Year in Review: Physicians Highlight the Most Important Interventional News of 2012

From ischemia-based revascularization to reimbursement for transcatheter aortic valve replacement (TAVR), the past year has seen important developments in the field of interventional cardiology. TCTMD asked several prominent interventionalists to share their views on the most significant events of 2012.

Our physician panel referenced several seminal trials from the past year including FAME 2, FREEDOM, and WOEST. Another landmark event was the decision made by the Centers for Medicare and Medicare Services (CMS) to cover TAVR, keeping abreast with the treatment as it evolves.

FAME 2

Full results of the FAME 2 trial were presented by Bernard De Bruyne, MD, of OLV Clinic (Aalst, Belgium), on August 28, 2012, at the European Society of Cardiology Congress in Munich, Germany, and simultaneously published online ahead of print in the New England Journal of Medicine.

Speaking to the vexed issue of when elective PCI is justified, FAME (FFR-Guided Percutaneous Coronary Intervention Plus Optimal Medical Therapy vs. Medical Therapy Alone in Patients with Stable Coronary Artery Disease) 2 showed that—in patients with stable CAD and at least 1 proven ischemic stenosis—PCI guided by fractional flow reserve (FFR) plus optimal medical therapy markedly reduces the need for urgent revascularization compared with optimal medical therapy alone.

Dr. De Bruyne and colleagues looked at 1,220 patients with stable CAD who had angiographically assessed stenosis in at least 1 coronary vessel and evaluated those stenoses with FFR. The 888 patients who were determined to have at least 1 flow-limiting lesion (FFR ≤ 0.8) were randomized to optimal medical therapy with (n = 447) or without (n = 441) FFR-guided PCI. The remaining 332 patients were enrolled in a registry and treated with optimal medical therapy.

Baseline characteristics of randomized and registry patients were similar, except for more peripheral arterial disease and multivessel disease in the randomized cohort.

Enrollment was halted prematurely after an interim analysis determined that, compared with those on optimal medical therapy alone, FFR-guided patients had a substantially lower rate of the primary composite endpoint of all-cause death, MI, or urgent revascularization (4.3% vs. 12.7%; HR 0.32; 95% CI 0.19-0.53; P < 0.001). The difference was driven by a decrease in urgent revascularization in the PCI group (0.7% vs. 9.5%; HR 0.07; 95% CI 0.02-0.22; P < 0.001). A landmark analysis at 7 days found an interaction between time and treatment, suggesting that the benefit of PCI may become more apparent with time.

By contrast, only 3% of patients in the registry suffered a primary endpoint event, with low rates of mortality, MI, and any revascularization.

Commentary

The presentation and publication of the FAME 2 study was a very important development in interventional cardiology during the last year.

FAME 2 showed that up-front PCI of FFR-positive lesions was associated with fewer unplanned hospitalizations for urgent revascularization compared to medical therapy alone. Although long-term data are limited, 1-year event rates suggest that ultimately the number needed-to-treat with PCI to prevent 1 such hospitalization is 7.

Unfortunately, because FAME 2 was terminated early, it is difficult to assess whether this strategy might prevent MI or death. The ongoing National Institutes of Health-funded ISCHEMIA trial will hopefully provide insight when its results are released in approximately 2018.

What is clear from FAME 2, however, is that the up-front PCI strategy carries no harm, much as was found in the COURAGE trial. In addition, despite the fact that patients receiving PCI in FAME 2 were less likely to be given anti-anginal drugs than those on medical therapy alone, they experienced less angina. PCI, therefore, appears to improve symptoms, further supporting the idea that invasive treatment carries quality of life benefits in patients with functionally significant lesions.

FREEDOM

At the American Heart Association Scientific Sessions in Los Angeles, CA, the FREEDOM trial made waves by showing that CABG is superior to PCI over the long-term in patients with diabetes and advanced CAD. Findings were presented on November 4, 2012, and simultaneously published online ahead of print in the New England Journal of Medicine.

For the FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial, Valentin Fuster, MD, PhD, of Mount Sinai School of Medicine (New York, NY), and colleagues randomized 1,900 patients with diabetes and multivessel CAD to undergo either PCI with DES (n = 953) or CABG (n = 947) at 140 international centers. Intravenous abciximab was given to PCI patients during the procedure and clopidogrel and aspirin were prescribed for at least 12 months.

At 5 years, the primary composite endpoint of death, stroke, and MI occurred more often in patients treated with PCI. However, while the individual endpoints of all-cause mortality and MI were lower in the CABG cohort, the stroke rate was higher (table 1).

Table 1. Five-Year Clinical Outcomes

WOEST

Patients taking oral anticoagulants while undergoing PCI face heightened bleeding from standard dual antiplatelet therapy with aspirin and clopidogrel. Results from the WOEST trial, presented August 28, 2012, at the European Society of Cardiology Congress in Munich, suggest, in fact, that it may be possible to eliminate aspirin but keep the clopidogrel.

For WOEST (What is the Optimal antiplatelet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing), Willem Dewilde, MD, of Sint Antonius Hospital (Nieuwegein, The Netherlands), and colleagues randomized 573 patients on oral anticoagulants who were undergoing PCI at multiple centers in the Netherlands and Belgium to clopidogrel 75 mg daily with (n = 284) or without (n = 279) aspirin 80 mg.

Total TIMI bleeding was greater with triple therapy at 1 year, with an early divergence between the group taking all 3 drugs or just 2 (clopidogrel plus an anticoagulant; 19.5% vs. 44.9%; HR 0.36; 95% CI 0.26-0.50; P < 0.001).

For the secondary combined endpoint of stroke, death, MI, stent thrombosis, and TVR, dual therapy again bested triple therapy (11.3% vs. 17.7%; HR 0.60; 95% CI 0.38-0.94; P = 0.025). While dual therapy only showed a statistically significant benefit for death (HR 0.39; 95% CI 0.16-0.93; P = 0.027), positive trends existed for all other individual component endpoints except TVR.

Commentary

I would rank FREEDOM and WOEST as 2 of the most important stories from 2012.

Prior to the FREEDOM trial, I had assumed that the improvements in medical therapy (to stabilize plaque) and DES (to reduce restenosis) would negate the outcome difference between PCI and CABG in diabetic patients. The results of FREEDOM combined with the subgroup analysis from SYNTAX (Groot MW. Herz. 2012;37:281-6) suggest that diabetic patients with 2- or 3-vessel CAD should not undergo ad-hoc PCI. Either these patients should be referred for CABG or should be offered PCI only after a detailed discussion that preferably involves a heart team.

Regarding WOEST, the risk of bleeding in patients who are on triple therapy is so high that we always worry when stenting patients who are on oral anticoagulants. This study, although small and needing replication, found a meaningful reduction in bleeding without an increase in thrombosis by foregoing aspirin. I hope that we will have further data to support this strategy but, irrespective, I have to commend the investigators for an important study that has obvious practical implications for all interventionalists.

TAVR Developments

Two paired events dramatically changed the landscape of treatment for aortic valvular stenosis. In November 2011, the US Food and Drug Administration (FDA) approved the Sapien Transcatheter Heart Valve as the first percutaneously delivered artificial valve in the United States for use in patients with severe aortic stenosis who are ineligible for surgery. Then, in May 2012, CMS formally decided to cover transcatheter aortic valve replacement (TAVR).

Commentary

The approval of TAVR by the FDA and subsequent reimbursement by CMS together represent a landmark in valvular heart disease intervention and probably all of interventional cardiology. The FDA approval by itself is not remarkable, given the overwhelmingly positive outcome of the PARTNER trial in terms of a dramatic mortality benefit for inoperable patients with aortic valve stenosis. Rather, the landmark is in the details of the CMS reimbursement policy.

The promulgation of a national coverage decision by CMS, supported by both cardiology and cardiovascular surgical societies, represents a new approach to the introduction of new device technology into practice in the United States. The flexibility of the decision, which allows expanded indications as trial results become available, is central to this critical development. It allows for expanded CMS reimbursement as trial data become available and FDA labeled indications for TAVR expand. This policy is an important step toward obtaining balance between the evidence base for a new therapy and its application in practice. It is in contrast to past practice where new devices would be introduced with a narrow FDA label but rapidly be utilized off label in clinical practice.

 

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Sources:
1. Kirtane AJ, Marshall JJ.  The benefit of ischemia-based revascularization for stable ischemic heart disease: The impact of FAME 2.  Catheter Cardiovasc Interv. 2012; Epub ahead of print.

2. De Bruyne B, Pijls NHJ, Kalesan B, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012; 367:991-1001.

3. Farkouh ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. Epub ahead of print.

4. Dewilde WJM. WOEST: First randomized trial that compares two different regimens with and without aspirin in patients on oral anticoagulant therapy (OAC) undergoing coronary stent placement (PCI). Presented at: European Society of Cardiology Congress; August 28, 2012; Munich, Germany.

 

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