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2 New HIV CVD/Heart Disease Drugs: PCSK9 inhibitor & 1st CVD Anti-Inflammatory Canakinumab
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2 New HIV CVD/Heart Disease Drugs: PCSK9 Inhibitors - Evolocumab Studied in HIV+ in a Pilot Study results presented at CROI/2015; FOURIER Trial results reported at ACC2017. Canakinumab pilot Study in HIV+ at CROI2017, Novartis Announced Results from Phase 3 June 26 2017.
CROI/2015: PCSK9 inhibition with Evolocumab dramtically lowers (a) LDL-C, (b) Lp(a) and (c) other atherogenic lipids.
PCSK9 is Elevated in HIV+ Patients And May Mediate HIV-Associated Dyslipidemia - (03/11/15)
Studied in pilot HIV study:
CROI/2017:IL-1β (canakinumab) INHIBITION SIGNIFICANTLY REDUCES ATHEROSCLEROTIC INFLAMMATION IN TREATED HIV - Priscilla Hsue
University of California, San Francisco, San Francisco, CA, USA
http://www.croiwebcasts.org/console/player/33597?mediaType=slideVideo&
Amgen Announces Positive Top-Line Results From Phase 3 GLAGOV Imaging Study Of Repatha® (Evolocumab) - (01/04/16)
Evolocumab - FOURIER Further cardiovascular Outcomes Research with PCSK9 Inhibition in subjects with Elevated Risk (05/02/17)
The FOURIER trial shows that evolocumab, which is a fully human monoclonal antibody against PCSK9, causes a significant reduction of 15% in the primary end-points of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization; in addition, it also causes a significant reduction of 20% in some secondary end-points of cardiovascular death, myocardial infarction, or stroke. Notably, the benefit was driven by reductions in the incidence of nonfatal AMI, stroke, and coronary revascularization, but the incidence of cardiovascular (CV) death remained similar in both groups. However, it is important to note that cost issues were of concern even in the USA. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469080/
Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events
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1st CVD Anti-Inflammatory Canakinumab with Positive Phase 3 Results Announced - Studied in HIV at CROI - (06/26/17)
1st CVD Anti-Inflammatory - Novartis Phase III study shows ACZ885 (canakinumab) reduces cardiovascular risk in people who survived a heart attack - (06/26/17)
Coronary Aging in HIV-Infected Patients: "Increased vascular age was observed in 162 patients (40.5%), with an average increase of 15 years"...."you are 50 years old but your heart's age is 65"......http://www.natap.org/2010/HIV/092310_04.htm
higher CD4 count was associated with greater risk, perhaps due to activation/inflammation.....For each 100 cell/μL increase in CD4+ cell count, a loss of 1 year of life was predicted.'....."it is conceivable-albeit speculative-that the ART-induced increase in CD4+ cell count may be coresponsible for the development of atherosclerosis in HIV-infected patients....The left arm of the curve (low CD4+ cell count) may be associated with increased cardiovascular risk due to acute inflammatory processes promoting cardiovascular events as well as opportunistic infections involving increased cytokine expression and vascular damage. On the other end of the curve, an increased CD4+ cell count may be associated with chronic ongoing inflammatory processes (possibly related to immune activation) and could promote atherosclerosis development. In our study, the most recent CD4+ cell count was representative of the right arm of this putative U-shaped curve."....In univariable analyses, chronological age, male sex, systolic blood pressure, duration of ART, fasting glucose level, fasting serum triglyceride level, total cholesterol level, low-density and high-density lipoprotein cholesterol levels, hypertension, and the presence of the metabolic syndrome were associated with increased vascular age. In multivariable linear regression analyse, current CD4+ cell count was the only predictor of increased vascular age (beta=0.51; p=.005). Conclusions. Increased vascular age is frequent among HIV-infected patients and appears to be associated with CD4+ cell count. If these findings were to be confirmed in prospective trials, a positive response to ART with an increase in CD4+ cell count may become a marker of increased risk of atherosclerosis development.
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