Adenosine sestamibi SPECT post-infarction evaluation (INSPIRE) trial: A randomized, prospective multicenter trial evaluating the role of adenosine Tc-99m sestamibi SPECT for assessing risk and therapeutic outcomes in survivors of acute myocardial infarction John J. Mahmarian, MD, Leslee J. Shaw, PhD, Gerald H. Olszewski, Bradley K. Pounds, Maria E. Frias, and Craig M. Pratt, MD, for the INSPIRE Investigators Background. Preliminary studies indicate that adenosine myocardial perfusion single photon tomography (SPECT) can safely and accurately stratify patients into low and high risk groups early after acute myocardial infarction (AMI). Methods and Results. INSPIRE is a prospective, randomized multicenter trial which enrolled 728 clinically stable survivors of AMI. Following baseline adenosine sestamibi gated SPECT, patients were classified as low, intermediate or high risk based on the quantified total and ischemic left ventricular (LV) perfusion defect size (PDS). A subset of high risk patients with a LV ejection fraction >35% were randomized to a strategy of either intensive medical therapy or coronary revascularization. Adenosine SPECT was repeated at 6-8 weeks to determine the relative effects of anti-ischemic therapies on total and ischemic PDS (primary endpoint). All patients were followed for one year. The baseline demographic, clinical and scintigraphic characteristics of the study population are presented. Adenosine SPECT was performed within 1 day of admission in 12% of patients and in 64% by Day 4. Conclusion. The unique study design features of INSPIRE will further clarify the role of adenosine sestamibi SPECT in defining initial patient risk after AMI and in monitoring the benefits of intensive anti-ischemic therapies. (J Nucl Cardiol 2004;11:458-69.) Comment: The widespread acceptance of a routine invasive strategy as the community standard of care (modality of choice in patients with STEMI and in those whom clinical instability develops during acute coronary syndrome) for evaluating and treating patients and improving patients outcome after uncomplicated AMI has developed despite the lack of definitive support from controlled clinical trials. In fact intensive medical therapy has been independently shown to significantly reduce myocardial ischemia in patients after AMI and improve patients outcome. Due to this reason, INSPIRE trial was conceived to answer the following two questions: 1) may adenosine Tc-99m sestamibi gated SPECT define the initial patient risk after uncomplicated AMI and assess subsequent patient outcome after intensive anti-ischemic therapies; 2) may it also compare the relative temporal benefit of intensive medical therapy versus PCI/CABG for suppressing myocardial ischemia in stable but MPS high risk survivors of AMI.

High risk pts with LVEFt35% assigned to strategy 1 (Figure 1) received med therapy titrated to max tolerated doses over a period of 4 to 8 wks: long-acting mononitrate at doses of 60 mg to 120 mg/d. Pts with LVEF<40% atenolol was recommended, whereas in pts with LVEFt40% both long-acting diltiazem and atenolol were recommended. Pts assigned to Strategy 2, all had angiography with intent to PCI. CABG was recommended in pts who had >50% LM stenosis, 3VD or diabetes and MVD. All pts enrolled in INSPIRE (protocol in Figure 2), based on gated SPECT LVEF <40% and anterior Q-wave AMI receive ACEI as well as E-blockers therapy. All pts receive ASA and/or anti-dislipidemic med if necessary. Figure 3 shows that the timing of test was in 12% of pts within 1 day of admission and 68% by day 4. Race, HR, BP, fam hx, lipidemia, smoking hx, prior CAD, NYHA, peak TnI/T, AMI location and TIMI risk score were comparable among all the groups.

Two very important aspects of INSPIRE trial have to be underlined about risk stratification: 1) after VANQUISH study, it the first to use “state of the art” imaging techniques with introduction of quantitative SPECT analysis which adds a new dimension to risk stratification by accurate estimate of total stress induced LV PDS and the extent of scintigraphic ischemia. 2) Its prospective assignment of risk based on previous Adenosine SPECT pilot data (JACC ’95 and ’97). About the assessing PostAMI therapy, INSPIRE has the feature of commitment to randomise pts with high risk scintigraphic study to either an invasive interventional strategy or an aggressive medical strategy. A very notable feature of INSPIRE study design was a very aggressive algorithm to maximize med therapy in the med limb which distinguish INSPIRE trial from DANAMI, FRISC and TACTICS but supported by PROVE-IT results. Also INSPIRE requires a second Adenosine gated-SPECT test in randomised pts after 6 weeks after the initial study to chek how SPECT tracks risk after medical or interventional therapy. The revelations from INSPIRE may well alter clinical standards of risk stratification as well provide pilot data to plan large-scale randomised trials about the noninvasive assessment with gated-SPECT of pts surviving uncomplicated AMI. Marco Mazzanti, MD, FESC