“I’m Gonna Make A Change,
For Once In My Life
It’s Gonna Feel Real Good,
Gonna Make A Difference
Gonna Make It Right . . .”

— Michael Jackson ("Man in the Mirror")

I haven't brought it lately. The last couple of posts have shown a dearth of evidence on the topics chosen. Instead, I filled them with mild entertaining pictures and excerpts from various forums on the internet. Well that's changing today. This post is going to be dry. Instead of referencing pop culture, I will be referencing large trial after large trial. Instead of humor, I bring you data drier than Ben Stein doing dry humor on a dry eyes solution commercial. Get ready for it, you're going to hate it.

I forgot to mention.

I'm also picking one of the most lackluster topics imaginable - hypertension. But guess what, we're Family Medicine. We champion preventative medicine. But in all honestly, it was a bit exciting seeing some new hypertension recommendations come out. I mean, look what we have to work with. JNC 8 is no where to be found. ATP 4-lite came out recently with some controversial recommendations about statins. Yet somehow we're quickly approaching the ICD-10 and DSM-V era. Killing me here. But when the ESH/ESC guidelines came out (and recommending things to my liking), I quickly felt as though my favorite song came on the radio. Awwwww yeah, that's my jam!

We also tend to forget stats like there's only a NNT of 20, twenty, for primary prevention of cardiovascular events when treating moderate-severe hypertension (SBP >160). [1] That's real change (shout out to Edward McClain) even though you don't see immediate results. So my question...

“What are the changes made from JNC 7 to the new ESH/ESC guidelines?”

Tier Based Treatment of Hypertension

ESC/ESH: No preferred antihypertensive agent, should be based on comorbidities and contraindications.
JNC 7: Preferred treatment regimen to begin with thiazide diuretics for most. Can consider other agents.

I'm going to try to start from most pertinent to least pertinent to appease those like myself with short attention spans. In my opinion, doing away with the tier based treatment of hypertension is one of the bigger changes made. Previously we would typically start with thiazide diuretics or ACE inhibitors then work our way down to calcium channel blockers and beta-blockers. So on and so forth. Now it appears the evidence is favoring that simply lowering the blood pressure is the main mechanism of benefit, regardless of the specific agent. Now this is looking at the population as a whole. There are several studies that show one agent being superior, such as ACEi in all-cause mortality when compared to ARBs [2], CCBs being superior to ACE's in stroke prevention [3], or low dose thiazides reducing all morbidity and mortality in comparison to ACE inhibitors and CCBs. [4]. But larger meta analysis appear to not show any significant differences between agents [5,6]. Let's break things down even a bit further.

Diuretics: Traditionally our first line treatment. Their specific discussion on diuretics detailed that they took into account that in the ACCOMPLISH trial [7] there was some superiority of CCBS + ACEi over diuretics + ACEi. However, there hasn't been a randomized study showing direct superiority of CCBs over diuretics and that the study needed replication. They also discussed that there has been no direct head-to-head large randomized trial of chlorthalidone vs. HCTZ to merit using chlorthalidone over HCTZ.
ACE Inhibitors/ARBs: Dispelled the notion that ARBs may be inferior to ACEi in all-cause mortality, stroke, and CV events as evidenced by the ONTARGET trial. [8]
CCBs: Did highlight that there is some limited data supporting stroke prevention and CCBs. Also discussed that one meta analysis found CCBs inferior to BBs, ACEi, and diuretics in prevention of heart failure (lowered rates 19% compared to placebo vs. 24% for other agents).
Beta Blockers: Quite a convoluted discussion on beta-blockers as they cited a number of specific scenarios that they may be inferior to other agents. Some of those included being inferior to CCBs and ACEi in stroke prevention, worse than CCBs in total mortality (but equivalent to diuretics and ACEi), or possibly less effective in reducing LVH. They also bring up something I wasn't privy to which was a study in 2010 showing LESS COPD exacerbations and possibly better survival in patients who used beta-blockers. [9] Huh.

Strict BP Control is Special Populations (DM, CKD, CHF, Elderly)

ESC/ESH: DM and CKD patients with goal of <140 mmHg SBP with the exception of those with proteinuria having a goal of <130/80 mmHg. Intensive BP management for dialysis patients but no absolute value recommendation. CHF patients can take anything with exception of acute/sub-acute period after MI then ACEi and BB recommended.
JNC 7: DM and CKD patients should have a goal BP of <130/80 mmHg. CHF/CHD patients recommended to have "fastidious" BP control but no number given. ACEi and BBs recommended in asymptomatic patients with LV dysfunction. ACEi, ARB, BBs, and aldosterone blockers along with loop diuretics for symptomatic patients. In the elderly, no specific goals given but overall emphasized BP control if no signs of orthostatic hypertension.

Overall, the name of the game here is a <140 mmHg SBP across the board, with one exception detailed later on. Previously in the JNC 7, they recommended keeping diabetics at a goal of < 130/80 due to significant CVD risks as well as possibly preventing microvascular changes (retinopathy/nephropathy). Per the ESH/ESC, there isn't any convincing evidence at this point to support anything more aggressive. The only two large trials showing CV event reduction had an average SBP of 139. Yup, 139. [10,11]. The authors also point to the ACCORD trial back in 2010 that showed no benefit between the 120 mmHg and 140 mmHg DM2 groups. [12]. Also regarding microvascular changes, the ADVANCE trial [13] showed no change in retinopathy between BP groups and the authors cite the lack of evidence consistently showing that proteiniuria reduction leads to reduction in hard CV outcomes.

CHF/CHD is more of the same. When previous JNC recommendations advised for "fastidious" BP control, the new ESC/ESH recommendations are a flat < 140 mmHg SBP. Main evidence of this for CHD is the INVEST study [14] showing outcome incidence was inversely related to SBP control once past < 140 mmHg. Also, the medications used are a bit more simplified with recommendations for BBs and ACEi in the post-MI period and any anti-hypertensive showing benefit after that as long as the BP was controlled. [15]

With regards to CKD (diabetic or non-diabetic), this is one of the few times I've run across anything other than the <140 mmHg SBP recommendation. The authors recommend < 140 mmHG SBP for those with renal disease but with the caveat that those with overt proteinuria should have a goal of < 130 mmHg. This was partly based on the observational follow up of the AASK trial [16] which found there was a significant benefit in mortality and progression to ESRD in the intensive BP management cohort (BP < 130/80) that had protein-to-creatinine ratio of more than 0.22 to begin with. [1 7]. Finally, they recommend more intensive BP management for those on dialysis but do not give a goal number as the meta-analysis that showed this benefit did not report on absolute BP values. [18]

FInally, the elderly. A group near and dear to our hearts at SFH since we have a pretty robust geriatric population at our clinics and residency. JNC 7 did a good job of presenting the data and leaving it up to the physician to make up their own minds. They cited the now elderly (1986) SHEP study [1 9] which showed an all-cause mortality benefit with chlorthalidone versus placebo. The chlorthalidone group averaged a BP of 140/67 while the placebo averaging 154/72. On the flip side, they did discuss the Honolulu Heart Study [2 0] which found a significant relationship between orthostatic hypotension and premature death, falls, and fractures in the elderly. Sixty-four percent age adjusted increase to be exact. ESC/ESH roughly mirrors the sentiment of JNC 7 in that they don't recommend a specific antihypertensive but go into a little more depth. The Very Elderly Trial (HYVET, great name) in 2012 reported a reduction in major CV events and all-cause mortality in those greater than 80 year old with initial SBP > 160 mmHg who were controlled to SBP values < 150 mmHg [2 1]. Granted these were healthy patients as frail, ill, and those with orthostatic hypotension were excluded. Regarding those younger than 80, they cited numerous studies showing mortality and CV event benefit in those controlled < 160 mmHg with most studies reducing the BP to < 150 mmHg but not 140 mmHg.

Home Blood Pressure (HBPM) and Ambulatory Blood Pressure Monitoring (ABPM)

ESC/ESH: Clinical indications for ABPM or HBPM expanded from JNC 7 (discussion below).
JNC 7: ABPM warranted in certain scenarios which includes: suspicion of "white coat" hypertension in the absence of target organ injury, hypotensive symptoms, drug resistance, episodic hypertension, and autonomic dysfunction.

So one of the other changes from JNC 7 was the expanded role for home and ambulatory BP monitoring. In a nutshell, JNC 7 advocated for ABPM being an adjunct to in-office BP monitoring but had a limited number of scenarios that it was indicated in. ESC/ESH expand upon that role as they have found 24 hour average BP and ABPM have been shown to be more sensitive in predicting CV outcomes such as stroke or fatal coronary events.[22, 23]. This is not earth shattering news to many of you as it's something we all knew or suspected from experience, but it's nice to have it on paper now. Here are some of those expanded roles:

Suspicion of masked hypertension
Considerable variability in office BP
Elevated office BP or suspected pre-eclampsia in pregnant women
Marked discordance between office and home BP (indication for ABPM)
All of the previous indications in JNC 7

It's not a huge change but they are essentially acknowledging that in-office BP are considered still the "gold standard" but really it does have its limitations and that ABPM and HBPM can be preferred in some cases.

So, what did I learn? Basically, that I have more flexibility to work with my patients. There is no more algorithm that I have to follow and I can treat hypertension more like depression in where we can look at the side effect profile and commorbidities when deciding on medications. It's also nice to hear that we don't have to beat our diabetic patients into the ground with strict BP control as it feels like that has always been dogma. Except for those with overt proteinuria, that's the only exception really. Finally, it's nice to have a reminder sometimes that the occasionally mundane work we do with hypertension does have real, meaningful outcomes for our patients. Good for you primary care physicians, keep doin' work!

TL; DR: No more tier based algorithm for hypertension. No more strict controls of special populations (<130/80) with exception of diabetes with overt proteinuria. Consider more ABPM/HBPM for patients as the role has expanded.