Our work in the cath lab moves forward when supported by better patient outcomes, better safety and better cost savings. Much of what we used to do in the cath lab has changed based on comparisons between groups of patients treated in the ‘conventional’ way with that of a potentially better method, drug or device. This year, especially in the fall after the October 2008 TCT meeting, there were many new trials presented, some of which are likely to have importance for the cardiac cath lab. I thought it would be worthwhile to take a moment and review 7 studies presented over the past year that I think are worth remembering and may ultimately change the way we practice.

Question: Do we have an oral antiplatelet agent better than Plavix? Is prasugrel better than clopidogrel for percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS)?

Category: Post PCI care
Study Name: TRITON-TIMI 38

The Trial to Assess Improvement in Therapeutic Outcomes optimizing platelet inhibition with Prasugrel (TRITON-TIMI 38) was presented by Dr. Elliott Antman at the American Heart Association in Orlando, Florida in November 2007 and subsequently published (NEJM 2007;357:2001-2015). This study randomized 12,000 patients, 6,813 to prasugrel (loading dose and 10 mg maintenance) or clopidogrel, [(n=6795) 300 mg loading and 75 daily] with average follow up of 14.5 months. Cardiovascular death, myocardial infarction (MI) or stroke were lower in the prasugrel group compared with clopidogrel (10 vs. 12%, p < 0.001), with similar results in non-ST elevation MI (NSTEMI) and STEMI. Definite or probable stent thrombosis occurred less frequently in the prasugrel group than in the clopidogrel group (1.1 versus 2.4%, p < 0.001). However, the key safety endpoint of major non-coronary artery bypass graft surgery (CABG) TIMI bleeding was higher in prasugrel than clopidogrel (2.4 versus 1.8%, p = 0.03) and was consistent across the different categories of bleeding, ranging from life-threatening to nonfatal. The use of prasugrel among patients undergoing planned PCI for ACS demonstrated some benefit at an increased risk of bleeding. While more potent platelet inhibitors appear to provide higher and less variable levels of platelet inhibition, the balance between reduced clinical events and bleeding remains of concern. Identification of subgroups at highest risk of bleeding without improved efficacy will determine in which populations new therapy should be withheld.

Question: Can multivessel drug-eluting stents (DES) do as well as CABG for patients with 3-vessel disease (VD) or left main (LM) disease?

Category: Multivessel (MV) PCI
Study Name: SYNTAX

This trial compared CABG versus DES-PCI (using Boston Scientific’s Taxus stents) in all patients coming to the cath lab with severe 3-VD or LM disease, who were deemed eligible for either CABG or PCI. The hypothesis was DES-PCI would be non-inferior to CABG in the management of patients with 3-VD and/or LM disease. The incidence of the primary endpoint of major adverse cardiac and cerebrovascular events (MACCE) at 12 months was lower in the CABG arm compared with PCI (12.1% vs. 17.8%, p = 0.0015), and PCI was not equal to CABG, due to a significant reduction in the repeat revascularization in the CABG arm compared with PCI (5.9% vs. 13.7%, p = 0.0001). There was no difference in the incidence of death (p > 0.05) or MI between the two arms (p = 0.11). The incidence of cerebrovascular accident was significantly higher in the CABG arm (2.2% vs. 0.6%, p = 0.003), whereas the incidence of symptomatic graft occlusion and stent thrombosis was similar between the two arms (3.4% vs. 3.3%, p = 0.89).

In LM patients, the overall 12-month MACCE event rate was lower with CABG (13.7% vs. 15.8%), although patients with LM only (8.5% vs. 7.1%) and LM + 1-VD (13.2% vs. 7.5%) seemed to do slightly better with PCI. Patients with LM + 2-VD (14.4% vs. 19.8%), LM + 3-VD (15.4% vs. 19.4%), or 3-VD alone (11.5% vs. 19.2%) seemed to do better with CABG than PCI.

SYNTAX demonstrated that in patients with LM disease and/or severe 3-VD, CABG (with the use of at least one arterial graft) is superior to PCI with the Taxus DES, predominantly driven by the need for repeat revascularization in the PCI arm. CABG is, however, associated with a higher risk of cerebrovascular accidents (CVA) at 12 months, compared with PCI. As suggested in earlier PCI/CABG trials, the largest benefit from CABG seemed to be in patients with diabetes mellitus. Questions remain whether sirolimus-eluting stents (SES) may be associated with better outcomes in diabetic patients, compared with paclitaxel-eluting stents (PES), especially in the need for repeat revascularization. It is thus unknown if the use of SES instead of PES, or newer stents such as everolimus-eluting stents, would be associated with better outcomes in patients like these who undergo PCI.

Question: If you have an STEMI at a non-PCI hospital, should you get heparin, half dose reteplase and abciximab then PCI or immediate transfer for rescue PCI?

Category: STEMI management
Study Name: CARESS

This study was presented by Dr. Krzysztof Zmudka at the European Society of Cardiology Congress, August/September 2008, Munich, Germany and published this year [Di Mario C, Dudek D, Piscione F, et al. Immediate angioplasty versus standard therapy with rescue angioplasty after thrombolysis in the Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI): an open, prospective, randomized, multicentre trial. Lancet 2008;371:559-68]. Study patients were admitted to hospitals without PCI capabilities and treated initially with heparin, half-dose reteplase, and abciximab, then randomized to immediate transfer for urgent PCI (n = 299) or standard therapy and rescue PCI if needed (n = 301). The primary endpoint of death, reinfarction or refractory ischemia at 30 days occurred less frequently in the immediate PCI group (4.4% vs. 10.7%, p = 0.005), driven by a reduction in refractory ischemia (0.3% vs. 4.0%, p = 0.003). Reinfarction rates, death rates, stroke rates and major bleeding were similar (all p = ns). At 1 year, MACE occurred in 11.4% of the immediate PCI group versus 16.4% of the standard therapy group (p = 0.07). Recurrent PCI occurred less frequently in the transfer group (14.4% vs. 42.4%, p < 0.0001), with no difference in mortality.

Among STEMI patients admitted to centers without PCI facilities and initially treated with heparin, half-dose reteplase, and abciximab, immediate transfer for PCI had benefit at 30 days compared to transfer for rescue PCI. Benefit (although less) was still seen from lysis and transfer at 1 year. Facilitated (thrombolysis + PCI) intervention compared to primary PCI revealed that primary PCI is the preferred strategy when PCI facilities are readily available. In fact, facilitated PCI appears harmful, with increased bleeding, stroke and death. A primary difference in these approaches is that facilitated PCI involves immediate PCI after lysis, whereas in the CARESS study, transportation delayed this time by approximately 2 hours. This approach has appeal for the large number of STEMI patients who cannot receive angioplasty within the 90-minute, guideline-recommended timeframe. CARESS suggests that for high-risk STEMI patients younger than 75 years of age who present to a facility without PCI capabilities, an approach of aspirin, heparin, half-dose reteplase and abciximab, followed by immediate transfer for PCI, may be superior to standard care and rescue PCI if needed.

Question: What’s the best way to treat a bifurcation lesion – Simple T or Complex Crush/Culotte?

Category: Bifurcation PCI Technique
Study Name: BBC-ONE

The BBC ONE (British Bifurcation Coronary study: Old, New and Evolving strategies) trial compared a simple stepwise provisional T-stent strategy to a more complex total lesion coverage with crush or culotte techniques for bifurcation lesions. In the simple strategy, the operator stented the main vessel, followed by kissing inflation and then T-stenting. In the complex strategy arm, either culotte (wire both vessels, stent first vessel, then rewire main vessel, and then stent the second vessel, with mandatory kissing) or crush (stent side vessel, crush with balloon/stent, then stent the main vessel, then recross the side vessel, with mandatory kissing) techniques were employed. At 9 months, the composite endpoint of death, MI or target vessel failure (TVF) occurred more in the complex strategy arm compared with the simple strategy arm (15.2% vs. 8.0%, p = 0.009). The incidences of mortality (0.8% vs. 0.4%), TVF (7.2% vs. 5.6%) and stent thrombosis (2.0% vs. 0.4%) trended (p = ns) higher with the complex strategy.

Periprocedural MACE was higher in the complex strategy arm (7.6% vs. 2.0%, p = 0.003). TIMI major bleeding, procedure time (78 vs. 57 minutes), radiation exposure (7900 vs. 6140 cGy • cm2), and number of stents used (2.21 vs. 1.17) were all higher with the complex strategy (all p < 0.001). A simple stepwise T-stent strategy is superior to a complex strategy. Full publication of these results will provide further details important to the practioners.

Question: Does cooling the patient protect the kidneys from contrast-induced nephropathy?

Category: Contrast-induced nephropathy (CIN)
Study Name: COOL RCN

Would systemic hypothermia to 33–34°C be associated with a decreased incidence of CIN compared with routine management? This study reduced body core temperature to 33°C in 70 patients, before contrast administration and maintained it until 3 hours after the procedure with rewarming at a rate of 1°C/hr. In addition, all patients received intravenous (IV) hydration with normal saline (1.5 cc/kg/hr) or one-half normal saline (for patients with congestive heart failure or left ventricular dysfunction at 1.0 cc/kg/hr) for 2–12 hours precatheterization. One hour prior to cath, normal saline was stopped, and a bicarbonate drip at 3 ml/kg/hr was initiated for 1 hour, followed by 1 ml/kg/hr for 5–7 hours post-procedure. There was no difference in the incidence of CIN [serum creatinine at 24 hours (p = 0.3), 48 hours (p = 0.09), or 72–96 hours (p = 0.18)] between the hypothermic and normothermic patients (22.4% vs. 18.6%, p = 0.59). All other 30-day adverse events, including the need for dialysis, were similar between the two groups. Systemic hypothermia was not superior to routine hydration despite being more invasive and technically difficult. One significant limitation is that although the COOL RCN trial aimed for, and was powered for, 400 patients, only 136 patients could be enrolled.

Question: Is the outcome of stenting better by looking directly at the stent with optical coherence tomography (OCT)?

Category: PCI technique
Study Name: ODESSA

Optical coherence tomography (OCT) accurately visualizes strut coverage and malapposition in long lesions (>20 mm), especially those requiring overlapping stents.

This study used OCT to examine sirolimus-eluting (SES), paclitaxel-eluting (PES), zotarolimus-eluting (ZES) and bare-metal stents (BMS) 6 months after implantation.

The proportion of uncovered and/or malapposed struts when stents were overlapped tended to be higher with DES compared with BMS (5.4% vs. 1.8%, p = 0.08). The proportion of uncovered and/or malapposed struts was highest with SES (8.7%), followed by PES (8.3%) and then ZES (0.05%) (p < 0.05 for all comparisons). When DES were not overlapped, the incidence of malapposed or uncovered struts was still highest with SES (7.9%), followed by PES (2.3%) and then ZES (0.01%), compared with BMS (0.5%) (p < 0.05 for all comparisons). There seemed to be an inverse relationship between uncovered and/or malapposed struts and intimal hyperplasia: % intimal hyperplasia was 19.3% versus 31.5% versus 45.2% versus 57.8% for SES, PES, ZES and BMS, respectively (p < 0.05), as measured with OCT. There was also a high correlation between OCT and intravascular ultrasound (IVUS) findings for intimal hyperplasia, although OCT demonstrated intimal hyperplasia more often than IVUS.

The in-hospital adverse event rate was very low, with no difference between the four groups. On 6-month follow-up, there was only one death, which occurred in the SES group due to probable stent thrombosis. The incidence of repeat revascularization was lowest in the SES group, but it was not statistically significant (4.5% vs. 9.1% vs. 13.6% vs. 36.4%, p = 0.07). The ODESSA trial demonstrates the utility of OCT in studying strut coverage and malapposition in vivo. While the OCT findings are unique and interesting, the clinical significance of these findings is unclear. Moreover, even in this small study, the investigators had to analyze more than 50,000 struts. Hence, until this methodology is standardized, automated and validated, its applicability in routine practice is limited.

Question: Does the patient do better with multivessel PCI guided by fractional flow reserve (FFR) or by angiography alone?

Category: PCI Technique
Study Name: FAME

The FAME study, which stands for “Fractional flow reserve versus Angiography for Multivessel Evaluation,” tested whether FFR-guided PCI in multivessel disease would be superior to angiography-guided intervention alone. Twenty U.S. and European cardiovascular centers randomized 1,005 patients who had at least 2 major vessel stenoses of > 50%, excluding LM disease, previous bypass surgery and acute STEMI. The FFR ischemic threshold was ≤ 0.80 and those lesions were treated with DES, while vessels with FFR > 0.80 were treated medically. All patients were followed for one year. Four hundred ninety-six (496) patients were randomized to the angiographic and 509 patients to the FFR-guided strategies. There were no differences between groups with regard to clinical, angiographic or procedural characteristics.

After one year, the FFR-guided approach used fewer stents per patient (2.7 ± 1.2 for the angio group and 1.9 ± 1.3 for the FFR group, p < 0.001), less contrast usage (302 mL versus 272 mL, p < 0.001), and had a lower procedure cost ($6,007 versus $5,332 for the FFR group, p < 0.001), and shorter hospital stay (3.7 versus 3.4 days, p = 0.05). Clinically, the FFR-guided approach was associated with fewer major adverse cardiac events (18.4 versus 13.2% with the FFR group, p = 0.02), combined death or MI (11 vs. 7.3%, p = 0.04), and a lower total number of MACE (76 versus 113, p = 0.02). The differences between the 2 groups for event-free survival favored the FFR-guided group and continued to widen over the one-year follow-up. It appears that there is benefit to the routine measurement of FFR for multivessel DES PCI compared to the standard angiographic approach, with approximately a 30% reduction in mortality and a 35% reduction in death or MI at one year.

As we look ahead to 2009, I hope these studies will stimulate more questions and generate interest in understanding how we can get the best out of the lab and our current patient care to improve outcomes for those coming to the cath lab.