TCT
TCT
Perspective from Grant W. Reed, MD, MSc
Source/Disclosures
Source:

Stone GW, et al. Late-breaking clinical science session I, co-sponsored by Circulation. Presented at: TCT Connect; Oct. 14-18, 2020 (virtual meeting).

Disclosures: The study was funded by the Cardiovascular Research Foundation and The Medicines Company. Stone reports he receives speaker honoraria from Cook; consults for Abiomed, Ablative Solutions, Ancora, Cardiomech, Gore, HeartFlow, Miracor, Neovasc, Robocath, TherOx, Valfix and Vectorious; and has equity/options from Ancora, Applied Therapeutics, Aria, Biostar family of funds, Cagent, Cardiac Success, Orchestra Biomed, Qool Therapeutics, SpectraWave and Valfix. Kirtane reports he received institutional research grants from Abbott Vascular, Boston Scientific, Cardiovascular Systems Inc., Medtronic, Philips, ReCor Medical and Siemens.
October 18, 2020
4 min read
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Bivalirudin may reduce risk for 30-day mortality after PCI in STEMI

Perspective from Grant W. Reed, MD, MSc
Source/Disclosures
Source:

Stone GW, et al. Late-breaking clinical science session I, co-sponsored by Circulation. Presented at: TCT Connect; Oct. 14-18, 2020 (virtual meeting).

Disclosures: The study was funded by the Cardiovascular Research Foundation and The Medicines Company. Stone reports he receives speaker honoraria from Cook; consults for Abiomed, Ablative Solutions, Ancora, Cardiomech, Gore, HeartFlow, Miracor, Neovasc, Robocath, TherOx, Valfix and Vectorious; and has equity/options from Ancora, Applied Therapeutics, Aria, Biostar family of funds, Cagent, Cardiac Success, Orchestra Biomed, Qool Therapeutics, SpectraWave and Valfix. Kirtane reports he received institutional research grants from Abbott Vascular, Boston Scientific, Cardiovascular Systems Inc., Medtronic, Philips, ReCor Medical and Siemens.
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Compared with heparin, bivalirudin reduced the risk for 30-day mortality, serious bleeding and net adverse clinical events in patients with STEMI undergoing PCI despite increased rates of stent thrombosis and MI, researchers found.

Gregg W. Stone

“The mortality benefit of bivalirudin in STEMI patients was pronounced in those treated with a post-PCI bivalirudin infusion, either low dose or high dose, although the high-dose infusion mitigated the MI and stent thrombosis risk,” Gregg W. Stone, MD, director of academic affairs for the Mount Sinai Heart Health System, professor of medicine (cardiology) and of population health sciences and policy at The Zena and Michael A. Wiener Cardiovascular Institute at Icahn School of Medicine at Mount Sinai, said during a press conference at the virtual TCT Connect.

puzzle pieces in shape of heart
Source: Adobe Stock.

This study also found that bivalirudin reduced the rates of serious bleeding at 30 days in patients with non-STEMI compared with heparin, although rates were similar for MI, mortality and stent thrombosis.

In this individual patient data-pooled analysis, researchers analyzed data from 27,409 patients with STEMI or non-STEMI undergoing PCI from eight randomized trials comparing bivalirudin (n = 13,346; median age, 64 years; 24% women) with heparin (n = 14,063; median age, 64 years; 24% women).

“Most of these trials were performed over the last decade with MATRIX and VALIDATE-SWEDEHEART being quite recent,” Stone said during the discussion portion of the press conference.

The primary effectiveness outcome was mortality at 30 days. The primary safety outcome was serious bleeding, defined as TIMI major or minor bleeding, Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding or otherwise, at 30 days.

In the STEMI group, compared with heparin, patients assigned bivalirudin had reductions in all-cause mortality (2.5% vs. 2.9%; adjusted HR = 0.8; 95% CI, 0.64-1.01) and cardiac death (2.1% vs. 2.7%; aHR = 0.72; 95% CI, 0.57-0.91). These reductions were present despite increases in reinfarction (2.4% vs. 1.7%; aHR = 1.29; 95% CI, 1.02-1.64) and stent thrombosis (1.7% vs. 1.2%; aHR = 1.45; 95% CI, 1.05-1.91). There were no significant differences between the groups related to stroke, clinically driven target vessel revascularization or overall MACCE, which included all-cause mortality, MI, stroke or clinically driven TVR.

“This also points out the limitations of MACCE as an endpoint because you have different components of that endpoint going in different directions,” Stone said during the press conference.

Patients with STEMI assigned bivalirudin also had a significant reduction in serious bleeding compared with those assigned heparin (3.5% vs. 6%; aHR = 0.57; 95% CI, 0.47-0.68). This was observed both for access site-related bleeding (0.7% vs. 1.3%; aHR = 0.45; 95% CI, 0.31-0.67) and nonaccess site-related bleeding (2.8% vs. 4.7%; aHR = 0.61; 95% CI, 0.5-0.75). This led to a reduction in net adverse clinical events, defined as MACCE or serious bleeding (8.7% vs. 11.2%; aHR = 0.78; 95% CI, 0.7-0.88).

“I can only give you a hypothesis, but if you look at the absolute differences, the absolute increases in myocardial infarction and stent thrombosis in the overall were relatively small,” Stone said during the discussion in the press conference regarding a question about a decrease in cardiac death despite increases in MI and stent thrombosis. “If you look at the decreases in major bleeding, [they] were substantially larger. The prevention of bleeding is more important than that of increased risk of thrombosis events.”

For patients with non-STEMI, “the story was quite different,” Stone said during the press conference. No differences were observed between the bivalirudin and heparin groups regarding ischemic endpoints. The reduction in serious bleeding was similar to that observed in patients with STEMI (3.3% vs. 5.3%; aHR = 0.63; 95% CI, 0.52-0.76). This was seen both for access site-related (0.8% vs. 1.9%; aHR = 0.5; 95% CI, 0.35-0.73) and nonaccess site-related bleeding (2.4% vs. 3.5%; aHR = 0.7; 95% CI, 0.56-0.88). There was a borderline reduction in net adverse clinical events in patients assigned bivalirudin compared with heparin (12.8% vs. 14.1%; aHR = 0.91; 95% CI, 0.82-1.01).

Researchers also assessed different combinations, including heparin with and without planned glycoprotein IIb/IIIa inhibitors and bivalirudin with or without an infusion based on dose. Patients who did not receive a post-PCI infusion of bivalirudin did not have a reduction in mortality (aHR for STEMI = 1; 95% CI, 0.75-1.33; aHR for non-STEMI = 1.2; 95% CI, 0.78-1.84). Patients with STEMI who received a post-PCI bivalirudin infusion had a significant reduction in mortality compared with heparin (aHR = 0.67; 95% CI, 0.5-0.89). This was consistent both with high-dose and low-dose post-PCI infusions.

“This held whether or not the heparin was with or without a planned glycoprotein [IIb/IIIa inhibitor] use,” Stone said during the press conference.

These findings were also significant for cardiac death.

Although the dose of post-PCI bivalirudin infusion did not make a difference for all-cause and CV mortality, it did make a difference for MI and stent thrombosis. A low-dose infusion did not mitigate the increased risk for MI or stent thrombosis in patients with STEMI assigned bivalirudin, although the high-dose infusion did impact this risk compared with heparin.

“There were substantial benefits in the STEMI patients with bivalirudin,” Stone said during the discussion at the press conference. “Now that it’s generic, the cost is not very different, so I don’t see why it wouldn’t be used.”

Ajay Kirtane

“It’s interesting. It’s a full cycle with bivalirudin,” Ajay Kirtane, MD, professor of medicine at Columbia University Vagelos College of Physicians and Surgeons, said during the discussion at the press conference. “It was an orphan drug, then usage took off after a company bought it and ran a series of trials against IIb/IIIa inhibitors, then new trials came out and people cast it away. Now it’s generic again, and here we have these data. It is a pretty interesting synthesis, certainly because we saw some of these presentations on bivalirudin data at TCTs in the past. It’s nice to see the follow-up synthesis of all this at this current TCT.”