The AngelMed Guardian implantable device is as safe as using a pacemaker, with comparably low complication rates, and fewer delays in care than reliance on symptoms alone. It also has a higher positive predictive value and lower false positive rate for detecting coronary occlusive events in high-risk patients. Data from an expanded analysis of the prospective randomised trial to assess ST segment elevation (STEMI) in patients with coronary disease were simultaneously presented at a late-breaking trial session at Cardiovascular Research Technologies (CRT) 2019 (2–5 March, Washington DC, USA) and published online in the Journal of the American College of Cardiology (JACC).
C Michael Gibson (Harvard Medical School, Boston, USA), outlined the findings on behalf of the ALERTS (AngeLMed for early recognition and treatment of STEMI) investigators. He said: “The device was safe, and had a complication rate similar to that of pacemakers; there was 96.7% freedom from system-related complications, which in the Bayesian analysis was highly significantly non-inferior to a regular pacemaker [posterior probability >0.999]. The primary endpoint was not met, but in an expanded analysis, in conjunction with the FDA, there was a higher positive predictive value, and lower false positive rates [with the device], and 42 silent myocardial infarctions were found.”
Between 30 and 35% of acute myocardial infarctions are silent, with atypical chest symptoms, a rate he described as “somewhat shocking”; every 30 minutes of delay in treatment leads to a 7.5% relative increase in mortality, and there is an increased emphasis in getting patients to the cath lab quicker. But, he said: “The bad news is, that for four decades now, the time from when someone has symptoms to when they get to the hospital has not changed at all. It is about two hours.”
The reasons for this delay can be attributed to the fact that symptoms can be atypical and may be confused with gastrointestinal problems, or there may not be symptoms. He said that denial also plays a big role. And advancing age (>65 years) and a history of either diabetes or myocardial infarction are associated with even greater delays in seeking care.
But, Gibson asked: “What if, instead of a symptom, there was a signal … that said ‘you are having ischaemia and go to the hospital’? That is the basis for this device, the guardian device.”
The AngelMed Guardian System is the size of a pacemaker, and is inserted in the same way to monitor ST segments. Any deviation in ST segments in the absence of an elevated heart rate is indicative of an occlusive event, and triggers an internal and external alarm that tells the patient to seek medical attention.
Participants in ALERTS were acute coronary syndrome patients considered high risk if they had either diabetes (type I or type II), compromised renal function, or a thrombolysis in myocardial infarction risk score >3. Investigators implanted the device in 907 participants and then performed a 14-day stress test to train it to recognise anticipated ST deviation. Alarms were set for ST elevation without increased heart rate. In the control group (n=456) the alarm was deactivated for six months; the treatment group (n=451) had their alarms activated from the onset of the trial.
He explained: “Half the people had the device turned on, and half the people had the device turned off. This was a real sham controlled study.”
The primary endpoint was cardiac or unexplained death, new Q-wave myocardial infarction, or a symptom-to-door time >two hours for a documented occlusive event. Average age in both groups was about 59 years old, about half of whom had had a myocardial infarction and half had diabetes.
The safety endpoint was met, with 96.7% freedom from complications. “For the primary pre-specified [efficacy] endpoint, the event rates were 4.7% vs. 3.1%. Here, the posterior probability did not achieve statistical significance. But that was looking back seven days. If you capture the silent myocardial infarctions looking back 90 days you do see a significant result.” Additionally, he said: “People got to the hospital quicker, much quicker, with the device; 85% of people got to the hospital within two hours with the alarm being on [compared to] only 5% of those who relied on symptoms.”
An expanded analysis looked at the positive predictive value beyond randomisation, in which alarms were on in both control and treatment groups: “That makes about six years of data to compare to the alarms off group. If you came to the emergency room, what are the odds that you are really having a heart attack? They were higher if you had the alarming system. [25.8% alarms on with or without symptoms vs. 18.2% alarms off symptoms only].” There was also a reduction in the false positive rate, dropping from 0.678 per patient year in the alarms off symptoms only group to 0.164 per patient year in the group with alarms on with or without symptoms. “Two-thirds of the patients coming in a year were false positives symptoms. That level went down to 0.16, to about a quarter of it, with the device. So rather than increase consumption, this actually gave fewer false positives; In conjunction with symptoms, it could be more accurate.”
He emphasised: “We can detect these events. We can get people to the hospital quicker, we can detect silent myocardial infarction—so the science seems to be very well founded.”