The combined use of a polypill plus aspirin in an intermediate-risk population of people without cardiovascular disease (CVD) resulted in a 31% reduction in CVD, with an even larger benefit seen in sensitivity analyses that accounted for those patients who had to discontinue treatment for no-medical reasons such as drug supply issues.
This was according to data from the International Polycap Study (TIPS)-3 trial presented at a late-breaking science news briefing from the American Heart Association Scientific Sessions 2020 by Salim Yusuf, MD, BS, DPhil, professor of medicine at McMaster University School of Medicine in Toronto.
“A strategy of using a polypill produced about a 30% to 40% relative reduction in cardiovascular events,” Dr. Yusuf said. “Given that CVD is the common condition in the world this very important globally.”
Dr. Yusuf said that they estimate that if only half of the people eligible to use the polypill use them, between 3 to 5 million CVD events would be prevented each year.
The polypill tested contained atenolol 100 mg plus ramiprik 10 mg plus HCTZ 25 mg plus simvastatin 40 mg. The hypothesis for the polypill is based on the fact that CVD is a large societal problem affecting billions of people. It is estimated that 18 million people die of CVD globally and two to three times that number experience nonfatal MI or stroke.
The TIP-3 study included 5,700 people considered at intermediate risk for developing CVD and randomly assigned them to the 75 mg aspirin daily, the polypill, the polypill plus aspirin, or vitamin D. Each intervention included a control group who received placebo.
Patients were men aged 50 or younger and women aged 55 or younger with an INTERHEART Risk Score (IHRS) or 10 or greater, or men and women aged 65 or older with an IHRS of 5 or greater. More than 80% had history of hypertension or elevated BP, and about one-third had diabetes or elevated glucose.
The polypill had a modest effect on risk factors, Dr. Yusuf said. Initially there was about a 10 mm lowering of blood pressure (BP), but overtime this attenuated.
“This cannot be explained by adherence decreasing,” Dr. Yusuf said. “I think the body just gets used to the effect of the BP lowering and there are compensatory mechanisms.”
The LDL reduction was lower than expected. The mean difference was 19 mg/dL (P<.0001), which was only half of what the researchers expected, Dr. Yusuf said.
Adherence was carefully monitored. The mean difference between adherence to the polypill and placebo group was 80% for BP medication and 82% for statins. Non-adherence was 19% at 2 years and 32% at 4 years. In the 1.5 years there was a substantial decline in adherence because of problems with the drug supply.
For the primary composite outcome there was a 21% relative risk reduction in CV death, MI, stroke, heart failure, cardiac arrest and revascularization for patients assigned the polypill (HR=0.79; 95% CI, 0.63-1.00; P=.05). Similarly, aspirin alone reduced cardiovascular death, MI, or stroke by 14%.
Looking at polypill plus aspirin compared with double placebo the primary outcome occurred in 4.1% of patients assigned the active drugs compared with 5.8% of patients assigned placebo (HR=0.69; 95% CI, 0.50-0.97; P=.031), a 31% reduction.
Safety was excellent, Dr Yusuf said. Serious adverse events were slightly lower with the polypill than the placebo. Other adverse like dizziness or hypertension (2.7% vs. 1.1%) or cough (1.1% vs. 0.6%) were higher with polypill but reversable when medication was stopped. There were no differences in major or minor bleeding or GI bleeding.