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Meta-analysis of drug-induced adverse events associated with intensive-dose statin therapy.
Clin Ther 2007; 29(2):253-60CT

Abstract

BACKGROUND

Randomized trials evaluating intensive dose statin therapy have found enhanced protection against cardiovascular (CV) events compared with moderate-dose statin therapy in patients with acute coronary syndromes (ACS) or stable coronary artery disease (CAD). However, the potential for an increase in the risk of drug-induced adverse events with such therapy has not been quantified.

OBJECTIVE

This meta-analysis was performed to compare the incremental risks associated with intensive- and moderate-dose statin therapy.

METHODS

MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from 1995 to 2006 using the following terms: acute, coronary syndrome, stable coronary artery disease, atorvastatin, simvastatin, rosuvastatin, pravastatin, lovastatin, and fluvastatin. Prospective, randomized controlled trials evaluating intensive- and moderate-dose statin therapy for the reduction of CV events were included in the review. The safety end points examined were elevations in creatine kinase (CK) >or= 10 times the upper limit of normal (ULN), elevations in alanine or aspartate aminotransferase >or=3 times the ULN, rhabdomyolysis, drug-induced adverse events requiring discontinuation of therapy, and any drug-induced events. The efficacy end points examined were all-cause mortality, CV death, nonfatal myocardial infarction (MI), and stroke. Each analysis compared the effect of intensive- or moderate-dose statin therapy on statin-induced adverse events and clinical efficacy outcomes. Simple absolute risk, the number needed to treat, and the number needed to harm were also calculated to quantify the incremental benefit or harm associated with intensive-dose statin therapy.

RESULTS

Four trials were included in the analysis.Together, they included 27,548 patients with ACS or stable CAD followed for a mean of 3.4 years, representing 108,049 patient-years of clinical-trial experience. Intensive-dose therapy with atorvastatin or simvastatin 80 mg was associated with a significant increase in the risk for any adverse event (odds ratio [OR] = 1.44; 95% CI, 1.33-1.55; P < 0.001) and adverse events requiring discontinuation of therapy (OR = 1.28; 95% CI, 1.18-1.39; P < 0.001). Intensive-dose therapy also was associated with an increased risk for abnormalities on liver function testing (OR = 4.48; 95% Cl, 3.27-6.16; P < 0.001) and elevations in CK (OR = 9.97; 95% CI, 1.28-77.92; P = 0.028). The benefits of intensive-dose statin therapy included reductions in CV death (OR = 0.86; 95% CI, 0.75-0.99; P = 0.031), MI (OR = 0.84; 95% CI, 0.76-0.93; P < 0.001), and stroke (OR = 0.82; 95% CI, 0.72-0.94; P = 0.004).

CONCLUSIONS

Although intensive-dose statin therapy was associated with a reduced risk for important CV events, it was also associated with an increased risk for statin-induced adverse events. Therefore, moderate-dose statin therapy may be the most appropriate choice for achieving CV risk reduction in the majority of individuals, whereas intensive-dose statin therapy may be reserved for those at highest risk.

Authors+Show Affiliations

Department of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences-Worcester/Manchester, Massachusetts, USA.

Pub Type(s)

Comparative Study
Journal Article
Meta-Analysis

Language

eng

PubMed ID

17472818

Citation

Silva, Matthew, et al. "Meta-analysis of Drug-induced Adverse Events Associated With Intensive-dose Statin Therapy." Clinical Therapeutics, vol. 29, no. 2, 2007, pp. 253-60.
Silva M, Matthews ML, Jarvis C, et al. Meta-analysis of drug-induced adverse events associated with intensive-dose statin therapy. Clin Ther. 2007;29(2):253-60.
Silva, M., Matthews, M. L., Jarvis, C., Nolan, N. M., Belliveau, P., Malloy, M., & Gandhi, P. (2007). Meta-analysis of drug-induced adverse events associated with intensive-dose statin therapy. Clinical Therapeutics, 29(2), pp. 253-60.
Silva M, et al. Meta-analysis of Drug-induced Adverse Events Associated With Intensive-dose Statin Therapy. Clin Ther. 2007;29(2):253-60. PubMed PMID: 17472818.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Meta-analysis of drug-induced adverse events associated with intensive-dose statin therapy. AU - Silva,Matthew, AU - Matthews,Michele L, AU - Jarvis,Courtney, AU - Nolan,Nicole M, AU - Belliveau,Paul, AU - Malloy,Michael, AU - Gandhi,Pritesh, PY - 2007/01/16/accepted PY - 2007/5/3/pubmed PY - 2007/8/8/medline PY - 2007/5/3/entrez SP - 253 EP - 60 JF - Clinical therapeutics JO - Clin Ther VL - 29 IS - 2 N2 - BACKGROUND: Randomized trials evaluating intensive dose statin therapy have found enhanced protection against cardiovascular (CV) events compared with moderate-dose statin therapy in patients with acute coronary syndromes (ACS) or stable coronary artery disease (CAD). However, the potential for an increase in the risk of drug-induced adverse events with such therapy has not been quantified. OBJECTIVE: This meta-analysis was performed to compare the incremental risks associated with intensive- and moderate-dose statin therapy. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from 1995 to 2006 using the following terms: acute, coronary syndrome, stable coronary artery disease, atorvastatin, simvastatin, rosuvastatin, pravastatin, lovastatin, and fluvastatin. Prospective, randomized controlled trials evaluating intensive- and moderate-dose statin therapy for the reduction of CV events were included in the review. The safety end points examined were elevations in creatine kinase (CK) >or= 10 times the upper limit of normal (ULN), elevations in alanine or aspartate aminotransferase >or=3 times the ULN, rhabdomyolysis, drug-induced adverse events requiring discontinuation of therapy, and any drug-induced events. The efficacy end points examined were all-cause mortality, CV death, nonfatal myocardial infarction (MI), and stroke. Each analysis compared the effect of intensive- or moderate-dose statin therapy on statin-induced adverse events and clinical efficacy outcomes. Simple absolute risk, the number needed to treat, and the number needed to harm were also calculated to quantify the incremental benefit or harm associated with intensive-dose statin therapy. RESULTS: Four trials were included in the analysis.Together, they included 27,548 patients with ACS or stable CAD followed for a mean of 3.4 years, representing 108,049 patient-years of clinical-trial experience. Intensive-dose therapy with atorvastatin or simvastatin 80 mg was associated with a significant increase in the risk for any adverse event (odds ratio [OR] = 1.44; 95% CI, 1.33-1.55; P < 0.001) and adverse events requiring discontinuation of therapy (OR = 1.28; 95% CI, 1.18-1.39; P < 0.001). Intensive-dose therapy also was associated with an increased risk for abnormalities on liver function testing (OR = 4.48; 95% Cl, 3.27-6.16; P < 0.001) and elevations in CK (OR = 9.97; 95% CI, 1.28-77.92; P = 0.028). The benefits of intensive-dose statin therapy included reductions in CV death (OR = 0.86; 95% CI, 0.75-0.99; P = 0.031), MI (OR = 0.84; 95% CI, 0.76-0.93; P < 0.001), and stroke (OR = 0.82; 95% CI, 0.72-0.94; P = 0.004). CONCLUSIONS: Although intensive-dose statin therapy was associated with a reduced risk for important CV events, it was also associated with an increased risk for statin-induced adverse events. Therefore, moderate-dose statin therapy may be the most appropriate choice for achieving CV risk reduction in the majority of individuals, whereas intensive-dose statin therapy may be reserved for those at highest risk. SN - 0149-2918 UR - https://www.unboundmedicine.com/medline/citation/17472818/Meta_analysis_of_drug_induced_adverse_events_associated_with_intensive_dose_statin_therapy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(07)00049-5 DB - PRIME DP - Unbound Medicine ER -