This article originally appeared in the May 2004 Harvard Heart Letter and is provided courtesy of Harvard Health Publications.

Timing, target critical for cholesterol-lowering statins

Whether you are just starting a statin or have been taking one for years, make sure you’re getting a “therapeutic dose” and hit your target.

Many clinical studies drop into the ever-expanding pool of medical knowledge without leaving a trace. A few make small ripples. Every once in a while, a tsunami of a study immediately changes how doctors practice their craft. That’s the case for the recent Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) trial.

PROVE IT provided an unusual head-to-head comparison of two popular cholesterol-lowering statins — standard-dose Pravachol (pravastatin) and high-dose Lipitor (atorvastatin) — among people who had survived a heart attack or episode of chest pain at rest (unstable angina). It showed that the further you lower your level of “bad” LDL cholesterol after one of these so-called acute coronary syndromes the better, even if your LDL is already at or below the current recommended target.

These provocative results are already altering statin use. Some doctors now set lower LDL goals for all their patients with cardiovascular disease or at risk for it, not just for those who have had a heart attack or unstable angina (see Ahead of the curve below).

Two other lessons from PROVE IT and similar studies are also finding their way into practice. These have to do with the timing of statin therapy and the dose.

The right time
One of the surprises of PROVE IT was how quickly aggressive LDL-lowering therapy paid off. In most previous statin trials, it took two years or more to see differences between standard cholesterol-lowering strategies. In PROVE IT, it took just 30 days for the investigators to start seeing fewer heart attacks, strokes, deaths, and other problems in the super-low-LDL group.

“ The sooner you start a statin after a heart attack or unstable angina, the better,” says study leader Dr. Christopher P. Cannon, of Harvard’s Brigham and Women’s Hospital. Until now, many doctors would wait for a month or two after a heart attack to check fasting cholesterol levels and, if high, to prescribe a low starting dose. With this leisurely process, it might take six months or a year to get LDL levels where they need to be — below 100 milligrams per deciliter (mg/dL). “By that time many people would have missed out on the early benefit of a statin,” says Dr. Cannon.

The right dose
Each statin comes in a range of doses (see Starting on statins below). Conventional wisdom suggests starting with the lowest dose and, if that doesn’t do the trick, gradually working your way up to a stronger one that gets your LDL below your target. It’s a prudent strategy, aimed as much at minimizing your chance of having a bad reaction as it is at hitting your LDL target. But it isn’t the best for your cardiovascular health.

The go-slow approach doesn’t quickly stabilize so-called vulnerable plaques. These leaky pockets of cholesterol, white blood cells, and debris embedded in the lining of blood vessels are thought to be the source of the blood clots that cause heart attacks and unstable angina. Faster, deeper cholesterol lowering is more effective at sealing the leaks.

The other problem with starting low is that more than half of people who take a statin don’t meet their LDL target. Some of this gap occurs because people forget to take the medication or decide not to take it. But some is also due to what’s called clinical inertia — doctors’ failure to intensify treatment when needed.

The right strategy
How best to use statins is still evolving. Here’s what we’ve learned from the latest trials. Other refinements are in the offing:

Starting a high-dose statin before leaving the hospital after a heart attack or episode of unstable angina and sticking with it can help prevent a future heart attack or stroke or keep you from dying prematurely.

If you are just starting a statin or taking one over the long term, your prescription needs to be strong enough to drive your LDL down to your target.