Invasive vs. Conservative Strategy in Unstable Angina
Abstract & Commentary
Synopsis:For every 100 patients who underwent an early invasive strategy, two lives would be saved and two myocardial infarctions would be avoided. The cost would be 15 more patients with bypass surgery and 21 more with percutaneous coronary interventions. Thus, an early invasive strategy should be the preferred approach to high-risk unstable angina patients.
Source: Wallentin L, et al. Lancet 2000;356:9-16.
The fragmin and fast revascularization during instability in Coronary artery disease II trial (FRISC II) that compared an early invasive vs. noninvasive strategy in unstable angina patients recently reported their one-year outcomes. Patients were included with accelerating or rest angina and either ECG changes or elevated serum markers. In addition to the usual exclusion criteria, patients older than age 75 were eliminated. The study was carried out in 16 Scandinavian tertiary centers, where 2457 patients were randomized to four treatment groups involving the low molecular weight heparin dalteprin for three months vs. placebo; and a direct coronary angiography early and revascularization of lesions of 70% or more narrowed within seven days vs. an initial noninvasive strategy with invasive procedures for medical treatment failures. The primary end point was the composite of death or myocardial infarction (MI). Revascularization was accomplished within seven days in 71% of the invasive group and 9% of the noninvasive group, and within one year in 78% and 43%, respectively. After one year, 2% of the invasive group and 4% of the noninvasive group had died (risk ratio [RR], 0.57, 0.36-0.90; P = 0.02). The composite end point was 10% vs. 14%, respectively (0.74, 0.60-0.92; P = 0.005). Assignment to dalteprin or placebo did not affect the results. Wallentin and associates conclude that for every 100 patients who underwent an early invasive strategy, two lives would be saved and two MIs would be avoided. The cost would be 15 more patients with bypass surgery and 21 more with percutaneous coronary interventions. Thus, an early invasive strategy should be the preferred approach to high-risk unstable angina patients.
Comment by Michael H. Crawford, MD
As with many controversies in medicine, further studies often clarify the issues. FRISC II seems to be such a trial. The other two trials in this area disagreed. TIMI IIIb was a study of thrombolysis vs. standard therapy for unstable angina and an early invasive strategy vs. conservative. T-PA increased the incidence of MI or death and is not considered appropriate for unstable angina. However, the early invasive strategy was associated with less revascularization and angina, but no reductions in death or MI vs. the conservative approach. VANQUISH was a study of non-Q MI patients randomized to an early invasive vs. early conservative approach. The patients assigned to the invasive strategy had a higher death rate over one year. These results are markedly different than the result of TIMI IIIb and FRISC II.
What’s going on here? All these studies dealt with fairly high-risk patients: FRISC patients had to have either ST changes or serum markers of ischemia; TIMI patients had to have ST changes; and VANQUISH patients had to have ECG and enzyme evidence of non-Q MI. Almost all the patients in the invasive arm had catheterization in these three studies. The number failing medical therapy who crossed over to catheterization in the conservative group was lowest in VANQUISH (48%) and FRISC (52%) and highest in TIMI (64%), but these rates do not explain the mortality differences. The major difference between the three trials was the proportion of patients in each group who actually underwent revascularization (see Table).
| Table | |||
| Percent of Patients Revascularized | |||
| Invasive | Conservative | Difference | |
| VANQUISH | 44% | 33% | 11% |
| TIMI | 64% | 58% | 6% |
| FRISC | 78% | 40% | 38% |
Thus, in TIMI there was little difference in the proportion undergoing revascularization in the two strategies, so significant differences in outcome would not be expected based upon the strategy. FRISC had the largest difference, which probably explains why the invasive group had the lowest mortality, because most got revascularized. Why did VANQUISH show a higher mortality in the invasive arm? Probably because, less than half in this arm got revascularized. Also, FRISC used modern revascularization techniques including stents, ticlopidine, abciximab, and statins. VANQUISH used balloon angioplasty, largely without the benefit of stents, statins, platelet glycoprotein IIb/IIa inhibitors, or ticlopidine.
Using modern invasive approaches early in high-risk unstable angina patients, FRISC II showed a 43% relative risk reduction in mortality and 26% in MI at one year. These robust results suggest that an early, but not necessarily immediate, invasive strategy with aggressive revascularization of appropriate patients should be the approach in patients with a history suggestive of unstable angina and either ECG changes or elevated serum markers. Lower risk patients should be initially managed conservatively.
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