Coronary Artery Disease Trials

By Steven Lome

4S TRIAL

The 4S trial randomized 4444 patients with acute coronary syndromes to simvastatin versus placebo. All-cause mortality, fatal coronary events and coronary revascularization procedures were reduced in the simvastatin group. This was regardless of the baseline HDL or LDL cholesterol levels. It is not recommended that all acute coronary syndrome patients take life-long statin therapy regardless of their HDL or LDL levels. More detail

ACCORD TRIAL

The ACCORD trial evaluated cardiovascular risk in type II diabetes patients with intensive glycemic control (hemoglobin A1c < 6.0%) versus standard glycemic control (hemoglobin A1c 7.0-7.9%). The primary endpoint of annual rate of all-cause mortality including cardiovascular mortality was significantly increased in the intensive glycemic control arm and thus the trial was stopped early. More detail

ASCERT TRIAL

Evaluated percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in a retrospective manner with a primary endpoint of all cause mortality. CABG reduced all cause mortality at 4 years compared to PCI. At 1 year there was no difference in all cause mortality. More detail

BARI-2D TRIAL

Evaluated percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) with a medical therapy control arm in a randomized fashion in patients with diabetes mellitus type II and severe coronary disease. Revascularization (either by PCI or CABG) did not reduce mortality or cardiovascular events compared to medical therapy. CABG reduced cardiovascular events while PCI did not reduce the primary endpoint (mortality) or the secondary endpoint (composite rate of death, MI or stroke). More detail

CHARISMA TRIAL

Evaluated 15,603 patients with documented coronary disease or risk equivalents with aspirin alone or aspirin plus clopidogrel for secondary prevention. The primary composite endpoint of MI, stroke and death was no different in the two groups. There was a significant benefit in the secondary endpoint which was reduction of hospitalization for ischemic events. Aspirin and clopidogrel had a significant increase in moderate bleeding and a trend towards an increase of severe bleeding (did not reach statistical significance). Concluded that aspirin alone should be used for secondary prevention of acute coronary syndromes, stroke and death in patients with coronary artery disease or risk equivalents. More detail

COURAGE TRIAL

Evaluated percutaneous coronary intervention (PCI) using bare metal stents versus optimal medical therapy in patients with stable coronary artery disease or Canadian Cardiovascular Society (CCS) class IV anginal symptoms. The primary endpoint of composite all-cause mortality and nonfatal MI was not different in the two groups. There was no difference in hospitalization for acute coronary syndromes. PCI resulted in better symptom relief compared to medical therapy at 24 months, however this disappeared at 36 months likely from progression of the coronary disease. PCI was not found to be cost-effective compared to medical therapy. More detail

FAME TRIAL

Evaluated using fractional flow reserve (FFR) guided percutaneous coronary intervention (PCI) versus standard therapy in patients with at least 2 stenosis of 50% or greater in major coronary vessels. The primary composite endpoint of all-cause mortality, nonfatal MI or coronary artery bypass grafting or repeat PCI was significantly reduced in the FFR guided PCI group. More detail

FAME-2 TRIAL

Evaluated using fractional flow reserve (FFR) guided percutaneous coronary intervention (PCI) versus best medical therapy. The primary endpoint of composite all-cause mortality, nonfatal MI or unplanned hospitalization leading to urgent PCI was significantly reduced in the FFR guided PCI group. More detail

FREEDOM TRIAL

Evaluated coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in diabetic patients with 3-vessel coronary disease. The primary composite endpoint of all cause mortality, non-fatal MI and non-fatal stroke was  reduced with CABG, but not PCI at 5 years. There was decreased mortality and MI in CABG patients, however increased stroke. More detail

HOPE TRIAL

Evaluated ramipril with or without vitamin E versus placebo in patients with coronary disease, stroke, peripheral arterial disease or diabetes. The primary composite endpoint of death from cardiovascular causes, myocardial infarction or stroke was significantly reduced. Each individual component of the composite endpoint was significantly reduced. There were fewer revascularization procedures, diabetic complications, new diabetes diagnosis and new heart failure diagnosis. Vitamin E had no benefit. More detail

MUST-EECP TRIAL

Evaluated Enhanced External Counterpulsation (EECP) versus placebo EECP (at non-therapeutic pressures). The primary endpoint of angina and time to 1 mm ST depression on a treadmill ECG test was reduced with EECP. There was no adverse events. No benefit in exercise tolerance or nitroglycerine use was seen. More detail

ONTARGET TRIAL

Evaluated telmisartan versus ramipril versus the combination of both in patients with coronary disease, peripheral arterial disease, stroke and diabetes. The primary composite endpoint of death from cardiovascular causes, MI, stroke or hospitalization for heart failure was no different between the two drugs (telmisartan non-inferior). The combination of the two had no benefit and increased the risk of renal impairment. More detail

SATURN TRIAL

Evaluated rosuvastatin 40 mg daily versus atorvastatin 80 mg daily in patients with coronary disease, not previously on statin therapy and an LDL level > 100 mg/dL. The primary endpoint of a decrease percent atheroma volume was equal in the two groups. Rosuvastatin reduced LDL levels and raised HDL levels more than atorvastatin. There was increased liver function abnormalities with atorvastatin, higher risk of proteinuria with rosuvastatin and no difference in diabetes control. More detail

SYNTAX TRIAL

Evaluated coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI). The primary endpoint of composite death from any cause, stroke, MI or repeat revascularization at 12 months was not different in the two groups, however PCI had higher cardiovascular death and revascularization rates than CABG. More detail

VALUE TRIAL

Evaluated valsartan or amlodipine in patients with hypertension AND coronary disease, cerebrovascular disease, peripheral arterial disease or left ventricular hypertrophy (high risk patients). The primary composite endpoint of 7 factors including sudden cardiac death, fatal or nonfatal MI, recent MI on autopsy, thrombolytic therapy or coronary intervention, death during coronary intervention, new heart failure and heart failure death was not different in the two groups. Amlodipine controlled blood pressure more effectively than valsartan.  More detail