The Lipid Modification Guideline recently published by the National Institute for Health and Clinical Excellence (NICE) has sparked debate in the British Medical Journal.
Two letters express opinions that the guideline is flawed. The first letter states the risks could be over estimated by adding together heart and stroke risks. NICE opted to use Framingham rather than QRISK for risk calculation.
The second letter questions the feasibility of aspirational cholesterol targets of less than 4 mmol/L for total cholesterol and 2 mmol/L for low density lipoprotein (LDL) cholesterol when the statin recommendation is simvastatin 40mg for all patients.
Action: Clinicians should familiarise themselves with the guidance fully before changing practice or attempting implementation. Audit standards remain at cholesterol levels of 5mmol/L and LDL of 3mmol/L.
The New England Journal of Medicine has published two papers this week that compared intensive treatment of blood glucose in diabetes with usual care.
The first, the ACCORD study, involved 10,251 patients with type two diabetes. Average age was 62 and diabetes had been present for an average of 10 years. Participants were randomly assigned to treatment with any number of glucose lowering therapies, including insulin, to achieve a target HbA1c of 6% or less.
The study was stopped early, after 3.5 years of follow up, when it became clear that all-cause mortality (5% versus 4%) and cardiovascular mortality (2.6% versus 1.8%) was higher in the intensive group of the study.
In the ADVANCE study, 11,140 participants (mean age 66, diabetes for 8 years) were randomly assigned to intensive treatment with modified release gliclazide to achieve a target HbA1c of 6.5% or less. After 5 years follow up, HbA1c was 6.5% in the intensive group and 7.3% in the control group.
The study found no differences in all cause mortality, cardiovascular mortality or major cardiovascular events. A statistically significant difference was detected in microvascular outcomes (hazard ratio 0.86, 95% CI 0.77 - 0.97, P=0.01) mainly driven by a reduction in nephropathy. This difference was also reflected in the composite primary outcome of combined major macrovascular and microvascular events.
An accompanying editorial illustrates the similarities and differences between these two studies and attempts to place the results in the context of the existing evidence. The authors point out that diabetes care should be comprehensive and include smoking cessation, dietary and exercise advice, blood pressure control, cardiovascular risk reduction (using aspirin, statins and possibly metformin) and finally, attainment of current glycaemic targets.
Action: Clinicians should ensure that diabetes care does not concentrate solely around glycaemic control. In fact, intensive glycaemic control should only be considered after other interventions aimed at smoking cessation, blood pressure and cardiovascular risk have been optimised.
The Archives on Internal Medicine has published the results of a prospective observational study that examined the association between non-steroidal anti-inflammatory drug (NSAID) use and risk of stroke.
The study collected data on 7,636 participants who had never had a stroke, the average age was 70 years old and over half were female. 807 people developed a stroke (460 ischaemic, 74 haemorrhagic, and 273 unspecified).
The hazard ratio for users of non-selective NSAIDs was 1.72 (95% CI 1.22 - 2.44) and for users of COX-II selective NSAIDs it was 2.75 (95% CI 1.28 - 5.95). The authors conclude that there is a ,"greater risk of stroke with current use of non-selective and COX-2–selective NSAIDs".
Advice issued by the Medicines and Healthcare products Regulatory Agency in 2006 warned that NSAIDs carry a thrombotic risk that had the potential to increase heart attacks and strokes. This study is further confirmation that there is an increased risk of stroke.
Action: Clinicians should be aware of all of the risks associated with NSAIDs use. Assessment of overall cardiovascular risk, including strokes, should be undertaken before starting treatment and during medication reviews.
The Scottish Medicines Consortium has issued its monthly advice on new medicines.
Glucosamine (Alateris®) has been rejected for the relief of symptoms in mild to moderate osteoarthritis of the knee. This decision was based upon data from trials that indicated little or no benefit over placebo in improving symptoms
Perindopril arginine (Coversyl Arginine®) has been accepted for the treatment of hypertension and heart failure. The advisory documentation also warns that generic versions of perindopril are not dose equivalent with the arginine version and that these generic versions are available at a lower cost.
Perindopril in combination with indapamide (Coversyl Arginine plus®) has also been accepted for use in hypertension when blood pressure is not adequately controlled on perindopril alone. It should be noted that prescribing the constituents as separate generic items would be available at a lower cost.
Action: Clinicians should be aware of the recommendations of the SMC. Routine use of rejected medicines should be avoided.
The Wall Street Journal has linked rimonabant (Acomplia®) to five deaths in the United Kingdom.
According to the Drug Analysis Print produced by the Medicines and Healthcare products Regulatory Agency (MHRA) there have been over 2,000 adverse drug reactions reported up to May 2008 including the five deaths.
Both the MHRA and WSJ point out that spontaneous reporting of adverse drug reactions does not demonstrate a causal link. The WSJ also notes that rimonabant is not licensed in America, as previously reported, although an application is expected in 2009 as a treatment for Type 2 diabetes. Rimonabant is currently unlicensed in the UK for use as a treatment in diabetes; as such responsibility would rest entirely with the prescribing clinician.
Action: Clinicians should continue to adopt a cautious approach to using rimonabant. Changes in lifestyle, including Diet and exercise, are key to sustained weight loss. Rimonabant must not be used as a treatment for diabetes.