Statins Can Cut Heart Attacks in Moderate-Risk Patients, Study Finds

Taking statins can prevent heart attacks and strokes in patients at moderate risk for heart disease, but the same cannot be said for blood pressure medication, according to findings from a large trial presented today at the 65^th Scientific Session of the American College of Cardiology (ACC) in Chicago.

Results from the HOPE-3 trial, which involved 12,705 patients, were also reported today in 3 separate papers in the New England Journal of Medicine.^1-3 While both statins and therapy to lower blood pressure (BP) have been shown to reduce cardiovascular (CV) events in patients with known risk of heart disease, HOPE-3 set out to gauge whether these drugs could prevent heart attacks and strokes in a broader population.

While treatment with cholesterol-lowering rosuvastatin (10 mg per day) brought a 24% reduction in CV events, with an absolute reduction of 1.1 percentage points, treatment with candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) did not significantly lower risk in the overall group, researchers reported.

Results are likely to only increase discussion of who should take statins—a topic that has caused considerable debate since the ACC and the American Heart Association (AHA) revised treatment guidelines 2 years ago. One study author said today’s results show statins, with their cholesterol-lowering powers, have more value than previously known in preventing CV events.

“Most of the hypertension guidelines right now focus on what agents to use and what blood pressure to aim for, and there has been very little emphasis on the importance of statins in treating patients with hypertension,” said Salim Yusuf, MB, BS, DPhil, professor of medicine, and executive director of the Population Health Research Institute, McMaster University, in Hamilton, Canada.

“Our approach, which used a combination of moderate doses of 2 blood pressure lowering-drugs plus a statin, appears to produce the biggest ‘bang,’ in terms of reducing events, with few side effects.”

The 2x2 trial design allowed scientists to create 4 groups of patients—those receiving both a cholesterol lowering and a BP-lowering medication, those receiving a cholesterol drug plus placebo, those receiving a BP drug plus placebo, and those receiving 2 placebos. Patients were followed for an average of 5.6 years; men were at least 55 years old, and women were at least 65 years old at the start of the study.

Results found:

· Among patients taking both drugs, heart attacks and strokes occurred among 3.5% of the patients, compared with 5% of those taking only placebo. The relative risk reduction was 30% overall, including 40% for those with elevated blood pressure and 20% for those who did not have elevated blood pressure.

· In the analysis of patients taking only statins, 3.7% of the patients met the endpoint of composite CV deaths, heart attacks and strokes; compared with 4.8% of those taking placebo.

· In the statin group, 4.4% reached a second endpoint, a composite of deaths plus heart failure, resuscitated cardiac arrest and revascularization, compared with 5.7% taking placebo.

· Patients who took statins saw their low-density lipoprotein (LDL) cholesterol drop 39.6 mg/dL, or 25% after 12 months on average.

Researchers noted that statins benefited patients across all ethnic groups, and the effects on LDL cholesterol were similar regardless of where a patient’s levels were at the start, which also suggested that lowering cholesterol, not just blood pressure, could hold the key to preventing CV events.

By contrast, patients’ response to the BP therapy varied: those with systolic levels > 143 mm Hg showed reduced CV events, indicating they should be treated, while those in the other subgroups did not; in fact, those with the lowest systolic BP levels indicated some risk of harm.

Some patients complain that statins cause muscle aches or weakness, especially at higher doses, but the study authors said in this population, cutting the dose could generally eliminate these problems.

Fellow presenters Eva Lonn, MD, professor of cardiology and director, Vascular Research Ultrasound Laboratory; and, Jackie Bosch, PhD, associate professor of rehabilitation science at McMaster University and director of the Prevention Program, both at the Population Health Research Institute at McMaster, touted HOPE-3 unique design, which did not have strict parameters for entry into the trial and captured a wide group of ethnic groups from around the world.

This allowed the researchers to see the effects of the 2 drugs at different LDL cholesterol and BP levels. As Yusuf explained, one of their hopes was to investigate the potential use of a combination drug, or “polypill,” as a prevention measure in large populations. Support for that would seem to be limited except among those with high BP levels, based on the results. But that was fine with Yusuf.

It’s not enough, he said, for trials to tell if a therapy is safe and that it work. “They should also tell you in whom it works and whom it doesn’t and that’s what this trial does,” Yusuf said.

“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,” said Bosch, who led the report that focused on rosuvastatin in isolation.

When the revised ACC/AHA guidelines appeared to broaden the groups of patients who would get statins, there was considerable controversy. Valentin Fuster, MD, of Mount Sinai Hospital and editor of the Journal of the American College of Cardiology, said in commenting on the HOPE-3 study that the movement toward prevention is not only redefining who should be treated with statins, but how the field describes who is sick and who is well.

“This study fulfills the concept of those of us who feel the lower the LDL (cholesterol), the better,” he Fuster said.

In an accompanying editorial in NEJM, William C. Cushman, MD, and David C. Goff, Jr., MD, PhD, wrote, “Although these results do not exclude the possibility that more effective therapy for blood pressuring lowering might be beneficial in a relatively low-risk, older population, they provide support for the use of statins as a safe and effective intervention to prevent cardiovascular events in such patients.”⁴

References

1. Lonn EM, Bosch J, López‑Jaramillo P, et al. Blood-pressure lowering in intermediate risk persons without cardiovascular disease [published online April 2, 2016]. N Engl J Med. 2016; 2016, DOI: 10.1056/NEJMoa1600175.

2. Yusuf S, Bosch J, Dagenais G, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease [published online April 2, 2016]. N Engl J Med. 2016; DOI: 10.1056/NEJMoa1600176.

3. Yusuf S, Lonn EM, Pais P et al. Blood-pressure and cholesterol lowering in persons without cardiovascular disease [published April 2, 2016]. N Engl J Med. 2016; DOI: 10.1056/NEJMoa1600177.

4. Cushman WC, Goff DC. More HOPE for prevention with statins [published online April 2, 2016]. N Engl J Med. DOI:10.1056/NEJMe1603504.