Systematic review with meta-analysis: risk of adverse cardiovascular events with proton pump inhibitors independent of clopidogrel.

BACKGROUND: Clopidogrel's anti-platelet effects may be attenuated by a pharmacokinetic interaction with co-prescribed proton pump inhibitors, which inhibit oxidative pathways that convert clopidogrel into its active metabolites. Despite this, the impact of PPIs on cardiovascular risk in the absence of clopidogrel is not well defined. AIM: To report on a systematic review and meta-analysis of the association between PPIs and cardiovascular risk, independent of clopidogrel. METHODS: The databases of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and ClinicalTrials.gov were systematically searched in October 2017. The primary outcome was association between PPI monotherapy and any adverse cardiovascular event. The secondary outcome was association between proton pump inhibitor monotherapy and acute myocardial infarction. Studies were excluded if they reported or did not adjust for concomitant anti-platelet therapy or involved participants aged less than 18 years. RESULTS: A total of 22 studies were included in the systematic review. Data from 16 studies were included in the meta-analysis (involving 447 408 participants). Of these, eight were randomised controlled trials, seven were observational studies and one was a retrospective analysis of a randomised controlled trial. An increased risk of any adverse cardiovascular event with PPI monotherapy was observed using pooled data from observational studies (risk ratio 1.25, 95% CI 1.11-1.42, I2 81%, P < 0.001), but not from randomised controlled trials (risk ratio 0.89, 95% CI 0.34-2.33, I2 0%, P = 0.85). CONCLUSION: There is no clear evidence of an association between PPI monotherapy and increased cardiovascular risk.

The cost-effectiveness of PCSK9 inhibitors - The Australian healthcare perspective.

BACKGROUND: For patients in whom statins are not tolerated or effective as monotherapy, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a new class of lipid lowering therapies that may reduce low-density lipoprotein cholesterol (LDL-C) levels by up to 50% and lower cardiovascular events. While an important treatment option, the cost-effectiveness of PCSK9i in Australia remains unknown. This study aimed to determine the cost-effectiveness of PCSK9i compared to placebo in the prevention of atherosclerotic cardiovascular disease (CVD). METHODS AND RESULTS: A Markov cohort state-transition model was developed in Microsoft Excel. A hypothetical sample of 1000 individuals based on subjects in the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial populated the model. With each five-year cycle, model subjects could have non-fatal CVD events (myocardial infarction and/or stroke), or die from CVD or other causes. Follow-up was simulated for 25 years. CVD risk reduction, cost and utility data were gathered from published sources. At current acquisition prices (AU$8174 per person per year), the incremental cost effectiveness ratio (ICER) was AU$308,558 per quality-adjusted life year (QALY) saved. Acquisition prices would need to be reduced to approximately AU$1500 per person per annum for PCSK9i to reach the arbitrary cost-effectiveness threshold of AU$50,000 per QALY saved. CONCLUSION(S): PCSK9i are an effective alternative for those with existing CVD or at high risk of CVD in whom statin therapy alone is ineffective, but are not cost-effective to the Australian healthcare system based on current prices.