Yonsei Med J.  2017 Jan;58(1):90-98. 10.3349/ymj.2017.58.1.90.

Impact of Diltiazem Alone versus Diltiazem with Nitrate on Five-Year Clinical Outcomes in Patients with Significant Coronary Artery Spasm

• Park T
• Park JY
• Rha SW
• Seo HS
• Choi BG
• Choi SY
• Byun JK
• Park SH
• Park EJ
• Choi JY
• Park SH
• Lee JJ
• Lee S
• Na JO
• Choi CU
• Lim HE
• Kim JW
• Kim EJ
• Park CG
• Oh DJ

• KMID: 2374193
• DOI: http://doi.org/10.3349/ymj.2017.58.1.90

Abstract

PURPOSE
Calcium channel blockers diltiazem and nitrate have been used as selective coronary vasodilators for patients with significant coronary artery spasm (CAS). However, no study has compared the efficacy of diltiazem alone versus diltiazem with nitrate for long-term clinical outcomes in patients with CAS.
MATERIALS AND METHODS
A total of 2741 consecutive patients without significant coronary artery disease with positive CAS by acetylcholine (Ach) provocation test between November 2004 and May 2014 were enrolled. Significant CAS was defined as a narrowing of >70% by incremental intracoronary injection of 20, 50, and 100 µg of Ach into the left coronary artery. Patients were assigned to either the diltiazem group (n=842) or the dual group (diltiazem with nitrate, n=1899) at physician discretion. To adjust for potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. After PSM analysis, two well-balanced groups (811 pairs, n=1622, C-statistic=0.708) were generated.
RESULTS
At 5 years, there were similar incidences in primary endpoints, including mortality, myocardial infarction, revascularization, and recurrent angina requiring repeat coronary angiography between the two groups. Diltiazem alone was not an independent predictor for major adverse cardiovascular events or recurrent angina requiring repeat coronary angiography.
CONCLUSION
Despite the expected improvement of endothelial function and the relief of CAS, the combination of diltiazem and nitrate treatment was not superior to diltiazem alone in reducing mortality and cardiovascular events up to 5 years in patients with significant CAS.

Keyword

Diltiazem; nitrate; coronary vasospasm

MeSH Terms

Acetylcholine
Aged
Angina Pectoris/diagnosis
Calcium Channel Blockers/therapeutic use
Cardiovascular Agents/*therapeutic use
Coronary Angiography/adverse effects
Coronary Artery Disease/prevention & control
Coronary Vasospasm/diagnosis/*drug therapy
Diltiazem/*therapeutic use
Drug Therapy, Combination
Female
Humans
Incidence
Male
Middle Aged
Myocardial Infarction/prevention & control
Nitrates/*therapeutic use
Propensity Score
Time Factors
Vasodilator Agents/therapeutic use
Acetylcholine
Calcium Channel Blockers
Cardiovascular Agents
Diltiazem
Nitrates
Vasodilator Agents

Figure

• 

  Fig. 1 Kaplan-Meier curves of major adverse cardiac events (MACE) between the two groups. Figure shows the cumulative incidences of MACE includings composite of death, myocardial infarction, or de novo percutaneous coronary intervention MACE. The diltiazem only group (indicated by dotted line) received diltiazem without nitrates. The dual group (indicated by black) received both of diltiazem and nitrates. CAS, coronary artery spasm.

• 

  Fig. 2 Kaplan-Meier curves of recurrent angina requiring coronary angiography between the two groups. Figure shows the cumulative incidences of recurrent angina requiring repeat coronary angiography. The diltiazem only group (indicated by dotted line) received diltiazem without nitrates. The dual group (indicated by black) received both of diltiazem and nitrates. CAS, coronary artery spasm.

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