Primary prevention strategy successful in a U.S. group with low socioeconomic status
One pill combining four antihypertensive and cholesterol-lowering medications lowered blood pressure and cholesterol in underserved patients in the U.S., researchers found from the experience of a safety net health center.
A polypill containing 10 mg atorvastatin (Lipitor), 2.5 mg amlodipine (Norvasc), 25 mg losartan (Cozaar), and 12.5 mg hydrochlorothiazide reduced systolic blood pressure by 9 mm Hg (vs 2 mm Hg with placebo, P=0.003) and LDL cholesterol by 15 mg/dL (vs 4 mg/dL, P<0.001) by 12 months, according to Thomas Wang, MD, of Vanderbilt University Medical Center in Nashville, and colleagues.
"The observed reductions in systolic blood pressure and LDL cholesterol level were statistically and clinically significant. On the basis of meta-analyses of cardiovascular-outcomes trials in primary prevention, we estimate that such changes, if sustained, would lead to an approximate 25% reduction in the incidence of cardiovascular events," the investigators wrote in the New England Journal of Medicine
Study participants were 303 patients at the Franklin Primary Health Center in Mobile, Alabama, a federally qualified community health center. Notably, this was a group that was 96% black and of whom three-quarters lived with annual incomes below $15,000, Wang's group reported.
"Challenges in implementing cardiovascular disease prevention that are due to lack of income, underinsurance, and multiple visits for testing and drug-dose adjustment may be especially problematic in populations with low socioeconomic status. Thus, the simplicity and low cost of the polypill regimen make this approach attractive when such barriers are common."
Adherence to the polypill at 12 months was estimated at 86% by pill counts.
No serious adverse events judged to be related to the trial occurred. The polypill group had a 1% incidence of myalgia and another 1% incidence of hypotension or light-headedness; there was no abnormal liver function observed in testing.
"Polypills are not widely available in the U.S. but they could be very useful as an approach for preventing a first heart attack or stroke. It is important to note that polypills use low dosages of medications and, therefore, have few side effects. This should increase their tolerability and adherence," commented Paul Muntner, MD, of the University of Alabama at Birmingham, who was not involved in the study.
Patients were enrolled with a mean estimated 10-year cardiovascular risk of 12.7% but no history of cardiovascular disease. Inclusion criteria included systolic blood pressure >120 mm Hg on no more than two antihypertensive medications, LDL cholesterol <190 mg/dL, eGFR at least 60 ml/min/1.73 m2, and normal potassium levels.
After randomization to once-daily polypill or usual care, the two arms shared similar baseline characteristics.
The final cohort had baseline blood pressure averaging 140/83 mm Hg and an LDL of 113 mg/dL. Mean age was 56 and women accounted for 60% of the group. The average BMI was >30, Wang and colleagues noted.
Polypills cost investigators $26 per month per person.
"Participants in the polypill group were not charged for the trial medication, which introduced the possibility that reduced drug cost contributed to the results," Wang's group noted.
"However, our trial site had a 340B pharmacy program that provided medications free of charge or nearly free of charge to all uninsured patients. The only expense would have been a copayment of $3 or less for a 90-day supply of medication. Thus, drug cost was probably not a substantial barrier in the usual-care group."
However, the authors did acknowledge other study limitations, including its open-label design and single-center nature.
"We recognize that a 'one size fits all' approach to cardiovascular disease prevention runs counter to current trends in precision medicine ... Although the precision approach has clear virtues, a broader approach may benefit patients who face barriers to accessing the full advantages of precision medicine," Wang and colleagues maintained.
The study was funded by the American Heart Association Strategically Focused Prevention Research Network and the NIH.
Wang disclosed a relevant relationship with Novartis.
Muntner disclosed support from Amgen.
New England Journal of Medicine
Source Reference: Muñoz D, et al "Polypill for cardiovascular disease prevention in an underserved population" N Engl J Med 2019; DOI: 10.1056/NEJMoa1815359.
Read the original article on Medpage Today: Positive Results With Polypill for Cutting BP, LDL Cholesterol