Rosuvastatin

Rosuvastatin belongs to the statin family. It competitively inhibits HMG-CoA reductase, the enzyme that converts HMG-CoA into mevalonate. This reaction is the rate-limiting step in the production of cholesterol in the liver, along the so-called mevalonate pathway. To reach its site of action, the molecule must first enter the hepatocyte: to do so it uses an uptake transporter, OATP1B1, which captures it and concentrates it in the liver.

By slowing this synthesis, rosuvastatin lowers cholesterol inside the liver cell. The liver responds by increasing the number of LDL receptors on its surface. These receptors capture the LDL cholesterol circulating in the blood and remove it from the circulation, which lowers blood LDL. Rosuvastatin is also a hydrophilic statin, weakly metabolized: about 10 percent of the dose is found as a metabolite, mainly N-desmethyl, through a minor CYP2C9 pathway, and most of it is eliminated unchanged.

Rosuvastatin is prescribed to lower cholesterol and reduce the risk of myocardial infarction and stroke. The LDL it lowers is the one that seeps into the artery wall and forms atheroma plaques there. By removing it from the circulation, it slows this process, which is the origin of heart attack and stroke. It is intended both for people who have never had an event but are at high risk and for those who need to avoid a recurrence.

Its action is not limited to lipids. Statins exert what are called pleiotropic effects, anti-inflammatory and antioxidant, which promote the stability of the atheroma plaque and limit platelet aggregation. A stable plaque ruptures less easily, and it is this rupture that triggers the formation of a clot. The share these effects take in the cardiovascular benefit remains debated, this benefit being attributed mostly to the lowering of LDL.

Rosuvastatin has a long elimination half-life, on the order of 19 hours. This duration of action explains why a single dose a day is enough, at any time of day, with or without food. You choose a fixed time and stick to it, because regularity matters more than the chosen moment. The tablet is swallowed whole, without splitting, chewing or crushing it.

The treatment is meant for the long term. Cholesterol rises again if the dose is interrupted, without anything signaling it, since excess LDL causes no symptom. So you do not stop rosuvastatin on your own initiative, even in the absence of any discomfort felt, but you discuss it with the doctor who prescribed it. A diet low in fat and cholesterol accompanies the treatment and prolongs its effect.

In clinical trials, the adverse effects occurring in at least 2 percent of patients, and more often than with placebo, were headache (5.5 percent), nausea (3.4 percent), myalgia or muscle pain (2.8 percent), asthenia (2.7 percent) and constipation (2.4 percent). Muscle pain is the effect that causes the most concern, because it directly affects daily life. The most serious muscle complication, rhabdomyolysis, exists but its occurrence remains rare.

Statins, including rosuvastatin, can also slightly raise fasting blood glucose and glycated hemoglobin. In the JUPITER trial, diabetes was reported in 2.8 percent of patients on rosuvastatin, versus 2.3 percent on placebo. It is precisely this type of variation that biological monitoring seeks to detect.

Food works on the same ground as the treatment. A diet low in fat and cholesterol accompanies rosuvastatin and supports the lowering of LDL. It pays to favor oily fish, rich in omega-3, olive oil and nuts for their good fats, as well as green vegetables in abundance. These choices act on the same LDL that the medicine removes from the circulation.

One point deserves attention on the nutrient side. Coenzyme Q10, also called ubiquinone, is made by the same mevalonate pathway as cholesterol: by slowing this pathway, statins also lower its concentration in the blood, with reported decreases of 16 to 54 percent. Some trials suggest that an intake of coenzyme Q10 improves the muscle pain and weakness associated with statins, without lowering blood creatine kinase, but the benefit remains debated depending on the studies. The plate provides little of it, mainly through oily fish and meats, and the body makes the greater part itself. When this production slows, a targeted intake makes sense, in addition to the treatment, never in its place.

Some combinations increase exposure to rosuvastatin and, with it, the risk of muscle damage. Ciclosporin multiplies exposure, that is the area under the curve, by about 7, and gemfibrozil by about 1.9. Fibrates, erythromycin, fusidic acid and anticoagulants are also among the medicines to report to the doctor and pharmacist. Heavy alcohol consumption adds a risk to the liver.

Biological monitoring frames the treatment. A fasting lipid panel is done at initiation, then 4 to 12 weeks later, to check that LDL falls as expected. Liver enzymes are measured before starting, then when the clinical situation justifies it. In case of muscle pain, creatine kinase is measured, the marker that reflects muscle distress.