Table 2.
Studies Not Meeting Inclusion Criteria but with Assessments of Microvascular Function
| Treatment | Baseline CFR <2.5 | No CAD ≥50% stenosis | Mode of Assessing CFR or MPR | Patients (n) | Findings | Authors |
|---|---|---|---|---|---|---|
| Renin/Angiotensin/Aldosterone Inhibitors | ||||||
| Eplerenone 25 mg | No | Yes | IC Doppler | 25 | Angina ↔, CFR ↔ | Bavry et al. 2014 (44) |
| Candesartan 4–8mg | NA | No | IC Doppler | 14 | CFR ↑ | Iino et al. 2012 (74) |
| Enalapril 5mg 2x daily | No | Yes | IC Doppler | 10 | Angina ↑, CFR ↑ | Chen et al. 2002 (75) |
| Enalapril 10mg–20mg/day | No | Yes | Argon Dilution | 15 | Symptoms ↑, CFR ↑ | Motz et al. 1996 (43) |
| Enalapril 5mg 2x daily | No | Yes | PET | 10 | Exercise capacity ↑ | Kaski et al. 1994 (42) |
| Statins | ||||||
| Fluvastatin 40mg | Yes | Yes | TTDE | 23 | Angina ↑, CFR ↑ | Zhang et al. 2014 (50) |
| Atorvastatin 80mg | No | No | IC Doppler | 20 | CFR ↔ | Eshtehardi et al. 2012 (52) |
| Atorvastatin 20mg | Yes | Yes | TTDE | 20 | CFR ↑ | Caliskan et al. 2007 (51) |
| Nitric Oxide Modulators | ||||||
| L-Arginine infusion 1 time infusion | No | Yes | IC Doppler | 11 | CBF ↓ | Gellman et al. 2004 (58) |
| Tetrahydrobiopterin 1 time infusion | No | No | IC Doppler | 23 | CBF ↑ | Setoguchi et al. 2001 (76) |
| L-Arginine infusion 3gm 3x daily | No | No | IC Doppler | 13 | Angina ↑, CFR ↔ | Lerman et al. 1998 (59) |
| L-Arginine infusion 1 time infusion | No | No | IC Doppler | 8 | CBF ↑ | Egashira et al. 1996 (57) |
| Calcium Blockers | ||||||
| Diltiazem 90mg | No | Yes | TTDE | 23 | Angina ↑, CFR ↑ | Zhang et al. 2014 (50) |
| Lidoflazine 240 to 360mg | No | Yes | Thermodilution | 11 | Angina ↔, MBF ↑, Arrhythmias* | Cannon et al. 1990 (48) |
| Verapamil 80mg 4x daily | No | Yes | Thermodilution | 17 | Angina ↑ | Cannon et al. 1985 (47) |
| Nifedipine 10mg 4x daily | No | Yes | Thermodilution | 9 | Angina ↑ | Cannon et al. 1985 (47) |
| Alpha blockers | ||||||
| Doxazosin 2mg | No | Yes | PET Scan | 11 | Angina ↔, CBF ↔, | Rosen et al. 1999 (61) |
| Anti-Anginals & Nitrates | ||||||
| Ivabradine 5mg | Yes | Yes | TTDE | 16 | Angina ↑, CFR ↔ | Villano et al. 2013 (68) |
| Isosorbide dinitrate 5mg (SL) | NA | Yes | TTDE | 29 | Stress Testing ↔ | Russo et al. 2013 (69) |
| Ranolazine 500 mg – 1000mg | No | Yes | CMR | 20 | Angina ↑, CFR ↔ | Mehta et al. 2011 (67) |
| Isosorbide dinitrate 10mg (SL), 2mg (IV) | NA | Yes | Thermodilution | 11 | Angina ↓, CBF ↓ | Bugiardini et al. 1993 (70) |
| Estrogens | ||||||
| 17β-estradiol 1mg + drospirenone 2mg | No | NA | PET | 27 | MPR ↑ | Knuuti et al. 2007 (63) |
| Devices | ||||||
| EECP | Yes | Yes | TTDE | 24 | Angina ↑, CFR ↑ | Luo et al. 2012 (65) |
| TENS | NA | Yes | IC Doppler | 13 | CBF ↓ | Sanderson et al. 1996 (66) |
| Other | ||||||
| Bariatric Surgery | Yes | NA | TTDE | 50 | CBF ↑ | Nerla et al. 2012 (71) |
| Congac | No | NA | TTDE | 18 | CFR ↔ | Kiviniemi et al. 2008 (77) |
| Vitamin C 3g infusion | No | NA | PET | 19 | CFR ↑ in asymptomatic smokers | Kaufmann et al. 2000 (78) |
| Exercise Training | No | No | PET | 13 | CFR ↑ | Czernin et al. 1995 (79) |
Studies of therapies in patients who did not meet strict inclusion criteria nor had evidence of structural heart disease, heart failure, or untreated HTN, but which did assess coronary microvascular function.
TTDE = transthoracic Doppler echocardiography, IC = intracoronary, PET = positron emission tomography, CFR = coronary flow reserve, MPR = myocardial perfusion reserve, CBR = coronary blood flow, EECP = enhanced external counterpulsation, SL = sublingual, IV = intravenous
(↑) = improved with therapy; (↔) = not statistically different; (↓) = worse with therapy (NA) = not assessed
(*) = treatment intervention associated with increased risk of arrhythmias.