global Computed Tomography (CT) Scanners Devices and Equipment Market Report 2020: Major Players are GE Healthcare, Koninklijke Philips, Hitachi,... - November 7th, 2019 [November 7th, 2019]