Relative safety profiles of high dose statin regimens

Figures & data

Table 1 NCEP-ATP III LDL cholesterol objectives and cutpoints drug therapy according to risk categories (Adapted from Grundy et al 2004)

Risk category	LDL-C objective	LDL-C level at which to consider drug therapy
High risk: CHD or CHD risk equivalent (10-year risk >20%)	<100 mg/dL (2.58 mmol/L); optional goal <70 mg/dL (1.82 mmol/L) in very high risk patients	≥100 mg/dL (2.58 mmol/L); <100 mg/dL (2.58 mmol/L) consider drug options
Moderately high risk: 2 or more risk factors (10-year 10 year risk 10 to 20%)	<130 mg/dL (3.36 mmol/L)	≥130 mg/dL (3.36 mmol/L); 100 to 129 mg/dL consider drug options
Moderate risk: 2 or more risk factors (10-year risk <10%)	<130 mg/dL (3.36 mmol/L)	≥160 mg/dL (4.13 mmol/L)
Lower risk: 0 to 1 risk factor	<160 mg/dL (4.13 mmol/L)	≥190 mg/dL (4.91 mmol/L); 160 to 189 mg/dL consider drug options

Notes: CHD risk equivalents include noncoronary forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and carotid artery disease), and diabetes mellitus. Risk factors include age, hypertension, family history of premature CHD cigarette smoking, low HDL cholesterol.

Abbreviations: CHD, coronary heart disease; LDL-C, low density lipoprotein-cholesterol.

Figure 1 Risk of coronary risk or any cardiovascular event (myocardial infarction, stroke, hospitalization for unstable angina or revascularization) (Cannon et al 2006).

Abbreviations: CVD, cardiovascular diseases; CHD, coronary heart disease; prav, pravastatin; ator, atorvastatin; sim, simvastatin; std, standard.

Table 2 Clinical characteristics that increase the probability of presenting side effects from randomized clinical trials (modified from Davidson and Robinson 2007)

Clinical characteristics	Situation that increases risk
Age	≥75 years
Heart failure	Left ventricular ejection fraction <30%
Intercurrent illness, surgery, or trauma	Concomitant use of statins when major surgery, severe illness, or major trauma is present
Comorbidities or concomitant treatments	Multiple comorbidities or therapies
Alcohol intake	Excessive alcohol intake (>2 drinks per day)
Concomitant lipid-lowering therapy	Fibrates, especially gemfibrozil
Cytochrome P450 inhibitors	Concomitant use of: macrolide antibiotics, antiviral drugs (especially HIV protease inhibitors), systemic azole antifungals (itraconazole and ketokonazole), nefazadone, grapefruit juice >1 quart/day
Immunosuppressive therapy	Especially ciclosporine
Muscle function	CK >3 × ULN unless explanationHistory of muscle disease Continuing with statin therapy after strenuous exercise
Hepatic function	Active hepatic disease ALT and AST >2 × ULN
Renal function	Creatinine >1.5 × ULN Glomerular filtration rate <60 ml/min/1.73 m^2 History of nephrotic syndrome

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CK, creatine kinase; ULN, upper limit of normal.

Table 3 Severe adverse events from large randomized trials of intensive statin therapy (data from Cannon et al 2004; de Lemos et al 2004; LaRosa et al 2005; Pedersen et al 2005)

	PROVE-IT (n = 4,162)	A-to-Z (n = 4,497)	TNT (n = 10,001)	IDEAL (n = 8,888)
AST and/or ALT >3 × ULN Higher vs lower	3.3% vs 1.1%, p < 0.001	0.9% vs 0.4%, p = 0.05	1.2% vs 0.2%, p < 0.001	0.97% vs 0.11%, p < 0.001
CK >10 × ULN Higher vs lower	0.1% vs 0.15%, p = NS	0.4% vs 0.04%, p = 0.02	0% vs 0%, p = NS	0.14% vs 0.25%, p = NS
Rhabdomyolysis Higher vs lower	0% vs 0%, p = NS	0.1% vs 0%	0.04% vs 0.06%, p = NS	0.05% vs 0.07%, p = NS

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CK, creatine kinase; ULN, upper limit of normal.

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