LDL cholesterol levels

The latest ATP III guidelines now recommend that LDL cholesterol levels be brought below 100 mg/dL in high-risk and moderate risk patients and that consideration should be given to lowering it to < 70 mg/dL in high risk individuals. To assess your cardiac risk see http://heartdisease.about.com/od/assessyourrisk/a/assessrisk.htm .

Pitavastatin- a potent statin which inhibits HMG-CoA reductase and decreases LDL-cholesterol levels even at low dosages.

In Japan, Pitavastatin was approved in July 2003 and launched under the brand name Livalo in September of the same year. In Japan, Livalo is categorized as a potent statin which inhibits HMG-CoA reductase and decreases LDL-cholesterol levels even at low dosages. Kowa estimates that Livalo sales in Japan will achieve USD 300M in fiscal 2008.

Kowa Company, Ltd. (Kowa), headquartered in Nagoya, Japan, today announced that Kowa has submitted a New Drug Application dated October 1 to the US Food and Drug Administration (FDA) for Pitavastatin Calcium tablets (Pitavastatin) for the treatment of primary hyperlipidemia and mixed dyslipidemia, through its US subsidiary, Kowa Research Institute, Inc. (KRI), located in North Carolina.
Once approved, the novel compound will be launched under the brand name Livalo (name subject to approval by the FDA) by Kowa through Kowa Pharmaceuticals America, Inc. (KPA), a recently acquired US subsidiary located in Montgomery, Alabama. KPA, formerly known as ProEthic Pharmaceuticals Inc., and acquired by Kowa in July 2008, changed its name effective September 1, 2008. A Marketing Authorization Application for Pitavastatin was also filed in 16 EU countries on August 29, 2008 with their respective regulatory agencies including the United Kingdom's Medicines & Healthcare Products Regulatory Agency (MHRA) who is acting as Reference Member State (RMS).

(Additional information available on http://www.kowapharma.com ).

Impact of JUPITER

In the newest analysis, investigators used data from the National Health and Nutrition Examination Survey (NHANES 1999–2004) to estimate the size of the population that would be affected by the JUPITER findings as well as to describe the population for whom statin therapy might now be indicated.
The group identified 2322 individuals with complete data to determine statin eligibility. More than half, 57.9%, and representing more than 33 million US adults, had a National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) indication for statin therapy. Of these, only 42% were currently taking a statin.
Of the remaining 976 subjects, 13.9%, representing eight million US adults, met the strict JUPITER criteria of hs-CRP >2.0 mg/L and LDL cholesterol <130 mg/dL. Another 5.3%, representing three million adults, had an extended JUPITER indication--elevated CRP and LDL-cholesterol levels between 130 and 160 mg/dL--for statin therapy.
"In the middle-aged and older population, there are already a huge number of people--58%, or 33 million Americans--who meet the current recommendations to take a statin," Spatz told heartwire. "If we are to adopt JUPITER to clinical practice, this would add an additional 11 million people, or another 20% of the population."
As noted, the secondary analysis of the NHANES data revealed that less than half of patients currently meeting the existing recommendations for statin therapy are receiving the lipid-lowering drugs.
In looking at patient characteristics, the researchers noted that compared with individuals in whom statins would not be indicated, the JUPITER patients were more likely to be female and older. There were also more likely to be obese, hypertensive, and have the metabolic syndrome. They also noted that many of JUPITER patients shared similar characteristics, including sociodemographic factors, abdominal obesity, and hypertension, as those who qualified for statin therapy based on the NCEP ATP III guidelines.
An analysis of cardiovascular risk scores showed that Framingham risk score (FRS) was higher in patients who met the NCEP ATP III guidelines for statin therapy but similar in the JUPITER patients and patients without an indication for statin therapy. The Reynolds risk score, which includes additional risk factors beyond the FRS, including hs-CRP, was able to differentiate risk between those who met the criteria for statins based on JUPITER patients and those without an indication for the drugs, said Spatz

rosuvastatin reduces the risk of cardiovascular events by 54% in people who do not have high cholesterol level after 2 years

The JUPITER (Justification for the Use of Statins in Primary Prevention Intervention) trial has shown that rosuvastatin reduces the risk of cardiovascular events by 54% in people who do not have high cholesterol level but have raised high sensitive C reactive protein. The trial was scheduled for a follow up of 4 years, but after nearly two years as there was a significant reduction in the primary end point at two years tyhe trial was stopped.

The original research article and an editorial was recently published in NEJM. There are two important issues regarding the results of this trial

1. Long term safety of rosuvastatin is not yet established. If we are going to start rosuvastatin for a low risk subject without any clinical disease for primary prevention, he will be taking it for a long period say 20 years. In such case without long term safety being established, it should not be advised.

2. Secondly the patency of rosuvastatin is now held by Astra Zeneca and the drug is very costly now. If this protective effect is a class effect then the cheaper statins which have become generic can be substituted.