Differences exist in treatment, outcomes and baseline characteristics in acute coronary syndrome (ACS) patients who participated in randomized clinical trials (RCTs) compared to those tracked in registries, according to a study published online Oct. 8 in the American Journal of Cardiology.
Adam B. Hutchinson-Jaffe, MD, of the Terrence Donnelly Heart Centre, University of Toronto in Ontario, and colleagues evaluated the differences of clinical characteristics and in-hospital and discharge management of 13,556 patients admitted to the hospital with non-ST-segment elevation ACS.
The present study included only patients with non–ST-segment elevation ACS (14,205 patients)— 649 patients were excluded due to missing data. Patients were enrolled from 51 centers in ACS I (3,125 patients, 1999 to 2001), 36 centers in ACS II (1,956 patients, 2002 to 2003), and 48 centers in the GRACE/CANRACE (8,475 patients, 2004 to 2008). All of the aforementioned were prospective, multi-center, observational registries of ACS patients admitted to the hospital.
Hutchinson-Jaffe and colleagues used the data to stratify patients into subgroups: those who participated in RCTs and those who did not.
According to the researchers, 8.3 percent of participants were in RCTs: 388 patients from the Canadian ACS I and 216 from the ACS II registries and 522 patients from GRACE and CANRACE.
“Patients enrolled in clinical trials were more likely to be administered acetylsalicylic acid, unfractionated heparin, and glycoprotein IIb/IIIa inhibitors within 24 hours of admission,” the authors wrote. Additionally, they also were more likely to undergo coronary angiography, PCI, CABG or a revascularization procedure and were more likely to be discharged on acetylsalicylic acid and thienophyridine.
The researchers found that there was a significantly higher mortality rate in patients who were not enrolled in RCTs. After the researchers adjusted for a baseline risk using the GRACE risk score, they found that being enrolled in a randomized clinical trial was not an independent predictor of in-hospital mortality. However, they did find that there were a higher number of deaths and re-MIs for patients who were not enrolled in the GRACE/CANRACE clinical trials.
Looking at one-year follow-up data from the ACS I and II registries, the researchers found that patients enrolled in clinical trials were more likely to be prescribed acetylsalicylic acid, oral antiplatelets or anticoagulants and lipid-lowering therapies.
Mortality rates were higher for those not enrolled in clinical trials compared to patients who were enrolled in clinical trials, 8.9 percent versus 6.3 percent, respectively (ACS data). However, death/re-MI rates were similar, 15.7 percent versus 14.7 percent, respectively.
Cardiac arrest, previous heart failure, female gender, older age, creatinine levels (per 10-µmol/L higher) and higher heart rates (per 10-beats/min higher) were independent negative predictors of enrollment.
“In the present study of four registries accrued over the previous decade (1999 to 2008), patients enrolled in clinical trials were more likely to be given evidence-based therapies during hospitalization and at one-year follow-up,” the authors wrote.
At one year, the researchers found significantly less use of lipid-lowering drugs and invasive procedures in patients not enrolled in randomized clinical trials.
The researchers said that limitations stemmed from the fact that "these data are observational in nature, and thus no conclusion regarding cause and effect can be formulated." But, they wrote that because it is "not feasible to randomize patients to RCT participation (vs no participation), only observational studies can address such issues.
“Our findings suggest that undertreatment, or lower adherence to proved therapies, may in part account for the worse outcome of patients not enrolled in clinical trials,” they noted. The researchers urged that large scale RCTs are needed, particularly for patients at high-risk—such as those with renal and heart failure.
“Clinicians in the ‘real world’ need to treat each patient as an individual, taking into account the risks and benefits of a particular intervention, while attempting to apply evidence-based therapies whenever possible,” the authors concluded.