NEW YORK (Reuters Health) – Not only do high-dose statins more effectively prevent first cardiovascular events compared to moderate doses, the higher doses are also better at preventing recurrences, according to two reports in the December 15/22 Journal of the American College of Cardiology.

Years ago, in the PROVE IT—TIMI 22 trial, atorvastatin 80 mg was more effective than pravastatin 40 mg at reducing the first occurrence of the primary composite end point of death, myocardial infarction, stroke, unstable angina requiring rehospitalization, or revascularization occurring at least 30 days after the index event.

Now, in a post hoc exploratory analysis, Dr. Eugene Braunwald and colleagues at Brigham and Women’s Hospital in Boston extended the follow-up of the original PROVE IT—TIMI 22 cohort for two years.

“We know that patients with coronary artery disease are at a lifelong risk of heart attack and other cardiac events, and so we wanted to look at the full picture of all events,” co-author Dr. Christopher P. Cannon told Reuters Health.

When the number of events was compared between the two study arms in the more recent analysis, intensive therapy had reduced the total number of cardiovascular events by 16% compared to moderate therapy (p = 0.009).

Whereas the number of patients that would need to be treated in order to prevent a first event was 26, the number needed to treat to prevent any event was “much lower”:14.

“Patients should definitely stay on their statin treatment for the long term — and additional benefits will occur,” Dr. Cannon concluded.

The second article reports a similar post hoc analysis of the IDEAL trial, in which 8888 patients with a history myocardial infarction were randomly assigned to take simvastatin 20 to 40 mg daily or atorvastatin 80 mg daily.

As in the PROVE-IT—TIMI follow-up, Dr. Matti J. Tikkanen, from Helsinki University Central Hospital, Finland, and colleagues looked beyond the first events that were the primary endpoint of the original study, to assess rates of a wide variety of subsequent cardiovascular events.

They report in their paper that they used “the broadest secondary end point…consisting of…coronary heart disease death, nonfatal myocardial infarction, resuscitated cardiac arrest, plus the following: stroke, revascularization, hospitalization for unstable angina pectoris, hospitalization for congestive heart failure, and peripheral artery disease.”

Dr. Tikkanen told Reuters Health, “A significant number of events in a trial are recurrences beyond the first. In our trial, the number of events increased by 40% when the recurrences were included. The greatest danger for a patient after the first event is to have another, potentially fatal event.”

Compared to patients taking moderate-dose simvastatin, patients who took high-dose atorvastatin had a 17% lower relative risk of a first cardiovascular event, a 24% lower risk of a second event, and 19%, 24% and 28% lower risks of third, fourth, and fifth events, respectively.

“After a myocardial infarction or other CVD event, treat with high-dose statin to reduce the risk of recurrent attacks,” Dr. Tikkanen advised. “If the patient has a conventional dose of statin, start high-dose statin. If high-dose for some reason is not suitable, treat with low dose statin plus ezetimibe.”

In a related editorial, Dr. Steven E. Nissen from the Cleveland Clinic Foundation, Ohio, writes, “The findings of these two re-analyses are interesting, although perhaps not surprising.”

He takes exception to their use of soft end points – anything other than cardiovascular death, myocardial infarction, and stroke. “The risks of overstating the benefits of any studied therapy are considerable, and the reliability of efficacy analyses may be compromised.”

In response, Dr. Tikkanen said, “The clinical picture of cardiovascular disease is changing. Effective preventive treatments reduce mortality, and timely interventions such as percutaneous transluminal coronary angioplasty in acute coronary syndromes may alter the course of the disease. In the future it may be necessary to move away from the demand of ‘hard end points’ in trials to more inclusive end points (because hard end points become rarer).”

Reference:
J Am Coll Cardiol 2009;54;2353-2357,2358-2362,2363-2365.