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Logo of thijTexas Heart Institute JournalSee also Cardiovascular Diseases Journal in PMCSubscribeSubmissionsTHI Journal Website
 
Tex Heart Inst J. 2010; 37(3): 309–311.
PMCID: PMC2879203

Interventional Cardiology

The Repertoire Continues to Expand
R. David Fish, MD, FACC

Interventional cardiology encompasses a broad repertoire of therapies, and recent developments highlight its increasing range. This brief review describes innovations in primary percutaneous coronary intervention (PCI) for acute myocardial infarction, antiplatelet drugs and strategies for PCI, proton pump inhibitors and clopidogrel, dual antiplatelet therapy after PCI and stenting, device closure of the left atrial appendage, and percutaneous heart valve therapy.

Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction

Coronary stents, glycoprotein IIb/IIIa inhibitors, and thienopyridine antiplatelet agents have each been established as beneficial in PCI for ST-elevation myocardial infarction (STEMI). Recently, drug-eluting stents (DESs) and direct thrombin inhibitors, which are established therapies in elective PCI, have been applied in the STEMI setting. However, this practice has given rise to lingering questions. Late thrombosis of DESs showed cardiologists that long-term dual antiplatelet therapy (DAPT) is necessary and raised the concern (although without direct evidence) that DESs were prothrombotic and, therefore, counterproductive in STEMI. Bivalirudin, a direct thrombin inhibitor shown to be beneficial in PCI for a broad range of patients—primarily because it decreases bleeding complications—has, in some analyses, shown a small excess of ischemic events, suggesting that its benefits might not be expressed in STEMI.

The HORIZONS-AMI trial1 dealt with both of these issues by enrolling 3,600 patients within 12 hours of STEMI onset. In the first of two levels of randomization, bivalirudin was compared with combined heparin and GPIIb/IIIa inhibition at PCI; in the second level, the Taxus® DES (Boston Scientific Corporation; Natick, Mass) was compared with bare-metal stents. At two years, bivalirudin reduced major bleeding, all-cause death, cardiac death, and reinfarction. Although patient selection could be criticized, the study showed no excess of ischemic events and strongly implied that bivalirudin is better than heparin plus GPIIb/IIIa inhibition for STEMI patients. In the stent comparison, the Taxus DES reduced repeat revascularization events without posing an excess risk of stent thrombosis. Thus, bivalirudin and the Taxus DES appear to be safe and effective in primary PCI for STEMI.

New Antiplatelet Drugs and Strategies for PCI

Compared to the standard agent, clopidogrel, prasugrel is a new, more potent thienopyridine platelet inhibitor with a more rapid onset. Use of these agents in PCI was evaluated in the TRITON–TIMI 38 trial,2 which showed that prasugrel reduced the occurrence of combined cardiovascular death, myocardial infarction, and stroke (the primary endpoint), as well as nonfatal myocardial infarction, urgent revascularization, and stent thrombosis, at the cost of an increase in bleeding events. Therefore, prasugrel is generally preferred, especially for patients in whom the role of coronary thrombosis is most direct—such as the acute coronary syndrome and STEMI groups—but should be avoided in patients with a higher risk of bleeding (such as those older than age 75 or with a history of recent stroke). More recently, in PLATO,3 ticagrelor, a non-thienopyridine adenosine diphosphate P2Y12 receptor blocker, showed an efficacy superior to that of clopidogrel, with relatively equivalent safety in patients with acute coronary syndrome.

It has long been speculated that an intravenous form of thienopyridine would be helpful in preparation for PCI, to achieve potent and rapid onset of effective platelet inhibition; in the CHAMPION trial,4 however, when cangrelor was given intravenously pre-PCI, it was not superior to clopidogrel or even to placebo5 in reducing the composite primary endpoint of death, myocardial infarction, or ischemia-driven revascularization at 48 hours.

The post-PCI duration of DAPT was examined in the TYCOON registry,6 a consecutive series of 447 DES patients that compared 12 months of clopidogrel therapy with 24 months. This relatively small trial showed that 24 months of DAPT with 0.4% stent thrombosis was superior to 12 months with 3.0% stent thrombosis. Large-scale registry data suggest that the horizon for stent thrombosis events may be closer to 3 years, and many cardiologists have adopted this DAPT duration.

Proton Pump Inhibitors and Clopidogrel

Like many other cardiovascular drugs, clopidogrel is a prodrug. Proton pump inhibitors such as omeprazole are frequently prescribed to PCI/DES patients to prevent gastric bleeding during protracted DAPT, but proton pump inhibitors may interfere with the metabolism of clopidogrel and reduce its antiplatelet effectiveness. Some registry data have suggested that the concomitant administration of these drugs increases the rate of ischemic events, including stent thrombosis. This has led to admonitions from pharmaceutical and insurance companies, even the U.S. Food and Drug Administration, against concomitant administration—but without well-formed evidence. Recently, COGENT,* a prospective randomized trial of combined clopidogrel and omeprazole versus clopidogrel with placebo, was conducted in patients with ST-elevation acute coronary syndrome, STEMI, or stent PCI. At up to 390 days, the 2 groups had no difference in cardiovascular events, myocardial infarction, or revascularization, but a near-double rate of gastrointestinal events was observed in patients not taking omeprazole. Therefore, cardiologists may feel justified in adding a proton pump inhibitor but should consider individualizing such therapy—for example, withholding it from patients with high-risk anatomy and complex stenting but no significant gastrointestinal bleeding risk.

Dual Antiplatelet Therapy after Percutaneous Coronary Intervention with Drug-Eluting Stents

If DAPT must be stopped after PCI with DES or if a patient is noncompliant, what can be expected? Eisenberg and associates7 examined the timing of late stent thrombosis events after discontinuation of clopidogrel, aspirin, or both. After discontinuation of both agents, late stent thrombosis occurred early—90% of the events within 15 days. If clopidogrel alone was discontinued while aspirin was continued, however, late stent thrombosis occurred more slowly, taking a year to reach 70% of such events. Stent-thrombosis events tended to occur at a median of 7 days after both agents were stopped and at a median of 122 days after clopidogrel alone was stopped. These observations suggest that the risk of late stent thrombosis is real but may be mitigated by continuation of aspirin. Subsequent resumption of clopidogrel, however, is necessary in these cases, because late stent thrombosis events continue to accumulate.

Device Closure of the Left Atrial Appendage

Atrial fibrillation is a cause of thromboembolism and stroke. In more than 90% of cases, the thrombus originates in the left atrial appendage. The mainstay of therapy for chronic atrial fibrillation has long been warfarin anticoagulation, which mitigates the risk of cardiogenic thromboembolism but imposes a bleeding risk. Targeted structural therapy for closing the left atrial appendage has recently been developed. In the PROTECT-AF trial,8 the Watchman® device (Atritech, Inc.; Plymouth, Minn) (Fig. 1), implanted into the left atrial appendage, was compared with warfarin therapy. In more than 900 patient-years of follow-up, there were more early complications with device implantation but more hemorrhagic strokes with warfarin. There was no difference in the ischemic-stroke rates for the 2 groups; that is, device therapy was noninferior to warfarin for all-cause stroke and all-cause death. Longer-term follow-up evaluation may strengthen the case for device implantation, because warfarin events are likely to continue accumulating and the safety of device implantation may improve. Meanwhile, device therapy might be preferred whenever clinical risk factors for hemorrhagic stroke are present.

figure 10FF1
Fig. 1 The Watchman® device for closing the left atrial appendage (LAA). Courtesy of Atritech, Inc. (Plymouth, Minn).

Percutaneous Heart Valve Therapy

The Edwards SAPIEN balloon-expanded device (Edwards Lifesciences LLC; Irvine, Calif) (Fig. 2) and the Medtronic CoreValve® self-expanded device (Medtronic CV Luxembourg S.a.r.l.) are commercially available in the European Union for percutaneous heart valve procedures, principally transcatheter aortic valve implantation; roughly 3,000 percutaneous heart valve procedures were performed there in 2008 and more than 10,000 in 2009. Grube and associates9 recently reported their 1-year results after CoreValve transcatheter aortic valve implantation. In the latter part of the study, when investigators were using an improved version of the device, the death rate was still 16%, although this was better than the 30% mortality rate encountered in the early cohort. More recent reports concerning both valve designs have cited death rates of 20% to 25%.10 Other investigators have reported lower rates,11,12 which presumably reflect improved experience, technique, patient selection, and devices.

figure 10FF2
Fig. 2 The Edwards SAPIEN transcatheter heart valve. Courtesy of Edwards Lifesciences LLC (Irvine, Calif).

In the United States, the PARTNER trial, the first pivotal trial of the Edwards SAPIEN transcatheter heart valve, recently completed enrolling about 1,000 patients. In this doubly randomized study, transcatheter aortic valve implantation is being compared with surgical aortic valve replacement and with medical therapy. The first results of this landmark study are eagerly awaited. In addition, both the Edwards SAPIEN and the Medtronic Melody® transcatheter pulmonary valves (Medtronic, Inc.; Minneapolis, Minn) are being studied for use in pulmonary conduits in congenital heart disease.

Summary. As these innovations continue to evolve—along with others too numerous to include in this brief review—they will broaden the practice of interventional cardiology and improve the options available for the nonsurgical treatment of heart disease.

Footnotes

*Bhatt DL. COGENT. Press-conference presentation at the Transcatheter Cardiovascular Therapeutics 21st Annual Scientific Symposium (San Francisco), 2009 Sep 24.

Address for reprints: R. David Fish, MD, FACC, Director, Interventional Cardiology Research & Education, Texas Heart Institute at St. Luke's Episcopal Hospital, 6624 Fannin St., Suite 2220, Houston, TX 77030

E-mail: moc.etageulb@renrutm

Presented at the 9th Texas Update in Cardiovascular Advancements; Houston, Texas; 4–5 December 2009

Program Director: James T. Willerson, MD

References

1. Stone GW, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008;358(21):2218–30. [PubMed]
2. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357(20):2001–15. [PubMed]
3. Cannon CP, Harrington RA, James S, Ardissino D, Becker RC, Emanuelsson H, et al. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet 2010;375(9711):283–93. [PubMed]
4. Harrington RA, Stone GW, McNulty S, White HD, Lincoff AM, Gibson CM, et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med 2009;361(24):2318–29. [PubMed]
5. Bhatt DL, Lincoff AM, Gibson CM, Stone GW, McNulty S, Montalescot G, et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med 2009;361(24):2330–41. [PubMed]
6. Tanzilli G, Greco C, Pelliccia F, Pasceri V, Barilla F, Paravati V, et al. Effectiveness of two-year clopidogrel + aspirin in abolishing the risk of very late thrombosis after drug-eluting stent implantation (from the TYCOON [two-year ClOpidOgrel need] study). Am J Cardiol 2009;104(10):1357–61. [PubMed]
7. Eisenberg MJ, Richard PR, Libersan D, Filion KB. Safety of short-term discontinuation of antiplatelet therapy in patients with drug-eluting stents. Circulation 2009;119(12):1634–42. [PubMed]
8. Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbinder M, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial [published erratum appears in Lancet 2009;374(9701):1596]. Lancet 2009;374(9689):534–42. [PubMed]
9. Grube E, Buellesfeld L, Mueller R, Sauren B, Zickmann B, Nair D, et al. Progress and current status of percutaneous aortic valve replacement: results of three device generations of the CoreValve Revalving system. Circ Cardiovasc Interv 2008;1 (3):167–75. [PubMed]
10. Baan J, Yong ZY, Koch KT, Henriques JP, Bouma BJ, de Hert SG, et al. Percutaneous implantation of the CoreValve aortic valve prosthesis in patients at high risk or rejected for surgical valve replacement: clinical evaluation and feasibility of the procedure in the first 30 patients in the AMC-UvA. Neth Heart J 2010;18(1):18–24. [PMC free article] [PubMed]
11. Avanzas P, Munoz-Garcia AJ, Segura J, Pan M, Alonso-Briales JH, Lozano I, et al. Percutaneous implantation of the CoreValve self-expanding aortic valve prosthesis in patients with severe aortic stenosis: early experience in Spain [in English, Spanish]. Rev Esp Cardiol 2010;63(2):141–8. [PubMed]
12. Piazza N, Wenaweser P, van Gameren M, Pilgrim T, Tsikas A, Otten A, et al. Relationship between the logistic EuroSCORE and the Society of Thoracic Surgeons Predicted Risk of Mortality score in patients implanted with the CoreValve ReValving system–a Bern-Rotterdam Study. Am Heart J 2010;159 (2):323–9. [PubMed]

Articles from Texas Heart Institute Journal are provided here courtesy of Texas Heart Institute