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Short-term rehabilitation after an acute coronary event
Published in K Sarat Chandra, AJ Swamy, Acute Coronary Syndromes, 2020
Manish Bansal, Rajeev Agarwala
The duration of high-intensity statin therapy remains debatable, particularly in Indian patients. The long-term studies conducted in the Western populations have not shown any appreciable safety concern with the prolonged use of high-intensity statin therapy [11]. However, similar long-term studies in Indian subjects are lacking, though the preliminary evidence from short-term studies does not suggest any major safety issue [12,13]. Nonetheless, it is a common practise among Indian cardiologists to reduce the dose of statin to a maximum 40 mg/d of atorvastatin or 20 mg/d of rosuvastatin at 3 months after an ACS. Such a strategy is reasonable if LDL-C is <40 mg/dL on two consecutive occasions. However, if the LDL-C remains elevated, it is preferable to continue with the maximum tolerated dose of statin. In patients who are unable to tolerate the required dose of statin or have any safety concerns, the dose of statin should be reduced, and ezetimibe should be added [10]. If LDL-C remains >70 mg/dL despite a combination of maximum-tolerated statin and ezetimibe, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor should be used [10]. One of the PCSK9 inhibitors (evolocumab) is now available in India. A lower-intensity statin therapy is acceptable in elderly individuals above 75 years of age.
Hypertension Associated with Peripheral Artery Disease
Published in Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei, Manual of Hypertension of the European Society of Hypertension, 2019
Old and recent evidence has taught us that PAD patients often present with elevated lipid levels and that decreasing that level leads to better prognosis. This can be achieved by adapted food intake and in most cases, statin therapy. The goal is to bring L-cholesterol down to 70 mg% (1.8 mmol/L) or lower. The benefit of statin therapy to decrease CV events and total mortality was shown in randomized clinical trials (24) and was particularly striking in the Reduction of Atherothrombosis for Continued Health (REACH) (25). Combination with ezitimibe may further improve the results (26). The results obtained in the subgroup of PAD patients in the recent FOURIER trial of evolocumab, a monoclonal antibody to proprotein convertase subtilisin-kexin type 9 (PCSK9) (27), confirmed that decrease of L-cholesterol leads to reduction of CV events.
Disorders of lipid metabolism
Published in Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich, Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Injectable PCSK9 inhibitors have also become important lipid-lowering agents, with several well-executed clinical trials demonstrating their safety and efficacy. In the Global Assessment of Plaque Progression with a PCSK9 Antibody as measured by Intravascular Ultrasound (GLAGOV) trial, patients randomized to evolocumab for a 76-week treatment period had a LDL-C level of 37 mg/dL compared to 93 mg/dL in the placebo group, and the percent atheroma volume decreased by 0.95% in the evolocumab group compared to no change in the placebo group. The Further Cardiovascular Outcomes Research with PCSK9 inhibition in Subjects with Elevated Risk (FOURIER) trial examined the safety and efficacy of evolocumab in patients on maximally tolerated statin therapy with LDL-C ≥70 mg/dL. Evolocumab significantly reduced LDL-C by 59% to 30 from 92 mg/dL, and reduced risk of the primary endpoint, a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, and coronary revascularization, with a number needed to treat of 67 over the short trial duration of two years.
Coronary microcirculatory dysfunction in hypercholesterolemic patients with COVID-19: potential benefit from cholesterol-lowering treatment
Published in Annals of Medicine, 2023
Alpo Vuorio, Petri T. Kovanen, Frederick J. Raal
Apart from statins, lipoprotein apheresis and PCSK9 inhibitors as cholesterol-lowering strategies can also reverse CMD [27,28]. The benefit of the PCSK9 inhibitor evolocumab was shown in a recent randomized study of 60 hospitalized patients with severe SARS-CoV-2 infection [29]. Within 30 days of observation, the patients treated with a 140 mg subcutaneous injection of evolocumab had lower mortality and less need for intubation compared to the placebo group (23.3 vs. 53.3%; 95% CI −53.4 to − 6.59%). It has been shown earlier that in Dengue virus infection, a PCSK9 inhibitor could interfere with the production of IL-6, thereby reducing the inflammatory response [30]. In addition, the favorable mechanisms of PCSK9 inhibitors, especially in HeFH, could be argued to also result from an effective reduction in the levels of LDL-C and to a lesser extent in the reduction of Lp(a) levels, with a resultant improvement in endothelial function [31,32].
Estimating the public economic consequences of cardiovascular disease-attributable events and evolocumab treatment in Australia
Published in Journal of Medical Economics, 2021
Nikolaos Kotsopoulos, Mark P. Connolly, Jinjing Li
Previous studies have shown PCSK9 inhibitors to be a cost-effective option for those patients not responding to standard cholesterol-reducing therapy8,9. Whilst cost-effectiveness is useful for establishing value for money to health services, it fails to capture the broader economic consequences associated with preventing events that could lead to early retirement. In this analysis, we applied a public economic framework to evaluate consequences for the Australian Government following the introduction of a novel cardiovascular medicine proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor antibody therapy, evolocumab, for the prevention of myocardial infarction and stroke in adults with atherosclerotic cardiovascular disease (ASCVD). In Australia, evolocumab is indicated for the prevention of cardiovascular events, including primary hypercholesterolaemia and familial hypercholesterolaemia, in combination with optimally dosed statins or other lipid-lowering therapies. We constructed a disease state model that reflects different at-risk groups in Australia and estimated the likelihood of ASCVD events for those treated with evolocumab compared to the current standard of care. Factoring in the relationship between ASCVD events and future labour market choices made by these individuals, we estimated changes in fiscal outcomes for government using a public economic or “government perspective” comparative analytic framework10.
Preclinical discovery and development of evolocumab for the treatment of hypercholesterolemia
Published in Expert Opinion on Drug Discovery, 2020
Etienne Khoury, Diane Brisson, Daniel Gaudet
In order to provide a possible novel treatment for patients with high cholesterol levels who are intolerant to statins, evolocumab was specifically tested in this patients' subgroup under the GAUSS-2 trial (NCT01763905). This 12-week, placebo-controlled phase 3 trial evaluated the safety and efficacy of evolocumab, compared with ezetimibe, in patients with hypercholesterolemia and who are unable to tolerate statin therapy mostly due to muscle-related side effects. Evolocumab showed significant reductions in LDL-C levels from baseline (56% at 140 mg every-2-weeks and 53% at 420 mg once-a-month), whereas ezetimibe (10 mg) and placebo groups reached a mean decrease of 37% and 39%, respectively. Muscle-related side effects were reported in 12% of patients treated with evolocumab versus 23% with ezetimibe. No differences in treatment-emergent adverse events nor abnormal laboratories were observed across both groups [68]. Similar observations were also reported in the GAUSS-3 trial (NCT01984424), which evaluated the efficacy of evolocumab (420 mg monthly) in patients with high cholesterol who experienced muscle-related side effects upon statin rechallenge [74].