Top 5 Challenges for the Cath Lab 2015

Disclosure: Dr. Kern reports he is a consultant and speaker for St. Jude Medical and Volcano Therapeutics, and a consultant for Boston Scientific, Opsens, ACIST Medical, and Merit Medical.Cardiology never stands still. At this mid-point in 2015, I thought it would be worthwhile highlighting some of the advances and issues pertinent to all cath lab staff for the daily care of their patients.  Breaking traditional approaches to treating non-ST-elevation myocardial infarction (NSTEMI) and STEMI, identifying the optimal regimens of antiplatelet drugs, and selecting the best left ventricular (LV) support for shock patients are just a few. I have selected my top 5 challenges for this year to summarize and share some thoughts on the potential implementation of good ideas. [NB: As most of these are still controversial questions, I anticipate many of our colleagues may have some argument with my bottom lines. Feel free to express yourself.]

Early invasive strategy for NSTEMI

ACC/AHA/SCAI/ESC^* guidelines currently recommend “early” invasive intervention within 24-72 hours in stable NSTEMI-acute coronary syndrome (ACS) patients. On review of this group of ACS patients, about 25% are at low risk and do not require cath; about 5% are at high risk who need immediate percutaneous coronary intervention (PCI), leaving a large percent of patients falling between strategies of defer cath (i.e. treat medically and stress test for an appropriate indication) or perform urgent cath, which now means within 24-72 hours, a very generous time window. The reevaluation of the need for urgent cath is prompted by improvements in anti-ischemic pharmacology (better anti-thrombins and antiplatelet agents) and studies showing no long-term benefit from immediate intervention in the stabilized ACS patient (e.g. ISAR-COOL¹ and ICTUS studies²). Current data do not appear strong enough to revamp the conventional approach to immediate cath in all NSTEMI patients, including those who are not at very high risk or unstable. For the management of the NSTEMI patient, the shortening of time to cath, correct diagnosis and revascularization is probably helpful to the patient in shortening the time to correct diagnosis and treatment, and to the hospital system (shortening the length of stay).  

Bottom line for NSTEMI:  Cath/PCI is clearly indicated for a high-risk ACS presentation. For other patients, provided there are no outstanding conditions that need correction, earlier intervention still appears better than waiting several days.

How long should we continue DAPT?

Dual anti-platelet therapy (DAPT) is required to reduce the chances of a potentially fatal stent thrombosis, but is also associated with increased bleeding in some patients, which is a potential cause of increased mortality as well. A shorter duration of DAPT (<6 months) is associated with lower rates of bleeding, while a longer (>12-18 months) duration of therapy is associated with fewer MIs and stent thromboses. Guidelines from both Europe and United States are struggling with current evidence from newly arriving studies in support of both viewpoints on what should be the best duration of DAPT. DAPT duration trials with bare-metal stents (BMS) (e.g. CREDO³ and PCI-CURE⁴) established the current recommendations between 9 to 12 months of DAPT. The question continued to be addressed for drug-eluting stents (DES). The SIRIUS trial⁵ of sirolimus-eluting stents and the TAXUS IV trial⁶ suggested a shorter (3-6 months) duration of DAPT would be acceptable. However, high rates of stent thrombosis were associated with the first generation of DES, leading to the minimum 1 year of DAPT recommendation, which became incorporated into the guidelines.  Recently, the Harvard Clinical Research Institute study⁷ of DAPT duration, reporting on 11,648 randomized patients, of which 9961 received a DES and 1687 received a BMS, found that patients who were treated for an additional 18 months over the standard 12-month period had lower rates of stent thrombosis, but higher rates of moderate-to-severe bleeding, (2.5 versus 1.6%, P=0.001). Reduced MI and stent thrombosis rates applied in the 18-month DAPT group regardless of clinical presentation or stent type. It was interesting to note that most myocardial infarctions were not related to the stent placement. Stopping dual antiplatelet therapy and its increased event rate has not been seen in most other studies of this type. 

Other meta-analyses of short-term DAPT (Table 1) showed a large variation of results among the studies. Differences of the sample population size may account for some variability and reduced confidence of the outcomes. With larger number of patients, the stent type, such as first- vs second-generation DES, appeared to show a clinically important difference, an issue of focus for future research into the controversial factors about DAPT duration.

Bottom line for duration of DAPT: Our current approach should employ individualized therapy type and duration. Patients with high bleeding risk will benefit from shorter duration of antiplatelet therapy and those with low risk of bleeding will benefit from a longer duration (the best duration is yet unknown, but seems to be >12-18 months). Of the two adverse events, stent thrombosis is a more fatal outcome and thus a heavier factor weighing the balance in favor of more prolonged therapy.

Continued role for glycoprotein IIb/IIIa receptor blockers?

Interventionalists are currently enjoying the benefits of strong oral antiplatelet agents, namely the family of P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor, and the newly approved cangrelor) as well as direct thrombin inhibitors like bivalirudin. With use of such agents, the role of intravenous (IV) glycoprotein IIb/IIIa receptor blockers (GBPs) (abciximab, eptifibatide, and tirofiban) has fallen out of favor in some circles. Current 2014 guidelines for NSTEMI-ACS still give GBPs a class I (A) recommendation for use in NSTEMI/high-risk patients who are not adequately pretreated with P2Y12 inhibitors and a class IIa for patients treated with unfractionated heparin at the time of PCI⁸. However, reports of serious bleeding and late adverse outcomes put the use of these drugs in question. ESC 2014 guidelines recommend use only for bailout situations, a recommendation supported principally by consensus evidence.  

Bottom line for GPBs: Current recommendations suggest use for only the highest risk NSTEMI patients at the time of PCI (not pretreated) or when thrombotic complications appear.

Does an intra-aortic balloon pump (IABP) benefit patients in cardiogenic shock? 

There are no patients sicker than those with cardiogenic shock. The mortality of this condition exceeds 50% despite the best medical and mechanical therapies. It was always hoped that mechanical support would improve survival, with the IABP as the only available percutaneous LV support until the last few years. With the evolution of more potent LV support devices over the last decade, like the Impella pump (Abiomed) or TandemHeart system (CardiacAssist), the paradigm of the IABP predominance for the cardiogenic shock patients shifted toward use of stronger support devices to favorably influence outcomes.  

Recommendations for the use of IABP in shock were based on early registry data. Data from current randomized trials suggest that the IABP may not be powerful enough to support the shock patient and ultimately improve long-term survival. Most striking are the results from IABP-SHOCK II⁹, which randomized 600 patients to IABP or medical therapy alone after early PCI or coronary artery bypass graft surgery (CABG). Survival at 30 days was the same (40% vs 41%, P=ns) with no differences in bleeding, sepsis, and cerebrovascular accident (CVA), and no differences noted at 12 months of follow-up. These data led to reduction of the recommendation level for IABP to a class IIb level and supports an approach employing alternative LV assist devices in patients with refractory cardiogenic shock. The declining role of IABP was also hastened by the favorable data for Impella in high-risk patients (PROTECT¹⁰ and PROTECT II¹¹) as well as the benefit of early PCI in which the use of IABP increased in-hospital mortality compared to no IABP use, as noted in the IABP-SHOCK II study.  However, it should be remembered that when PCI was delayed, the IABP did reduce mortality (35% vs 52%, P<0.001).  

Although the IABP is struggling against the data from the SHOCK trials, further information about the larger volume (50cc) IABP suggest both physiologic and survival advantages.¹² The degree of hemodynamic compromise should dictate the need for the intensity of LV support and the best device to provide additional cardiac power, leading to better survival. 

Bottom line for IABP use in shock patients: Consider more potent LV support devices than the IABP for the most critically ill patients.

Does iFR replace FFR yet?

Translesional stenosis physiology determines the ischemic potential of a given coronary stenosis.  While FFR-guided compared to angiographic-guided stenting is now strongly associated with superior outcomes, FFR is still infrequently (<15% of appropriate cases) used in most labs. One of the postulated reasons for such low utilization is the need for IV adenosine and its perceived uncertain hyperemic response. The notion that a hyperemia-free index can accurately determine the ischemic potential of the stenosis is conceptually appealing, but fundamentally challenging. Can a resting pressure/flow measurement equal or surpass a hyperemic measurement to predict whether an intermediate stenosis is associated with ischemia?  

The instantaneous wave-free ratio, iFR, developed and tested against FFR in the last several years, has great appeal, providing a simplified approach to lesion assessment. While FFR predicts ischemia with >90% sensitivity and specificity, it is unknown how iFR compares to FFR in a prospective fashion and whether these findings will produce equivalent short- or long-term outcomes. The most recent and impactful iFR study is the ADVISE II study¹³. The results of iFR and FFR from 690 pressure recordings provided by 598 patients meeting inclusion criteria found that a pre-specified iFR cut-off of 0.89 correctly classified 83% of the stenoses, with a sensitivity of 73% and specificity of 88%, using FFR as the standard (P<0.001). The proportion of stenoses properly classified by iFR outside of the pre-specified treatment (<0.85) and deferral (>0.94) values was 92%. When combined with FFR use, a pre-specified hybrid iFR-FFR approach correctly classified 94%. The hybrid iFR-FFR approach permitted lesion assessment without adenosine in about 65% of patients. The ADVISE II study provided support for using FFR only when the resting iFR lies within its gray zone for correct classification relative to FFR.Of course, the use of FFR as the standard remains strong, with a decade of supporting outcome data. Regarding adenosine variability, recent studies have shown that selecting the lowest Pd/Pa ratio during hyperemia produces the highest reproducibility of FFR over the course of the IV adenosine infusion.¹⁴  

Bottom line for iFR: FFR is the standard for in-lab physiologic lesion assessment. iFR can be used today as complementary with FFR in a hybrid iFR-FFR approach. Future studies will provide outcome data similar to that of the FAME studies. 

I hope this brief review will stimulate the cath lab to continuously assess current practices and look for better ways of providing the best care to our patients. 

References

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3. Watanabe H, Morimoto T, Natsuaki M, Furukawa Y, Nakagawa Y, Kadota K, et al; CREDO-Kyoto PCI/CABG registry cohort-2 investigators. Antiplatelet therapy discontinuation and the risk of serious cardiovascular events after coronary stenting: observations from the CREDO-Kyoto Registry Cohort-2. PLoS One. 2015 Apr 8;10(4):e0124314. doi: 10.1371/journal.pone.0124314. 

4. Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, Natarajan MK, et al; Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001 Aug 18; 358(9281): 527-533.

5. Weisz G, Leon MB, Holmes DR Jr, Kereiakes DJ, Popma JJ, Teirstein PS, et al. Five-year follow-up after sirolimus-eluting stent implantation results of the SIRIUS (Sirolimus-Eluting Stent in De-Novo Native Coronary Lesions) Trial. J Am Coll Cardiol. 2009 Apr 28; 53(17): 1488-1497. doi: 10.1016/j.jacc.2009.01.050.

6. Ellis SG, Stone GW, Cox DA, Hermiller J, O’Shaughnessy C, Mann T, et al; TAXUS IV Investigators. Long-term safety and efficacy with paclitaxel-eluting stents: 5-year final results of the TAXUS IV clinical trial (TAXUS IV-SR: Treatment of De Novo Coronary Disease Using a Single Paclitaxel-Eluting Stent). JACC Cardiovasc Interv. 2009 Dec; 2(12): 1248-1259. doi: 10.1016/j.jcin.2009.10.003.

7. Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, et al; DAPT Study Investigators. N Engl J Med. 2014 Dec 4;371(23): 2155-2166. doi: 10.1056/NEJMoa1409312.

8. Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, et al; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; American Association for Clinical Chemistry. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Dec 23; 64(24): e139-e228. doi: 10.1016/j.jacc.2014.09.017.

9. Thiele H, Zeymer U, Neumann FJ, Ferenc M, Olbrich HG, Hausleiter J, et al; IABP-SHOCK II Trial Investigators. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med. 2012 Oct 4; 367(14): 1287-1296. doi: 10.1056/NEJMoa1208410.

10. Dixon SR, Henriques JP, Mauri L, Sjauw K, Civitello A, Kar B, et al. A prospective feasibility trial investigating the use of the Impella 2.5 system in patients undergoing high-risk percutaneous coronary intervention (The PROTECT I Trial): initial U.S. experience. JACC Cardiovasc Interv. 2009 Feb; 2(2): 91-96. doi: 10.1016/j.jcin.2008.11.005.

11. O’Neill WW, Kleiman NS, Moses J, Henriques JP, Dixon S, Massaro J, et al. A prospective, randomized clinical trial of hemodynamic support with Impella 2.5 versus intra-aortic balloon pump in patients undergoing high-risk percutaneous coronary intervention: the PROTECT II study. Circulation. 2012 Oct 2; 126(14): 1717-1727. doi: 10.1161/CIRCULATIONAHA.112.098194.

12. Kapur NK, Paruchuri V, Majithia A, Esposito M, Shih H, Weintraub A, et al. Hemodynamic effects of standard versus larger-capacity intraaortic balloon counterpulsation pumps. J Invasive Cardiol. 2015 Apr; 27(4): 182-188.

13. Escaned J, Echavarría-Pinto M, Garcia-Garcia HM, van de Hoef TP, de Vries T, Kaul P, et al; ADVISE II Study Group. Prospective Assessment of the Diagnostic Accuracy of Instantaneous Wave-Free Ratio to Assess Coronary Stenosis Relevance: Results of ADVISE II International, Multicenter Study (ADenosine Vasodilator Independent Stenosis Evaluation II). JACC Cardiovasc Interv. 2015 May; 8(6): 824-833. doi: 10.1016/j.jcin.2015.01.029.

14. Gould KL, Johnson NP. Myocardial Bridges: Lessons in Clinical Coronary Pathophysiology. JACC Cardiovasc Imaging. 2015 Jun; 8(6): 705-709. doi: 10.1016/j.jcmg.2015.02.013.