I - The Courage Trial
The COURAGE trial (1) randomised 2287 patients with chronic stable coronary artery disease (angiographically at least one stenosis >70%, objective evidence of ischemia) to either initial PCI strategy (+ optimal medical therapy) or initial optimal medical therapy (with later PCI only for progressive / persisting symptoms). The key findings are in table 1.
Table 1: The COURAGE trial key findings
|35 539 patients screened, 6% of them randomized group||PCI||Medical therapy group|
|Death / nonfatal MI during 4,6 years follow-up||19%||18,5%|
|Hospital admission for acute coronary syndrome||12,4%||11,8% *|
|Additional revascularization (any, PCI or CABG)||21,1%||32,6%|
|Freedom from angina at 1 year||66%||58%|
|Freedom from angina at 5 years||74%||72%|
|Lost for follow-up (vital status not known)||8,6%||8,3%|
* significant difference
The trial conclusion is that patients with chronic stable coronary artery disease should be initially treated by the optimal medical therapy alone. PCI is indicated when symptoms cannot be controlled by this optimal medical therapy - in approximately one third of patients only.
The trial conclusion is applicable only to patients with no or mild to moderate symptoms: 42% of the trial patients had angina CCS class 0-I and 37% patients CCS class II. Only 21% patients had class III angina and class IV angina was exclusion criterion.
Several previous trials (2-5) had already failed to show any prognostic benefit from elective PCI performed in patients with chronic stable coronary artery disease, yet the COURAGE trial triggered hot discussions about its results and their implementation.
I strongly believe that these discussions should also include the results of trials with PCI done for acute coronary syndromes (6-10).
Only when we analyse the data of both acute and chronic forms of coronary artery disease, can we properly evaluate the role of PCI in modern cardiology. While 85% of all PCI procedures done in the United States in 2004 were still done for chronic stable forms of coronary artery disease (11), many European countries' practice already reflected these data and acute coronary syndromes today represent over 50% of their PCI case load. E.g. 62% of PCI procedures in the Czech Republic 2006 were done for acute coronary syndromes (34% for STEMI, 28% for non-STE ACS) and only 38% for chronic stable coronary disease. In our center elective PCI for chronic stable angina represents today only cca 25-30% of all PCI procedures, 70-75% being done for acute coronary syndromes.
II - MASS II
Another randomised trial, MASS II (12) compared 5 years outcomes after CABG, PCI and optimal medical therapy alone in 611 patients with multivessel disease (single vessel disease was exclusion criterion, thus the MASS II patients had higher baseline risk when compared to the COURAGE patients). Bypass surgery resulted in the lowest rates of death (12,8% CABG vs. 15,5% PCI vs. 16,2% medical therapy), myocardial infarction (8,3% vs. 11,2% vs. 15,3%) and reintervention (3,5% vs. 32,2% vs. 24,2%) during the 5 year follow-up.
Table 2 summarises the COURAGE and MASS II findings with a focus on the natural course of chronic forms of CAD vs. risk of periprocedural complications related to PCI.
|Chronic stable CAD||ACS (STEMI / non-STEMI)|
|Risk of death within 1 year in medical therapy group||<2% (COURAGE)||13% (PRAGUE-2)|
|Risk of death within 5 years in medical therapy group||7,1% (COURAGE)16,2% (MASS-II)||23% (PRAGUE-2)|
|Risk of death after PCI (death as complication of PCI)||2,4% (MASS-II)||0,2% (PRAGUE-2)|
|Risk of (re-) infarction at 5 years in medical therapy group 11,4% (COURAGE)||15,3% (MASS-II)||19% (PRAGUE-2)|
|Risk of clinical periprocedural MI (during PCI)||3,2% (COURAGE)3% (MASS-II)||0 (PRAGUE-2)|
|Risk of stroke at 5 years in medical therapy group||1,3% (COURAGE)
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
PCI does not improve prognosis in chronic stable coronary artery disease : Why?
The natural course is generally very good in this setting, especially with modern medical therapy. It is thus difficult to improve it further by any mechanical intervention
The small difference between the low natural vs. low periprocedural risk of death, (re-) infarction or stroke increases the impact of any periprocedural complication on the result of any comparative study (by decreasing the potential benefit from the intervention). See table 2, chronic stable CAD column: the risk of death after PCI is similar to the risk of death with optimal medical therapy alone.
No culprit lesion exists in chronic stable patients. PCI site is „blind“ in chronic stable patients. Nobody knows, which coronary plaque in the stable patient will become unstable in future – most likely it will not be the plaque with highest degree of angiographic stenosis. The „plaque sealing“ concept of PCI cannot work in chronic stable patients, because theoretically all existing plaques should be „sealed“ by full metal jacket of all coronary tree......
PCI improve prognosis in acute coronary syndromes : Why ?
The natural course is generally poor in this setting, despite modern medical therapy. It is thus possible to improve it further by a mechanical intervention, which opens the occluded artery and/or stabilizes the unstable plaque.
The difference between the high natural vs. low periprocedural risk is large (see table 2, ACS column). The risk of death, (re-) infarction or stroke as periprocedural complication in this setting is similarly low as in chronic stable patients. Thus, the a comparative study is more lilely to show the benefit from the intervention.
The culprit lesion can be identified by angiography in most patients with acute coronary syndromes. Thus, the unstable coronary plaque can be angiographically recognized and treated (PCI is not „blind“ in acute coronary syndromes). The "plaque sealing“ concept of PCI works perfectly well in acute coronary syndromes (opposite to chronic stable disease). This difference could be compared with stomatology: PCI in acute coronary syndromes is similar to treating the acute dental pain: the acutely ill tooth (plaque) is sealed and the patient is fine untill the next tooth (plaque) will become unstable and needs re-intervention. Between these exacerbations dental hygiene (medical therapy) is the best treatment.
Lessons to be learned
PCI centers should focus its resources (both human and financial) mainly on the treatment of acute coronary syndromes, where PCI was clearly shown to improve the patients outcomes
Patients with chronic stable coronary artery disease should be initially treated medically and PCI should be performed upon patient’s request (when medical therapy failed) to aleviate the symptoms (patients should be informed, that PCI will not prolong their life in this setting)
The proportion of acute / elective PCI cases can be used to evaluate the effectivity of health care systems (regional, national, local): PCI for acute coronary syndromes should exceed 50% of all PCI workload (probably should be around 60-70%) in a modern PCI center.
Bypass surgery remains a viable alternative for chronic stable patients with multivessel coronary artery disease.