**4. Results**

Male patients (70%) were the more frequent users of statins, with mean age 60±10 years. The most frequent race that used statins was Chinese (37.6%), followed by Malays (34.4%), Indians (26.6%) and foreigners (1.4%). Small numbers of patients were cigarette smoker (12%) and alcohol consumers (9%).

Higher number of patients had dyslipidemia with primary type (51.5%) based on the Friedewald et al18 and Stone et al19 classifications. For primary subtypes of dyslipidemia, the most common subtype was IIa (50.6%), while common subtype of secondary dyslipidemia was diabetes (86.3%). The common type of statin used was lovastatin (81%), followed by simvastatin (9.4%) and atorvastatin (8%). The low dose (20 mg) of statin was the common prescribed to these patients. The mean duration of statin therapy was 3.5 years and the most frequent range of duration was 1-5 years (52.5%), as shown in Table 1.

Statistical regression analysis was used to exclude symptoms related to other medications and diseases. It found only few symptoms from 27 ADRs that correlated significantly with statins were; fatigue (59.4%), muscle pain (53.6%), joint pain (53.4%), back pain (47.8%), insomnia (44.8%) and visual disturbances (44.2%).

Cross-sectional with convenient sampling study conducted for volunteer outpatients from the cardiac clinic of Penang Hospital in Pulau Pinang State of Malaysia. Study protocol was approved by Clinical Research Committee of Penang General Hospital, and signed consent forms were obtained from all participants. The patients included in this study were at least 18 years old and voluntarily to participate in this study. They have to used statins and could understand Malay Language (the National Language of Malaysia) or English Language, since Malaysia is a multiracial country. Patients who allergies to statin, pregnant or lactating women, or changing in types or dosage of statin used were excluded from this study. These types of patients excluded because their conditions may affected outcomes of the study. The study period was 5 months, and 1900 patients presented in the cardiac clinic within this study period. Depending on inclusion and exclusion criteria, 500 patients voluntarily agreed to participate in this study. A validated questionnaire form (Cronbach's alpha is 0.853) were used for reporting of ADRs. The patients were asked whether they have experience of common statin-related ADRs while they were on statin therapy and give their answers on the self-report questionnaire forms. This questionnaire form has some questions on demographic data and undesired symptoms that patients had during statin therapy. There were 27 ADRs of statin listed in the questionnaire form. They were required to tick yes or no on these listed ADRs. They can tick more than one ADR. In order to ensure these ADRs really related with statin therapy these patients had to indicate in the questionnaire form that these ADRs occurred while they were receiving statin therapy and these symptoms

Statistical Package for Social Science software (SPSS) version 18 used to analyze the data for this study. Odd ratio and Chi-square and logistic regression tests were used to ensure these ADRs were related with stain therapy and to determine their predictors. The results with *p*

Male patients (70%) were the more frequent users of statins, with mean age 60±10 years. The most frequent race that used statins was Chinese (37.6%), followed by Malays (34.4%), Indians (26.6%) and foreigners (1.4%). Small numbers of patients were cigarette smoker

Higher number of patients had dyslipidemia with primary type (51.5%) based on the Friedewald et al18 and Stone et al19 classifications. For primary subtypes of dyslipidemia, the most common subtype was IIa (50.6%), while common subtype of secondary dyslipidemia was diabetes (86.3%). The common type of statin used was lovastatin (81%), followed by simvastatin (9.4%) and atorvastatin (8%). The low dose (20 mg) of statin was the common prescribed to these patients. The mean duration of statin therapy was 3.5 years and the most

Statistical regression analysis was used to exclude symptoms related to other medications and diseases. It found only few symptoms from 27 ADRs that correlated significantly with statins were; fatigue (59.4%), muscle pain (53.6%), joint pain (53.4%), back pain (47.8%),

should continuously occurred at least for 3 months.

value less than 0.05 was considered statistically significant.

frequent range of duration was 1-5 years (52.5%), as shown in Table 1.

insomnia (44.8%) and visual disturbances (44.2%).

**2. Method** 

**3. Statistics** 

**4. Results** 

(12%) and alcohol consumers (9%).


Table 1. Demographic data of 500 cardiac outpatients in Penang General Hospital

Predictors of the Common Adverse Drug Reactions of Statins 463

NS NS NS NS NS NS

NS NS NS NS NS NS

In term of predictor, females significantly had joint pain (61.74%, OR = 1.864) and back pain (56.38%, OR = 1.73). However, there was no significant relation between gender with fatigue, muscle pain, insomnia and visual disturbance. Indian patients had significantly higher incidence of fatigue (68.42%, OR= 1.81), muscle pain (66.92%, OR =1.94), back pain (62.4 %, OR = 2.18), and visual disturbances (49.62 %, OR = 1.738) when compared to other races. No significant relationship found between smoking and statin related-ADRs. Patients who consumed alcohol significantly had fatigue (76.6%, OR = 3.0), back pain (65.96%, OR = 3.584) and insomnia (59.57%, OR = 2.893). Age was without effect on incidence of statin related-ADRs. Patients used statins for more than 5 years significantly had fatigue (53.41%,

For secondary dyslipidemia types, renal induced dyslipidemia significantly caused higher incidence of insomnia when compared to the other secondary subtypes (64.71%, OR = 3.7). For subtypes of primary dyslipidemia, subtype IIb patients had significantly back pain

No significant relationship found between statin related-ADRs and statin types, the patients used simvastatin had a higher incidence of fatigue (65.96%), joint pain (57.45%), back pain (55.32%) and visual disturbance (53.19%). Patients used lovastatin had insomnia (45.68%), while patients used atorvastatin had higher incidence of muscle pain (52.17%). No significant relationship found between doses of statins and other ADRs except for lovastatin dose. Patients used 60 mg dose of lovastatin had significantly fatigue than patients used lower doses (72.73%, OR = 1.904). No significant relation found between the combination

After two decades of statin marketing, significant incidences of adverse drug reactions still presented during therapy. Number of studies of medications' ADRs always increased after first years of launching, but it found this matter is different with type of statin used20. Most of previous studies focused on serious ADRs of statin like muscle toxicity, elevation of liver enzymes, renal toxicity and polyneuropathy21,22. Although serious ADRs caused mortalities and death to patients, but their incidences are lower than other adverse reactions of statin

with other lipid lowering agents and incidence of ADRs (as shown in Table 2).

NS NS NS NS NS

Simvastatin dose (40mg)

Lovastatin doses (60mg)

Combination therapy

NS= no significant

(81.82%, OR = 2.5).

**5. Discussion** 

72.73%, P=0.003, OR= 1.90, CI= 1.25- 2.89)

Table 2. Relationship between statin related ADRs and predictors

OR = 1.83) and muscle pain (60.23%, OR =1.958), as shown in Table 2.




NS= no significant

462 Dyslipidemia - From Prevention to Treatment

P=0.007, OR= 1.864, CI= 1.18-2.94

Smokers NS NS NS NS NS NS

Age NS NS NS NS NS NS

NS NS NS 33.90%,

NS NS NS NS 64.71%,

NS NS NS NS NS NS

Statin types NS NS NS NS NS NS

NS NS 65.96%,

**pain Joint pain Back pain Insomnia** 

NS 62.4%,

NS 57.95%,

56.38%, P= 0.02, OR= 1.73, CI= 1.09- 2.75

P=0.007, OR= 2.18, CI= 1.23- 3.72

P= 0.003, OR= 3.58, CI= 1.53- 8.38

P=0.001, OR=2.61, CI= 1.50- 4.54)

P= 0.014, OR= 2.50, CI= 1.21- 5.19)

**Visual disturbances** 

P=0.016, OR= 1.74, CI= 1.11- 2.73)

NS

NS NS

NS 49.62%,

59.57%, P=0.006, OR= 2.89, CI= 1.36- 6.15

NS NS

NS NS

NS

P= 0.33, OR= 3.7, CI= 1.11- 12.33

**Predictors ADRs (percentage, P value, OR, CI)** 

**Fatigue Muscle** 

68.42%, P=0.027, OR= 1.81, CI= 2.14- 2.75)

P= 0.011, OR= 3.0 CI= 1.29- 7.01)

53.41%, P=0.036, OR= 1.83, CI= 1.04- 3.23)

Alcoholic 76.60%,

Duration More than 5 years

Primary subtypes (type IIb)

Secondary subtypes (renal disease)

Atorvastatin doses (20mg)

NS NS 61.74%,

66.92%, P= 0.016, OR=1.94, CI= 1.13- 3.32)

60.23%, P=0.016, OR=1.96, CI= 1.133- 3.39

Gender (female)

Race (Indian)

Table 2. Relationship between statin related ADRs and predictors

In term of predictor, females significantly had joint pain (61.74%, OR = 1.864) and back pain (56.38%, OR = 1.73). However, there was no significant relation between gender with fatigue, muscle pain, insomnia and visual disturbance. Indian patients had significantly higher incidence of fatigue (68.42%, OR= 1.81), muscle pain (66.92%, OR =1.94), back pain (62.4 %, OR = 2.18), and visual disturbances (49.62 %, OR = 1.738) when compared to other races. No significant relationship found between smoking and statin related-ADRs. Patients who consumed alcohol significantly had fatigue (76.6%, OR = 3.0), back pain (65.96%, OR = 3.584) and insomnia (59.57%, OR = 2.893). Age was without effect on incidence of statin related-ADRs. Patients used statins for more than 5 years significantly had fatigue (53.41%, OR = 1.83) and muscle pain (60.23%, OR =1.958), as shown in Table 2.

For secondary dyslipidemia types, renal induced dyslipidemia significantly caused higher incidence of insomnia when compared to the other secondary subtypes (64.71%, OR = 3.7). For subtypes of primary dyslipidemia, subtype IIb patients had significantly back pain (81.82%, OR = 2.5).

No significant relationship found between statin related-ADRs and statin types, the patients used simvastatin had a higher incidence of fatigue (65.96%), joint pain (57.45%), back pain (55.32%) and visual disturbance (53.19%). Patients used lovastatin had insomnia (45.68%), while patients used atorvastatin had higher incidence of muscle pain (52.17%). No significant relationship found between doses of statins and other ADRs except for lovastatin dose. Patients used 60 mg dose of lovastatin had significantly fatigue than patients used lower doses (72.73%, OR = 1.904). No significant relation found between the combination with other lipid lowering agents and incidence of ADRs (as shown in Table 2).
