The aim of this review was to identify SET-related complications in patients with IC as a means to determine its safety. To our knowledge, this is the first study addressing the safety issue of SET. Eight complications were false-positive rate is observed in patients with chest pain, whereas this percentage is even higher in asymptomatic patients.30 A false-positive test result will incorrectly and unnecessary exclude IC patients from a first-choice treatment.1,7 In addition, false-positive results may lead to unnecessary (invasive) interventions (eg, coronary angiography) with accompanied morbidity, mortality, and costs. The risk of a false-negative test result after CPET is also present, as illustrated by one study.31 A cardiac arrest was reported during exercise although no obstructive CAD was found during prior testing. Cardiac screening may therefore create a false sense of safety. Moreover, CPET itself also harbors a risk of cardiac complications. Approximately one to five complications per 10,000 tests were reported,27,32 a percentage that clearly exceeds any risk caused by SET. Some have suggested that CPET is useful in detecting silent ischemia.33 Because most patients with IC will experience myocardial ischemia as anginal pain during exertion, some 17% to 47% will be asymptomatic (ie, silent ischemia type I).34 Extensive research has been done in patients with diabetes mellitus, a condition associated with an even higher prevalence of silent ischemia.35 A difference between silent and symptomatic CAD with respect to prognosis was never found.34,36,37 Patients with IC may potentially benefit from routine CAD screening through detection of silent ischemia; however, considering the high prevalence of silent ischemia and assuming that these patients were also present in our review, a larger number of incidents would have been expected. The value of CPET is therefore also questionable from this perspective. Lastly, CPET is potentially useful as a tool allowing for training optimization. A recent review attempted to identify the most important exercise components resulting in an optimal training protocol for patients with IC. The study concluded that intensity, duration, and program con- tent were not independently associated with improvement of maximal of pain-free walking distance.25 Therefore, selection of SET components based on CPET does not seem to be a useful strategy.
Our study has limitations associated with its retrospective methodology and the possibility of publication bias. Only 35 of 74 studies explicitly reported the possible occurrence of adverse events, whereas a detailed description was sometimes lacking. Therefore, it remains uncertain whether all reported events indeed occurred during SET. On the other hand, some complications may have been missed. However, these were most likely minor events pre- venting the patient from stopping any activity. By our strategy of using information on dropouts, the number of patient-hours was increased, as was the chance on some extra uncertainty. The included studies were very heterogenic in content of the SET program, and an exact description of intensity was often lacking. Therefore, identifying any potential as- sociation between intensity of SET and complication risk was not possible. Subgroup analyses were impossible due to the small number of adverse events. An additional disadvantage of the present study is that the most of the participants were men. Consequently, the safety of SET is not demonstrated in female IC patients, although gender differences regarding the response to SET were never reported.
A major methodological concern is that some studies excluded patients with limited exercise capacity due to angina, heart failure, chronic obstructive pulmonary dis- ease, arthritis, poorly controlled hypertension, or recent myocardial infarction. Exclusion of these vulnerable cardiac patients might have resulted in an underestimation of the number of adverse events. Therefore, generalizing these results to IC patients with major comorbidities is hazardous. On the other hand, one must appreciate that exercise training also reduces the all-cause mortality in patients with congestive heart failure by 11%.38 Others demonstrated in patients with stable CAD that a 12-month program of regular physical exercise resulted in superior event-free survival and exercise capacity compared with percutaneous coronary angioplasty (88% vs. 70%; P ¼ .023).39 As a consequence, patients with (cardiac) comorbidity should not routinely be excluded from SET in daily practice. However, each patient obviously requires careful monitoring.