Henry R. Black, MD; David J. Maron, MD; Ileana L. Pina, MD; Carol Peckham
Posted: 11/23/2011
10. Death Rates Diverge but no Change in Advice: SYNTAX (or CABG remains KING)
SYNTAX was an 1800-patient trial conducted in Europe and the United States that randomized patients with left main coronary disease and/or 3-vessel disease to either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) using the Taxus® drug-eluting stent (DES; Boston Scientific Corp., Quincy, Massachusetts).[1] At 3 years, rates of the primary endpoint, major adverse cardiac and cerebrovascular event (MACCE), remained statistically lower in the CABG-treated patients, driven by the lower rates of repeat revascularization procedures — just under 11% in the CABG-treated patients vs nearly 20% in the PCI/DES group. For the hard composite endpoint of all-cause death, stroke, and MI out to 3 years, there were no differences between groups.
On October 25th, 2011 at the European Association for Cardio-Thoracic Surgery (EACTS) Annual Meeting, 4-year data from the SYNTAX trial showed, for the first time, a divergence in death rates between the patients who were treated with bypass surgery and those who underwent PCI with a Taxus stent. All-cause mortality and cardiac death were both significantly higher in the PCI group compared with the surgery group, as was MI, and the excess rate of strokes initially observed in the CABG group has now leveled out.
In a discussion about who had “won” the SYNTAX trial, Dr Michael Mack (Medical City Dallas Hospital, Texas), a surgeon and chair of the session, said, “The surgeon would say the longer you go in follow-up, the better surgery looks. We knew this was going to look good 4 to 5 years out. But as an interventionalist, you might say, “We don’t use Taxus stents any more, we use the everolimus-eluting Xience® [Abbott Laboratories], and the results wouldn’t be the same.”
Read the full news story on this trial here.
9. STICH: Viability Testing Didn’t Affect Treatment Outcomes
At the American College of Cardiology 2011 meeting, results of a substudy of STICH were presented and were later published in The New England Journal of Medicine.[2] STICH (see no. 8 for main results) is a randomized comparison of CABG surgery and medical therapy alone in 1212 patients with a left ventricular ejection fraction (LVEF) less than 35% and coronary artery disease amenable to CABG. The substudy found that overall, substantial viable myocardium evident at baseline imaging studies had no independent bearing on all-cause mortality over 5 years; and such viability didn’t influence the relative effectiveness of the 2 treatment strategies, either for all-cause mortality or the secondary endpoints of cardiovascular (CV) mortality and CV hospitalization.
The substudy also questions the value of the decades-old practice of assessing myocardial viability with perfusion scans or other functional imaging methods to predict benefit from coronary revascularization — at least in the type of patients included in STICH: considered amenable to CABG, LVEF less than 35%, and no significant left-main coronary disease.
Read the full news story on this trial here.
8. STICH “Hypothesis One” Supports CABG in Heart Failure
Also at the ACC 2011 meeting in April, Dr. Eric Velazquez (Duke Clinical Research Institute, Durham, North Carolina) presented the long-awaited results of “hypothesis one” from the National Institutes of Health-sponsored STICH.[3] The primary endpoint was all-cause death. CABG was associated with an early risk of death as a result of the surgical intervention, but this disadvantage for surgery disappeared 2 years after the procedure. Over a median follow-up of 56 months, 41% of the medical therapy group and 36% of the CABG group died (P = .12), but the difference was statistically significant following adjustment for baseline characteristics. Dr. Bernard Gersh (Mayo Clinic, Rochester, Minnesota) called it “…an incredible trial. A stunning achievement.” ACC 2011 co-chair Dr. Edward McNulty (University of California, San Francisco) agreed, saying that the STICH study was “…precisely the kind of comparative-effectiveness study that is vitally needed.”
Read the full news story on this trial here.
7. DOSE Trial Published: How to Give Intravenous Diuretics in Acute Heart Failure
The DOSE trial published in March 2011 provided solid guidance on the question of whether high-dose IV diuretics might compromise the kidneys and even survival compared with low-level dosing in acute decompensated heart failure and relieved the uncertainty over the efficacy of intermittent intravenous bolus compared with continuous administration. In a Heartwire interview, Dr. Gregg C Fonarow (Ronald Reagan University of California, Los Angeles Medical Center) suggested that the lesson learned from the trial was that “aggressive decongestion is a critical part of achieving good outcomes in acute heart failure. It may seem to come at the cost of transient worsening renal function, but that doesn’t seem to be a major problem, as long as it’s monitored carefully.”
Read the full news story on this trial here.
6. PARTNER Cohort A: TAVI Noninferior to Surgery [in the short-term/ in very select high risk patients]
Long-awaited results from the PARTNER cohort A,[4] comparing transcatheter valve replacements (TAVR) with surgery for severe aortic stenosis, were announced at the April ACC meeting. Principal investigator Dr. Craig Smith (Columbia University, New York, New York) said that the results “indicate that TAVR is an acceptable alternative to aortic valve replacement in selected high-risk operable patients.” One of the panel members discussing the presentation, Dr. Martyn Thomas (London, UK), called it “an absolutely spectacular trial.” Dr. David Moliterno (University of Kentucky, Lexington), another panelist who was not involved in the study, told members of the press: “You really are witnessing history in the making. This is one of the biggest steps in cardiovascular medicine in our lifetime.”
[Cartagena readers:: Note that this is a 'non-inferiority study'..
Read the full news story on this trial here.
5. The NICE Hypertension Guidelines: A Monitoring Revolution
In August 2011, the UK's National Institute for Health and Clinical Excellence launched an update of their Hypertension Guideline -- the first guidelines in the world to formally recommend ambulatory blood-pressure monitoring as a "key priority" in diagnosing suspected hypertension, particularly if a clinic blood pressure reading is 140/90 mm Hg or higher, according to the chair of the writing committee. According to a long-time "reference standard" for tricky blood pressure readings, ambulatory monitoring should now become the go-to test for diagnosing hypertension in all patients, authors of a new analysis say.
In a Medscape commentary, Rajiv Agarwal, MD (Indiana University School of Medicine; Indianapolis) observes, "I think that they are revolutionary. Ambulatory blood pressure monitoring has never been recommended by any guideline to confirm the diagnosis of hypertension, but we have known for a long time that white-coat hypertension and masked hypertension are real problems. This is the first guideline that takes this problem and addresses it by asking to do ambulatory blood pressure monitoring in all patients at the first visit."
Watch the complete commentary from George Bakris and Rajiv Agarwal.
4. AIM-HIGH: Results Raise Controversy Over Early Discontinuation
The AIM-High study was designed to examine whether raising HDL using extended-release niacin would be beneficial in patients who had been treated with statin therapy for elevated low-density lipoprotein (LDL)-cholesterol levels, but who had low levels of high-density lipoprotein (HDL) cholesterol. The AIM-HIGH trial randomized 3414 patients with established heart disease, low HDL levels, and increased triglyceride levels to extended-release niacin (1500-2000 mg per day) or placebo. All patients also received simvastatin plus ezetimibe if needed to maintain LDL levels below 80 mg/dL, On April 25, 2011, the study's independent data and safety monitoring board made a decision to stop the trial after a mean follow-up of three years. The statement from the National Heart Lung and Blood Institute at the time said that niacin was showing no additional benefits over placebo and there was also a small, unexplained increase in ischemic stroke in the niacin group.
However, the final results of the trial that were presented at AHA 2011 and published in The New England Journal of Medicine[5] appear to suggest that the signal of increased ischemic stroke with niacin could have been the play of chance, with the final P value for ischemic stroke coming in at a nonsignificant .11. At 2 years, niacin therapy had increased HDL levels from a median of 35 to 42 mg/dL, decreased triglyceride levels from 164 to 122 mg/dL, and decreased LDL levels from 74 to 62 mg/dL. Speculation on the reason for the lack of benefit with niacin is focusing on the low LDL level achieved in the trial. Lead investigator Dr. William Boden (University at Buffalo School of Medicine, New York) commented to Heartwire: “if you are starting off with an LDL of 70, it may not be possible to show any incremental benefit.”
Read the full news story on this trial here.
3. FDA Approves Rivaroxaban for Stroke Prevention in Atrial Fibrillation
In November 2011, the US Food and Drug Administration (FDA) approved rivaroxaban, an oral factor Xa inhibitor, for treating patients with atrial fibrillation. Following dabigatran, rivaroxaban is the second in a surge of novel oral anticoagulants to go before the FDA’s advisors for the atrial fibrillation/stroke indication. The approval for rivaroxaban is based largely on the results of ROCKET-AF. One of the biggest hurdles rivaroxaban faced with the FDA advisory committee was in its comparison to warfarin, and more specifically, the amount of time the warfarin-treated patients spent at the optimal international normalized ratio (INR). In ROCKET-AF, the warfarin-treated patients spent just 57.8% of the time in therapeutic range, which was lower than that in other trials with warfarin, including the RE-LY trial with dabigatran etexilate (Pradaxa®, Boehringer Ingelheim).
A third drug, apixaban (Eliquis®, Bristol-Myers Squibb/Pfizer), is approved in Europe, but not the United States, for the prevention of venous-thromboembolic events in patients who have undergone elective hip- or knee-replacement surgery. The ARISTOTLE trial suggests that apixaban is noninferior to warfarin in the atrial fibrillation/stroke setting.
Read the full news story on this trial here.
2. New Data Show COURAGE Findings Are Not Being Implemented
In 2007, the landmark COURAGE study found that in patients with stable coronary artery disease, optimal medical therapy was just as good at preventing future events as receiving a stent on top of optimal medical therapy.[6] In May 2011, a survey covering almost 500,000 patients from > 1000 hospitals in the ACC National Cardiovascular Data Registry[7] showed that, at least among patients ultimately treated with PCI, there was little change in prescribing practice from pre- to post-COURAGE. The author of COURAGE, Dr. William E Boden (Buffalo General Hospital, New York), told Heartwire that he was not really surprised by the registry data. “This is consistent with other observations that have been made previously for years, that there is this ‘phase lag’ — an educational gap — between the results of a randomized trial and them being incorporated into clinical practice.”
Read the full news story on this trial here.
And the Top Game Changer Is…
1. The results of the EMPHASIS-HF trial, published in January 2011,[8] showed that aldosterone antagonist eplerenone (Inspra®, Pfizer) produced large reductions in both the risk for death and the risk for hospitalization compared with placebo in patients with systolic heart failure and mild symptoms. Aldosterone blockade, with either spironolactone or eplerenone, had already shown benefits in class 3-4 heart failure and in post-MI patients with heart failure. These results extended the benefit to patients with mild heart failure, a much broader population. As reported in Heartwire, Dr. Mariel Jessup (University of Pennsylvania School of Medicine, Philadelphia) said: “We have very good data now that aldosterone antagonists work for patients with heart failure and are saving lives, but we need to better understand the hyperkalemia and how exactly these drugs are working. This is an exciting day indeed, as we have a large new patient population for this drug, but we still have a lot of work ahead of us.”
Read the full news story on this trial here.
The EPHESUS trial,[9] published in October 2011, found that at least 3 separate therapeutic properties of the aldosterone antagonist contributed to the drug’s significant clinical benefits vs placebo. The authors stated that the clinical gains with eplerenone “cannot be explained solely by the drug’s diuretic and potassium-sparing properties.” They concluded that the analysis provides strong evidence for beneficial pleiotropic effects of the drug in patients with heart failure, at least in the post-MI setting.
Read the full news story on this trial here.
References
- Kappetein AP, Feldman TE, Mack MJ, et al. Comparison of coronary bypass surgery with drug-eluting stenting for the treatment of left main and/or three-vessel disease: 3-year follow-up of the SYNTAX trial. Eur Heart J. 2011;32:2125-2134. Abstract
- Bonow RO, Maurer G, Lee KL, et al; STICH Trial Investigators. Myocardial viability and survival in ischemic left ventricular dysfunction. N Engl J Med. 2011;364:1617-1625. Abstract
- Velazquez EJ, Lee KL, Deja MA, et al. STICH Investigators. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364: 1607-1616. Abstract
- Smith CR, Leon MB, Mack MJ. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364:2187-2198. Abstract
- The AIM-HIGH investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011; DOI:10.1056/oa1107579.
- Boden WE, O’rourke RA, Teo KK, et al; COURAGE Trial Co-Principal Investigators and Study Coordinators.The evolving pattern of symptomatic coronary artery disease in the United States and Canada: baseline characteristics of the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial. Am J Cardiol. 2007;99:208-212. Abstract
- Borden WB, Redberg RF, Mushlin AI, Dai D, Kaltenbach LA, Spertus JA. Patterns and intensity of medical therapy in patients undergoing percutaneous coronary intervention. JAMA. 2011;305:1882-1889. Abstract
- Zannad F, McMurray JJ, Krum H, et al; EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364:11-21. Abstract
- Rossignol P, Ménard J, Fay R, et al. Eplerenone survival benefits in heart failure patients post-myocardial infarction are independent from its diuretic and potassium-sparing effects: insights from an EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) substudy. J Am Coll Cardiol 2011;58:1958-1966.