Search

Statins have been shown to substantially reduce the risk of cardiovascular disease and mortality over the past two decades. However there remain questions around their initiation, biological mechanisms, efficacy and safety, particularly in certain population subgroups. The aim of this thesis was to investigate some of the major uncertainties. Patient level meta-analyses were performed using data from 27 randomised statin trials to explore the effects of statins by gender and by age. The accuracy of common cardiovascular risk calculators used to guide the initiation of statin therapy was also investigated. A meta-analysis of trials with extended follow-up examined whether earlier statin treatment confers long-term legacy benefits. And an approach to serial aortic plaque imaging using optical coherence tomography (OCT) in a cholesterol fed rabbit model +/- statin therapy was developed, to explore plaque changes and guide methods for ongoing anti-atherosclerotic research. We found statins have similar, significant proportional vascular and mortality benefits in women compared to men, and are effective across all risk levels. Efficacy and safety in those age >75 years without heart failure or dialysis is also similar to younger adults, but there remains insufficient evidence in the primary prevention setting. Newer UK and US risk calculators perform better than the Framingham calculator, but persisting inaccuracies require clinical consideration. In long term trial follow up, there appear to be legacy effects from prior statin therapy for at least five years which would support an earlier approach to lipid lowering. Serial OCT imaging of rabbit atherosclerotic plaque is feasible, with preliminary findings that statins significantly slow plaque progression. More accurately characterising which individuals should commence statin, or potentially newer lipid lowering therapies, based on risk/benefit profiles will be the major ongoing focus in this area.

Inappropriate sinus tachycardia (IST) is an incompletely understood condition characterised by an elevation in heart rate (HR) accompanied by wide ranging symptoms, in the absence of an underlying physiological stimulus. The condition often takes a chronic course with significant adverse effects on quality of life. Currently there is no effective treatment for IST. Beta-blockers, generally considered the cornerstone of treatment, are often ineffective and poorly tolerated. Ivabradine is a novel sinus node If "funny current" inhibitor which reduces the HR. It has been approved for the treatment of beta-blocker refractory chronic systolic heart failure and chronic stable angina, but more recently shown promise in the treatment of IST. This review provides an overview of IST prevalence and mechanisms, followed by an examination of the evidence for the role and efficacy of ivabradine in the treatment of IST.

Heart failure causes significant morbidity and mortality, with recognised underutilisation rates of guideline based therapies. Our aim was to review current evidence for heart failure treatments and derive a mnemonic summarising best practice which might assist physicians in patient care. Treatments were identified for review from multinational society guidelines and recent randomised trials, with a primary aim of examining their effects in systolic heart failure patients on mortality, hospitalisation rates and symptoms. Secondary aims were to consider other clinical benefits. MEDLINE and EMBASE were searched using a structured keyword strategy and the retrieved articles were evaluated methodically to produce an optimised reference list for each treatment. We devised the mnemonic BANDAID2, standing for Beta-blocker, ACE inhibitor/ARB, Hydralazine-Isosorbide DiNitrate (or potentially Neprilysin inhibitor), Diuretics, Aldosterone antagonist, Ivabradine, Devices (AICD, CRT or both) and Digoxin as a representation of treatments with strong evidence for their use in systolic heart failure. Treatment with omega-3 fatty acids, statins or anti-thrombotic therapies has limited benefits in a general heart failure population. Adoption of this mnemonic for current evidence based treatments for heart failure may help improve prescribing rates and patient outcomes in this debilitating, high mortality condition.

Background Whether statin therapy is as effective in women as in men is debated, especially for primary prevention. We undertook a meta-analysis of statin trials in the Cholesterol Treatment Trialists' (CTT) Collaboration database to compare the effects of statin therapy between women and men. Methods We performed meta-analyses on data from 22 trials of statin therapy versus control (n=134 537) and five trials of more-intensive versus less-intensive statin therapy (n=39 612). Effects on major vascular events, major coronary events, stroke, coronary revascularisation and mortality were weighted per 1·0 mmol/L reduction in LDL cholesterol and effects in men and women compared with a Cox model that adjusted for non-sex differences. For subgroup analyses, we used 99% CIs to make allowance for the multiplicity of comparisons. Findings 46 675 (27%) of 174 149 randomly assigned participants were women. Allocation to a statin had similar absolute effects on 1 year lipid concentrations in both men and women (LDL cholesterol reduced by about 1·1 mmol/L in statin vs control trials and roughly 0·5 mmol/L for more-intensive vs less-intensive therapy). Women were generally at lower cardiovascular risk than were men in these trials. The proportional reductions per 1·0 mmol/L reduction in LDL cholesterol in major vascular events were similar overall for women (rate ratio [RR] 0·84, 99% CI 0·78–0·91) and men (RR 0·78, 99% CI 0·75–0·81, adjusted p value for heterogeneity by sex=0·33) and also for those women and men at less than 10% predicted 5 year absolute cardiovascular risk (adjusted heterogeneity p=0·11). Likewise, the proportional reductions in major coronary events, coronary revascularisation, and stroke did not differ significantly by sex. No adverse effect on rates of cancer incidence or non-cardiovascular mortality was noted for either sex. These net benefits translated into all-cause mortality reductions with statin therapy for both women (RR 0·91, 99% CI 0·84–0·99) and men (RR 0·90, 99% CI 0·86–0·95; adjusted heterogeneity p=0·43). Interpretation In men and women at an equivalent risk of cardiovascular disease, statin therapy is of similar effectiveness for the prevention of major vascular events. UK Medical Research Council, British Heart Foundation, Australian National Health and Medical Research Council, European Community Biomed Program.

OBJECTIVES: Optimising secondary prevention of cardiovascular disease has the greatest potential to reduce recurrent events, yet despite major guidelines there are ongoing treatment gaps. FFSAABC (Fish oils, Fibrates, Statins, Aspirin, Angiotensin converting enzyme inhibitors or angiotensin 2 receptor antagonists, Beta blockers and Clopidogrel) is one mnemonic previously adopted to assist clinicians in remembering medications for use in secondary prevention. The aim of this narrative review is to examine the current evidence base for medications recommended for patients with established cardiovascular disease and the current applicability of this, or a revised mnemonic for their use. STUDY DESIGN: Randomised controlled trials and systematic reviews were sought examining Fish oils, Fibrates, Statins, Aspirin, Angiotensin converting enzyme inhibitors or angiotensin 2 receptor antagonists, Beta blockers or Clopidogrel vs placebo in secondary prevention. The emerging evidence base for other contemporary therapies including the P2Y12 inhibitors (ticagrelor and prasugrel) and aldosterone antagonists was also reviewed. RESULTS: Definitive evidence supports the use of statins, aspirin, angiotensin converting enzyme inhibitors or angiotensin 2 receptor antagonists, and P2Y12 antagonists (clopidogrel, ticagrelor or prasugrel) for the secondary prevention of cardiovascular disease. Aldosterone antagonists have strong evidence in the presence of systolic heart failure. There is a weaker evidence base for the routine use of omega-3 fatty acid supplementation although this therapy carries minimal harms. Fenofibrate reduces cardiovascular events in dyslipidaemic patients, with additional benefits in patients with diabetes. CONCLUSIONS: Mnemonic upgrading from a Fairly Fast SAAB Convertible to a Fairly Fast SA2A2B (Fish oils, Fibrate, Statin, Antiplatelets (Aspirin+Other), ACE/ARB, Aldosterone Antagonist, Beta-blocker) may help to ensure patients receive best practice evidence-based pharmacotherapies for the secondary prevention of cardiovascular disease.