Impact of secondary prevention medical therapies on outcomes of patients suffering from Myocardial Infarction with NonObstructive Coronary Artery disease (MINOCA): A meta-analysis

Highlights

• MINOCA are associated with a not negligible incidence of impaired prognosis and recurrent ischemic events.

• There is a paucity of data investigating the impact of cardioprotective therapies on outcomes in this subset.

• This meta-analysis suggests that beta-blockers, statins and DAPT are associated with a survival benefit for MINOCA patients

• ACE-inhibitors/ARB provide a beneficial effect on reducing composite endpoints such as major adverse cardiovascular events.

• None of the investigated therapies has a significant impact on lowering the risk of acute myocardial infarction.

Abstract

Aims

To assess the impact of secondary prevention medical therapies (statins, ACE-inhibitors/Angiotensin Receptor Blockers (ARB), beta-blockers (BB) and Dual Antiplatelet Therapy (DAPT)) on outcomes of patients with myocardial infarction with nonobstructive coronary artery disease (MINOCA).

Methods

Five adjusted observational studies encompassing 10,546 were included in this meta-analysis. All-cause death was the primary endpoint, while Major Adverse Cardiovascular Events (MACE) and acute myocardial infarction (AMI) were the secondary endpoints.

Results

After 24 months of follow up, statins (tested in 8093 patients) were associated with a reduced risk of all-cause death (HR 0.60:0.45–0.81, p 〈0,001), while ACE-inhibitors/ARB (on 9666 patients) were not. Aggregate data from two studies (n = 9720, 7719 on beta-blockers, 6423 on DAPT) indicated that beta-blockers and DAPT (median follow-up 34.1 and 15.7 months, respectively) were both associated with a significant reduction of all-cause death (HR0.81:0.66–0.99, p = 0.04, and HR0.73:0.55–0.98, p = 0.03, for beta-blockers and DAPT, respectively). Among the investigated therapies, only ACE-inhibitors/ARBs entailed a reduced risk of MACE (HR0.65:0.44–0.94, p = 0.02, all CI 95%) over 36.5 months (four studies, n = 10,150). None of the investigated therapies was associated with a reduced risk of AMI.

Conclusions

Data from adjusted observational studies suggest that beta-blockers, statins and DAPT are associated with a survival benefit among MINOCA patients. ACE-inhibitors/ARB entail a reduced risk of MACE while none of the investigated secondary prevention therapies is associated with a reduced risk of AMI. Randomized controlled trials are warranted to confirm these findings.

Introduction

Myocardial infarction with nonobstructive coronary artery disease (MINOCA) accounts for 2 to 6% of all Myocardial Infarction (MI). [1,2] Although patients suffering from MINOCA are likely to be younger and affected by a less relevant burden of cardiovascular risk factors as compared with patients with obstructive coronary artery disease [3], such medical issue is not a benign condition. Previous studies showed indeed a not negligible risk of death associated with MINOCA, estimated to be around 3.5–4.5% over a mid-term follow-up [2,4,5]. The most recent consensus stress the relevance of an underlying coronary ischemic process to establish a final diagnosis of MINOCA [6]. According to the underlying pathophysiological mechanisms, MINOCA are therefore differentiated between type I and type II MIs: type 1 MI caused by atherosclerotic plaque disruption, and type 2 MI due to non-atherothrombotic mechanisms (epicardial coronary vasospasm, coronary microvascular dysfunction, coronary thromboembolism, spontaneous coronary artery dissection, supply-demand mismatch [7]. Further diagnostic criteria include no evidence of angiographic coronary obstruction (that is coronary stenosis <50%) and the exclusion of an alternative diagnosis for the acute presentation (i.e. sepsis, pulmonary embolism, etc.) [6]. Therefore, both patients with normal coronary arteries (no stenosis >30%) and those with mild coronary atheromasia (stenosis >30% but <50%) may be included. In this context, the commitment of patients with MINOCA to appropriate prevention medical therapies represents a relevant and undetermined issue, due to the uncertainties in the underlying pathophysiology and diagnosis. Most pharmacological treatments used for secondary prevention in patients with obstructive CAD aim to prevent progression of atherosclerotic disease and to reduce the risk of recurrent acute events [8,9]. However, plaque progression may not represent the most relevant issue in MINOCA, leading to question the use of standard secondary prevention medical therapies.

Several observational studies evaluated the impact of Dual AntiPlatelet Therapy (DAPT), beta-blockers, Renin-Angiotensin Aldosterone System (RAAS) inhibitors and statin use on major cardiovascular events occurrence and mortality in MINOCA patients, showing conflicting results [3,[10], [11], [12], [13]]. Therefore, the main objective of the present systematic review and meta-analysis is to investigate the effect of standard secondary prevention medical therapies therapy on cardiovascular morbidity and mortality in MINOCA patients.