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Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019
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Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
Results of the ISCHEMIA trial, viewed by many as the moment of truth for PCI in ischemic heart disease, and its sibling ISCHEMIA-CKD, plus several other major trials greeted attendees at the American Heart Association (AHA) Scientific Sessions 2019, held November 16 to 18 in Philadelphia.
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
The AHA meeting returned for a second year in its pared down, 3-day format but maintained a full line-up of clinical trial findings. Among the key presentations this year:
ISCHEMIA: Early Invasive Strategy Strikes Out Against Optimal Meds
COLCOT: Colchicine Shows Promise to Reduce Events After MI
ORION-9 and ORION-10: Inclisiran Shows Large Reduction in LDL
DAPA-HF: Heart Failure Toolbox Poised to Add New SGLT-2 Drug Family
TWILIGHT-ACS: Ticagrelor Monotherapy Affirmed in High-Risk ACS
RECOVERY: Early Surgery Best in Severe Asymptomatic AS?
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
ISCHEMIA: PCI, Surgery Strike Out vs Meds
Viewed by many as the last chance to determine the true value of revascularization in stable ischemic heart disease, the ISCHEMIA trial failed to show fewer major cardiovascular (CV) events with an early invasive strategy than with optimal medical therapy (OMT). Over a median 3.3 years of follow-up, Kaplan-Meier curves for the primary end point — composite of CV death, myocardial infarction (MI), hospitalization for unstable angina, hospitalization for heart failure, and resuscitated cardiac arrest — were similar with the invasive and conservative strategies. The curves crossed at 2-year follow-up, with absolute rates favoring OMT at 6 months by 1.9% and favoring early angiography followed by percutaneous coronary intervention (PCI) or bypass surgery at 4 years by 2.2%. The same pattern was seen for the major secondary end point of CV death or MI. "We calculate that if asymptomatic patients didn't get PCI, we would save over $500 million dollars every year," ISCHEMIA chair Judith Hochman, MD, NYU School of Medicine, New York City, said to rousing applause.
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
ISCHEMIA-CKD: No Gain From Initial Invasive Strategy
Most patients with advanced chronic kidney disease (CKD) and moderate to severe ischemia at stress testing won't live longer or be any more protected from MI if they go straight to the cath lab for possible revascularization, according to the ISCHEMIA-CKD trial, a rare randomized trial focusing on this high-risk group. "An overall initial invasive strategy did not demonstrate a reduced risk of clinical outcomes, compared to an initial conservative strategy," said principal investigator Sripal Bangalore, MD, MHA, NYU Langone Health, New York City. He cautioned though, that the findings apply only to patients with CKD like those entered into the study – those without a recent acute coronary syndrome who are not highly symptomatic or who have a left ventricular ejection fraction less than 30%, treated at centers experienced in the low-contrast and no-contrast interventional techniques.
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
COLCOT: Colchicine Shows Promise to Reduce Events After MI
Adding the anti-inflammatory agent colchicine to standard of care within 30 days of MI significantly reduced a composite end point of cardiovascular events, compared with placebo, in the COLchicine Cardiovascular Outcomes Trial (COLCOT). In the evaluation of 4745 people who experienced a recent MI, low-dose colchicine, 0.5 mg daily, significantly decreased the risk for first ischemic cardiovascular events by 23%, compared with placebo. Colchicine also reduced combined first and recurrent ischemic cardiovascular events by 34%. "By repurposing well-known medications like colchicine, we can help address the major public health issue of subsequent cardiovascular events after an MI in a cost-effective manner to help patients worldwide overcome the cost barriers of their treatment," said lead study author Jean-Claude Tardif, MD, from the Montreal Heart Institute.
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
ORION-10: 58% Reduction in LDL With Inclisiran
A second phase 3 trial with the novel lipid-lowering agent inclisiran (The Medicines Company), which is administered just twice yearly via subcutaneous injection, have shown impressive reductions in patients already taking statins. The ORION-10 study showed a 58% reduction in low-density lipoprotein (LDL) cholesterol over the 18-month study period, with no difference in safety compared with placebo in patients with established atherosclerotic cardiovascular disease already taking statins. The results are similar to those seen in ORION-11, the first phase 3 trial of inclisiran previously reported. "Our results show that inclisiran is a new novel treatment for lowering LDL," lead investigator, R. Scott Wright, MD, concluded. "It is easy to use in prefilled syringes, safe, and its effects are potent and durable." Wright, from Mayo Clinic, Rochester, Minnesota, noted that LDL lowering is the most effective intervention to change the course of atherosclerotic cardiovascular disease, yet substantial residual risk remains despite aggressive treatment. "There is a compelling need for novel therapies to further lower LDL on top of current LDL-lowering treatments," he said. "Inclisiran is one such therapy."
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
ORION-9: 50% LDL Reduction With Inclisiran in Familial Hypercholesterolemia
A third phase 3 trial of twice-yearly inclisiran also gave impressive results in reducing LDL-cholesterol levels, consistent with the previous two studies, this time in patients with familial hypercholesterolemia (FH). The trial, ORION-9, yielded a 50% reduction in LDL cholesterol over an 18-month period in FH patients who were already on maximum tolerated doses of statins; half of those patients were also taking ezetimibe. "Inclisiran shows potential to address the unmet need of high-risk FH patients," said presenter Frederick Raal, MBBCh, head of the Division of Endocrinology and Metabolism at the University of the Witwatersrand, Johannesburg, South Africa. The ORION-9 results are in line with those from ORION-10, which showed a 58% reduction in LDL cholesterol in patients with established atherosclerotic cardiovascular disease, and with those from ORION-11, which showed a 54% reduction in LDL cholesterol in a mix of patients with atherosclerotic cardiovascular disease and those at high risk for cardiovascular disease but with higher baseline LDL-cholesterol levels.
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
Silencing Novel Target Genes: A New Strategy for Lipid Lowering
Two other novel lipid-lowering therapies based on silencing specific genes involved in lipid metabolism have shown promising preliminary results in initial clinical trials. The two new products target the genes for apolipoprotein C-III (APOC3) and angiopoietin-like 3 (ANGPTL3), proteins that inhibit triglyceride metabolism. The siRNA molecules targeting these genes are both in development by Arrowhead Pharmaceuticals. ARO-APOC3 is being developed for severe hypertriglyceridemia and familial chylomicronemia syndrome, and ARO-ANG3 for dyslipidemias such as FH and other metabolic diseases. Presenting the initial data with the APOC3 product was Christie Ballantyne, MD, Baylor College of Medicine, Houston, and in a second presentation, Gerald F. Watts, DSc, University of Western Australia, Perth, described the experience so far with the siRNA product targeting the ANGPTL3.
"The siRNAs work in a catalytic way in that the same molecule can destroy multiple aspects of the RNAs in a way that provides substantial longevity in terms of their duration of effect, which is quite remarkable," commented lipid expert Daniel Rader, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, who was not involved in the trials.
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
DAPA-HF: Heart Failure Toolbox Poised to Add New Drug Family
In the DAPA-HF trial, treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga, AstraZeneca) on top of standard meds for heart failure with reduced ejection fraction (HFrEF), compared with standard meds only, significantly lowered risk not only for its clinical composite primary end point, but for mortality and a slew of other meaningful secondary outcomes. The benefits were not mediated by the well-recognized antiglycemic effects of dapagliflozin, as the drug seemed to benefit patients with and without type 2 diabetes to a nearly equal extent for its primary end point of CV death, HF hospitalization, or urgent HF visit requiring IV therapy, as well as those events individually, plus all-cause mortality and other important end points. Importantly, dapagliflozin's effect on the primary end point was virtually the same regardless of baseline glycosylated hemoglobin (A1c) levels. "It's quite remarkable," said presenter John McMurray, MBChB, MD, University of Glasgow, United Kingdom.
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
Ticagrelor Monotherapy Affirmed in High-risk ACS: TWILIGHT-ACS
Patients with acute coronary syndrome (ACS) appear to derive the same benefits as other high-risk patients from ticagrelor monotherapy after PCI, according to results of the TWILIGHT-ACS trial, reported here by Usman Baber, MD, MS, Icahn School of Medicine at Mount Sinai, New York City. Current guidelines explicitly recommend dual antiplatelet therapy (DAPT) for 1 year in the presence of ACS. The parent TWILIGHT trial, however, showed that dropping aspirin after 3 months and continuing ticagrelor monotherapy cut the risk of bleeding without increasing ischemic events in PCI patients with at least one angiographic and one clinical high-risk feature. The ACS substudy zeroed in the patients who presented with unstable angina or non-ST-segment elevation MI. At 1 year, the primary end point of BARC (Bleeding Academic Research Consortium) 2, 3, or 5 bleeding occurred less often with ticagrelor monotherapy than it did with ticagrelor plus aspirin. Importantly, "relative reductions on the order of 50% to 60% indicated a uniform benefit of ticagrelor monotherapy, irrespective of underlying risk level," Baber said.
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
Colchicine Before PCI Cuts Inflammatory Markers but Not MACE
A single dose of the anti-inflammatory drug colchicine before PCI failed to significantly reduce PCI-related myocardial injury or 30-day major adverse cardiovascular events, compared with placebo, in the double-blind, randomized Colchicine-PCI study. However, colchicine was associated with significant reductions in some inflammatory markers after PCI, including interleukin-6 and high-sensitivity C-reactive protein. "The study dose of colchicine used in our trial given 1 to 2 hours pre-procedure did not lower the rates of microdamage to the heart, but did, for the first time, show that colchicine can prevent a rise in vascular inflammation during an acute injury," said lead study author Binita Shah, MD, associate director of research, Cardiac Catheterization Laboratory, NYU School of Medicine, New York City, who presented the findings. "Our group has previously shown that colchicine decreases the attachment of inflammatory cells to injured or inflamed vascular endothelium and platelets," she added.
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
Sacubitril/Valsartan Benefits Extend to HF With Mildly Reduced EF
Further analyses of the PARADIGM and PARAGON heart failure trials of sacubitril/valsartan (Entresto, Novartis) appear to show that the benefits of the drug combination established in patients with low ejection fraction (EF) appear to extend to patients with mildly reduced EF, and to a higher EF range in women than men. PARADIGM, reported in 2014, showed clear benefits of sacubitril/valsartan in patients with HF who have reduced ejection fraction versus enalapril. However, in the more recent PARAGON trial in patients with symptomatic HF but preserved EF, sacubitril/valsartan was associated with a more modest reduction in events that failed to meet statistical significance, compared with valsartan alone. "The interesting finding from PARAGON HF is that women appeared to get more benefit from the sacubitril/valsartan combination for the primary outcome than men, said John McMurray, MD, University of Glasgow, United Kingdom, who presented the new analysis of PARAGON.
Photo courtesy of Novartis
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
GALILEO, GALILEO 4D: Mixed Results in Post-TAVR Anticoagulation
The results of the first randomized prospective trial of an anticoagulation strategy vs standard DAPT for patients undergoing transcatheter aortic valve replacement (TAVR) show that routine anticoagulation is not suitable for all comers in a high-risk population. In the main GALILEO trial of elderly patients after TAVR, those who received an investigational anticoagulation strategy with the direct factor Xa inhibitor rivaroxaban had worse survival and more thromboembolic and bleeding events than patients who received standard DAPT. However, in the GALILEO 4D substudy of patients who underwent four-dimensional CT, those in the rivaroxaban group were less likely to show subclinical leaflet motion abnormalities and leaflet thickening. Despite the positive imaging finding in GALILEO 4D, "there is no reason to give 10 mg rivaroxaban-based treatment routinely after TAVR in patients who don't need anticoagulation," said lead author in the main GALILEO trial, George D. Dangas, MD, PhD, Mount Sinai Hospital, New York City. However, because rivaroxaban had an effect in reducing the clots on leaflets, he said, further investigation is required to determine the optimal therapeutic strategy after TAVR.
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
EVAPORATE: Early Mechanistic Clues to Vascepa's CV Benefits
Interim results from a study designed to explain the striking results from the REDUCE-IT trial with icosapent ethyl (Vascepa, Amarin) show that the high-dose eicosapentaenoic acid (EPA) therapy slows, but does not reverse, coronary plaque progression. Among 67 statin-treated patients with high triglycerides, there was no significant difference in the primary end point (change in low attenuated plaque) between those treated with icosapent ethyl and those treated with placebo in the EVAPORATE study. There was significantly less progression, however, in total, noncalcified, fibrous, and calcified plaque in the icosapent ethyl group on interim CT angiography at 9 months, reported Matthew Budoff, MD, UCLA School of Medicine, Torrance, California. The original trial design used noncalcified plaque as the primary end point, but the steering committee changed the end point to low attenuated plaque based on recent Japanese work. Still, icosapent ethyl showed "remarkable consistency" across almost all end points. "I think that you should look at the range of the end points and see that, overall, we hit statistical significance for four of them, [with] a trend in the right direction for our primary and, again, it is an interim analysis," Budoff said.
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
RECOVERY: Early Surgery Best in Severe Asymptomatic AS?
The results of the RECOVERY trial show early aortic valve replacement resulted in a lower risk for operative mortality or death from cardiovascular causes than conservative care in asymptomatic patients with severe aortic valve stenosis. Secondary analysis also showed a reduced risk for all-cause mortality. "Our RECOVERY trial provides the evidence to support preemptive aortic valve replacement for asymptomatic severe aortic stenosis," said Duk-Hyun Kang, MD, PhD, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, South Korea. However, the trial population is quite different from the populations enrolled in transcatheter aortic valve replacement (TAVR) trials, and so the results cannot be directly applied to early TAVR for asymptomatic severe aortic stenosis, the researchers conclude. Similarly, the results may not apply to lower-volume centers or to patients at higher operative risk.
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
COACT at 1 Year: Later Angiography Okay in Non-STEMI Cardiac Arrest
Patients who survived an out-of-hospital cardiac arrest and did not have signs of ST-elevation MI (STEMI) had similar 1-year survival whether they had immediate or delayed coronary angiography in an extension of the COACT trial. At 1 year, there were also no significant differences in secondary outcomes of MI, revascularization, hospitalization due to heart failure, or implantable cardiac defibrillation shocks with the two different angiography strategies, reported lead author Jorrit S. Lemkes, MD, Amsterdam University Medical Center. These results extend the 90-day findings from COACT reported earlier this year. These 1-year outcomes "aren't really surprising," said Lemkes,"but I think it is important to report them because I think cardiologists are changing their approach" and delaying angiography for patients, such as those in COACT. The new findings show that delaying angiography in these patients is a "wise decision," not only for short-term outcomes, but also for long-term outcomes, he said.
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
TST: Treating LDL to Below 70 Reduces Recurrent Stroke
Treating patients to a lower LDL cholesterol target after an ischemic stroke of atherosclerotic origin resulted in fewer recurrent strokes or major CV events than a higher LDL cholesterol goal, even though the trial was stopped early because of lack of funding. "In the Treat Stroke to Target [TST] trial, we showed that the group of patients with an atherosclerotic stroke achieving an LDL cholesterol of less than 70 mg/dL had 22% less recurrent ischemic stroke or other major vascular events than the group achieving an LDL cholesterol between 90 and 110 mg/dL.We avoided more than one recurrence in five," said lead author Pierre Amarenco, MD, Bichat Hospital, Paris. Discussant Mitchell S.V. Elkind, MD, MPhil, AHA president-elect, called the TST findings "practice confirming" of a strategy many cardiologists already follow for patients who have suffered a stroke. "The TST study is only the second trial that was done in neurology for stroke prevention using statins and lipid-lowering therapy, and that's what makes it a hopeful and real advance," he said.
Top News From AHA 2019: Slideshow
Steve Stiles; Patrice Wendling; Damian McNamara; Susan Hughes; Marlene Busko; Darby Rotach; Hannah Yoon; Megan Brooks | December 9, 2019 | Contributor Information
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