HPS trial post hoc analysis

The results of Heart Protection Study  post-hoc analysis have been publishedd in the latest issue of Lancet.(1) The HPS tested the hypothesis that the effects of statin therapy differ according to baseline concentrations of CRP and LDL cholesterol.

Patients were categorised into six baseline CRP groups (<1·25, 1·25—1·99, 2·00—2·99, 3·00—4·99, 5·00—7·99, and ≥8·00 mg/L), each including about 3000 patients.

Results showing the effect of Simvastatin on LDL_C levels have been published earlier. Results of this post-hoc analysis:

·        Allocation to simvastatin produced a significant 24% (95% CI 19—28) proportional reduction in the incidence of first major vascular event after randomisation.

·        There was no significant trend in the proportional risk reduction with increasing baseline CRP, with significant reductions in each of the baseline CRP groups, including in participants with CRP concentration less than 1·25 mg/L (29% risk reduction, 99% CI 12—43; p<0·0001).

·        Indeed, even in those with baseline CRP concentration less than 1 mg/L, there was a significant 27% (99% CI 5—44) reduction in risk (166 [13·7%] allocated to simvastatin vs 218 [18·3%] allocated to placebo; p=0·0022).

·        Allocation to simvastatin reduced the incidence of first major coronary event by 27% (95% CI 21—33), of first stroke by 25% (15—34), and of first revascularisation by 24% (17—30), with no significant trend in the proportional risk reduction with increasing baseline CRP concentration for any of these outcomes.

·        There was also no significant trend in the proportional reduction in vascular death with increasing baseline CRP.

·        The proportional risk reduction in participants with low LDL cholesterol and low CRP (27%, 99% CI 11—40; p<0·0001) was statistically similar to that in participants with high LDL cholesterol and high CRP (23%, 10—35; p<0·0001). The authors have mentioned that even when the threshold used to define low LDL cholesterol was reduced to 2·8 mmol/L (which was the median baseline concentration in the JUPITER trial), the proportional reduction in major vascular events in participants with low LDL cholesterol and low CRP (92 [13·6%] vs 128 [18·2%]; risk reduction 0·73, 99% CI 0·52—1·04; p=0·0213) was still similar to the reduction recorded overall.

According to the authors the results of this post-hoc analysis does not lend support to the hypothesis that baseline CRP concentration modifies the vascular benefits of statin therapy materially.

The discussion on the hypothesis has been done on http://www.theheart.org/article/1177999.do

(1) http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62174-5/fulltext?_eventId=login#bib2