Hamilton, Ontario—With so many patients already on statins, is it possible that even more could benefit by taking the drugs to lower cholesterol?

New global studies presented at the American College of Cardiology's 65th Annual Scientific Session in Chicago and published simultaneously in the New England Journal of Medicine suggest it is.

Three separate reports from the large HOPE-3 trial finds that lowering cholesterol with statins significantly reduced adverse cardiovascular events in people with average cholesterol and blood pressure levels, even though they were considered to be only at intermediate risk for heart disease. Previous studies have focused on how cholesterol and blood pressure-lowering drugs affected those with established cardiovascular or renal disease, diabetes, other high-risk conditions or in those with markedly elevated cholesterol or blood pressure levels.

The industry-supported studies found that statins, alone or in combination with blood pressure-lowering drugs, were superior to placebo for both the study's first co-primary endpoint, a composite of cardiovascular deaths, heart attacks, and strokes, and its second co-primary endpoint, a composite of those events plus heart failure, resuscitated cardiac arrest, and revascularization procedures, such as bypass surgery or angioplasty. While blood pressure drugs were found to improve outcomes compared with placebo only in patients with elevated blood pressure for those endpoints, antihypertensives were associated with no improvements in patients without elevated blood pressure, and there was a trend toward worse outcomes in those with relatively low blood pressure.

"The implications for practice are huge—I think we certainly should consider using statins much more widely than we have used them thus far,” said a senior member of the research team, Salim Yusuf, MBBS, DPhil, professor of medicine at McMaster University and executive director of the Population Health Research Institute of McMaster University and Hamilton Health Sciences. “In particular for patients with hypertension, our study suggests you can essentially double the benefit of lowering blood pressure in hypertensives if you also lower cholesterol simultaneously.”

All participants in the trial, which included 12,705 people in 21 countries on six continents, had at least one known cardiovascular risk factor, such as smoking, an elevated waist-to-hip ratio, or a family history of heart disease. None had been diagnosed with cardiovascular disease, however.

For the study over a median of 5.6 years, participants were randomly assigned to receive daily either a cholesterol-lowering drug—10 milligrams of rosuvastatin—or a placebo pill and either a blood pressure–lowering drug—a combination pill with 16 milligrams of candesartan and 12.5 milligrams of hydrocholothiazide—or a placebo pill. That created four categories: those receiving both a cholesterol-lowering drug and a blood pressure–lowering drug; those receiving only a cholesterol-lowering drug; those receiving only a blood pressure–lowering drug; and those receiving only placebo pills.

Results indicate that cardiovascular death, heart attack, or stroke occurred in 3.5% of patients receiving both drugs and in 5% of patients receiving only placebo. The study notes that the relative risk reduction in those taking both drugs was 30% overall, 40% in those with elevated blood pressure, and 20% in those without elevated blood pressure, with results similar for both endpoints.

In a separate analysis looking only at statins, 3.7% of participants on those drugs experienced the first co-primary endpoint, a composite of cardiovascular deaths, heart attacks and strokes, compared to 4.8% on placebo. As for the second co-primary endpoint, a composite of the events in the first co-primary endpoint plus heart failure, resuscitated cardiac arrest and revascularization procedures, such as bypass surgery or angioplasty, 4.4% met that compared to 5.7% taking a placebo. On average, participants taking statins experienced a drop in low-density lipoprotein, or LDL, cholesterol of 39.6 mg/dL, about 25%, after 12 months.

“The take-home message is that statins are safe and effective, and that because benefits were similar irrespective of pretreatment cholesterol levels or levels of inflammatory markers, no baseline blood tests are required to identify the patients who will derive benefits from this treatment,” the lead author of the report focused on rosuvastatin, Jackie Bosch, PhD, associate professor of rehabilitation science at McMaster University and director of the prevention Program at the Population Health Research Institute, said in an American College of Cardiology press release. “Our results were remarkably consistent across all subgroups.”

Study authors note that participants will be tracked for an additional 3 to 5 years with analyses examining the effects on cognitive decline, erectile dysfunction, and vision, along with a focus on potential differences among ethnic groups and geographic regions.

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