Blog entry by Meguid El Nahas

Anyone in the world
The BLOOD PRESSURE LOWERING TREATMENT TRIALISTS COLLABORATION (BPLTTC)

BP LTTC published this month in the BMJ, the Meta-Analysis of 23 major trials involving more than 150,000 participants and >30,000 with CKD and showed: No CVD protection advantage of RAAS inhibitors over calcium antagonists (CA) or diuretics/beta-Blockers.
They showed that what mattered in terms of Cardio-Protection was BP REDUCTION. They reported a reduction of Major Adverse Cardiovascular Events (MACE) by a SIXTH for every reduction of SBP of 5mmHg, regardless of the class of antihypertensive agent used. They showed equal cardioprotection in CKD and non-CKD patients and the level of cardioprotection was not affecetd by the severity of CKD. They also failed to show that more intensive BP control levels had advantages over standard BP control targets.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789583/pdf/bmj.f5680.pdf

This comprehensive and well conducted meta-analysis confirms my long held bias that cardio-protection relies primarily on lowering BP regardless of the agent used. This was also the conclusion of a number of studies and meta-analysis including ALLHAT and the Meta-Analysis of Casas and colleagues in ther Lancet a number of years ago. http://www.ncbi.nlm.nih.gov/pubmed/16338452

We are often referred to the seminal study HOPE arguing that the cardioprotection conferred by RAS inhibitors is independent from their BP lowering effect and is a class specific effect that justifies their use above other anti-hypertensive agents in those at CV risk: http://www.ncbi.nlm.nih.gov/pubmed/10675071

This Mantra...like many in Nephrology has been repeated over and over again by Nephrologists keen to do their best for their patients and egged on by the Pharmaceutical Industry keen to do its best for its shraeholders....and the story went on for more than a quarter of a century inspite of dissending voices questioning the dissociation of the protective effect from the anti-hypertensive effect of RAAS inhibitors. I personally questionned that myth as far back as 2000: http://www.ncbi.nlm.nih.gov/pubmed/10754405

The confusion and issues are due to a number of reasons:

1. Pharma Industry hold of Key Opinion Leaders and Clinical Trialists over the last quarter of a century. I recollect conducting a study on progression comparing Lisinopril versus Placebo (with equal BP control) in the late 80s and study impact on progression: Result: NO difference. Outcome: Never Published...???!!!!

2. Lack of Critical Reading or Appraisal skills by most of those of us who read published material and Clinical Trials Reports; most dont bother to read the methodology section; abstracts or even title is often enough to embrace a new idea...treatment...or myth...and run with it!

3. Physicians commercialism; always keen to impress (and hence charge more...) patients with the latest treatments stemming from the latest publications even if they half understand their scientific implications as long as they fully understand their financial incolme generation implication.

4. MOST IMPORTANTLY....the alleged dissociation between the cardioprotective effect of RAAS inhibitors from their anti-hypertensive effects stems to a large extent from the fact that BP is RCTs (Clinical Trials) is seldom measured correctly; often if not invariably relying on causal office BP reading after a few minutes of rest...this is the least valuable, accurate or predictive method in terms of CVD outcomes as nocturnal, day:night and 24h Ambulatory BP measurement (ABPM) have proved much more reliable and predicitve.

In fact and of relevance, is the observation of a HOPE sub-study itself by Svensson et al (2001) who compared office BP and 24h ABPM and concluded: "Although, OBP is the correct comparator when comparing with previous large intervention trials and epidemiological studies, the effects on cardiovascular morbidity and mortality seen with ramipril in the HOPE study may, to a larger extent than previously ascribed, relate to effects on blood pressure patterns over the 24-hour period" .

http://www.ncbi.nlm.nih.gov/pubmed/11751742

So to conclude:

What seems to matter in the cardioprotection of CKD pateints is good BP control (KDIGO recommends <140/90mmHg) with due consideration to patients age and co-morbidities, this regardless of the class of antihypertensive agents used. Considerations should be then given to patients tolearbility, Risk versus Benefits of a given clkass of agents as well as Cost : Benefit ratio in countries where patients have to pay for their medication; a factor that greatly impacts on compliance and quality of BP control.

Finally, let us not forget that even in the US the majority of those with Hypertension are either NOT treated or POORLY CONTROLLED:

http://www.ncbi.nlm.nih.gov/pubmed/19710486

[ Modified: Thursday, 1 January 1970, 1:00 AM ]