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Statins, nonstatin LDL-lowering therapies associated with similar CV benefit
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Statin and nonstatin therapies yield similar risk reduction of major CV events, according to a meta-regression analysis published in JAMA.
“As per current guidelines, when tolerated, statins should be the first-line therapy given the large reductions observed for LDL, the excellent safety profile, the demonstrated clinical benefit and low cost (now that most are generic),” Michael G. Silverman, MD, and colleagues wrote. “However, the data in the present meta-regression analysis raise the possibility that other interventions, especially those that ultimately act predominantly through upregulation of LDL receptor expression, may prove additional options and may potentially be associated with the same relative clinical benefit per each 1-mmol/L reduction in LDL.”
The researchers conducted a systematic review and trial-level meta-regression analysis of 312,175 participants (mean age, 62 years; 24% women) from randomized clinical trials to evaluate the association between LDL and relative CV risk reduction across statin and nonstatin therapies.
The outcomes of interest were the RRs of major vascular events — defined as CV death, acute MI or other ACS, coronary revascularization or stroke — associated with absolute level of LDL reduction and 5-year rate of coronary death or MI linked to the LDL level achieved.
Similar risk reduction
There were 25 statin trials included in the analysis. All 1 mmol/L (38.7 mg/dL) LDL level reductions were associated with an RR of 0.77 (95% CI, 0.71-0.84) for major vascular events. For nonstatin interventions working via upregulation of LDL receptor expression, including diet, bile acid sequestrants, ileal bypass and ezetimibe (Zetia, Merck), the RR per 1 mmol/L reduction in LDL for major vascular events was 0.75 (95% CI, 0.66-0.86; P for between-group difference = .72). For all five therapies working via upregulation of LDL receptor expression, the RR for major vascular events was 0.77 (95% CI, 0.75-0.79), according to Silverman, from the TIMI Study Group, division of cardiovascular medicine, Brigham and Women’s Hospital and Harvard Medical School, and colleagues.
According to the researchers, observed vs. expected RRs based on degree of LDL reduction documented in trials were as follows:
niacin: observed, 0.94 (95% CI, 0.89-0.99); expected, 0.91 (95% CI, 0.9-0.92);
fibrates: observed, 0.88 (95% CI, 0.83-0.92); expected, 0.94 (95% CI, 0.93-0.94);
cholesterol ester transfer protein inhibitors: observed, 1.01 (95% CI, 0.94-1.09); expected, 0.9 (95% CI, 0.89-0.91); and
PCSK9 inhibitors: observed, 0.49 (95% CI, 0.34-0.71); expected, 0.61 (95% CI, 0.58-0.65).
Lower LDL affected outcomes
Additionally, there was a significant association between LDL and 5-year event rates of coronary death or MI over the range of LDL studied. This association was seen both in the primary (1.5% lower event rate per 1-mmol/L lower LDL; 95% CI, 0.5-2.6) and secondary (4.6% lower event rate per 1-mmol/L lower LDL; 95% CI, 2.9-6.4) prevention trials.
“The implications of these results deserve careful consideration in light of the strength of the available trial evidence for different types of therapies,” the researchers wrote. – by Dave Quaile
Disclosure: Silverman reports no relevant financial disclosures. Please see the full study for a list of the other researchers’ relevant financial disclosures.
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