Beneficial and detrimental effects of lidoflazine in microvascular angina.
Lidoflazine, a piperazine derivative calcium antagonist, was investigated as therapy in 22 patients with microvascular angina (chest pain, angiographically normal coronary arteries and left ventricle, microvascular constrictor response to pacing after ergonovine administration and limited coronary flow response to dipyridamole). Eighteen of 22 patients reported symptom benefit while taking lidoflazine 360 mg daily. Compared to baseline exercise treadmill testing, lidoflazine resulted in significant improvement in exercise duration (812 +/- 337 vs 628 +/- 357 seconds, p less than 0.01) and time to onset of chest pain (530 +/- 343 vs 348 +/- 246 seconds, p less than 0.01). The 5 patients with ischemic ST-segment changes during baseline testing demonstrated an almost 4-minute delay in ST-segment depression (3 patients) or no ST-segment depression (2 patients) while taking lidoflazine. Repeat invasive study of coronary flow in 11 patients taking lidoflazine demonstrated significantly greater coronary vasodilation at rest, during pacing, during pacing after ergonovine and after dipyridamole administration (all p less than 0.03), compared to the initial drug-free study. During the randomized, placebo-controlled phase of the study with 7-week treatment periods, 9 of 11 patients who completed this phase of the study preferred lidoflazine and all demonstrated improved exercise capacity with lidoflazine compared to placebo. However, 3 patients developed malignant ventricular arrhythmias, and 1 died while taking lidoflazine, resulting in termination of the study. Limited coronary vasodilator response in microvascular angina has a reversible vasoconstrictor component and may be due to elevated systolic calcium levels. Despite the hemodynamic, symptom and exercise benefit, lidoflazine may be unsafe for clinical use because of its propensity to cause potentially fatal ventricular arrhythmias.
Cannon
R O
RO
Cardiovascular Diagnosis Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Brush
J E
JE
Schenke
W H
WH
Tracy
C M
CM
Epstein
S E
SE
D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008013:Lidoflazine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008833:Microcirculation / Q000503:physiopathology; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
D010879:Piperazines; D008013:Lidoflazine