Sunday, May 28, 2023
AHA 2011 Key Trials
AIM-HIGH: Stopped early due to increase in ischemic stroke in the niacin group vs placebo
SATURN: High-dose statin therapy resulted in significant regression of coronary atherosclerosis
ATLAS: Rivaroxaban has shown promising results
ELEVATE: Clopidogrel for patients with one loss-of-function allele
PALLAS: Dronedarone a hazard in high-risk CV patients with permanent AF
TRACER: Novel thrombin blocker vorapaxar ups bleeding risk in ACS
POWER: Internet intervention achieves and maintains weight loss
FAST: Surgical ablation bests catheter ablation in drug-refractory AF
C-PORT E: Elective PCI doesn't require surgical backup
Mi FREEE: Cutting copays for post-MI drugs helps outcomes
ADOPT: Extended apixaban no better than standard enoxaparin for VTE
NHBLI: Expert panel recommends universal cholesterol screening for kids
AIM-HIGH
Stopped early at 3 years due to unexplained increase in ischemic stroke in the niacin group vs placebo; experts now say trial should not have stopped
Results: Final results of the AIM-HIGH trial appear to suggest that the signal of increased ischemic stroke with niacin, which was one of the reasons the study was stopped early, could have been the play of chance, with the final P value for ischemic stroke coming in at a nonsignificant 0.11. This has provoked a backlash from researchers in the field against the National Institutes of Health (NIH) sponsors of the study who made the decision to terminate the trial.
"When the NIH stopped the trial, there was an increase in ischemic stroke of borderline significance," said lead investigator Dr. William Boden. "I think they saw neutral outcome data, and because of a potential ethical safety issue they decided to stop the trial. But there was no signal of an increase in fatal stroke or of all-cause or cardiac mortality. And now that we have all the data, the effect is far from significant, and when we look just at strokes that occurred when the patients were actually on treatment, we have 21 on niacin vs 18 on placebo. The earlier numbers were clearly an aberration—just the play of chance."
See:
AIM-HIGH: Results Raise Controversy Over Early Stopping
AIM-HIGH Fallout: Experts Disagree Over Niacin's Niche
SATURN
High-dose statin therapy resulted in significant regression of coronary atherosclerosis
Results: High-dose statin therapy with atorvastatin or rosuvastatin resulted in a significant regression of coronary atherosclerosis in the SATURN trial, despite differential effects on LDL- and HDL-cholesterol levels with the 2 most popular lipid-lowering medications. Treatment with rosuvastatin 40 mg resulted in lower LDL- and higher HDL-cholesterol levels than atorvastatin 80 mg, but the effect on percent atheroma volume (PAV) measured by intravascular ultrasound (IVUS) did not significantly differ. Less than 5% of patients with stable coronary disease are treated with maximum-dose statins, and this remains one of the challenges in secondary prevention.
"We're very good at prescribing statins; we're just not so good at increasing the doses," said Dr. Stephen Nicholls. "Safety is one of the elements of it, but the other element is that people question what the added benefit is. The incremental LDL lowering is about 5% or 6% every time you double the dose. I think what we're seeing here is very reassuring for patients. Over a 24-month period, patients with largely stable disease tolerated these agents very well at these doses. They achieved very effective levels of LDL and HDL cholesterol, and if you're looking for benefit, I see the removal of the disease from the artery wall that ultimately causes the clinical event as a very reassuring extra benefit for the doses of these agents."
See: Rosuvastatin and Atorvastatin Equally Regress Atherosclerosis
ATLAS
Rivaroxaban 2.5 mg has shown promising results, with a reduction in overall and cardiovascular mortality vs placebo, despite an increased risk for bleeding and ICH
Results: The lower of the 2 doses of the new oral anticoagulant rivaroxaban tested in the ATLAS ACS 2 TIMI 51 trial has shown promising results, with a reduction in overall and cardiovascular mortality vs placebo, despite an increased risk for bleeding and intracranial hemorrhage (ICH). The trial compared 2 doses of rivaroxaban with placebo in ACS patients. All patients were taking low-dose (75-100 mg) aspirin and 93% were also on clopidogrel. Study treatment was started an average of 4.6 days after the ACS event. Patients with a previous stroke or transient ischemic attack (TIA) were excluded, as this group has been shown to have a particularly high risk for ICH in previous trials of other antithrombotic agents. The population was high-risk, with half having had an ST elevation myocardial infarction (STEMI).
Both rivaroxaban doses reduced the primary endpoint of cardiovascular death/MI/stroke, at the cost of increased bleeding rates. The 2.5-mg twice-daily dose had the better benefit/risk balance, due to a lower bleeding risk than with the 5-mg twice-daily dose.
"Thus, the addition of very low-dose anticoagulation with rivaroxaban may represent a new treatment strategy in patients with a recent acute coronary syndrome," the ATLAS investigators conclude in the New England Journal of Medicine paper, published online to coincide with the AHA presentation. "We have shown a 32% relative reduction in all-cause mortality with the 2.5-mg dose in the whole population and a 36% reduction in those on dual antiplatelet therapy. This translates into 1 death prevented for every 56 patients treated for 2 years. This is big news," said ATLAS investigator Dr. Michael Gibson.
See: Low-Dose Rivaroxaban Looks Good in ACS: ATLAS ACS 2
ELEVATE-TIMI 56
Tripling the maintenance dose of clopidogrel in stable heart disease patients carrying 1 clopidogrel loss-of-function allele achieved levels of platelet reactivity similar to those seen with the standard dose in noncarriers
Results: The ELEVATE-TIMI 56 trial results show that tripling the maintenance dose of clopidogrel to 225 mg daily in stable heart disease patients carrying 1 clopidogrel loss-of-function allele (CYP2C19*2) achieved levels of platelet reactivity similar to those seen with the standard 75-mg dose in noncarriers. In contrast, in patients with 2 loss-of-function alleles, doses as high as 300 mg daily did not result in comparable degrees of platelet inhibition.
"If I knew someone's genotype [indicated loss of function], I would feel uncomfortable treating them with standard doses of clopidogrel," said Dr. Jessica Mega, adding that there are also other agents available, prasugrel and ticagrelor, that have been shown to reduce events in "all-comers." That's despite the fact that ELEVATE did not look at effects on patient outcomes. "It is important to understand that this is a pharmacodynamic study . . . but I think it gives us a great deal of insight into the optimal ways of treating different patients with clopidogrel."
See: Clopidogrel 225 mg for Patients With CYP2C19*2 Allele?
PALLAS
Dronedarone a hazard in high-CV-risk patients with permanent AF
Results: The PALLAS data indicate that the dronedarone-related CV events over a median follow-up of 3.5 months consisted largely of stroke, heart failure, CV death, and arrhythmic death. Those events contributed to significant increases, by a factor of about 2, in the trial's pair of coprimary endpoints: stroke, MI, systemic embolism, or CV death; and death or unplanned CV hospitalization. The significant effect of dronedarone on those endpoints held regardless of NYHA functional class or LVEF. The PALLAS results were published in the New England Journal of Medicine, coinciding with their presentation at AHA 2011.
"Our data show that dronedarone is hazardous in such patients," write the publication's authors, led by Dr. Stuart J Connolly. "It is reasonable to conclude that dronedarone should be avoided in patients with heart failure and other advanced cardiovascular disease, particularly when they also have permanent atrial fibrillation."
See: Dronedarone a Hazard in High-Risk Patients With Permanent AF
TRACER
Novel thrombin blocker vorapaxar stumbles in ACS, ups bleeding risk
Results: In the international TRACER trial of more than12,000 patients with non-ST-elevation ACS who were mostly already on dual-agent antiplatelet therapy, adding the investigational antithrombotic agent vorapaxar to standard therapy significantly raised the risk for major bleeding complications, including intracranial hemorrhage (ICH), over 2 years.
That wasn't a complete surprise, as TRACER had been halted earlier this year when an interim safety analysis saw a jump in ICH among vorapaxar patients with a history of stroke.
"The magnitude of the increase [in bleeding] was not expected on the basis of preclinical and phase 2 data" for [protease-activated receptor 1] PAR-1 blockade, which suggested no risk increase when added to aspirin and clopidogrel, TRACER investigators write in the New England Journal of Medicine, where their report was published online to coincide with its scheduled presentation here at the AHA sessions.
However, they continue, "The results from our study are consistent with previous evidence indicating that more potent antithrombotic therapy incrementally increases the risk of bleeding."
See: Vorapaxar Stumbles in ACS, Ups Bleeding Risk: TRACER
POWER
Phone and internet intervention achieves and maintains weight loss
Results: The randomized, 2-year POWER trial showed that a weight-loss program conducted solely by telephone and via Internet was just as effective as a program attended in person, with face-to-face coaching, at promoting meaningful weight loss and helping to keep it off.
About half of the patients participating in either weight-loss intervention lost at least 5% of their initial body weight (the primary endpoint) within 6 months. The lost weight stayed off after 2 years in about 40% of both groups. The degree of weight loss achieved was similar to that of other weight-loss studies.
"In contrast with the findings in most weight-loss trials, however, participants sustained weight loss to the end of the trial," commented lead author Dr. Lawrence J. Appel.
See: Phone, Internet Intervention Achieves, Maintains Weight Loss
FAST
Surgical ablation bests catheter ablation in treatment of drug-refractory AF
Results: The FAST trial was a randomized comparison between surgical ablation and radiofrequency catheter ablation for the treatment of antiarrhythmic-drug-refractory atrial fibrillation. It showed that the surgical approach is superior in achieving freedom from arrhythmias at 1 year. The minimally invasive surgical approach is not without its drawbacks, however, with investigators reporting a significantly higher procedural adverse-event rate in the surgical ablation arm compared with catheter ablation. Of note, 67% of the patients included in the trial had failed a previous catheter-ablation procedure, "which could signify a predisposition to catheter-ablation failure."
"In this population of patients with atrial fibrillation with dilated left atrium and hypertension who had failed a prior catheter ablation, we found that minimally invasive surgical ablation was superior to catheter ablation to achieve freedom from atrial arrhythmias without antiarrhythmic drugs in follow-up to 12 months," said lead investigator Dr. Lucas Boersma during a press conference announcing the results. "Surgical ablation was accompanied by a higher adverse-event rate than catheter ablation, and we think this is important for physicians and patients when deciding which type of invasive therapy they need."
See: FAST: Surgical Ablation vs Catheter Ablation in Drug-Refractory AF
C-PORT E
Elective PCI doesn't require surgical backup
Results: During a late-breaking clinical-trial session, findings from the C-PORT E trial showed that patients who had elective PCI at experienced US hospitals without onsite cardiac surgery fared no worse than those who had the same procedure at institutions with surgical backup, a new study shows. The mortality rate after 6 weeks was almost the same for each group, at just under 1%.
"The key finding is that the patient-related medical outcomes, at least the short-term safety outcomes, of elective angioplasty are the same, regardless of the hospital type," said Dr. Thomas Aversano. He added that his team will have data on how patients fared 9 months after the procedure early next year. And, he stressed, "The purpose of the trial was not to expand the number of centers doing angioplasty but to give healthcare policy makers—who can make rational decisions about access, quality, and cost of angioplasty care in their state—some information on which to base their decision."
See: Elective PCI Doesn't Require Surgical Backup: C-PORT E
MI FREEE: Cutting copays for post-MI drugs helps outcomes, with no added cost to insurers
Results: The 5855-patient MI FREEE study shows that patients who had suffered an MI were significantly less likely to have another major cardiac event if the costs of statins, beta-blockers, ACE inhibitors, and angiotensin-receptor blockers were totally covered by insurance rather than if their insurance company charged them a copay for their drugs.
For the primary outcome of revascularization plus major cardiac events combined, the difference was not statistically significant. The patients with no copay paid 26% less overall for their drugs than the patients with copays. Over the 3 years of follow-up, the people with no copay actually cost the insurance company slightly less to care for than the people with 1 ($66 008 vs $71 778; P=.68).
"For essential medications—the meds we're talking about are highly evidence-based—we don't want people to stop using those meds when the copays are a relatively small part of cost relative to costs of hospitalizations, or even death, that result from not using the drugs," said study lead author Dr. Niteesh Choudhry. Not only does eliminating copays not cost the insurance company more in the long run, it's also an easy change to implement, Choudhry said. "Insurers that want to do this could do this tomorrow. It literally just means changing pharmacy authorization codes. It doesn't mean deploying armies of nurse health coaches or anything like that."
See: Cutting Copays for Post-MI Drugs Helps Outcomes
ADOPT
Extended apixaban no better than standard enoxaparin for VTE in medically ill
Results: Results of the ADOPT trial demonstrate that prolonging prophylaxis for venous thromboembolism in medically ill patients with a 30-day course of the new oral anticoagulant apixaban was not superior to a shorter 6- to 14-day course of subcutaneous enoxaparin—designed to represent standard in-hospital VTE prevention.
"The ADOPT trial does not provide evidence to justify a policy of extended prophylaxis in a broad population of medically ill patients after hospital discharge," said Dr. Samuel Z. Goldhaber in a press conference at the AHA meeting. However, the ADOPT findings, together with those from similar studies—such as the MAGELLAN trial with rivaroxaban and EXCLAIM with enoxaparin—show that "it is clear that the risk for VTE increases beyond the time of hospital discharge" in this patient population.
See: Negative Data for Apixaban in Extended VTE Prevention
NHBLI-appointed expert panel recommends universal cholesterol screening for kids
Results: The Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents presented new guidelines at the AHA meeting. They recommended that all children, regardless of family history, undergo universal screening for elevated cholesterol levels. The panel recommended that adolescents undergo lipid screening for nonfasting non-HDL-cholesterol levels or a fasting lipid panel between the ages of 9 and 11 years followed by another full lipid screening test between 18 and 21 years of age. They also recommend measuring fasting glucose levels to test for diabetes in children 10 years of age (or at the onset of puberty) who are overweight and have other risk factors for type 2 diabetes, including a family history.
The Expert Panel was appointed by the National Health, Lung, and Blood Institute (NHLBI) and endorsed by the American Academy of Pediatrics (AAP).
"The goal of the expert panel was to develop comprehensive evidence-based guidelines that address the known risk factors for cardiovascular disease to assist all primary pediatric care providers in both the promotion of cardiovascular health and the identification and management of specific risk factors from infancy into young adult life," write panel chair Dr. Stephen Daniels (University of Colorado School of Medicine, Denver) and colleagues in the journal Pediatrics.
See: Panel Recommends Universal Cholesterol Screening for Kids
Credits and disclosures
Editor:
Shelley Wood
Managing Editor, heartwire
theheart.org
Kelowna, British Columbia, Canada
Disclosure: Shelley Wood has disclosed no relevant financial relationships.
Contributors:
Steven Rourke
Manager, Editorial programming
theheart.org
Montreal, Quebec, Canada
Disclosure: Steven Rourke has disclosed no relevant financial relationships.
Katherin Vasilopoulos
Montreal, Quebec, Canada
Disclosure: Katherin Vasilopoulos has disclosed no relevant financial relationships.
Journalists:
Sue Hughes
theheart.org
London, United Kingdom
Disclosure: Sue Hughes has disclosed no relevant financial relationships.
Reed Miller
theheart.org
State College, Pennsylvania
Disclosure: Reed Miller has disclosed no relevant financial relationships.
Lisa Nainggolan
theheart.org
London, United Kingdom
Disclosure: Lisa Nainggolan has disclosed no relevant financial relationships.
Michael O'Riordan
theheart.org
Toronto, Ontario, Canada
Disclosure: Michael O'Riordan has disclosed no relevant financial relationships.
Steve Stiles
theheart.org
Fremont, California
Disclosure: Steve Stiles has disclosed no relevant financial relationships.
