A new look at benefits of drug therapy in silent myocardial ischaemia.

Over 25 years ago we prepared a classification system for silent myocardial ischaemia that we hoped would make it easier for future researchers to study the pathophysiogical basis for the syndrome, establish prognosis, and determine appropriate management protocols. In our categorization, Cohn Type I refers to asymptomatic individuals without known coronary artery disease (CAD) and Cohn Types II and III to patients with known CAD. Those with prior myocardial infarctions (MIs) who are asymptomatic are Type II, and those with CAD and both silent and symptomatic ischaemic episodes are Type III. In the last decade a dedicated group of Swiss cardiologists led by Dr Mathias Pfister of the Basel University Hospital have conducted a long-term series of clinical studies involving patients with Types I and II silent ischaemia. By providing a ‘new look’ at the syndrome of silent ischaemia they have contributed important clinical data to aid in its management. They have now described the results of anti-ischaemia drug therapy in Type I patients (studied in their SWISS I trial); their SWISS II data dealing with Type 2 patients and also recently published will be commented on later in this editorial. Investigations into silent ischaemia have been centred on either its pathophysiology, prevalence, prognosis, or treatment, or the effect of treatment on prognosis. Although recent pain studies have not yet been able to pinpoint the exact nature of the cardiac pain mechanism, there is increasing evidence linking adenosine to the process as a chemical mediator. Fortunately, much more is known about the cardiac haemodynamic abnormalities associated with silent ischaemic episodes than its causation. The prevalence of the three types has been estimated with a variety of techniques, and prognostic data are also abundant, but controversies arise when the therapeutic aspects are considered, especially as they apply to the totally asymptomatic Type 1 patients. Whereas Type 2 and 3 patients have known CAD, and treatment guidelines for silent ischaemia conform to those accepted for symptomatic patients, this is not true for Type I patients. This is why the studies of the Swiss investigators are so important. There is a distinct paucity of data in Type I patients even when CAD is diagnosed by multiple non-invasive tests and/or coronary angiography. In one of the most significant previous series of Type I patients, Erikson and Thaulow followed a group of 50 patients with angiographically proven CAD for 15 years and found that 14 out of 50 had died (including eight with three-vessel disease). No attempt was made to randomize medical or surgical therapy in this group once the diagnosis was made, but yearly mortality in the three-vessel group was computed to be 3% compared with 1% in the combined oneand two-vessel disease subgroups. These figures provide a yardstick to measure the effect of subsequent natural history and/or treatment/interventional studies. In their current report, the study population of Erne et al. consisted of 263 asymptomatic persons with at least one risk factor for CAD (plus a stress test with abnormal ECG and imaging results). Unfortunately, only 54 (21%) consented to randomization and the authors acknowledge this limitation. This was also a very well motivated subgroup, and for purposes of a pilot study this ‘bias’ is probably a plus rather then a minus. Clearly the 26 patients in the antianginal drug therapy group did better during the 11.2 year mean follow-up period in terms of mortality, morbidity, and the results of repeated non-invasive procedures than did the control group. There was no mortality in this group compared with 1.1% yearly for the control group. If anything, the full effects of medical therapy may have been underestimated over time, since patients in the control group often had anti-anginal drugs added as the years went by (see Fig. 2 in Erne et al.). What are the clinical implications of this study? Do the results mean that asymptomatic individuals with similar risk factor profiles to those in this report should be screened for silent ischaemia? Does the drug therapy used in this study employ the ‘correct’ anti-ischaemic agents? The prognostic significance of silent ischaemia in middle-aged and elderly persons with no apparent heart disease has most recently been evaluated in the Danish study of Sajadieh et al. The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.