麻豆传媒

The heparin frequently given before percutaneous coronary intervention (PCI) should be pushed to as early as possible in patients with ST-segment elevation myocardial infarction (STEMI), according to findings from the Chinese HELP PCI trial.

Patients who were pretreated with loading-dose unfractionated heparin at first medical contact at the PCI center had a better likelihood of Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 of the infarct-related artery at diagnostic angiography before primary PCI compared with those who received it later in the cath lab (23.6% vs 17.6%; relative risk 1.34, 95% CI 1.04-1.71).

This improvement in spontaneous reperfusion was consistent across prespecified subgroups and, importantly, was not accompanied by a greater risk of major bleeding (Bleeding Academic Research Consortium [BARC] 2 or greater at 30 days: 0.4% vs 1.2%; HR 0.33, 95% CI 0.08-1.30), reported Jing Chen, MD, of Renmin Hospital of Wuhan University in China, at the Transcatheter Cardiovascular Therapeutics (TCT) meeting.

The incidence of major adverse cardiac and cerebrovascular events (MACCE) at 1 year was no different between the early and late groups (5.5% vs 6.7%; HR 0.82, 95% CI 0.50-1.35). Also unchanged was the extent of epicardial and myocardial reperfusion post-PCI.

However, there were secondary endpoints favoring unfractionated heparin pretreatment, namely a reduced 30-day rate of MACCE (2.2% vs 4.7%; HR 0.47, 95% CI 0.24-0.91) and fewer heart failure hospitalizations (0% vs 1%, P=0.023), according to Chen.

"Pretreatment with loading-dose unfractionated heparin at first medical contact could be considered to reduce the inherent delay from first medical contact to cath lab in the current regional networks, thereby attenuating myocardial injury and improving clinical prognosis in patients with STEMI," she told the audience.

Regarding the angiographic improvement without MACCE benefit, "this is just a heparin bolus prior to PCI to make our job easier in the cath lab," said TCT discussant George Dangas, MD, PhD, of Mount Sinai Hospital in New York City. "Let's not be overachievers."

Dangas stressed the importance of the study, since heparin has been "grandfathered" in as treatment based on prior evidence that only "sort of made sense," lacking the detail and size of modern trials.

Chen clarified that HELP PCI had been conducted at 36 centers in China -- all established chest pain centers that already met PCI volume and quality criteria set by the government. These centers are allowed to diagnose STEMI within 10 minutes after the ECG, she noted. Most trial participants had been referred directly to these PCI-capable hospitals.

Symptom to heparin time was 3.10 hours in the late group compared with 2.85 hours in the early group (P=0.002). First medical contact to heparin time was 71 versus 35 minutes (P<0.001), and heparin to wire time was 12 versus 37 minutes (P<0.001).

According to Dangas, the trial set a "very high bar" for early heparin to succeed: it had to show benefit on top of the "very speedy" wire times and the "very strong" antiplatelet ticagrelor (Brilinta) given to most patients.

"Is this helping us in the cath lab? Of course ... The initial TIMI 3 flow has much to do with final TIMI 3 flow," he commented. "We work harder if a lower TIMI flow is present in the beginning."

The per-protocol cohort of HELP PCI included 999 patients ages 18 to 80 with STEMI and symptoms within 12 hours who were randomized to heparin (100 U/kg) given at first medical contact or in the cath lab. Exclusion criteria included CPR before randomization, a mechanical complication of myocardial infarction, active bleeding, and history of coronary artery bypass grafting surgery or heparin-induced thrombocytopenia.

Chen said that baseline characteristics were well matched between the two arms. Median age was 59 to 60 years, and about 82% were men; 43% had a history of smoking, which may differ from the stateside experience, Dangas suggested.

At first medical contact, both study groups received aspirin and a P2Y12 inhibitor (85% ticagrelor) at full doses in almost all cases.

The open-label design of the HELP PCI trial left room for bias, Chen acknowledged. She also cautioned that TIMI flow grade is just a surrogate marker of myocardial reperfusion.

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