Treadmill stress tests should not be part of “routine health check package”

A treadmill ECG stress test (TMT) often forms part of the popular health check packages recommended for people who are asymptomatic on the premise that it can detect disease at an early stage and treatment be prescribed to prevent or reduce future morbidity and mortality. Such a recommendation does not take into account the properties of this procedure as a diagnostic test. It has an average sensitivity and specificity of 68% and 77%, respectively. However, these figures depend on the probability of coronary artery disease (CAD) in the test subject. In asymptomatic persons with few or no risk factors, the likelihood of a false positive is high and will result in psychological stress and/or expensive and possibly invasive test. Recommendation for a TMT should be made by a physician after evaluating the subject to have at least an intermediate risk of having CAD.

Commercial conflict of interest and medical publication: What should the practising physician do about it.

I read with interest the comment by Mark Wilson, which deals with possible conflict of interest (CoI) affecting publications in academic medical journals. This comment has specifically targeted the New England Journal of Medicine (NEJM) and its editor-in-chief Jeffrey Drazen on the “Vioxx scandal” which broke 15 years ago. Wilson’s comment seems to be in response to a blog by Natarajan on CoI in medical publications. In the blog Natarajan writes of commercial CoI biasing publication of clinical trials and cites, among other examples, a publication in the NEJM on trials of voriconazole.

High sensitivity C-reactive protein (hsCRP) & cardiovascular disease: An Indian perspective.

The role of low grade systemic inflammation as evidenced by elevated high sensitivity C-reactive protein (hsCRP) levels in the pathogenesis of atherosclerotic vascular disease has been intensely investigated through observational studies and clinical trials in the past two decades. On the basis of evidence that has accrued, hsCRP measurement has been integrated into the Reynolds risk scoring system to predict cardiovascular risk. The JUPITER trial proved the benefit of statins in cardiovascular risk reduction in patients with low grades of systemic inflammation and ‘normal’ cholesterol levels. However, substantial evidence has been generated from western studies. We, therefore, conducted a scoping review for studies done in India with a view to identify gaps in evidence and make further recommendations. Most Indian studies had small sample sizes and short term follow ups. There were no large population based prospective studies where patients were followed up for long periods of time for major cardiovascular end points. An analysis of the hsCRP level from the control arms of case-control studies derived a mean hsCRP value of 1.88 mg/l, which is higher than the western population where values < 1 mg/l are classified as low cardiovascular risk. Further large prospective cohort studies with longer term follow ups are essential before we can make further recommendations to integrate hsCRP into risk prediction models for cardiovascular disease prevention.

P2Y12 inhibitors in acute coronary syndromes: Which and when.

Acute coronary syndromes (ACS) are the commonest acute manifestation of coronary artery disease and a major cause of hospitalization and death. Plaque rupture and subsequent platelet activation are the key factors in its pathogenesis. Platelet inhibitors are crucial in the management of ACS. Aspirin remains the standard antiplatelet but use of dual antiplatelet drugs is beneficial in ACS. Platelet P2Y12 receptor inhibitors are an important group of antiplatelet compounds that can be combined with aspirin in the management of ACS. P2Y12 inhibitors may belong to the thienopyridine or nonthienopyridine group of compounds. The former (clopidogrel, prasugrel) combine irreversibly with the receptor and therefore have a prolonged duration of action. On the other hand, the non-thienopyridine compounds (ticagrelor, elinogrel) have a reversible action and hence a shorter duration of action. Several new compounds in this group have become or are likely to become available. The newer agents have a more uniform and complete antiplatelet effect and are much less likely to be affected by genetic variability of CYP2C19 enzyme activity compared with that of clopidogrel. Large phase 3 trials have shown that ticagrelor and prasugrel reduce major cardiovascular events in ACS compared to clopidogrel when given in addition to aspirin. This is accompanied by some increase in bleeding. This review discusses the properties, clinical profile and possible place of P2Y12 receptor inhibitors in clinical practice.

Clinical judgement & evidence-based medicine: time for reconciliation.

There is a popular perception that clinical judgement and evidence-based medicine are at loggerheads with each other. We examine the concepts of evidence and judgment as applied to clinical practice, and attempt to understand the reasons behind this imaginary divide.

Polypharmacotherapy for primary prevention of cardiovascular disease.

India is likely to have the highest absolute burden of cardiovascular disease (CVD) related morbidity and mortality in the world. The prevalence of risk-factors (RFs) is high, particularly in the young, and a strategy to reduce RF prevalence in a large population needs to be developed. It is possible to modify risk factors at the individual level or at the population level. The latter is likely to have a greater impact. Current evidence shows that the reduction of risk factors such as BP or serum cholesterol from any level (rather than above a particular threshold) confers potential benefits. At present, lifestyle interventions have not demonstrated the benefits in reducing CVD related mortality and morbidity. A polypharmacotherapy strategy (2-3 BP lowering drugs, a statin, and aspirin) has promise to considerably reduce CVD-related mortality and morbidity. Such a therapy could target a large proportion of the population, intervene simultaneously on multiple RFs, and have wide acceptability. Cost and adherence are important issues for the success of this strategy. Adherence is suboptimal even for secondary prevention. A fixed-dose combination (FDC) of these drugs may improve adherence and reduce costs. But prior to recommending the wide-spread use of an FDC polypharmacotherapy strategy, studies are required to systematically evaluate its efficacy and safety and then determine the adherence, cost, and acceptability in the population. Studies are ongoing in India and other countries to determine the role of FDC polypharmacotherapy in the primary prevention of CVD. Such FDC therapy may reduce costs, improve adherence, and reduce CVD events at the population level; especially in developing countries such as India.

Two-year outcomes in patients admitted with non-ST elevation acute coronary syndrome: results of the OASIS registry 1 and 2.

BACKGROUND: Acute coronary syndrome continues to have significant long-term morbidity and mortality. This study sought to compare baseline characteristics, practice patterns and clinical outcomes for patients with non-ST elevation acute coronary syndrome from a broad range of low-, middle- and high-income countries. METHODS AND RESULTS: We compared the data from a prospective registry of patients with non-ST elevation acute coronary syndrome involving 4615 patients from 65 centers in 8 low and middle income countries (OASIS registry 2) with those obtained from 7987 patients from 95 centers in 6 middle and high income countries (OASIS registry 1). Patients in the OASIS registry 2 were younger, were more often males and smokers, presented later to the hospital after symptom onset and had a lower prevalence of diabetes at admission [with the exception of India, which had the highest age-adjusted prevalence (39.1%)]. There were marked variations in the angiography and intervention rates during the hospital stay, but the uses of proven pharmacological therapies were comparable. The two-year mortality rates adjusted for baseline covariates ranged from 6.9% to 15%. Patients from China had the lowest two-year mortality rate (6.9%) and patients from India had the highest rate (15%). Combining the two registries, the covariate-adjusted rate of death or myocardial infarction did not differ across countries with in-hospital angiographic rates of > or = 50% (17.1%), 25-49% (16.7%) or < 25% (16.5%). However, the covariate-adjusted rates for subsequent myocardial infarction (7.6%, 9.2% and 10.8% respectively, p < 0.0001), refractory angina (21.3%, 27.7% and 35.4% respectively, p < 0.0001) and the composite of death, myocardial infarction or refractory angina (34.9%, 40.7% and 46.8% respectively, p < 0.0001) differed depending on the angiographic rates. CONCLUSIONS: Among the participating countries there was a marked heterogeneity in patient characteristics, coronary interventions, resulting in differences in the two-year composite rates of death, myocardial infarction and refractory angina among patients admitted with non-ST elevation acute coronary syndrome.