EVOLVING TECHNOLOGIES

PERSPECTIVE

Current Coronary Interventional Alternatives David R. Holmes, Jr., MD, Mayo Clinic, Rochester, Minnesota

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he first percutaneous coronary revascularization procedure was performed on September 16, 1977. In the intervening 19 years, there has been an enor-

mous growth in procedures; it is estimated that 500,000 procedures were performed worldwide in 1995. This expo- nential growth has been the result of several factors: there have been great advances in the field, mcluding technolog- ical improvements; the development of a database which has facilitated analysis of initial safety and efficacy of the proce- dures, as well as data on long-term outcome; the planning and implementation of randomized trials comparing con- ventional percutaneous transluminal coronary angioplasty (PTCA) versus medical and surgical therapy, as well as comparing one device versus other devices; and the devel- opment and testing of new adjunctive therapeutic strategies such as IIb/IIIa receptor blocker drugs. These factors have led to the application of percutaneous techniques in an ever-widening number of patient and angiographic subsets who are potential candidates for treatment.

Some of the devices used are now mature technology, for example, conventional PTCA, and are characterized by mul- tiple iterations from several manufacturers, stable design, and a large database. Other devices are first generation and are evolving rapidly from the standpoints of materials and design, as well as optimal adjunctive treatment (i.e., intra- coronary stents).

Conventional PTCA

The first approach described, conventional dilatation, re- mains the most widely used technique, although now the use of alternative devices is increasing rapidly. PTCA is used as a stand-alone procedure as well as to optimize the initial result of virtually all new interventional devices, either for predilatation to facilitate device placement, or post-treatment to optimize the initial angiographic result.

Conventional PTCA has been tested against medical ther- apy (the ACME trial) and found to result in improved exercise tolerance and decreased need for cardiac medica- tions in carefully selected patients (1). It has also been evaluated in acute myocardial infarction (MI) and has been found to be associated with improved outcome, particularly in higher-risk patients. Conventional PTCA has also been compared with coronary artery bypass surgery in random- ized trials for multivessel coronary artery disease (EAST, CABRI, ERACI, GABI, RITA. and BARI) (2, 3). The large

body of data from these single and multicenter randomized trials indicate that in carefully selected symptomatic patients with multivessel coronary artery disease, the outcome of PTCA as the initial revascularization strategy is similar to coronary bypass graft surgery in terms of the hard end points of death and MI. During follow-up on these trials, which has ranged from 1 to 5 years, the incidence of death or MI is similar between PTCA and coronary bypass surgery, but the need for repeat procedures is increased in patients initially undergoing PTCA because of the phenomenon of restenosis.

Along with increasing knowledge about the success rates of conventional PTCA has come increasing information on the limitations of the technique which include abrupt clo- sure (occurring in 4% to 8% of interventional procedures), restenosis (occurring in 30% to 50% of patients), and prob- lems with adverse lesion morphology (which have been exemplified by the American Heart Association [AHA]/ American College of Cardiology [ACC] grading scheme) (4, 5). These limitations were the impetus for the development of new technology including atherectomy, laser angioplasty and stents. Each of these areas of new technology have developed and have gone through similar phases which have included initial small pilot results, larger registries which have often been industry funded, device approval by gov- ernmental agencies, and then randomized trials against ei- ther conventional PTCA or alternative newer technology. Following these phases, device usage patterns mature; this process is influenced by the results of the scientific studies, availability and success of other approaches, and a number of other factors.

DEVICES AND SPECIFIC LESION MORPHOLOGY

Device

Directional atherectomy

Rotational atherectomy

TEC atherectomy

Laser

Stents

Conventronal PTCA

Lesion Morphology

Bulky lessons, large vessels, selected large btfurcation lestons

Short or medmm length calctfied lesions, osual disease, iestons wtth excesswe recotl

Diffuse vem graft daease, selected lessons wth large thrombus burden

Long noncalcified chrome total occlusions, treatment of dtffuse in-stem restenosts

Preventton of restenosrs, treatment of high nsk lesrons, treatment of acute or threatened closure or subopttmal result wth PTCA. ? treatment of restenotic lessons

Treatment of tn.stent restenosis, optimtzmg results of atherectomy, laser and stents, treatment ot non-htgh nsk lessons, pretreatment for stent tmplantatton, treatment of acute mvocardial infarctron

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EVOLVING TECHNOLOGIES

Atherectomy

Three basic atherectomy devices are approved and used. Directional atherectomy was the initial device (6). It has been tested in four randomized trials, the results of three of which are known while the fourth is pending. In the three random- ized trials, mmal angiographic success rates were improved with directional atherectomy versus PTCA, but there was an increased incidence of complications, mainly non-Q-wave MI, and no clinically significant decrease in angiographic or clinical restenosis. These negative findings, plus widespread availability of stents and the fact that directional atherec- tomy is time- and resource-consuming and difficult, have led to a marked decrease in the application of this device. It is still important in a small number of settings. The pending release of the fourth randomized trial, a 1,000 patient group with optimal atherectomy versus conventional dilatation, will have a major impact on subsequent usage patterns.

Rotational atherectomy has also been evaluated in random- ized trials against conventional PTCA and excimer laser (7). Current trials continue. To date, the device, when used with adjunctive PTCA in selected lesions, appears to result in improved initial success rates but no change in restenosis. The device is more difficult to use and has increased rates of no reflow which may result in severe hemodynamic com- promise. Rotational atherectomy remains an important niche device used to extend the application of percutaneous techniques to higher risk lesions, particularly those with significant calcification or those in whom conventional dila- tation cannot be performed due to significant recoil.

Transluminal extraction catheter @EC) atherectomy has been used in a smaller number of patients; as yet, no ran- domized trial data is available. It is most useful in treating more diffuse vein graft disease or lesions with a large throm- bus burden. In these situations, in relatively small experi- ences, it has been associated with improved outcome.

Laser Angioplasty

Laser angioplasty was developed with great enthusiasm. It was studied in both registry experiences and randomized trials. After initial enthusiasm, interest has declined signifi- cantly for several reasons including cost, failure to treat calcified lesions, the unpredictable nature of the treatment particularly with the development of dissections, and the lack of an affect on restenosis. Recently, interest has been rekindled somewhat because of the development of a laser wire for chronic total occlusion. Whether this application will increase the use of laser is uncertain,

Stents

The most significant change m mterventional cardiology has been the growth in intracoronary stenting. First described in 1987 there has been exponential growth in the past 12

months. It is now estimated that 20% to 30% of all proce- dures involve the implantation of stents, and estimates are that it will increase to approximately 50% to 60%. This increase has already been seen in multiple centers in the United States as well as abroad, and has been the result of several factors: two randomized trials (STRESS and BENESTENT) (8,9) which have documented a reduction in angiographic and clinical restenosis in patients treated with stents compared to conventional PTCA; documentation of the improved outcome of stenting for abrupt or threatened closure (10); and documentation that high pressure dilata- tion post-stent implantation can obviate the need for intense anticoagulation regimens including coumadin. This latter change with reliance on aspirin and ticlopidine has de- creased the length of initial hospital stay as well as decreased the peripheral vascular complications from intense antico- agulation.

The current excellent results with stenting are being achieved with first generation devices. Newer devices with stent coatings and a variety of different geometric and me- tallic designs are under evaluation and appear to be substan- tially improved and should make the procedures easier and more predictable.

Pharmacologic Treatment

Non-device advances in interventional cardiology are also continuing (11). IIb/IIIa antagonists have been documented to improve the outcome of conventional PTCA in higher risk patients and are being tested in combination with stents. Other anticoagulant and antiplatelet agents also are being evaluated. These will have the potential to further improve outcome.

Conclusions

Interventional cardiology continues to grow; this growth is the result of expanded patient and lesion selection criteria, technological advances making the procedures safer and more predictable, and the continued results of scientific studies which document the long-term excellent palliation in patients with coronary artery disease. Table 1 suggests the current thinking relative to “fitting” the lesions and/or clin- ical indications with specific devices.

REFERENCES

1. Pans1 AF, Folland ED. Hartlgan P for the Veterans Affairs ACME Inves- tigators. A comparison of angloplasty with medical therapy in the treatment of smgle vessel coronaqr artery disease. N Engl J Med 1992;326:10.

2 RITA Trial Participants. Coronary angioplasty versus coronary artery bypass surgery: The Randomized Interventmn Treatment of Angma (RITA) Trial. Lancet 1993;341,573-80.

3. Kmg SB, Lembo NJ, Weintraub WS, et al. A randomized trial comparing coronary angloplasty -71th coronar) bypass surgery N Engi J Med 1994; 331.1044-50.

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4. Holmes DR Jr, Holubkov R, Vhetstra RE, et al. Complications during percutaneous transluminal coronar)r angioplasty from 1977 to 1981 and from 1985 to 1986, the NHLBI PTCA Registry J Am Co11 Cardiol 1988;12: 1149-55.

5. Ryan TJ, Faxon DP, Gunna RM. et al GuIdelines for percutaneous translummal coronary angloplasty: A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Dlag- nostic and Therapeutic Cardiovascular Procedures (PTCA). J Am Co11 Cardiol 1988;12:519.

6. Holmes DR Jr, Top01 EJ, Adelman AG, et al Randomized trials of dnectional coronary atherectomy: Implicanons for clinical practice and future investigation. J Am Co11 Cardiol 1994;24.431-9.

7. Davis KE, Foreman RD. Buchbinder M. Rotational atheroablanon’ atherectomy. In. Ellis SG, Holmes DR Jr, eds. Strategic approaches m coronary mtervention. Baltimore. Williams & Wllkms, 1996.17-26.

8. Fischman DL, Leon MB, Bairn DS, et al. A randomized comparison of coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994;331:496-501.

9. Serruys PW, De Jaegere P, Klemeney F, et al. A comparison of balloon expandable stent implantation wth balloon angloplasty m patients with coronav artery disease. N Engl J Med 1994;331:489-95.

10 George BS, Voorhees WE III, Roubm GS, et al Multlcenter investiga- tion of coronary stentmg to treat acute or threatened closure after percuta- neous transluminal coronary angloplasty, Climcal and anglographlc out- comes. J Am Co11 Cardiol 1993;22:135-43.

11. EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein lIb/IIa receptor m high risk angioplasty. N Engl J Med 1994;330:956-61

Address correspondence and reprint requests to David R. Holmes, Jr., MD, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905.

EDITOR’S NOTES

ACC Presentation Excerpt From a presentation by Dr. David Holmes at the American College of Cardiolog)l Annual Scientific Session, Orlando, Florida, March 1996.

A central conflict in cardiovascular medicine involves the demand for medical care with all its new technology and, on the other hand, the limited resources available. These issues are complex. There are the issues of charges versus cost, direct versus indirect costs, initial versus follow-up costs and they may be very different for different technologies. We must keep in mind that few modern innovations are cost- effective. For example, the new interventions in the cathe- terization laboratory may not prolong life, but they may have a dramatic impact on the quality of life or on quality- adjusted life years. It also might be kept in mind that new technologies may have more capital costs up front, for example. But if the patients are followed long enough, they may have a measurable longer term cost effectiveness.

As we think about new technology in the catheterization laboratory how could it potentially help with costs? These are several possibilities. First, new technologies could ex- pand the number of patients who can be treated percutane- ously instead of with a surgical approach. Second, new

technologies might decrease or prevent acute complications. Third, newer technologies could be used to treat acute complications, shorten the initial hospital stay and improve long-term outcome.

Examples from the CAVEAT trial follow:

Benefit of Preventing Complications

In the CAVEAT trial, the cost of acute closure was $24,000 in contrast to the group of patients without acute closure where the cost was approximately $9,000. For 1,000 pa- tients with acute closure the cost would be $1.5 million.

What if stents had been used to reduce an acute closure incidence of 6% to perhaps 3.5%. The total cost would be approximately $800,000, a significant savings.

Benefit to be Derived From Shortening Hospital Stay

Changing stent practices just by the use of high pressure balloons and no anticoagulants, hospital stay may be re- duced from 6 to 8 days to 3 days. Also vascular complica- tions are reduced, again reducing hospital stay.

New technologies can be used to cut costs if used: 1) to expand the number of patients that can be treated effectively percutaneously instead of with a surgical approach, 2) to prevent or treat acute complications, 3) to shorten initial hospital stay and stays due to complications, and 4) to improve long-term outcome.

TOWARD THE FUTURE: EVOLVING KNOWLEDGE AND ADJUNCTIVE TECHNOLOGIES FOR CORONARY INTERVENTIONAL PROCEDURES

EPILOG and CAPTURE Trials Halted Because of Positive Interim Results James J. Ferguron Ill. Clinical Cardiology Research, Texas Heart Institute, Houston, TX. Circulation I996;93:637.

On December 14,1995, Centocor Inc announced that it was stopping the EPILOG trial (Evaluation of PTCA to Improve Long-term Outcome by c7E3 GP IIb/IIIa Receptor Blockade) because of positive findings at the first interim analysis of 1500 patients, As originally designed, the trial was to have included 4800 patients, both low risk and high risk, under- going percutaneous intervention, randomized to a control arm: “standard”-dose heparin (100 U/kg bolus, titrated to an activated clotting time of 9300 s) plus placebo, or to one of two experimental arms: standard-dose heparin plus the GP IIb/IIIa antibody c7E3 Fab (ReoPro 0.25 mg/kg bolus plus 0.125 pg * kg-’ . min-l [up to a maximum of 10 pg/min] infusion for 12 hours), or “low’‘-dose heparin (70 U/kg bolus, to achieve an activated clotting time ~200 s) plus c7E3 Fab. An

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