Anti-ischemic medication during myocardial perfusion: with or without?

Stress and rest myocardial perfusion imaging (MPI) single photon emission computed tomography are widely used for the diagnosis and risk assessment of patients with known or suspected coronary artery disease (CAD) [1]. The results of MPI for the detection of CAD can be variably affected by anti-ischemic medications. The size and severity of the perfusion defects may decrease after the use of these anti-ischemic medications, causing false-negative results, and decreasing the diagnostic accuracy of the test [2,3]. However, continuation of anti-ischemic medication during stress MPI can be done when patients are tested for prognosis (e.g. after myocardial infarction, success of revascularization, and heart failure). Some additional anti-ischemic medication, such as nitrates during rest MPI, may also improve the detection of viable myocardium. Depending on the clinical question the continuation of anti-ischemic medication should be reconsidered and there may be a need to be withdrawn to increase the accuracy of MPI for the detection of ischemia. In the case of patients with known CAD, discontinuation may not be desired because the reason for MPI is not diagnosis but cardiac event risk stratification or monitoring of anti-ischemic medication treatment. This editorial evaluates the effect of anti-ischemic medication on MPI; should we perform it with or without? First, the effect of β-blockers may reduce diagnostic sensitivity in the setting of MPI with vasodilator stress agents such as adenosine and dipyridamole but findings in sensitivity are inconsistent [4]. However, the effect is more severe during bicycle stress and dobutamine stress MPI [5]. In addition, absolute myocardial perfusion and ratio assessment during adenosine on PET will be depressed [6]. The major anti-ischemic effect of β-blockers is a fall in heart rate leading to reduction in myocardial oxygen consumption both at rest and during stress [7]. Second, acute and chronic administration of calcium channel blockers may reduce defect size and severity in exercise stress MPI [8,9]. The primary benefit of calcium channel blockers leads to a reduction in myocardial oxygen demand, which is achieved by decreasing arterial tone, peripheral vascular resistance, intraventricular pressure, and wall stress [10]. Calcium channel blockers also enhance myocardial perfusion through their effects on myocardial microcirculation and metabolism. This may improve coronary flow in CAD by selectively dilating larger arterioles. Third, the acute administration of sublingual or short-acting nitrates and chronic administration of long-acting nitrates also significantly decreases the ischemic perfusion severity or size compared with placebo [11–15]. Nitrates decrease coronary vascular resistance, increase the diameter of large conduit vessels and microvessels distal to the coronary stenosis, but myocardial perfusion remains constant [16]. Another important characteristic of nitrates is that pretreatment with nitrates will significantly enhance the ability of rest MPI to detect myocardial viability, because of improved flow to ischemic areas and decreasing the demand for myocardial oxygen [17,18]. In a PET study, pretreatment with nitrates increased perfusion tracer uptake in ischemic myocardium, resulting in improved viability detection [19]. In addition, the prognostic value of MPI after nitrate was comparable with PET imaging [20]. Finally, lipid-lowering agents have, besides an inhibitory effect on cholesterol synthesis in the liver, an additional effect on vascular structures. Statins improve endothelial function and preserve coronary perfusion [21]. Several studies showed a decrease in the size of reversible defects by exercise MPI single photon emission computed tomography [22,23] and dipyridamole MPI PET [24] after lipid-lowering therapy. The use of anti-ischemic medications during MPI influences the perfusion defect size and severity. Anti-ischemic drugs may fail to induce flow differences and thus fail to detect or underestimate the extent of CAD. Withdrawal of anti-ischemic medication may also increase the number of ischemic events during stress testing and this must be strongly taken into account. The diagnostic physician must realize that discontinuation of anti-ischemic medications should always be discussed with the referrer of the patient for subsequent MPI study. Furthermore, it is unlikely that withdrawal of statins for a couple of days will directly influence the effect on MPI results. Nitrates, especially nitroglycerins, can be safely reduced in most cases, because the drug has a relatively short half-life. When MPI is performed for prognostic reasons, it is probably appropriate to study these patients while undergoing maximal medical therapy, because the scan outcome will provide a clinically relevant diagnosis [25,26]. In addition, anti-ischemic medication needs to be continued in patients with angina pectoris to evaluate ischemia despite anti-ischemic medication. When we take into account the official guidelines, the British and European guidelines recommend withdrawal of medications that may interfere with physiological exercise responses [27,28]. In contrast, the American College of Cardiology/American Heart Association guidelines recommend that anti-ischemic medication should not be discontinued before stress testing because of the fear of ischemic events [29]. Physicians should therefore use these recommendations at their local situation in close cooperation with the referrer in case of prognostic purposes, for the enhancement of ischemia detection or to monitor ischemia during anti-ischemic medication. Of importance, the majority of the earlier studies is based on small, mostly nonrandomized trials with important differences in patients' characteristics, and therefore less reliable in elucidating the true effects of anti-ischemic medication. Clearly more data and better study designs are warranted. Conclusion With the knowledge of earlier literature regarding the effect of anti-ischemic medication on myocardial perfusion, it is advisable to withdraw anti-ischemic medication to improve the detection of size and severity of myocardial perfusion defects. In contrast, these anti-ischemic drugs can be continued when testing patients for prognosis or for evaluation of anti-ischemic therapy. Withdrawal of anti-ischemic medications should always be discussed with the clinician. Nitrates may enhance the ability of rest MPI to detect myocardial viability and might therefore be useful in patients with left ventricular dysfunction. However, clearly, more data and better study designs regarding the effect of anti-ischemic medication on myocardial perfusion studies are warranted.