A review of the CATIS, ENGAGE AF-TIMI 48, TOPCAT, CORAL, NIAMI, and CTSN trials presented at the American Heart Association 2013 Scientific Sessions.
American Heart Association 2013 Scientific Sessions
Dallas, Texas, November 16-20, 2013
The American Heart Association Scientific Sessions is the leading cardiovascular meeting for basic, translational, clinical, and population science in the United States. More than 18,000 cardiovascular experts from more than 105 countries attended this years Sessions. More than 5000 presentations were made at the meeting, with 1000 invited faculty and 4000 abstract presentations from leaders in cardiovascular disease.
In this issue of Cardiology Review, we review 6 important studies presented during the Sessions: CATIS, ENGAGE AF-TIMI 48, TOPCAT, CORAL, NIAMI, and the CTSN trial.
CATIS: No Benefit Seen in BP Reduction in Acute Phases of Stroke
Researchers presenting data from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) study found that compared with no antihypertensive treatment, treating patients to achieve a target blood pressure (BP) with antihypertensive medications did not reduce the risk for major disability at 14 days or hospital discharge. Jiang He, MD, PhD, and colleagues from Tulane University School of Public Health and Tropical Medicine in New Orleans, LA, said that unless a patient’s systolic blood pressure (SBP) is 220 mm Hg or more, or their diastolic pressure is 120 mm Hg or more, the decision to lower blood pressure with antihypertensive treatments in patients with ischemic stroke does not improve or worsen outcome.
The study was published online in the Journal of the American Medical Association on November 17.
CATIS was a randomized, controlled, multicenter, single-blind study with blinded end points that examined whether moderate BP reduction within 48 hours of stroke onset would reduce death and major disability. It also assessed the effect of antihypertensive treatment in the acute phase on 3-month mortality, major disability, and vascular events at a post treatment follow-up. The study included 4071 Chinese patients.
Patients were randomized to receive antihypertensive therapy (n = 2038) with the aim of lowering systolic BP by 10% to 25% within 24 hours of randomization or to discontinue all hypertension medications taken prior to the stroke during their hospitalization (n = 2033). At discharge all patients were prescribed antihypertensive medica- tions according to clinical guidelines.
SBP reduction was achieved in both groups at both 24 hours/d and day 7 but was significantly lower in the treated group. At 7 days the SBP was even lower and still significantly lower between groups. The significant difference between SBP levels did not affect outcomes, however, either on the primary or secondary composite end point. The results of the CATIS trial indicate that antihypertensive treatment within 48 hours is not superior to routine management in patients with an acute ischemic stroke in reducing mortality and morbidity.
The study is available at: http://jama.jamanetwork.com/article.aspx?articleid=1778674. The study was supported by Tulane University and Collins C. Diboll Private Foundation; Soochow University; and the National Science Foundation of China.
ENGAGE AF-TIMI 48: Once-Daily Edoxaban Noninferior to Warfarin in AF
The investigational oral factor Xa inhibitor edoxaban (Lixiana) taken once daily at dosages of either 60 mg or 30 mg was noninferior to warfarin for preventing stroke or systemic embolism in a randomized atrial fibrillation (AF) trial of more than 20,000 patients in 46 countries. Follow-up was a mean of 2.8 years.
Both doses of edoxaban were associated with significantly less major bleeding than warfarin in the trial (ENGAGE AF-TIMI 48 [Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation—Thrombosis in Myocardial Infarction 48]).
Lead author Robert P Giugliano, MD, of Brigham and Women’s Hospital, Boston, MA, said the high-dose edoxaban regimen tended to be more effective than warfarin. The rate of ischemic stroke was similar with high-dose edoxaban and warfarin, but was higher with the low-dose edoxaban regimen. ENGAGE AF-TIMI 48 was published online in the New England Journal of Medicine.
Hemorrhagic strokes and cardiovascular mortality were both significantly lower on both factor Xa inhibitor regimens than on warfarin.
The risk of hemorrhagic stroke went down 46% for high-dose edoxaban and 53% for low-dose edoxaban compared with warfarin (P <.01 for both differences). For ischemic stroke, high-dose edoxaban versus warfarin was the same (P = .97) and the risk went up 41% with low-dose edoxaban versus warfarin (P <.001). The results of the ENGAGE AF-TIMI 48 study indicate that both edoxaban 60 mg daily and 30 mg daily are noninferior for stroke prophylaxis in patients with AF compared with warfarin.
The study is available at: www.ncbi.nlm.nih.gov/pubmed/24251359. The trial was funded by Daiichi Sankyo. Dr Guigliano discloses receiving consulting fees from Daiichi Sankyo, Janssen, and Merck; lecture fees from Bristol-Myers Squibb, Daiichi Sankyo, Merck, and Sanofi; and grant support through his center from Daiichi Sankyo, Merck, J&J, Sanofi, and AstraZeneca.
NIAMI Trial: Nitrites Don’t Protect Myocardium
Results of the Nitrites in Acute Myocardial Infarction (NIAMI) trial presented at the AHA 2013 Scientific Sessions show that a 5-minute infusion of sodium nitrite just prior to opening the culprit artery in patients with ST-segment-elevation MI (STEMI) had no effect on infarct size as measured by coronary magnetic resonance (CMR) imaging 6 to 8 days later. After 6 months, there was also no effect on measures of myocardial remodeling.
Lead author Nishat Siddiqui, MD, of the University of Aberdeen, Scotland, said that the current study is conclusive in stating that at this dose, and by this route, and at this point in ischemia, nitrite does not do anything to reduce infarct size. She noted that perhaps a different dose or longer infusion duration would be a possible point for future studies.
In NIAMI, 229 patients at 4 centers undergoing primary stenting for their first MI were randomized in a double-blind set-up to be infused right before stent expansion, with either 70 μmol of sodium nitrite in 5-mL saline or a placebo.
At CMR imaging on days 6 to 8, 118 patients who received the nitrite infusion showed minimal reduction of less than 1% (P = .34) in infarct size as a proportion of myocardial area at risk, compared with the 111 who received placebo. There were no significant differences in the secondary end points of plasma troponin or creatinine kinase at 72 hours.
After 6 months there were no significant differences in final infarct size, left ventricular ejection fraction, or left ventricular end-systolic or end-diastolic volumes.
There was a 4.5% improvement in infarct size among diabetics who received nitrites (n = 14), compared with those assigned to placebo (n = 19), but the difference was not significant.
This study was funded by the Medical Research Council of the United Kingdom.
Surgery and Repair Do Equally Well in Ischemic Mitral Regurgitation
A study sponsored by the National Institutes of Health and Canadian Institutes of Health Research found that both mitral-valve repair and chordal-sparing mitral valve replacement surgery did equally well with respect to left-ventricular (LV) reverse remodeling or major adverse cardiac or cerebrovascular events (MACCEs) at 12 months. The rates of death at 30 days and 12 months were similar in the 2 treatment arms of the Cardiac Surgery Clinical Research Network (CTSN). Results were published online in The New England Journal of Medicine.
Lead author Michael Acker, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, explained that mitral valve replacement provides a more durable correction of severe ischemic mitral regurgitation (MR). “Mitral valve recurrent MR might have an important effect on long-term outcomes,” he said, “but additional follow-up and subset analysis may provide some insight into predictors and the clinical impact of mitral insufficiency recurrence, allowing the optimization of therapeutic decisions for individual patients.”
Dr. Acker said that ischemic mitral insufficiency is not primary mitral valve disease but rather is the result of myocardial infarction (MI). The guidelines are not completely clear on what to do about this problem, he noted, as they are unclear on whether to repair or replace. In the United States the preference is for mitral valve repair over replacement.
In CTSN, 126 patients were randomized to mitral valve repair and 125 to mitral valve replacement. Mean LV end-systolic volume index (LVESVI) among patients who underwent repair was 54.6 mL/m2 of body surface area at 12 months; in the replacement group, mean LVESVI was 60.7 mL/m2 of body surface area. The mean change from baseline was -6.6 and -6.8 mL/m2, respectively.
There were no significant between-group differences in the risk of death at 30 days or 12 months, and no significant difference in the rate of a composite of major adverse cardiac or cerebrovascular events, function, or quality of life at 12 months. Valve replacement did allow for a more durable improvement in MR, however. The rate of moderate or severe MR at 12 months was 32.6% in the repair arm and just 2.3% in the replacement arm, a statistically significant difference.
The study is available at: www.nejm.org/doi/full/10.1056/NEJMoa1312808.
Stents Do Not Benefit Renal Artery Stenosis
No advantages are conferred by renal artery stenting in patients with renal artery stenosis over best medical therapy, according to the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study, funded by the National Heart, Lung, and Blood Institute. The study, which enrolled 947 patients with renal artery atherosclerosis (stenosis greater or equal to 60%), was launched in 2005.
CORAL patients had either systolic hypertension and were taking 2 or more blood pressure— lowering drugs, or chronic kidney disease. They were randomized to medical therapy alone or medical therapy plus renal artery stenting. Crossovers were strictly controlled.
The study showed that patients who have hypertension and renal artery disease do just as well with medical therapy versus interventional therapy. At a median follow-up of 43 months, the rate of primary composite end point was no different between the 2 groups. In both groups, the primary end point (death from cardiovascular or renal causes, MI, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or need for kidney replacement) occurred in 35% of patients. The investigators concluded that medical therapy without stenting is the preferred management strategy for the majority of people with atherosclerotic renal artery stenosis.
Study coauthors Michael Jaff, MD, of Massachusetts General Vascular Center, Boston, MA, said the bottom line is to make sure these patients are given “a really good try at intensive medical therapy long before you consider renal artery stents.”
The study was published in The New England Journal of Medicine. The study is available at: www.nejm.org/doi/full/10.1056/NEJMoa1310753.
Aldosterone Inhibitor Shows Promise for Heart Failure With Preserved EF
Fesults of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial suggest that spironolactone may improve clinical outcome in patients with heart failure with preserved ejection fraction (HFPEF). The study found that while patients who took spironolactone failed to show benefit for the clinical primary end point, they did have significantly fewer heart failure hospitalizations, a part of the primary end point, over the 3-plus years of follow-up.
TOPCAT randomized 3445 HF patients with an LVEF less than or equal to 45% to receive the aldosterone antagonist or placebo. Spirinolactone was titrated up to 30 mg/d to 45 mg/d. There were no significant differences in adverse events, except more hyperkalemia with spironolactone and more hypokalemia with placebo.
Although the primary end point wasn’t met for the overall population, the researchers were confident that hospitalizations for heart failure had been reduced by the medication. Margaret Redfield of the Mayo Clinic in Rochester, MN, said the trial showed a signal of benefit even though findings were not statistically significant. She noted that all-cause hospitalizations and mortality did not appear to be meaningfully affected by spironolactone, and cautioned that in clinical practice without the careful monitoring of creatinine and serum potassium in the trial, the prevalence of worsening renal function and hyperkalemia would be more common.
If safety issues are addressed, spironolactone is an option for patients with HFPEF, the researchers concluded.