Lipitor Regret, Stopping, and Restarting: What Real Patients Experience

What the trials can and cannot say about stopping

The randomized evidence compares atorvastatin with placebo, or 80 mg with 10 mg, in people who kept taking the assigned treatment. In ASCOT-LLA, 10,305 hypertensive patients took atorvastatin 10 mg or placebo; non-fatal MI plus fatal CHD occurred in 100 vs 154 people (HR 0.64) over a median 3.3 years [3]. In CARDS, 2,838 people with type 2 diabetes and no prior cardiovascular disease had 83 vs 127 major cardiovascular events on atorvastatin 10 mg vs placebo over a median 3.9 years, a 37% rate reduction [4]. In TNT, 10,001 people with stable coronary disease had 434 major cardiovascular events on 80 mg vs 548 on 10 mg (HR 0.78) over a median 4.9 years [5].

These trials show what happened while people stayed on treatment. They did not randomly assign people to stop atorvastatin and compare them with people who continued. That is the central limit on any claim that stopping causes a specific number of events.

What do the label data say about LDL on treatment?

The label's dose-response data describe LDL while on treatment. At 6 weeks, mean LDL fell 39% on 10 mg, 43% on 20 mg, 50% on 40 mg and 60% on 80 mg, compared with a 4% rise on placebo [1].

Atorvastatin has a half-life of about 14 hours, and its inhibitory activity has a half-life of 20 to 30 hours [1]. Those numbers describe drug exposure in the body.

Why people stop: muscle symptoms

In 17 placebo-controlled trials with 8,755 people on Lipitor and 7,311 on placebo, myalgia occurred in 3.5% vs 3.1%. Myalgia (0.7%) was the most common reason for stopping at a rate greater than placebo [1]. The label lists age 65 or older, uncontrolled hypothyroidism, renal impairment, interacting drugs and higher dose as risk factors for myopathy [1]. The label says to instruct patients to promptly report unexplained muscle pain, tenderness or weakness, especially with malaise or fever, and says muscle symptoms and CK elevations may resolve if Lipitor is discontinued [1].

STOMP tested atorvastatin 80 mg vs placebo for 6 months in 420 healthy, previously untreated people. Myalgia developed in 19 people on atorvastatin vs 10 on placebo (P=0.05). No individual CK value exceeded 10 times normal, but average CK rose 20.8 U/L on atorvastatin [2]. STOMP did not enroll people with prior statin muscle symptoms [2].

Starting dose and dosing rules in the label

The label's adult starting dose is 10 to 20 mg once daily, the range is 10 to 80 mg once daily, and LDL is assessed as early as 4 weeks after starting [1]. The label says a missed dose is skipped, and the next scheduled dose is taken [1].

The label recommends dose modifications for certain drugs. It says do not exceed 20 mg daily with clarithromycin or itraconazole; clarithromycin raised atorvastatin AUC 4.54-fold and itraconazole 3.32-fold [1]. It says cyclosporine and gemfibrozil are not recommended; cyclosporine raised atorvastatin AUC 8.69-fold [1]. It says to avoid large quantities of grapefruit juice, more than 1.2 liters daily [1].

The label gives specific information about 80 mg after a recent hemorrhagic stroke. In a post-hoc analysis of SPARCL, 2,365 people took atorvastatin 80 mg; hemorrhagic stroke occurred in 2.3% vs 1.4% on placebo (HR 1.68, 95% CI 1.09 to 2.59), fatal hemorrhagic strokes were similar (17 vs 18), and non-fatal hemorrhagic strokes were higher (38 vs 16) [1]. The label says to consider the risk and benefit of 80 mg after a recent hemorrhagic stroke [1]. Across the whole SPARCL population, 80 mg reduced fatal or non-fatal stroke (265 vs 311; HR 0.84) [6].