Both patients and doctors were hopeful that a fixed-dose combination of cardiovascular drugs would be the answer to improving risk factors for patients at a high risk of cardiovascular disease. Unfortunately, although patients were extremely adherent, their symptoms did not improve in a statistically significant way, say researchers from the University of Auckland in New Zealand.
Whereas the results were not what researchers had hoped, physicians found satisfactory or very satisfactory results on several measures: starting treatment, blood pressure (BP) control, cholesterol control, tolerability, and prescribing. Furthermore, patients found the regimen “very easy” to use—even 12 months later.
The study, IMPACT (Improving Adherence using Combination Therapy), involved 513 adults with a history of cardiovascular disease or a high risk of cardiovascular disease. Of the enrollees, 497 (97%) completed a 12-month follow-up.
The participants were randomly assigned to continue usual care or to a fixed-dose treatment with aspirin 75 mg, simvastatin 40 mg, and lisinopril 10 mg, with either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Their general practitioners could choose the combination, change combinations, or discontinue treatment at any stage during the trial. There were no limitations on the use of any concomitant (including cardiovascular) drugs.
At 12 months, 81% of fixed-dose patients were adherent to all 4 recommended drugs, compared with the 46% of usual-care patients. For each drug individually, the fixed-dose patients also showed greater adherence, although adherence was generally high in both groups. Improved adherence with the fixed-dose combination remained significant to the end of the trial (P < .001).
However, the study found no statistically significant improvement in control of risk factors between the 2 groups. The difference was only –2.2 mm Hg in systolic BP; –1.2 mm Hg in diastolic BP; and –0.05 mmol/L in low-density lipoprotein cholesterol. Despite some concern among the general practitioners that the fixed-dose combination treatment might impede their ability to individualize treatment, the study showed that this did not, in fact, lead to worsened risk factor control, even compared with a relatively high standard of usual care.
Of the fixed-dose group, 94 discontinued, usually because of an adverse effect. The researchers cite other factors that might have contributed to discontinuations: a lack of variety in the components and dosages of fixed-dose combination treatment, such as a version with an angiotensin-receptor blocker for patients who developed cough, and unfamiliarity with the treatment and the trial itself of doctors who were not part of the trial, such as those who treated participants during outpatient visits.
The main drawback seemed to be that the patients were already very well treated, with “little room for improvement,” the researchers say. At baseline, 82% were taking an antiplatelet, a statin, and at least 1 BP-lowering agent, compared with 59% nationally. Thus, the researchers found limited scope for truly testing the effects of the fixed-dose combination treatment among patients who most need strategies to improve adherence—those taking few or no preventive drugs.
However, as a treatment regimen, the fixed-dose combination was a success: Ninety percent of the general practitioners said they would start other heart failure patients on the treatment if it were available.
Source
Selak V, Elley CR, Bullen C, et al. BMJ. 2014;348:g3318.
doi: 10.1136/bmj.g3318.