PCSK9 inhibitor lowers CV risk in peripheral artery disease and in high-risk patients with previous MI
Evolocumab and Outcomes in Patients with Peripheral Artery Disease (Bonaca) & Clinical Benefit of Evolocumab in Patients with a History of MI: An Analysis from FOURIER (Sabatine)
Presented at AHA 2017 Scientific Sessions in Anaheim, CA, USA by Marc Bonaca and Marc Sabatine (Brigham and Women’s Hospital, Boston, MA, USA)News - Nov. 21, 2017
Findings in patients with PAD
- Evolocumab lowered the risk of CV death, MI and stroke in patients with PAD (RRR: 27%, HR: 0.73, 95%CI: 0.59-0.91, P=0.004, ARR: 3.5%, NNT-2,5jr: 29); a larger treatment effect than seen in patient without PAD (RRR: 19%, HR: 0.81, 95%CI: 0.73-0.90, P<0.001, ARR: 1.4%, NNT-2,5jr: 72).
- In patientst with PAD, but without MI and stroke (n=1505) ARR was 4.8% (NNT: 21, HR: 0.57, 95%CI: 0.38-0.88, P=0.0095).
- 42% Fewer MALE were seen in the evolocumab in the total study population (n=27.564, HR: 0.58, 95%CI: 0.38-0.88, P=0.0093).
- In evolocumab-treated patients with known PAD, the relative risk reduction in MALE was 37% (HR: 0.63, 95%CI: 0.39-1.03), and 63% in those without PAD (HR: 0.37, 95%CI: 0.16-0.88). No significant interaction was seen for PAD and treatment effect.
- In patients with PAD, but without MI and stroke, RRR for MALE on evolocumab was 57% (HR: 0.43, 95%CI: 0.19-0.99, P=0.042, ARR: 1.3%).
Findings in patients with MI
- Risk of CV death, MI or stroke was higher in placebo patients for whom qualifying MI was longer than 2 years ago (HR: 1.19, 95%CI: 1.04-1.37, P=0.01), as compared with <2 years.
- Risk of CV death, MI or stroke was higher in placebo patients with ≥2 previous MIs (HR: 2.04, 95%CI: 1.78-2.35, P<0.001), as compared with 1 previous MI.
- Risk of CV death, MI or stroke was higher in placebo patients with multivessel CAD (HR: 1.47, 95%CI: 1.27-1.70, P<0.001), as compared with no multivessel CAD.
- Multivariable adjusted analyses for the three factors yielded HR: 1.36 (95%CI: 1.18-1.57, P<0.001), HR: 1.90 (95%CI: 1.65-2.19, P<0.001) and HR: 1.34 (95%CI: 1.16-1.55, P<0.001) respectively.
- Treatment with evolocumab yielded 24% relative risk reduction in patients for whom the qualifying MI was <2 years ago and 13% for those for whom it was longer ago than 2 years. 21% RRR was seen in patients with ≥2 previous Mis and 16% with 1 previous MI. 30% RRR was seen with multivessel CAD and 11% in the absence thereof. All risk reductions were statistically significant.
It results from the PAD analysis that these patients, with a higher risk of both MACE and MALE, benefit from treatment with evolocumab in the reduction of these events. Benefits extend to PAD patients without prior MI or stroke. Thus, dr Bonaca concluded that LDL-C reduction to very low levels should be considered in patients with PAD, regardless of history of MI or stroke, to reduce the risk of MACE and MALE.
The other analysis showed that patients closer to their most recent MI, with multiple prior MIs, or with multivessel disease, are at 34-90% risk for major vascular events. These patients experience both substantial relative and absolute risk reductions with intensive LDL-C lowering with evolocumab. These readily ascertainable clinical features offer one approach to tailoring therapy.
- Our reporting is based on the information provided at the AHA 2017 congress -