Cardiology Today - Year in Review 2006

Cardiology Today’s Editorial Board scanned the headlines of 2006 and chose the 10 most important articles published in our pages during the year. To compile this list, our editorial staff asked our board members to select from a list of 30 articles we pulled from the headlines of Cardiology Today during the past 12 months. Their votes are the resulting Top 10 Stories.

News about drug-eluting stents possibly linked to higher mortality, and data from the Occluded Artery Trial (OAT) that showed the efficacy of optimal medical therapy without late percutaneous coronary intervention is efficacious topped the list.

Although our survey method is not scientific, we hope that our yearly Top 10 list provides our Editorial Board and our readers the opportunity to look back at the major developments in cardiovascular medicine during the past year. Please read summaries of the Top 10 below.

The Cardiology Today staff values your opinions. Let us know what you think about our Top 10. E-mail your comments to Judith Rusk, Managing Editor, at jrusk@slackinc.com.

Top story: Drug-eluting stents linked to mortality

Data presented at the World Congress of Cardiology 2006 that suggested drug-eluting stents may be associated with an increased risk for mortality tied for the top story of the year.

Edoardo Camenzind, MD, of the University Hospital in Geneva, presented a meta-analysis of nine previous clinical trials comparing both the sirolimus-eluting stent (Cypher, Cordis) and the paclitaxel-eluting stent (Taxus, Boston Scientific) with bare metal stents. Researchers found the rate of mortality and Q-wave MI among patients treated with sirolimus-eluting stents was 6.3% vs. 3.9% for patients treated with bare metal stents. For trials comparing the paclitaxel-eluting stent with bare metal stents, the rate of mortality and Q-wave MI was 2.6% among patients treated with a paclitaxel-eluting stent and 2.3% among patients treated with a bare metal stent.

Alain Nordmann, MD, of the Basel Institute for Clinical Epidemiology in Basel, Switzerland, examined 17 clinical trials comparing both drug-eluting stents with bare metal stents in a second meta-analysis.

Nordmann noted a trend toward increased mortality in patients treated with drug-eluting stents and a significant increase in noncardiac deaths associated with the sirolimus-eluting stent after two and three years of follow-up. Of a total 35 noncardiac deaths, 15 were attributed to cancer. This difference was not demonstrated for the paclitaxel-eluting stent.

Top story: Optimal medical therapy over PCI

Our Editorial Board also ranked as the top story of 2006 a story reporting the data from the Occluded Artery Trial that found that late percutaneous coronary intervention with stenting may not be the best option for some patients.

Judith Hochman, MD, of New York University School of Medicine, and colleagues tested whether PCI performed three to 28 days post-MI would reduce first occurrence of composite death, reinfarction, or NYHA Class IV HF by 25% compared with optimal medical therapy alone.

While presenting OAT results at the American Heart Association Scientific Sessions 2006 in November, Hochman said the four-year centrally adjudicated event rate for the group receiving medical therapy alone (n=1,084) was 15.6%, and 17.2% for the group receiving PCI and medical therapy (n=1,082).

Covariant adjusted and as-treated analysis compared successful PCI patients (n=937) with the medical therapy group that did not cross over to PCI within 30 days (n=1,057) and found similar results.

Primary end point events as determined by study sites occurred in 170 patients assigned to PCI and medical therapy and 142 patients assigned only to medical therapy.

Drug-eluting stents linked to late thrombosis

Earlier in 2006, prior to the mortality data presented at the World Congress of Cardiology, a review suggested that drug-eluting stents may be linked to systemic and intrastent hypersensitivity reactions associated with thrombosis or death in some cases.

Jonathan Nebeker, MD, and colleagues reviewed 5,783 reports filed to the Research on Adverse Drug/Device Events and Reports for hypersensitivity-like reactions with the sirolimus-eluting stent (Cypher, Cordis) and the paclitaxel-eluting stent (Taxus, Boston Scientific). They identified 262 unique events; 17 cases of hypersensitive reactions were identified as “probably” or “certainly” due to drug-eluting stents.

The researchers concluded that the polymer coating on the stents is the most probable cause of hypersensitivity in the majority of cases.

The data were published in the Journal of the American College of Cardiology (2006;47:175-181).

BASKET-Late: We need new strategies

Data from the BASKET-Late trial, presented at the American College of Cardiology 55th Annual Scientific Session in March 2006, showed that new strategies are needed to prevent late thrombotic events among patients receiving drug-eluting stents.

A total of 746 consecutive patients were treated with percutaneous coronary interventions and stenting. They received dual antiplatelet therapy, aspirin and clopidogrel (Plavix, Sanofi Aventis; Bristol-Myers Squibb) for six months.

Matthias E. Pfisterer, MD, a BASKET-Late researcher, concluded that after clopidogrel discontinuation, late stent thrombosis-related events were twofold to threefold more frequent after drug-eluting stents than after bare metal stents and carried a fourfold higher risk of cardiac death for MI vs. nonthrombosis-related events.

REPAIR-AMI, ASTAMI show conflicting results

Although the ASTAMI trial showed no improvement in ejection fraction with bone marrow cell infusion, REPAIR-AMI did. These conflicting results were top stories in 2006.

In ASTAMI, 1,608 patients with acute MI were randomized to a control group or treatment with bone marrow cells four to eight days after acute MI. At six months, the results showed EF by single photon emission CT increased to 49% from 42% at baseline in both groups with no differences between the groups for changes in EF, infarct size or end diastolic volume.

In REPAIR-AMI, patients were randomized to infusions of mononuclear progenitor bone marrow cells or to infusions of placebo three to five days post-acute MI. After about four months of follow-up, patients in the treatment group experienced a 5.5% increase in EF compared with a 3% increase in the placebo group.

The trials were presented at the American Heart Association Scientific Sessions 2005.

MEGA: Low-dose statins effective

Results of the MEGA study that demonstrated primary prevention treatment with low-dose pravastatin lowered the risk for coronary heart disease events among a healthy Japanese population was another news leader in 2006.

The MEGA study was the first statin trial conducted among an Asian population and included more women than previous statin trials, according to Daniel Rader, MD.

Treatment with pravastatin (Pravachol, Bristol-Myers Squibb) lowered cholesterol by 11.5% vs. 2.1% in the control group. LDL was reduced by 18% in the treatment group vs. 3.2% in the control group. CHD events were also reduced by 33%.

IDEAL results support aggressive statin therapy

The Editorial Board voted another statin study supporting secondary prevention with a high-dose statin as a top 10 story of 2006.

The IDEAL trial randomized 8,888 patients to 80 mg of atorvastatin (Lipitor, Pfizer) or 20 mg of simvastatin (Zocor, Merck). The researchers conducted 4.8 years of follow-up. During treatment, the simvastatin group had LDL of 104 mg/dL vs. 81 mg/dL for those in the atorvastatin group.

Major coronary events occurred in 10.4% of patients assigned simvastatin compared with 9.3% of patients assigned atorvastatin. Nonfatal MI, however, was reduced from 7.2% to 6% in the atorvastatin group. Atorvastatin also reduced the rate of CV events by 13% and any coronary event by 16%.

FDA approves angina treatment

Advancement in the treatment of angina was an important story for 2006.

In late January 2006, the FDA approved ranolazine (Ranexa, CV Therapeutics) for angina treatment in patients who have not responded to other agents. It is indicated for use in combination with amlodipine, beta-blockers or nitrates.

Louis G. Lange, MD, chairman and CEO of CV Therapeutics, said it was the first treatment for chronic angina approved in more than 10 years.

Clopidogrel, aspirin combo equal to aspirin, placebo

The Editorial Board found that data showing long-term clopidogrel plus aspirin therapy among patients with either clinically evident cardiovascular disease or multiple risk factors did not prove significantly beneficial was a top story for the year.

The results of the CHARISMA trial, presented by Deepak L. Bhatt, MD, at the American College of Cardiology 55th Annual Scientific Session in March 2006, demonstrated that patients taking clopidogrel (Plavix, Sanofi Aventis; Bristol-Myers Squibb) plus aspirin had a 6.8% rate of events compared with 7.3% among the placebo and aspirin group. Among those with clinically evident atherosclerosis, patients treated with clopidogrel plus aspirin had a 6.9% rate of the primary outcome (MI, stroke or death from CV causes) compared with 7.9% for the placebo group.

IVUS shows regression with rosuvastatin

The results of the ASTEROID trial also made the top 10 stories for 2006. This trial found that intravascular ultrasound showed evidence of disease regression in patients treated aggressively with rosuvastatin for 24 months.

ASTEROID was the first IVUS trial to show unequivocal evidence of disease regression, according to Steve Nissen, MD, who presented the results at the American College of Cardiology 55th Annual Scientific Session in March 2006.

ASTEROID examined 349 patients who were treated with rosuvastatin (Crestor, AstraZeneca) at 40 mg daily and were assessed at 24 months with IVUS.

LDL decreased by 53.2% from 130.4 mg/dL to 60.8 mg/dL; HDL increased by 14.7% from baseline 43.1 mg/dL to 49 mg/dL.