Recent Caffeine Ingestion Reduces Adenosine Efficacy in the Treatment of Paroxysmal Supraventricular Tachycardia

Abstract

Objectives: Caffeine, an adenosine receptor blocker, should theoretically reduce adenosine efficacy in the treatment of paroxysmal supraventricular tachycardia (SVT). We aimed to determine the effect of recent caffeine ingestion on the likelihood of reversion of SVT with adenosine.Methods: This was a multicenter, case-control study of adult patients with SVT treated with adenosine between September 2007 and July 2008. The primary endpoint was reversion to sinus rhythm (SR) after a 6-mg adenosine bolus, as a function of recent (within 2, 4, 6, and 8 hours) caffeine ingestion. Caffeine ingestion data were collected using a self-administered questionnaire.Results: Of 68 patients enrolled, 52 (76.5%, 95% confidence interval [CI] = 64.4% to 85.6%) reverted after a 6-mg adenosine bolus. There were no significant differences in age, sex, or daily caffeine ingestion between patients who did and did not revert (p > 0.05). However, as a group, patients who did not revert had recently ingested significantly more caffeine (p < 0.05). If caffeine had been ingested less than 2 or 4 hours before the adenosine bolus, the odds of reversion to SR were significantly reduced (odds ratio [OR] = 0.18, 95% CI = 0.04 to 0.93; and OR = 0.14, 95% CI = 0.04 to 0.49, respectively). If caffeine had been ingested less than 6 or 8 hours before the adenosine, the odds of reversion were not reduced (OR = 0.31, 95% CI = 0.09 to 1.02; and OR = 0.31, 95% CI = 0.09 to 1.08, respectively).Conclusions: Ingestion of caffeine less than 4 hours before a 6-mg adenosine bolus significantly reduces its effectiveness in the treatment of SVT. An increased initial adenosine dose may be indicated for these patients.

Adenosine receptors as drug targets — what are the challenges?

“…Therefore, pharmacokinetic and pharmacodynamic (PK/PD) interactions between caffeine and adenosine receptor ligands may contribute to the varying responses to an adenosine receptor-based drug in clinical trials (BOX 2). Indeed, PK/PD analyses show that recent caffeine ingestion (equivalent to two to four cups of coffee) affects A 2A receptor agonist-induced myocardial perfusion imaging 229 and reduces the efficacy of adenosine in the treatment of paroxysmal supraventricular tachycardia 230 . In this regard, it is somewhat surprising that several current clinical trials of adenosine receptor antagonists have not taken caffeine consumption into consideration in their clinical trial designs.…”

Cardiac purinergic signalling in health and disease

“…Dipyridamole, which inhibits the uptake of adenosine and thereby increasing its extracellular levels, was found to reduce the amount of adenosine required for the termination of PSVT involving the AV node [667]. In contrast, it has been suggested that caffeine (a non-selective adenosine receptor antagonist) ingestion reduces adenosine efficacy in the treatment of PSVT [668], although, the methodology of the latter study was subsequently criticised [669].…”

In Reply:

“…We thank Drs. Karydes and Bryant for their comments on our article 1 and agree that our study design had flaws that limit the strength of the conclusions. These limitations are well described in the article.…”