Effects of Oral Drugs on Coronary Microvascular Function in Patients Without Significant Stenosis of Epicardial Coronary Arteries: A Systematic Review and Meta-Analysis of Coronary Flow Reserve

Abstract

This study aims to investigate the impact of cardiovascular medications on the coronary flow reserve (CFR) in patients without obstructive coronary artery disease (CAD).Methods: We searched PubMed, EMBASE, and Cochrane databases from inception to 15 November 2019. Studies were included if they reported CFR from baseline to follow-up after oral drug therapy of patients without obstructive CAD. Data was pooled using random-effects modeling. The primary outcome was change in CFR from baseline to follow-up after oral drug therapy.Results: A total of 46 studies including 845 subjects were included in this study. Relative to baseline, the CFR was improved by angiotensin-converting enzymes (ACEIs), aldosterone receptor antagonists (ARBs) [standard mean difference (SMD): 1.12; 95% CI: 0.77-1.47], and statins treatments (SMD: 0.61; 95%CI: 0.36-0.85). Six to 12 months of calcium channel blocker (CCB) treatments improved CFR (SMD: 1.04; 95% CI: 0.51-1.58). Beta-blocker (SMD: 0.24; 95% CI: −0.39-0.88) and ranolazine treatment (SMD: 0.31; 95% CI: −0.39-1.01) were not associated with improved CFR.Conclusions: Therapy with ACEIs, ARBs, and statins was associated with improved CFR in patients with confirmed or suspicious CMD. CCBs also improved CFR among patients followed for 6-12 months. Beta-blocker and ranolazine had no impact on CFR.

Mechanisms and Clinical Implications of Endothelial Dysfunction in Arterial Hypertension

“…To date, renin–angiotensin system (RAS) inhibitors and statins are the main classes of drugs that have proven real effectiveness in reducing endothelial dysfunction in hypertension, thus restoring a vasodilatory and anticoagulant phenotype [ 87 ] while fighting microvascular dysfunction [ 88 ]. A number of other pharmacological and exercise-based strategies may positively impact endothelial homeostasis, microvascular function, and blood pressure.…”

“…ACE inhibitors and angiotensin II receptor blockers (ARBs) are key drugs in the treatment of hypertension, particularly in patients with multiple cardiovascular risk factors, heart failure, diabetes mellitus, and kidney impairment [ 89 ]. Therefore, given their capacity to reduce cardiovascular morbidity and mortality with an overall good tolerability [ 90 , 91 ], RAS inhibitors are widely prescribed as first-line drugs in essential hypertension [ 89 ] and coronary microvascular disease [ 88 ].…”

Untangling the pathophysiologic link between coronary microvascular dysfunction and heart failure with preserved ejection fraction

“…Small studies have demonstrated improvement of CFR with angiotensin converting enzyme inhibitors and statins. 43 Longitudinal studies are needed to assess whether this treatment strategy prevents the development of HFpEF in patients with CMD. To this effect, routine non-invasive monitoring of systemic microvascular function, via peripheral endothelial assessment or non-invasive coronary flow velocity reserve measurement, may permit focused titration of prognostic and anti-ischaemic therapy in patients with CMD.…”

COlchicine to Prevent PeriprocEdural Myocardial Injury in Percutaneous Coronary Intervention (COPE-PCI): Coronary Microvascular Physiology Pilot Substudy

“…Results of published therapies aimed at attenuating measures of coronary microvascular function have been mixed, most have not assessed RRR, and as yet specific targeted anti-inflammatory medications have not been trialed. A recent meta-analysis found overall long-term use of calcium channel blocking medications improves CFR [ 24 ], and results with beta-blocker medications are mixed [ 24 – 26 ]. ACE inhibitors are effective at improving CFR [ 8 , 9 , 24 ] and IMR [ 9 ] alone.…”