115trials as compared to men. Use of statins in women is associated with a higher rate
of complications such as myositis and cognitive impairment.
Statin therapy in women without cardiovascular disease is controversial, given
the insuffi cient evidence of benefi t. Sex-specifi c outcomes were analyzed in the
Justifi cation for the Use of Statins in Prevention: An Intervention Trial Evaluating
Rosuvastatin (JUPITER) and the results with prior trials were synthesized (Mora
et al. 2010 ). Participants included 6,800 women and 11, 000 men with high-
sensitivity C-reactive protein and low-density lipoprotein cholesterol randomized to
rosuvastatin versus placebo. Meta-analysis studies were randomized placebo-
controlled statin trials with predominantly or exclusively primary prevention in
women and sex-specifi c outcomes. This study demonstrated that in primary preven-
tion rosuvastatin reduced cardiovascular disease events in women with a relative
risk reduction similar to that in men, a fi nding supported by meta-analysis of pri-
mary prevention statin trials.
Role of Pharmacogenetics in Drug Safety
Variability in drug response among patients is multifactorial, including environmen-
tal, genetic, and disease determinants that affect the disposition of the drug.
Individual variation in response to drugs is a substantial clinical problem. Such
variations include failure to respond to a drug, adverse drug reactions (ADRs) and
drug-drug interactions when several drugs are taken concomitantly.
Adverse Drug Reactions
Susceptibility to ADRs varies with genetic make-up, age, sex, physiology, exoge-
nous factors, and disease state. The clinical consequences of ADRs range from
patient discomfort through serious clinical illness to the occasional fatality. Some
facts about ADRs are:
- There are 2.2 million hospitalizations due to ADRs per year in the US Of these
approximately 100,000 die. - Fatal ADRs are the fourth leading cause of death in the US.
- Twenty percent of all new drugs were eventually reported to be associated with
serious adverse reactions that were not known at the time of approval. - ADRs are a serious problem in infants and young children.
- ADRs are the biggest problem in the elderly – the fastest growing segment of the
population in the US. - The cost of managing adverse drug reactions exceeds $4 billion per annum in
the US. - Ethnic group may act as a marker for underlying genetic or environmental differ-
ences in the susceptibility to ADRs, e.g. during treatment with angiotensin con-
verting enzymes and thrombolytic drugs.
Role of Pharmacogenetics in Pharmaceutical Industry