Tag Archives: arb

CHF 2: medications

Tina revisits ACEI, ARB, BB, and Thiazides, which were covered previously with the hypertension episodes, and introduces a few new medications as well:

  • Mineralocorticoid Receptor Antagonists: spironolactone and eplerenone
  • Loop diuretic: furosemide
  • Digoxin
  • Vasodilators: hydralazine and isosorbite dinitrate

For a quick summary of the CCS 2013 recommendations:

ACE inhibitors:

  • all asymptomatic patients with an EF < 35%
  • all symptomatic HF patients and EF < 40%


  • if intolerant to ACEI
  • add to ACEI if intolerant or contraindicated for BB
  • add to ACEI and BB if NYHA class II-IV HF and EF ≤ 40% deemed at increased risk of HF events


  • all HF patients with an EF ≤ 40%
  • initiated at a low dose and titrated to the target dose or maximal tolerated dose


  • patients > 55 years with mild to moderate HF during standard HF treatments with EF ≤ 30% (or ≤ 35% if QRS duration > 130 ms) and recent (6 months) hospitalization for CV disease or
  • with elevated BNP or NT-proBNP levels
  • after an MI with EF ≤ 30% and HF or
  • EF ≤ 30% alone in the presence of diabetes
  • EF < 30% and severe chronic HF (NYHA IIIB-IV) despite optimization of other recommended treatments


  • for congestive symptoms
  • When acute congestion is cleared, the lowest dose should be used that is compatible with stable signs and symptoms
  • persistent volume overload despite optimal medical therapy and increases in loop diuretics, cautious addition of a second diuretic (a thiazide or low dose metolazone) may be considered as long as it is possible to closely monitor morning weight, renal function, and serum potassium


  • patients in sinus rhythm who continue to have moderate to severe symptoms, despite optimized HF therapy
  • patients with chronic atrial fibrillation (AF) and poor control of ventricular rate

Isosorbide dinitrate and hydralazine:

  • black Canadians with HF-REF
  • non-black HF patients unable to tolerate an ACE inhibitor or ARB

Drug information from:

  • Drug monographs
  • CPS: http://www.e-therapeutics.ca/
  • Therapeutic Choices: http://www.e-therapeutics.ca/
  • Rx Files: http://www.rxfiles.ca/rxfiles/modules/druginfoindex/druginfo.aspx

Hypertension 4: EBM Special

We reviewed some evidence on the treatment of hypertension that are contradictory to the CHEP 2013 guidelines summarized in our previous episodes.

Salt restriction for hypertension

CHEP 2013: 1500 mg of sodium per day is recommended for adults age 50 years or less; 1300 mg per day if age 51 to 70 years; and 1200 mg per day if age greater than 70 years

Tools for practice: “Cutting out the sodium: The bland supremacy?” http://www.acfp.ca/Portals/0/docs/TFP/20130204_084845.pdf

“The impact of salt intake on CVD outcomes is controversial. Trials demonstrating beneficial trends enrolled patients with an average sodium intake of 3900 mg/day and reduced their intake on average by 900mg/day. More evidence with clinical outcomes is required to better define benefits/harms with different levels of daily sodium intake.”

Hypertension treatment target for diabetes

CHEP 2013: BP target for diabetes is 130/80mmHg, and 140/90 for others

Cochrane: “Blood pressure targets for hypertension in people with diabetes mellitus” http://summaries.cochrane.org/CD008277/blood-pressure-targets-in-people-with-diabetes

“The only significant benefit in the group assigned to ‘lower’ systolic blood pressure was a small reduction in the incidence of stroke (ACCORD 1.1%ARR SBP <140 vs <120), but with a significantly larger increase in the number of other serious adverse events (ARI 2%). The effect of systolic blood pressure targets on mortality was compatible with both a reduction and increase in risk. There was no benefit associated with a ‘lower’ diastolic blood pressure target (trend towards less stroke RR 0.67, 95% CI 0.42 to 1.05)”

Tools for Practice: “When Treating Blood Pressure, what is the Evidence for Specific Targets?” http://www.acfp.ca/Portals/0/docs/TFP/20111028_103346.pdf

Treating mild hypertension

CHEP 2013: treatment threshold 160/100, treatment target 140/90 for uncomplicated hypertension

Cochrane: “Pharmacotherapy for mild hypertension” http://summaries.cochrane.org/CD006742/benefits-of-antihypertensive-drugs-for-mild-hypertension-are-unclear

“For individuals with mildly elevated blood pressures(systolic blood pressure (BP) 140-159 mmHg and/or diastolic BP 90-99 mmHg) treatment for 4 to 5 years with antihypertensive drugs as compared to placebo did not reduce total mortality (RR 0.85, 95% CI 0.63, 1.15). In 7,080 participants treatment with antihypertensive drugs as compared to placebo did not reduce coronary heart disease (RR 1.12, 95% CI 0.80, 1.57), stroke (RR 0.51, 95% CI 0.24, 1.08), or total cardiovascular events (RR 0.97, 95% CI 0.72, 1.32). Withdrawals due to adverse effects were increased by drug therapy (RR 4.80, 95%CI 4.14, 5.57), Absolute risk increase (ARI) 9%.”

Which first line agent for hypertension is actually first line?

CHEP 2013:  beta-blocker is considered a first line choice in patients younger than 60 years of age (Grade B), among ACEI, ARB, thiazides, CCB

Therapeutics Initiative Letter #82: “Clinical Hypertension Pearls from The Cochrane Library” http://www.ti.ubc.ca/letter82

Cochrane: “First-line drugs for hypertension” http://summaries.cochrane.org/CD001841/thiazides-best-first-choice-for-hypertension

mortality stroke CHD CVS
Thiazides (19 RCTs) RR 0.89, 95% CI 0.83, 0.96 RR 0.63, 95% CI 0.57, 0.7 RR 0.84, 95% CI 0.75, 0.95 RR 0.70, 95% CI 0.66, 0.76
Low-dose thiazides (8 RCTs) RR 0.72, 95% CI 0.61, 0.84
high-dose thiazides (11 RCTs) RR 1.01, 95% CI 0.85, 1.20
Beta-blockers (5 RCTs) RR 0.96, 95% CI 0.86, 1.07 RR 0.83, 95% CI 0.72, 0.97 RR 0.90, 95% CI 0.78, 1.03 RR 0.89, 95% CI 0.81, 0.98
ACE inhibitors (3 RCTs) RR 0.83, 95% CI 0.72-0.95 RR 0.65, 95% CI 0.52-0.82 RR 0.81, 95% CI 0.70-0.94 RR 0.76, 95% CI 0.67-0.85
Calcium-channel blocker (1 RCT) RR 0.86 95% CI 0.68, 1.09 RR 0.58, 95% CI 0.41, 0.84 RR 0.77 95% CI 0.55, 1.09 RR 0.71, 95% CI 0.57, 0.87
ARB (no RCT)

“Most of the evidence demonstrated that first-line low-dose thiazides reduce mortality and morbidity (stroke, heart attack and heart failure). No other drug class improved health outcomes better than low-dose thiazides, and beta-blockers and high-dose thiazides were inferior. Low-dose thiazides should be the first choice drug in most patients with elevated blood pressure. Fortunately, thiazides are also very inexpensive.”

Tools for Practice: “Is hydrochlorothiazide the best thiazide diuretic for hypertension?” http://www.acfp.ca/Portals/0/docs/TFP/20120206_092015.pdf

Cochrane: “Calcium channel blockers versus other classes of drugs for hypertension” http://www.ncbi.nlm.nih.gov/pubmed/20687074 

Cochrane: “Beta-blockers for hypertension” http://summaries.cochrane.org/CD002003/beta-blockers-for-hypertension

“Angiotensin receptor blockers versus ACE inhibitors: prevention of death and myocardial infarction in high-risk populations”. http://www.ncbi.nlm.nih.gov/pubmed/15701766

“Angiotensin-converting enzyme inhibitors (ACEIs), not angiotensin receptor blockers (ARBs), are preferred and effective mode of therapy in high cardiovascular risk patients.” http://www.ncbi.nlm.nih.gov/pubmed/19810392

What time should a patient take the blood pressure medications?

Tools for practice: “Taking blood pressure-lowering medications at night” http://www.acfp.ca/Portals/0/docs/TFP/20120109_102035.pdf

“Taking one or more BP meds before bed may potentially help reduce cardiovascular risk but due to limitations of the evidence, strong recommendations are difficult.”

MAPEC trialhttp://www.ncbi.nlm.nih.gov/pubmed/20854139

Side note about confidence interval worship

I mentioned how a statistically insignificant risk reduction in stroke could actually be clinically significant. Check out this article by Dr McCormack et al on “How confidence intervals become confusion intervals” on this very topic. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3818447/

(Originally published on January 18, 2014.)