It is called the risk that keeps on giving. PCI-related bleeding events potentially carry a host of unwanted consequences, including cascading complications, increased costs and even deaths. By adopting bleeding avoidance strategies and personalized approaches, interventional cardiologists can stanch the problem in the short and long term.

Early vigilance pays off

About three years ago, a bump in the major bleeding rate for PCIs at St. Vincent Health in Indianapolis set its cardiovascular thoracic council’s performance improvement process in motion. After all, even this blip first spotted in its monthly report could have an impact on patient safety. For instance, an analysis of the National Cardiovascular Data Registry (NCDR) CathPCI Registry found that PCI patients with major bleeding events had higher in-hospital mortality compared with patients with no bleeding complications, at 5.26 percent vs. 1.87 percent (JAMA 2013;309:1022-1029). The researchers estimated that 12.1 percent of deaths were related to bleeding complications.

The blip also potentially could affect costs, patient satisfaction and quality measures. Bleeding complications can add two to six days to the hospital length of stay and tag $6,000 to $8,000 or more onto hospital costs. PCI bleeding is one component in a 100-point score card by one of St. Vincent’s payers and is a metric reported on the NCDR. That prompted a root-cause analysis that identified “a multitude of things that we subsequently dealt with,” says Edward T. A. Fry, MD, chair of St. Vincent’s cardiology division.

Some were straightforward fixes, such as revising the training of personnel who remove sheaths to improve their competency. They didn’t stop there, though. Instead the team made PCI bleeding a priority project. “It more recently encouraged us to look at an overall strategy of identifying those who are at higher risk of bleeding and applying the risk score and periprocedurally modifying the procedural approach or the procedural drug therapy,” Fry says.

[[{"fid":"21121","view_mode":"default","type":"media","attributes":{"style":"height: 355px; width: 460px;","alt":"CVB-Abiomed_v6.jpg - Predicted Risk","class":"media-element file-default"}}]]

Rate of femoral or radial access according to predicted risk of transfemoral vascular access complications. Patients with higher predicted risk of complications via the transfemoral approach were less likely to receive a transradial approach. Source: J Am Heart Assoc. 2013;2:e000174

Interventional cardiologists continually try to find the sweet spot between safety and efficacy when treating patients who undergo PCIs and managing them after the procedure. The therapies that decrease ischemic risk typically increase bleeding risk, making that spot more of a dot, and a moving dot at that. “The strategies one uses to avoid bleeding are different between the periprocedural time period and the long-term events,” observes Robert W. Yeh, MD, MBA, co-director of the chronic total occlusion intervention program at Massachusetts General Hospital in Boston. “As a physician, one has to constantly be updating in one’s mind what one thinks the patient’s bleeding risk is at any given time.”

The St. Vincent group adopted a risk stratification model that allowed interventional cardiologists to categorize patients at high, intermediate or low risk and apply evidence-based strategies for reducing the bleeding risk. Low-risk included elective cases with stable angina; intermediate-to-high risk were urgent cases with non-STEMI and unstable angina; and high risk were emergent with STEMI. A decision tree assigned anticoagulant and antiplatelet therapy by risk category followed by the option of transradial or transfemoral access. Patients who underwent transfemoral access PCIs and who had a high risk of bleeding received the direct thrombin inhibitor bivalirudin (Angiomax, Medicines Company) as an anticoagulant rather than unfractionated heparin.

Fry characterizes the dozen interventional cardiologists at St. Vincent as early adopters but credits the group’s newer members and fellows for championing radial PCI, which is shown to lower bleeding rates but also has a learning curve. “[Physicians] say, ‘Patients like this; they don’t bleed as much; they can go home the same day; and it is not really that hard once you get over the hump,’” he says. “The barriers came down and it became a lot easier.”

In an analysis that compared PCIs between July 1 and Dec. 31, 2013, to St. Vincent’s historical data, PCI-associated major bleeding decreased 59 percent and the use of transradial PCI jumped from 19 percent to 43 percent. The use of bivalirudin remained relatively unchanged but its distribution pattern shifted from a roughly equal breakdown among all risk groups to about 80 percent going to high-risk patients. “So it was being used in the right people,” Fry notes.

Risk-treatment paradox      

St. Vincent’s interventional cardiologists may be ahead of their peers in applying these bleeding avoidance strategies. Radial access PCI lowers but doesn’t eliminate vascular access-site complication such as bleeding yet interventional cardiologists appear to favor a transfemoral approach in the patients who would benefit the most from radial PCI, according to a study by Yeh and his colleagues.

They assessed the use of radial and femoral access PCI in five hospitals in Massachusetts between 2008 and 2011 to develop a prediction model for access-site complications and to determine if the radial approach was being applied among the highest-risk patients (J Am Heart Assoc online May 24, 2013). Yeh’s group defined access-site complications as bleeding needing a transfusion, bleeding causing hematomas of 5 cm or more, retroperitoneal bleeding, vascular complications needing diagnostic testing or therapy and death from a vascular cause.

[[{"fid":"21120","view_mode":"default","type":"media","attributes":{"style":"height: 355px; width: 460px;","alt":"Features_CVB-SeptOct2015_indd___150_.jpg - Spontaneous Bleeding","class":"media-element file-default"}}]]

More than 80 percent of cases were transfemoral and 1.2 percent of those patients experienced access-site complications. They identified eight factors that pointed to increased risk of access-site complications: elevated age, being female, elevated troponin, chronic kidney disease, peripheral vascular disease and an emergent PCI. The highest-risk patients were least likely to be treated radially, though.

“That may be due to the technical complexities of doing radial procedures in elderly patients who are at high risk for bleeding, for example,” Yeh says. Other reasons may include concerns about meeting door-to-balloon times and a tendency to prefer lower-risk cases during the learning curve period. “But it does still mean that we haven’t optimized the utilization of our bleeding avoidance strategies to really get the most bang for the buck.”

Some cardiologists have questioned the benefit of radial PCI for reducing bleeding events, attributing the gains in observational studies to patient selection rather than access site. They argue that cardiologists preferentially choose lower-bleeding risk patients, which skews the results in radial’s favor. A team led by Steven M. Bradley, MD, of the Veterans Affairs Eastern Colorado Health Care System in Denver, put that to the test in a facility-level analysis of CathPCI data. They found that a radial approach not only improved outcomes but that the centers that were rapid adopters achieved the greatest drops in periprocedural bleeding.

“The patient mix shouldn’t really change much over time at a facility level,” Bradley says. “If a facility is using more radial PCI, and instead of looking at the patient-level outcomes we look at the outcomes for that facility, we should be able to have a better understanding of the impact of radial PCI at the facility without being confused so much by patient selection issues.”

They grouped hospitals by percentage of radial cases, from very low to high. Forty percent of hospitals retained a very low radial adoption rate, inching up from 0.2 percent at baseline in 2009 to 1.8 percent at the final quarter of 2012. Another 38.4 percent posted an increase from 0.9 percent to 8.9 percent; 16.6 percent of hospitals went from 1.6 percent to 27.2 percent; and 5 percent of centers leaped from 1 percent to 45.1 percent (Circ Cardiovasc Qual Outcomes 2014;7[4]:550-559).

Access-site bleeding decreased over the three-year period in all hospital groups. The moderate- to high-increase radial adopters achieved a 55 percent risk-adjusted reduction in access-site bleeding vs. a 35 percent reduction for the low and very low adopters. The trend remained the same in a secondary analysis that accounted for vascular closure devices and use of bivalirudin and antithrombotic strategies.

“Those facilities that are doing more radial appear to be outpacing their colleagues in terms of their bleeding event rates,” Bradley says, cautioning that other factors may contribute to the trend, too. “This should encourage systems to move toward the adoption of radial PCI.”

Long term & personal

Bleeding complications don’t disappear when the patient exits the hospital. Yeh and colleagues looked into clinically preventable 30-day readmissions after PCIs at Massachusetts General and Brigham and Women’s Hospital in Boston and discovered that 10 percent of these readmissions were due to PCI-related vascular and bleeding complications (J Am Heart Assoc online Sept. 26, 2014). They considered these complications, while relatively uncommon, highly preventable. 

Dhruv S. Kazi, MD, MSc, a cardiologist and health economist at the University of California, San Francisco, and his research colleagues expanded the time horizon even further in a retrospective cohort study of almost 33,000 PCI patients who survived to discharge in the Kaiser Permanente Northern California system between 1996 and 2008 (J Am Coll Cardiol 2015;65:1411-1420). At 4.42 years follow-up, they calculated the hospitalization rate for spontaneous bleeds was 2.14 per 100 person years, with events occurring at a median 100 days after discharge. Gastrointestinal and intracranial bleeds accounted for 77 percent and 15 percent of the spontaneous bleeds, respectively. 

On the flip side, the rate for MI hospitalizations was 4.26 per 100 person years at a median 127 days after discharge. Both bleeding and MI increased the odds of death compared with patients who didn’t experience either of these adverse outcomes.

“About a decade ago, we would have thought of a small GI bleed after a PCI as a nuisance bleed,” Kazi says. “I don’t think any of us think that way anymore. Our paper highlights we shouldn’t. Even though it is a different organ system, even though it occurred three months after the PCI, it still has real consequences in terms of mortality.”

Kazi and Yeh emphasize the need to use a personalized approach to manage patients after discharge, particularly when those patients receive dual antiplatelet therapy. They point to the delicate balance between therapy potent enough to prevent stent thrombosis and weak enough to avoid bleeding.

As part of the Dual Antiplatelet Therapy (DAPT) study, Yeh and the other DAPT researchers found that extending thienopyridine therapy plus aspirin in patients implanted with bare-metal or drug-eluting stents beyond 12 months to 30 months reduced MIs but at the price of increased bleeding (JAMA 2015;313 [11]: 1113-1121). The tradeoff existed for patients who presented with or without an MI (J Am Coll Cardiol 2015;65:2211-2221). Their next step, based on findings that could be presented within this year, is to provide practical guidance for clinicians.

“We hope to develop a set of clinical patient rules and strategies to help physicians be able to identify which patients will benefit the most from antithrombotic therapy and which would be patients who would be more likely harmed,” Yeh says. “That would be personalized medicine.”

Kazi sees oncology as a model for providing personalized medicine informed by the PCI patient’s genotype and phenotype. This approach would help tease out the subset of patients who truly benefit from what might be an expensive medication. “We have assumed a one size fits all, but [with] the availability of rapid and inexpensive genetic testing as well as a large dataset and the capacity for large data analytics, we are able to arrive at a more nuanced understanding of how to personalize care of patients with advanced cardiovascular disease,” Kazi says. “I think of this as an inflection point in how we practice cardiology.”

The cardiology program at St. Vincent keeps a close eye on the evidence emerging for dual and triple therapies and long-term outcomes, according to Fry, who expects the number of patients treated with aspirin, antiplatelet agents and anticoagulants such as warfarin to increase. Long-term outcomes will be even more critical as payers focus on population health, making the kinds of tools proposed by Yeh and Kazi welcome options.

“People do this in their head to a degree, but they don’t do it as formally as would be optimal,” Fry says. “It is like the check list idea. We probably do 99 percent of the things on the check list but it may end up being the way you do or don’t do one thing that becomes crucial.”