Under what circumstances should the patient with unstable angina undergo PTCA or CABG?

Until recently, published trials and registry data comparing early invasive and conservative strategies in patients with unstable angina (UA) and non-Q wave myocardial infarction (NQMI) suggested no overall benefit from an early invasive approach. Indeed, there was the impression that patients fared better with an initial conservative approach. However, the most recently published trial (FRISC II),1 reflecting modern interventional practice, new stent technology and adjunctive medical therapies (e.g. the glycoprotein IIb/IIIa antagonists) together with improved bypass and myocardial preservation techniques and greater use of arterial conduits has shown significant mortality
and morbidity benefit from an early invasive approach.

The first trial to assess these two management strategies, TIMI IIIB, randomised patients with UA/NQMI to angiography within 24–48 hours followed by PTCA/CABG if appropriate.2 The primary end point of death/MI/positive treadmill test at 6 weeks was 18.1% for the conservative strategy and 16.2% for the invasive strategy (p = NS). Death/MI occurred in 7.8% and 7.2% at 6 weeks (p = NS) and in 12.2% and 10.8% at 1 year (p = NS). However, 64% of patients crossed over to the invasive strategy
because of recurrent angina or an abnormal treadmill test, raising doubts about the clinical application of the trial results.

The VANQWISH study similarly randomised patients with NQMI.3 Death or non-fatal MI occurred in 7% (invasive) vs 3.2% (conservative, p = 0.004) at hospital discharge, in 10.3% vs 5.7% at 1 month (p = 0.0012) and in 24% vs 18.6% at 1 year (p = 0.05). However, with longer follow up (23 months) the mortality difference was lost. Of note, 9% of eligible patients were excluded due to very high-risk ischaemic complications. In contrast to TIMI IIIB, only 29% patients crossed over from the conservative arm.

The OASIS registry highlighted different management strategies for UA by country.4 Angiography rates varied from 2% (Poland) to 58% (US) and 60% (Brazil) at 7 days. Rates of PTCA and CABG by 7 days were highest in the US and Brazil (15.9% and 11.7%) and lowest in Canada/Australia/Hungary/Poland (5% and 1.6%). However, MI and death rates were similar for all countries during a 6 month follow up. Countries with high intervention rates had higher stroke rates but lower rates of recurrent angina and readmission for unstable angina.

The FRISC II study,1 comparing early invasive and conservative strategies, together with the effect of placebo-controlled long term low molecular weight heparin (dalteparin), showed a reduction in death and myocardial infarction in the invasive group (9.4% vs 12.1% in the non-invasive group at 6 months, p = 0.031). Symptoms of angina and readmission were also halved by the invasive strategy. The greatest benefit was seen in high risk patients, in whom potentially beneficial treatments are often denied
in routine clinical practice. By 6 months, 37% of the non-invasive group had crossed over to the invasive strategy. Although there was a higher event rate initially in the invasive group, associated with revascularisation, the event rate subsequently fell and the hazard curves crossed after 4 weeks. Thereafter, the event rate was consistently lower in the invasive group. Invasive treatment provided the greatest advantages in older patients, men, patients with a longer duration of angina, chest pain at rest and ST segment depression.

The favourable results of FRISC II reflect not only modern revascularisation technologies but probably also the intended delay prior to angiography and intervention. Patients in the invasive arm were initially stabilised medically, with the aim to perform all invasive procedures within seven days. The consensus of opinion has thus changed and, where facilities permit, intensive medical therapy followed by angiography with a view to revascularisation is the preferred option for patients with unstable coronary artery disease.