PCSK9 inhibitors for treating dyslipidemia in patients at different cardiovascular risk: a systematic review and a meta-analysis.

Statin-induced lowering of low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular morbidity and mortality, but many patients do not adequately reduce their LDL-C levels. Monoclonal antibodies targeting PCKS9 are currently in the advanced phase of development. We aimed to investigate the efficacy and safety of PCSK9 inhibitors in patients at different cardiovascular risk in a systematic review. Studies were searched on MEDLINE and EMBASE until January 2016. Differences in the outcomes among groups were expressed as mean differences, or pooled odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed-effects and a random-effects model. Statistical heterogeneity was evaluated using the I 2 statistic. 22 RCTs and 8833 patients were included. Six studies were performed in patients affected by homozygous or heterozygous familial hypercholesterolemia, or with increased cardiovascular risk, two in patients with statin intolerance, three in statin-naïve patients, and 10 in patients unable to achieve LDL-C target with statin therapy. PCSK9 inhibitors were associated with a statistically significant reduction of LDL-C (mean = -48.8%; 95% CI -54.1, -43.4; I 2 = 94%) compared to control groups, and with a statistically significant reduction in death for any cause (OR = 0.34; 95% CI 0.17, 0.69; I 2 = 0) and a favorable trend for cardiovascular events (OR = 0.79; 95% CI 0.61, 1.02; I 2 = 0%). PCSK9 inhibitors reduce LDL-C concentration in every group explored. A significant reduction in death by all cause was observed in the PCSK9 inhibitors groups, compared with control groups, even in the short time frame studied.

Drug Interaction Between Clopidogrel and Ranitidine or Omeprazole in Stable Coronary Artery Disease: A Double-Blind, Double Dummy, Randomized Study.

BACKGROUND: Proton-pump inhibitors (PPIs) are often prescribed to patients receiving dual antiplatelet therapy (DAPT). However, this class of medication, especially omeprazole, has been associated with a reduction in clopidogrel efficacy, leading many clinicians to substitute omeprazole with ranitidine. OBJECTIVES: Our objective was to compare the antiplatelet effect of clopidogrel before and after the addition of omeprazole or ranitidine. METHODS: We measured platelet aggregability at baseline and after 1 week of clopidogrel 75 mg daily. Subjects were then randomized in a double-blinded, double-dummy fashion to omeprazole 20 mg twice daily (bid) or ranitidine 150 mg bid. We repeated aggregability tests after 1 additional week, using VerifyNow P2Y12™ (Accumetrics; San Diego, CA, USA), depicting aggregability as percent inhibition of platelet aggregation (IPA). RESULTS: We enrolled 41 patients in the omeprazole group and 44 in the ranitidine group. IPA was significantly decreased after the addition of omeprazole to clopidogrel (from 26.3 ± 32.9 to 17.4 ± 33.1 %; p = 0.025), with no statistical significant changes observed in the ranitidine group (from 32.6 ± 28.9 to 30.1 ± 31.3 %; p = 0.310). The comparison of IPA in both groups at the end of the follow-up showed a trend toward significance (p = 0.07, 95 % confidence interval [CI] -1.19 to 26.59); after excluding homozygous patients for 2C19*2 genotype, the comparison of IPA between the groups reached statistical significance (32.7 ± 30.8 vs. 17.7 ± 33.4 %, respectively, for ranitidine and omeprazole groups; p = 0.04). CONCLUSIONS: Unlike omeprazole, ranitidine did not influence platelet aggregability response to clopidogrel. CLINICAL TRIAL REGISTRATION: NCT01896557.