Remote Postdischarge Treatment of Patients With Acute Myocardial Infarction by Allied Health Care Practitioners vs Standard Care: The IMMACULATE Randomized Clinical Trial

“β-Blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACE-I/ARBs) are beneficial after AMI [acute myocardial infarction], and adjustment of these medications to moderate to high doses is recommended in the setting of reduced LV ejection fraction (LVEF) or heart failure. Initiation and adjustment of these medications can be challenging during hospitalization, particularly among patients with borderline or low systemic blood pressure because of an emphasis on shortening length of stay and the challenges in organizing frequent face-to-face visits early after discharge.

Telemedicine has enabled the transition from face-to-face care and is set to play a key role in the post–coronavirus disease-19 era. However, there are few randomized clinical trials on the remote management of AMI after discharge. Therefore, we evaluated the safety and efficacy of postdischarge telehealth-enabled, allied health care practitioner–led remote intensive management (RIM) of AMI.

[Methods]
Improving Remodeling in Acute Myocardial Infarction Using Live and Asynchronous Telemedicine (IMMACULATE) was a multicenter randomized clinical trial of 6-month RIM compared with standard care (SC) among patients with recent AMI and who had a predischarge whole-blood N-terminal pro–b-type natriuretic peptide (NT-pro-BNP) concentration more than 300 pg/mL.

[..] Eligible participants were randomized 1:1 to RIM or SC. Baseline cardiac magnetic resonance imaging was performed between 5 to 10 days of the index admission and repeated at 6 months.

Participants randomized to RIM transmitted twice-daily blood pressure and heart rate measurements using a Bluetooth-enabled device immediately after the baseline cardiac magnetic resonance imaging. Weekly consultations were conducted via telephone for 2 months and then every 2 weeks for 4 months by nurse practitioners who remotely adjusted ACE-I/ARBs and β-blockers according to a standardized algorithm. The first measurements of serum creatinine and potassium concentration were performed at 30 days unless the nurse practitioners determined that earlier testing was required. Participants randomized to SC received regular face-to-face consultations with their cardiologists who would perform the medication adjustment.

The primary safety end point was a composite of hospitalization due to hypotension, bradycardia, hyperkalemia, or acute kidney injury. The primary efficacy end point was the indexed LV end-systolic volume (LVESV) at 6 months, adjusted for baseline LVESV. The secondary efficacy end points were LV ejection fraction and indexed LV mass at 6 months, reduction in NT-proBNP less than 20% from baseline to 6 months, difference in NT-proBNP concentration at 6 months, and β-blocker and ACE-I/ARB dose intensity at 1 month and 6 months.

[Results]
Of 489 participants enrolled, 301 participants had NT-proBNP concentration more than 300 pg/mL and were randomized to RIM (149 [49.5%]; mean [SD] age, 55.3 [8.5] years) or SC (152 [50.5%]; mean [SD] age, 54.7 [9.1] years). Baseline characteristics were balanced between groups with 15 patients (5.9%; 10 [7.5%] vs 5 [4.0%]) with an LVEF less than 40%; 130 RIM participants (87.2%) and 124 SC participants (81.6%) completed both baseline and 6-month scans and had images of sufficient quality to be included in the primary efficacy analysis.

The primary safety end point occurred in 0 RIM participants and 2 SC participants (1.4%). Twenty-three participants experienced 23 adverse events in the RIM group, and 19 participants experienced 22 adverse events in the SC group. Twenty-one participants experienced 19 serious adverse events in the RIM group, and 21 participants experienced 24 serious adverse events in the SC group.

There was no significant difference in β-blocker dose intensity at 1 and 6 months; the adjusted mean difference in β-blocker dose intensity over 6 months between RIM and SC groups was 0.12 (95% CI, −0.02 to 0.26). There was a nonsignificant increase in ACE-I/ARB dose intensity with RIM over SC at 1 and 6 months; the adjusted mean difference in ACE-I/ARB dose intensity over 6 months was 0.19 (95% CI, −0.02 to 0.40).

Comparing RIM vs SC, there was no significant difference in adjusted mean indexed LVESV at 6 months (28.9 mL/m2 vs 29.7 mL/m2; adjusted mean difference, −0.80 mL/m2 [95% CI, −3.20 to 1.60]). The adjusted mean difference in 6-month LVEF and LV mass index was 0.40% (95% CI, −1.49 to 2.29) and −2.07 g/m2 (95% CI, −4.29 to 0.15), respectively. NT-proBNP reduction was not significantly different between RIM and SC groups. Consistent findings were observed across subgroups.

Remote intensive management compared with SC participants had a mean (range) of 0.67 (0-2) vs 2.70 (1-5) face-to-face visits and 17.8 (0-26) vs 0 teleconsults respectively over 6 months. The 6-month per-participant cost of RIM was 3.6-fold higher than SC ($631 vs $176), largely attributable to the high frequency of teleconsults.

[Discussion]
Among patients hospitalized for AMI with predischarge NT-proBNP concentration more than 300 pg/mL, RIM, consisting of frequent remote consultation and medication adjustment led by nurse practitioners, had similarly low safety events and achieved similar dose intensities of ACE-I/ARBs and β-blockers but did not improve the indexed LVESV at 6 months compared with face-to-face cardiologist-led SC.

Other trials have tested telemedicine strategies to follow up and adjust medications in patients after hospitalization for heart failure. Instead, the IMMACULATE trial tested remote intensive follow-up and drug adjustment for patients in the early post-MI period. The limited window for ameliorating adverse post-MI remodeling presents itself as a unique opportunity for more cost-effective telemedicine deployment in contrast with chronic heart failure, which requires potentially perpetual deployment of telemedicine services to prevent recurrent hospitalization over a patient’s health span. Possible explanations for the present trial’s neutral primary end point were a lower-than-expected risk of participants enrolled with relatively young age, early revascularization, and preserved LVEF. [..]

[Conclusions]
Among patients hospitalized for AMI with elevated NT-proBNP concentration and preserved LVEF, a 6-month postdischarge multicenter RIM program by a centralized allied health care team had an equally low number of safety events and achieved similar β-blocker and ACE-I/ARB doses but did not improve LV remodeling outcomes compared with face-to-face SC by cardiologists. This feasibility study demonstrates the potential for RIM to be tested on a higher-risk AMI population with reduced LVEF or heart failure.”

Trial protocol
Drug equivalency across different classes
Full article, Chan MY, Koh KWL, Poh SC et al. JAMA Cardiology, 2020.12.30