Risk Secondary Prevention Research Articles

Antiplatelet Drugs – Do We Need New Options?

This review describes the current status of antiplatelet therapy in prevention of cardiovascular events of an atherothrombotic nature. The efficacy of aspirin clearly outweighs bleeding risk in secondary prevention, with the relevant exception of patients with peripheral arterial disease (PAD). In trials of primary prevention, aspirin has a limited advantage, which is challenged by the risk of major bleeding. A typical example is primary prevention in type 2 diabetes mellitus, in which a number of trials and a recent meta-analysis have confirmed these limitations. In various settings, clopidogrel has been shown to be marginally more effective than aspirin. Despite a non-negligible bleeding risk, the combination of aspirin-clopidogrel has provided satisfactory results in conditions at high thrombotic risk but rather disappointing results in the long-term treatment of chronic stable cardiovascular disease. The combination of aspirin-dipyridamole was shown to be superior to aspirin alone and equivalent to clopidogrel alone for secondary prevention in cerebrovascular patients. Limitations in the efficacy of antiplatelet agents are partly inherent in their mechanism of action and should not be considered simply as 'treatment failures'. Among other factors, individual variability of response to antiplatelet drugs also plays a meaningful role. Variability of response and 'resistance' may result from drug interactions, baseline and residual platelet hyperactivity, increased platelet turnover, pharmacogenetic factors and others. Poor biological response to aspirin and/or clopidogrel is also frequent in clinical settings such as diabetes, obesity and acute coronary syndromes. The correlation between biological resistance and impaired clinical efficacy of aspirin, and especially clopidogrel, is currently accepted, although with limitations due to the different methods used to assess platelet response. Indeed, the concept of individual 'tailoring' of antiplatelet regimens on the basis of previous laboratory or 'point of care' platelet function tests has been validated in a number of recent trials. The search for and validation of new antiplatelet agents with already known, or totally new, mechanisms of action have also been undertaken with increasing eagerness. Among new adenosine diphosphate receptor antagonists, prasugrel is already registered, and ticagrelor and cangrelor are being developed. New mechanisms being explored are blockade of thrombin-induced platelet aggregation (vorapaxar [SCH 530398]), and inhibition of collagen and ristocetin-mediated platelet functions (DZ-697b). Reappraisal of the neglected class of direct thromboxane A(2) antagonists was followed with less interest. Besides blocking the effects of thromboxane produced from platelets, drugs of this class (such as terutroban sodium and picotamide) may also protect cells from thromboxane produced by sources other than platelets, and some of them may preserve or enhance prostacyclin production. Terutroban is presently being tested in PAD and stroke prevention. Picotamide, marketed in Italy, was shown to reduce cardiovascular events and mortality in studies of PAD patients with diabetes. The results available with thromboxane inhibitors are particularly interesting because they are being obtained in conditions, such as type 2 diabetes and PAD, which are known to be refractory to aspirin.

MEMORY PROFILES IN SCHIZOPHRENIA: CATEGORIZATION VALIDITY AND STABILITY

There is a paucity of data on persistence of secondary prevention medications among stroke survivors in resource-limited settings where stroke is on a rapid upward trajectory and its management severely challenged. To avert new cardiovascular events after stroke, preventive medications should be promptly instituted and used continuously. We report 1-year rates and determinants of persistent utilization of secondary prevention therapies after stroke in Ghana.A retrospective observational study involving 418 stroke survivors enrolled into a Neurology clinic in a tertiary institution in central Ghana between January 2011 and December 2013. Data on demography, stroke type, risk factor profile and five secondary risk prevention medication classes namely antihypertensive, antiplatelet, statins, antidiabetic and anticoagulants were collected from patient charts. Persistence within first year after stroke was defined as continuation of all secondary preventive medications prescribed at enrollment to the Neurology clinic and it excluded 126 (≈ 30%) patients who could not complete 12 month follow up. Data was closed for analysis in June 2015 to allow for at least 12 months of follow-up.Rates of utilization of secondary preventive medications and its intensity were influenced by stroke type and prevailing vascular risk factors. In decreasing order, antihypertensive, lipid-modifying, anti-platelet, anti-diabetic medications and anti-coagulants were prescribed at frequencies (%) of 394 (94.3%), 303 (72.5%), 274 (65.6%), 61 (14.6%) and 2 (0.5%) respectively at enrollment into the Neurology clinic (n = 418). Overall, 92.1% of subjects (n = 292) under follow-up for 1 year were persistent on secondary prevention medications initiated at enrollment into the neurology clinic with medication class specific rates of 97.5% for antihypertensive, 94.8% for anti-platelets, 94.1% for statins, 85.7% for anti-diabetic and 50% for anticoagulants. Abuse of alcohol was significantly associated with non-persistence, adjusted OR (95% CI) of 3.08 (1.13–8.38).Persistence of secondary preventive medications among stroke survivors in this resource-limited setting is excellent and comparable to those in resource-replete countries. There is however the need to investigate the causes of high attrition rates from care.

Post-Menopausal Hormone Therapy and Cardiovascular Events: A New Paradigm Based On pharmacogenetics?

The risk of coronary heart disease (CHD) events increases in women after menopause and it was thought that hormone therapy (HT) would decrease this risk. However, numerous large randomized clinical trials have not demonstrated decreased risk in secondary prevention and some have actually shown increased risk of cardiovascular events with HT in primary prevention. Platelets are involved in CHD events and platelet glycoprotein single-nucleotide polymorphisms may help to identify risk and treatment efficacy. It may become a plausible strategy in the future for clinicians to identify, by genotyping, high-risk patients who would benefit from HT to reduce CHD risk as well as to identify patients with neutral risk for whom HT could be harmful.

Tissue angiotensin-converting enzyme inhibitors: Are they more effective than serum angiotensin-converting enzyme inhibitors?

Since their discovery in the 1980s, angiotensin-converting enzyme (ACE) inhibitors have been shown to decrease angiotensin formation, prevent breakdown of bradykinin, and may also act on peptides of the renin-angiotensin system. They are effective in reducing the risk of heart failure, myocardial infarction, and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure, and have been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure. They may preserve endothelial function and counteract initiation and progression of atherosclerosis. Broadly, ACE inhibitors can be divided into tissue specific or serum ACE inhibitors. Tissue-specific ACE inhibitors as a group are not superior to serum ACE inhibitors in the treatment of coronary artery disease. Pending direct comparator clinical trials between a tissue ACE inhibitor and a plasma ACE inhibitor, both ramipril and perindopril can be recommended for secondary risk prevention, based on the evidence.

Do All Patients With Coronary Artery Disease Benefit from Angiotensin Converting Enzyme Inhibitors?

Cumulative evidence supports the use of angiotensin-converting enzyme (ACE) inhibitors for stable coronary artery disease in patients with and without heart failure. The dose and unique properties of ACE inhibitors, trial data, differences in trial design and demographics, may all contribute to variable responses in clinical outcomes. Pending direct comparator clinical trials between a tissue ACE inhibitor vs a plasma ACE inhibitor, evidence indicates that both ramipril and perindopril can be recommended for secondary risk prevention.

Secondary prevention of coronary heart disease in the elderly.

To review relevant literature supporting the use of aspirin, beta-blockers, lipid-lowering agents, and angiotensin-converting enzyme (ACE) inhibitors for the secondary prevention of coronary heart disease (CHD) in an elderly patient population aged >/=65 years. A MEDLINE search (1990-May 2003) was conducted using the key terms coronary heart disease, secondary prevention and elderly. Primary and tertiary literature relating to the use of aspirin, beta-blockers, lipid-lowering agents, and ACE inhibitors in the elderly were reviewed. CHD is the leading cause of morbidity and mortality in persons >/=65 years of age, and the use of pharmacologic agents has created a considerable opportunity for reducing recurrent events in those with established disease. This, combined with the aging of the US population, is creating an increase in the number of older adults eligible for secondary prevention. In 2002, the American Heart Association issued a scientific statement on the benefits of specific secondary prevention risk factor interventions in older adults. This article reviews pertinent findings from this statement, along with additional data supporting the use of pharmacologic agents for the secondary prevention of CHD in the elderly. Data suggest that use of aspirin, beta-blockers, lipid-lowering agents, and ACE inhibitors are effective in secondary prevention of CHD in individuals aged >/=65 years. This benefit is similar to, and often greater than, that observed in younger patients. We believe that these agents should be prescribed for all elderly patients without contraindications. Ongoing studies and future clinical trials will more clearly elucidate the benefits of secondary prevention of CHD, particularly in persons >/=75 years of age, to determine the magnitude of benefits that can be achieved in this population.