Ultra-long acting calcium channel blockers may decrease accuracy of the acetylcholine provocation test

Int J Cardiol. 2017 Jun 1:236:71-75. doi: 10.1016/j.ijcard.2017.02.123. Epub 2017 Feb 28.

Abstract

Background: When drug-induced coronary spasm provocation tests are performed, a washout period of >48h for calcium channel blockers (CCBs) is uniformly recommended. However, each CCB has a distinct half-life, and little is known about the influence of prior oral administration of CCBs on acetylcholine provocation test to evaluate coronary vasomotor reaction.

Methods and results: We examined 245 consecutive patients with suspected vasospastic angina who had undergone acetylcholine provocation test. Of those patients, 29 patients had been on amlodipine, an ultra-long term acting CCB (group A), 34 on other CCBs (group O), and 182 patients on no CCB (group N). After CCBs had been withheld > 48h, we performed acetylcholine provocation, which resulted in 152 positive, 36 intermediate, and 57 negative reactions. We evaluated coronary artery tone calculated as follows: (luminal diameter after nitrate-baseline luminal diameter)÷(luminal diameter after nitrate)×100 (%). In group A patients, coronary artery tone was lower (A:9.1±6.9% vs. O:11.7±8.3% vs. N:12.1±8.5%, p=0.0011) and the positive rate of acetylcholine provocation test was lower than group O and group N (A:41% vs. O:68% vs. N:64%, p=0.047). Multivariate logistic analysis showed that taking amlodipine until 2days before acetylcholine provocation test was a significant inverse predictor for acetylcholine-provoked coronary spasm (odds ratio 0.327; 95% confidence interval 0.125-0.858, p=0.023).

Conclusions: Residual vasodilatory effects of ultra-long acting CCB may decrease coronary artery tone and the vasoconstrictive reaction to acetylcholine suggesting that a 2-day pre-test drug holiday may not be long enough.

Keywords: Acetylcholine provocation test; Calcium channel blocker; Coronary artery spasm; Coronary artery tone.

MeSH terms

  • Acetylcholine / administration & dosage*
  • Aged
  • Angina Pectoris, Variant / diagnosis*
  • Angina Pectoris, Variant / drug therapy
  • Calcium Channel Blockers* / administration & dosage
  • Calcium Channel Blockers* / classification
  • Calcium Channel Blockers* / pharmacokinetics
  • Coronary Angiography / methods
  • Coronary Vasospasm* / chemically induced
  • Coronary Vasospasm* / physiopathology
  • Coronary Vessels* / diagnostic imaging
  • Coronary Vessels* / drug effects
  • Coronary Vessels* / physiopathology
  • Dimensional Measurement Accuracy
  • Female
  • Half-Life
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Vasodilator Agents / administration & dosage
  • Withholding Treatment / standards*

Substances

  • Calcium Channel Blockers
  • Vasodilator Agents
  • Acetylcholine