In older adults, a polypill containing aspirin, an ACE inhibitor and a statin within 6 months after myocardial infarction lowered the risk for major adverse CV events compared with usual care, according to results of the SECURE trial.
The polypill strategy consisted of aspirin 100 mg, ramipril 2.5, 5 or 10 mg and atorvastatin 20 or 40 mg.
“Use of a cardiovascular polypill as a substitute approach could be an integral part of a broader strategy to improve secondary prevention,” Valentin Fuster, MD, PhD, director of Mount Sinai Heart, physician in chief of The Mount Sinai Hospital and general director of the National Center for Cardiovascular Innovation in Madrid, Spain, said in a press conference during the European Society of Cardiology Congress.
‘Striking’ reduction in risk
The phase 3, randomized, controlled SECURE trial enrolled 2,499 older adults who were randomly assigned to the polypill-based strategy or usual care, which consisted of taking the drugs separately at the treating physicians’ discretion according to current ESC guidance for this patient population. Patients were followed for 36 months.
The primary composite outcome of CV death, nonfatal MI, nonfatal ischemic stroke or urgent revascularization occurred in 9.5% of patients assigned the polypill-based strategy and in 12.7% assigned usual care (HR = 0.76; 95% CI, 0.6-0.96; P = .02).
Valentin Fuster
“The results were striking,” Fuster said during the press conference. “There are two points of importance. The curves begin to separate from the very beginning of the trial, and they continue to separate over time. So, one can begin to project the possibility that the results would be even more striking if the trial continues to move forward.”
The polypill-based strategy also lowered risk for the key secondary composite outcome of CV death, nonfatal type 1 MI or nonfatal ischemic stroke (8.2% vs. 11.7%; HR = 0.7; 95% CI, 0.54-0.9; P = .005).
The polypill was also safe. Adverse events were similar between the two groups, the researchers reported.
Death from any cause occurred in 9.3% of patients assigned the polypill-based strategy and 9.5% assigned usual care. Death from non-CV causes was slightly higher in the polypill group, at 5.4% compared with 3.7%, according to the results.
In addition, the treatment effect of the polypill for the primary outcome was similar across prespecified subgroups, including age, sex, location, prior vascular event, and presence or absence of diabetes or chronic kidney disease.
“It was completely consistent in the 16 (prespecified) groups in favor of the polypill vs. the pills taken conventionally,” Fuster said. “This really validates the importance of the study.”
The SECURE trial enrolled patients with recent type 1 MI within the previous 6 months. Median time from index MI to randomization was 8 days. Those enrolled were aged older than 75 years or at least 65 years or older with other risk factors such as diabetes, kidney dysfunction, and previous MI, coronary revascularization, CABG or stroke. The mean age was 76 years, 31% were women and the majority were white. Hypertension (78%), diabetes (57%) and history of smoking (51%) were common.
The trial was conducted at 113 centers in seven countries worldwide.
“The trial results are broadly applicable to the general population, especially considering that the average age at the time of a first myocardial infarction is now 65.6 years for men and 72 years for women, along with the high prevalence of diabetes mellitus, chronic kidney disease and previous coronary artery disease in these patients,” the researchers wrote in the simultaneous publication in The New England Journal of Medicine.
High adherence
The reductions in risk with the polypill observed in this trial “may be explained partly by increased adherence,” the researchers discussed in NEJM.
Overall patient-reported medication adherence was higher in the polypill group. At 6 months, high levels of adherence were observed in 70.6% of the polypill group and in 62.7% of the usual care group. This persisted at 24 months, when high levels of adherence were seen in 74.1% and 63.2%, respectively.
“Measuring adherence is always difficult, but we gave a survey of eight questions to determine high adherence, middle adherence and low adherence,” Fuster said at the press conference. “The results were very significant in favor of adherence to the polypill. Probably this is the most important reason of how this worked.”
Reference:
Perspective
This trial is a puzzle. The whole concept of the polypill is that you get much better adherence, better LDL and better BP reduction. In the SECURE trial, both the conventional treatment arm and the polypill arm had almost identical LDL, systolic BP and diastolic BP. So why was there a difference in outcomes? I don’t think it makes a good deal of sense. I am puzzled by it, as I am sure many people will be.
The reasons for the difference in outcomes were not really addressed in the manuscript. The authors talked about pleiotropic effects, which is what everybody says when they get a result they cannot explain. And I cannot explain the results. I cannot tell you that the results answer the question about the polypill in the absence of additional understanding of what is going on. The authors are going to have to do a lot of explaining.
I have been a skeptic about the polypill. I believe that good medicine is about individualizing care. Not everybody needs the same amount of BP reduction. I do not think it is a strategy for a sophisticated clinician in a higher-income country. It might be reasonable in low- or middle-income countries, but I still think it is a great puzzle. This trial takes us a little bit forward, but it leaves as many questions as it answers.
Steven E. Nissen, MD, MACC
Cardiology Today Editorial Board Member
Cleveland Clinic
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