ACC 2010: Top Research Highlights

The American College of Cardiology (ACC) 59th Annual Scientific Sessions and i2 Summit was held in Atlanta, Georgia, March 14 - 16, 2010. The highlights included the usual parade of acronyms, such as:

- ACCORD Lipid (Action to Control Cardiovascular Risk in Diabetes), which showed that fenofibrate plus simvastatin did not reduce the risk for fatal or nonfatal cardiovascular events or nonfatal stroke compared with statin therapy alone in high-risk diabetics;

- ACCORD BP, which showed no additional benefit with intensive lowering of systolic blood pressure to lower than 120 mm Hg;

- NAVIGATOR (Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research), which showed that neither agent reduced cardiovascular disease risk in high-risk patients with impaired glucose tolerance;

- EVEREST (Endovascular Valve Edge-to-Edge Repair Study), which showed that the MitraClip (Abbott) device — a percutaneous version of edge-to-edge mitral-valve repair — may lead to fewer early adverse events than traditional valve repair or replacement, with "noninferior" efficacy out to 1 year;

- INVEST (International Verapamil SR-Trandolapril), which showed that intensive blood pressure lowering with an angiotensin receptor blocker and an angiotensin-converting enzyme (ACE) inhibitor was associated with a higher mortality rate than usual blood pressure control in patients with diabetes and cardiovascular disease;

- SORT OUT III (Randomized All-comer Comparison of Zotarolimus-eluctin and Sirolimus-eluting Coronary Stents Trial), which showed that the sirolimus-eluting stent (Cypher) was superior to the zotarolimus-eluctin stent (Endeavor);

- MM-WES (Medco-Mayo Warfarin Effectiveness Study), which showed that genetic testing can be used to more accurately predict the best warfarin dose early on, with a 30% reduction in risk for adverse events;

- PLATO (Platelet Inhibition and Patient Outcomes) results showed that patients with acute coronary syndrome who received the investigational antiplatelet agent ticagrelor before coronary artery bypass graft were 50% less likely to die than those who received clopidogrel, but the difference in mortality was not explained by bleeding events;

- JETSTENT results showed that rheolytic thrombectomy was superior to direct stenting alone at ST segment resolution in patients with STEMI.

Combination therapy with fenofibrate and simvastatin failed to reduce the risk for fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, according to results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial, led by Henry N. Ginsberg, MD, from the Department of Medicine, College of Physicians & Surgeons, Columbia University, New York City.

The "findings do not support the use of combination fibrate-statin therapy, rather than statin therapy alone, to reduce cardiovascular risk in the majority of patients with type 2 diabetes who are at high risk for cardiovascular disease," Dr. Ginsburg told ACC attendees. See ACCORD: Fenofibrate No Benefit to Statin Therapy in High-Risk Diabetic Patients for more information.

New data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) BP study show that there is no benefit to be gained in diabetics with intensive systolic blood pressure lowering to a goal of less than 120 mm Hg compared with those receiving standard antihypertensive care, with a systolic blood pressure target of less than 140 mm Hg.

The ACCORD results highlight the need for flexible targets regarding the treatment of hyperglycemia, blood pressure, and dyslipidemia in patients with type 2 diabetes mellitus, said principal investigator William C. Cushman, MD, professor of preventive medicine and medicine, University of Tennessee, Memphis, and chief of the Preventive Medicine Section, Veterans Affairs Medical Center, Memphis. See ACCORD BP: Intensive BP Lowering Futile in Diabetics for more information.

"We don't know if the drug was effective at all. Not only was it a negative study, but we can't even begin to understand why."

Neither agent had any significant effect on cardiovascular risk in the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial of patients with impaired glucose tolerance and with — or at risk for — cardiovascular disease.

Patients on the angiotensin receptor blocker had a 14% lower risk for incident diabetes compared with those on the short-acting promoter of insulin secretion after 5 years, reported John J. McMurray, MD, from the British Heart Foundation Glasgow Cardiovascular Research Centre, Scotland.

"We don't know if the drug was effective at all. Not only was it a negative study, but we can't even begin to understand why," said Dr. McMurray. The 14% decrease in risk for diabetes in the valsartan group is modest compared with the benefits of lifestyle modification alone, he added. See NAVIGATOR Off Course to Diabetes Prevention With Valsartan, Nateglinide for more information.

Results of the Endovascular Valve Edge-to-Edge Repair Study (EVEREST) II show that the MitraClip (Abbott), a percutaneous edge-to-edge mitral-valve repair device, was safe at 30 days, with a reduced need for blood transfusion, and was associated with fewer early adverse events than traditional valve repair or replacement, with "noninferior" efficacy out to 1 year. See EVEREST II: Mitral-Clip Device Noninferior to Surgical Repair or Replacement for more information.

Intensive blood-pressure control in diabetics with heart disease was associated with a higher mortality rate than usual blood pressure control in the International Verapamil SR-Trandolapril (INVEST) trial. Lead investigator Rhonda Cooper-DeHoff, PharmD, MS, associate director, Cardiovascular Clinical Research Program, University of Florida, Gainesville, reported the findings.

"My personal opinion is that a target of less than 140 mm Hg is reasonable, and we should not keep giving extra drugs to get patients down to levels below 120 to 130 mm Hg," said late-breaking clinical trials session moderator Dr. William Cushman. His work with ACCORD BP had similar findings.

"It takes a lot of effort to get patients down to 120 or below, often with 3 or more antihypertensive drugs, so I would say that we now don't need to be doing this, and for most patients no more than 2 drugs should be adequate." See INVEST: Mortality Hazard With Lowest Blood Pressures in Diabetics With CAD? for more information.

The 18-month follow-up of the Randomized All-comer Comparison of Zotarolimus-eluctin and Sirolimus-eluting Coronary Stents Trial (SORT OUT III) showed that the sirolimus-eluting Cypher (Cordis) stent was superior to the zotarolimus-eluting Endeavor (Medtronic) stent in angiographic endpoints, with fewer major adverse events.

Lead investigator Michael Maeng, PhD, from the Department of Cardiology at Aarhus University Hospital, Denmark, cautioned that SORT-OUT III was not powered to assess clinical endpoints, but noted that his institution no longer uses the zotarolimus-eluting stent. See SORT OUT III: Cypher Bests Endeavor at 18 Months for more information.

The Medco-Mayo Warfarin Effectiveness Study (MM-WES) showed that genotyping patients treated with warfarin resulted in an approximate 30% reduction in risk for hospitalization for bleeding or thromboembolic events or hospitalization for any cause. Genotyping close to the time of therapy initiation was associated with the best outcome.

"Our study shows that genetic testing is a tool clinicians can use to more accurately predict the best warfarin dose early on. Patients may get to a stable dose more quickly, and therefore have a lower risk of negative outcomes," said Robert S. Epstein, MD, MS, from the Medco Research Institute, Franklin Lakes, New Jersey. See Warfarin Genotyping Reduces Hospitalizations for more information.

There was some surprise over the latest findings of the Platelet Inhibition and Patient Outcomes (PLATO) trial. Patients with acute coronary syndrome who received the investigational antiplatelet agent ticagrelor (AstraZeneca) and then underwent coronary artery bypass graft were 50% less likely to die than those who received clopidogrel.

This difference in mortality was not explained by bleeding events, which were similar between the 2 drug groups, so the findings are somewhat mystifying, reported principal investigator Claes Held, MD, from the Uppsala Clinical Research Center, Sweden. See PLATO CABG Analysis Confuses Cardiologists for more information.

Rheolytic thrombectomy was superior to direct stenting alone in the Comparison of AngioJet Rheolytic Thrombectomy Before Direct Infarct Artery Stenting to Direct Stenting Alone in Patients With Acute Myocardial Infarction (JETSTENT), reported David Antoniucci, MD, from the Division of Cardiology, Careggi Hospital, Florence, Italy.

At least 50% ST resolution at 30 minutes was achieved in 86% with rheolytic thrombectomy vs 79% with direct stenting alone (P = .043). Infarct size was 12% vs 13% (P = .40), respectively. TIMI major bleeding was 3.9% vs 1.6% (P = .12).

The major adverse cardiac event (MACE) rate at 6 months was 12.0% vs 20.7% (P = .012); death was 3.0% vs 4.9%; MI was 0.8% vs 1.3%; TVR was 7.7% vs 14.1%; and the stroke rate was 0.4% vs 0.4%, respectively. See JETSTENT: Improved Reperfusion and Short-Term Clinical End Points With Thrombectomy for more information.

Patients with drug-refractory paroxysmal atrial fibrillation treated with a novel balloon-based cryoablation technology (Arctic Front CryoAblation Catheter System, Medtronic) were significantly more likely to be free of arrhythmia at 1 year compared with those treated with another antiarrhythmic agent , according to the results of the Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP-AF) trial, reported by Douglas Packer, MD, from the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.

At 1 year, 70% of patients treated with the cryoballoon were free from atrial fibrillation compared with only 7% of patients who were treated with a second antiarrhythmic agent.

Results from the pilot Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) study showed similar superiority with catheter ablation over antiarrhythmic therapy, Dr. Packer said. See STOP-AF and CABANA: Trials Show Effectiveness of Ablation Over Drugs in AF for more information.

New analyses from the Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (ASCOT-BPLA): Blood Pressure Variability and Cardiovascular Outcomes trial show that variability in blood pressure is a much stronger determinant of both stroke and coronary disease outcome than average blood pressure throughout the trial, announced senior author Peter Sever, MD, from the International Centre for Circulatory Health, Imperial College London, and the Stroke Prevention Research Unit, University of Oxford, United Kingdom. See Is BP Variability a Stronger Determinant of CV Outcomes Than Mean Pressure? for more information.

Abdominal aortic calcification (AAC) is a predictor of obstructive coronary disease and all-cause mortality, and the absence of AAC is a predictor of no obstructive coronary disease, according to research presented by Steven Simpson, MD, from the Henry Ford Heart and Vascular Institute, Detroit, Michigan.

After a median follow-up of 27 months, 65 of 367 patients had died. Univariate analysis showed increasing abdominal aortic calcification was associated with increased mortality. Dr. Simpson said that AAC adds incremental prognostic information over clinical variables, coronary anatomy, and left ventricular function. Image courtesy of Dr Bryan Zweig, Henry Ford Heart and Vascular Institute. See Abdominal CT Exams May Reveal Patients at Higher Risk for Cardiovascular Disease for more information.

Individuals with low vitamin D levels who normalize their levels were a significant 30% less likely to develop cardiovascular events after more than 6 years of follow-up. A cut point of 30 ng/mL or less was used to define vitamin D deficiency. The study was presented during poster sessions.

"A 30% reduction in risk is about the same you could hope to get from taking a statin or treating your blood pressure, so we thought it was certainly promising. It doesn't eliminate the need for a real randomized trial, although I'm trying to figure out a good way to do one," said coauthor Joseph B. Muhlestein, MD, from the Intermountain Medical Center Heart Institute, Murray, Utah. See Death, CVD Risk Declines in People Who "Normalize" Vitamin-D Levels for more information.

A biophotonic technique adapted from oncology for precise "burning" of tissue may someday be used to treat atherosclerotic plaque.

Alexandr Kharlamov, MD, PhD, from the Urals State Medical Academy, Ekaterinburg, Russia, described his team's work in delivering 80-nm silica-gold nanoparticles to atherosclerotic coronary plaques. Near-infrared laser causes the particles to "detonate" and heat up to 50°C to 150°C, whereas surrounding tissue stays cooler than 40°C. The burning particles may also cause the cell cytoplasm and fluid in the intracellular spaces to boil, or cause acoustic waves that could cause inflammation in the vessel wall and promote vessel wall healing, but the technique will have to be refined to ensure that the damage does not promote too much inflammation or thrombosis. See Nanoparticle Detonations May Be Able to Burn Vascular Plaques for more information.

A aggressive, invasive treatment approach in patients with non-ST-elevation acute coronary syndrome leads to better long-term outcomes than a more conservative strategy, according to a meta-analysis, known as the FIR trial, that included the FRISC II, ICTUS, and RITA-3 trials — all of the relevant studies comparing an aggressive approach with a more conservative one.

"The key result is that five years after the randomization, there is a net absolute difference of 3.2% and a 19% relative risk reduction in cardiovascular death and MI in the routine invasive group, and I don't know of any pharmacological therapy that has that 5 years from randomization," Keith A. A. Fox, MB, ChB, professor of cardiology, Centre for Cardiovascular Science, University and Royal Infirmary of Edinburgh, Scotland, reported. See New Meta-Analysis: Routine Invasive Strategy Betters Selective Care for Non-ST-Elevation ACS for more information.

Triple antiplatelet therapy — with cilostazol (Pletal, Otsuka America) plus clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) and aspirin — was not associated with a significant reduction in clinical outcomes after drug-eluting-stent placement compared with clopidogrel and aspirin alone in the CILostazol-based triple anti-platelet therapy ON Ischemic Complication after drug-eluting stenT implantation (CILON-T) study. However, triple therapy did improve posttreatment platelet reactivity, and the trial was underpowered for hard clinical events.

"The most important result of this study is that posttreatment platelet reactivity was the key determinant of major adverse cardio- and cerebrovascular events, such as cardiac death, heart attack, or ischemic stroke, and we showed that platelet hyporesponsiveness is a problem even with triple antiplatelet therapy," announced lead investigator Hyo-Soo Kim, from the Seoul National University Hospital, Korea. See Is Triple Antiplatelet Therapy After PCI the Way Forward? for more information.

A novel, first-in-class antihypertensive agent, which inhibits both the angiotensin II receptor and neprilysin, showed greater reductions in blood pressure than valsartan alone in a new study in more than 1200 patients. The drug, LCZ696 (Novartis), was safe and effective in the trial, said Luis Miguel Ruilope, MD, from the Hospital 12 de Octubre, Madrid, Spain.

Before this agent, the most extensively studied inhibitor of neprilysin was omapatrilat (Bristol-Myers Squibb), which was never approved because it had the adverse effect of angioedema. Unlike omapatrilat, LCZ696 substitutes angiotensin II blockade for ACE inhibition. Because angiotensin-receptor blockers have a lower risk for angioedema than do ACE inhibitors, it is hoped that LCZ696 will offer cardioprotective effects without the risk for angioedema. See New Omapatrilatlike Drug Impressive in Hypertension for more information.

There is no difference in symptom relief, whether loop diuretics are given in a continuous or intermittent infusion or given in conventional or high doses to patients hospitalized with acute heart failure, according to the Diuretic Optimization Strategies Evaluation (DOSE) trial.

However, high intensification (2.5 × oral dose) of furosemide was associated with a significant improvement in net diuresis, weight loss, and symptom relief compared with low intensification. Co-principal investigator G. Michael Felker, MD, from the Department of Medicine, Division of Cardiology, Duke Clinical Research Institute, Durham, North Carolina, said the secondary findings suggest some possible advantages for the high-dose approach. See How to Diurese in Acute HF: Dosing Strategies Get an Evidence Base for more information.

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Photos courtesy of David Murray, Atlanta, Georgia.

For more information, see the following resources:

• Medscape Medical News from the American College of Cardiology (ACC) 59th Annual Scientific Session
• Medscape Cardiology
• eMedicine Cardiology
• American College of Cardiology
• theheart.org

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