Colin P. Rose

Questioning the benefits of statins

The assessment by Douglas Manuel and associates[1][1] of the 2003 Canadian dyslipidemia guidelines[2][2] is welcome, but they overlooked the all-cause mortality issue, where statins have essentially failed to deliver.[1][1] There are no statin trials with even the slightest hint of a mortality

Point: Why statins have failed to reduce mortality in just about anybody

This discussion was sparked by an editorial critique by Sniderman et al regarding the 2010 Cholesterol Treatment Trialists’ (CTT) meta-analysis that suggested a statin ‘‘event’’ benefit from maximal lowering of low-density lipoprotein cholesterol levels. There are two issues that deserve further attention: the components of the CTT study end points and, most importantly, the issue of reduction in all-cause mortality.

IN VIVO COMPARISON OF NON-GASEOUS METABOLITE AND OXYGEN TRANSPORT IN THE HEART

Oxygen transport has traditionally been approached as a specialized subject with little connection to the large amount of data on transport of other substances, equally essential for steady-state metabolism. Heuristically, there is no reason to expect a major difference but measurements of tissue PO2 with oxygen electrodes in organs with high oxygen consumptions have yielded data which are incompatible with the classical Krogh-cylinder model of capillary-tissue oxygen transport. A number of alternative models, including diffusional shunting and flow heterogeneity, have been developed on the assumption that oxygen transport is a special case, with little or no consideration of the overall, nature of organ transport as reflected in the transport of other substances equally essential for metabolism. As we shall show, when examined in this light, oxygen transport is not essentially different from that of other substances. With the understanding afforded by this approach and recent developments based on it, future investigational effort can now be profitably directed at more complex problems, such as the role of impaired oxygen transport in certain pathological states of vital organs.

Letter by Vos et al Regarding Article, “Primary Prevention With Statin Therapy in the Elderly: New Meta-Analyses From the Contemporary JUPITER and HOPE-3 Randomized Trials”

We read with interest the article by Ridker et al1 that proposes, based on 2 rosuvastatin trials, JUPITER (Justification for Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) and HOPE-3 (Heart Outcomes Prevention Evaluation), that there would be a probable statin mortality benefit in primary prevention in the elderly.2,3 The article relies on the combined end point of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death, but without separating these …

Regarding “Does simvastatin save lives; If so, when and in whom?”

pressure measurements in the endoleak nidus (flow channel) and the thrombus with the same technique and confirms a difference in pressure gradient between these two locations. The previously reported association of aneurysm shrinkage with intra-sac depressurization in the absence of endoleaks seems also to be present with endoleaks. The degree of depressurization seems nevertheless to be different. Pressure measurements in the presence of an endoleak need, therefore, to be assessed cautiously, no matter how the measurement was obtained. Implantable pressure sensors have the advantage of allowing repeated measurements over time. We share the view that pressure sensors may eventually become useful in the follow-up of patients after EVAR. Before that happens, the aforementioned issues common to all pressure measurement systems in the presence of endoleaks need to be solved and the long-term accuracy of implantable sensors needs to be established. Implantable devices have been validated in the immediate period after EVAR, but thrombus can change with time acquiring a non-uniform structure that can influence transmission of pressure. Some of these issues are expected to be answered by on-going trials, which will hopefully include a validation against the validated direct intra-aneurysm sac pressure measurements (DISP) with tip-pressure sensors.

Blood pressure drugs have no mortality benefit in diabetic patients

To the Editor: n nWe question the following statement in the article by Campbell et al (1): “Treatment of high blood pressure in people with diabetes results in large reductions in death...within a short period of time...” This statement was based on references 2 to 10. However, the first two references (2,3) found no mortality benefit from these angiotensin receptor blockers. n nThe next reference (4) reported a nonsignificant mortality difference after nine years from “tight blood pressure control”. Reference 5 is a subgroup of the Appropriate Blood Pressure Control in Diabetes (ABCD) trial. This trial showed no mortality benefit (P=0.8) from aggressive blood pressure control after 5.3 years, while reference 6 represented the balance of ABCD participants – those with higher baseline blood pressure – and demonstrated borderline significant mortality benefit (the given P=0.037 was erroneous). n nThe Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial (7) reported P=0.03 for mortality, but 79 diabetic patients would have to take perindopril plus indapamide for five years to postpone the death of one patient (78 representing the number needlessly treated). n nThe Micro Heart Outcomes Prevention Evaluation (MICRO-HOPE) substudy (8) found a nonsignificant mortality difference emerging after two years on ramipril, and 31 diabetic patients would have to take this drug for 4.5 years to postpone one death. Interestingly, the authors propose that much of the action of this angiotensin-converting enzyme inhibitor may be from mechanisms other than those that lower blood pressure (11). n nThe Systolic Hypertension in Europe (Syst-Eur) trial (9) reported no significant mortality benefit (P=0.09) from calcium channel blockade after two years. Ominously, the study mentioned potential harm from calcium channel blockers in diabetic patients. n nReference 10 was a meta-analysis of diabetic and nondiabetic patients suffering a total of 17,000 major cardiovascular events. In the diabetic patients, the above angiotensin receptor blocker and angiotensin-converting enzyme inhibitor effects were reflected, but because treatment durations were not given, numbers needed or needlessly treated cannot be calculated. n nThe authors, therefore, are not supported by evidence when suggesting short-term “major reductions in death”, and diabetic patients must be told. What is urgently needed are numbers needed or needlessly treated for individual end points – ie, death, ischemic (nontransient ischemic attack) and hemorrhagic stroke, myocardial infarction, heart and kidney failure and microangiopathies – for each of the available blood pressure drugs, for one to five years of treatment, rather than ‘relative combined end point risk reductions’ without defined treatment periods. n nWith such numbers needed or needlessly treated (and it is likely that none of them are less than 100 patient treatment-years per end point, which in itself, would make clinical relevance doubtful), we can clearly inform patients and consider other avenues to tackle diabetes, which, after all, is mostly a preventable metabolic disease (insulin resistance secondary to excess visceral fat due to junk food addiction) and of which blood pressure can be a symptom but not the cause.