Tag Archives: ebm

Dyslipidemia 4: EBM Special

We explore pieces of important evidence that offer a contrasting view on lipid control from the national guidelines.

We are also introducing a new EBM resource available to CMA members: InfoPOEMs, which highlights clinical studies that the editorial team finds relevant.  http://www.cma.ca/clinicalresources/infopoems

Treatment group

Tools for Practice 2013: “Is Diabetes a Coronary Heart Disease Equivalent?” http://www.acfp.ca/Portals/0/docs/TFP/20131021_093004.pdf

“Though diabetes does confer an increased risk of CV events, it is not automatically equivalent to having experienced a myocardial infarction (MI) (and thus does not always warrant aggressive pharmacotherapy).

CV risk should be predicted, and therapy guided, by taking into account individual risk factors.”

InfoPOEM: “Limited data to guide lipid lowering in octogenarians” http://www.ncbi.nlm.nih.gov/pubmed/20952373

either extremes of cholesterol levels (low or high) are associated with increased mortality in patients >80 years old

Non statin lipid medications

Tools for Practice 2010: “Ezetimibe: Lowers LDL cholesterol but what else?” http://www.acfp.ca/Portals/0/docs/TFP/20111028_105411.pdf

“Eight years after being licensed by the FDA, there is still no evidence that ezetimibe reduces cardiovascular outcomes. It may be worse than niacin and there is concern about a potential increased cancer mortality risk.”

Tools for Practice 2012: “Niacin added to statins for cardiovascular disease? 1 + 1 = 1” http://www.acfp.ca/Portals/0/docs/TFP/20120502_095745.pdf

“In patients with cardiovascular disease already on statin therapy, adding niacin does not improve cardiovascular events. Among lipid treatments, only statin monotherapy has strong evidence for CVD prevention (regardless of lipid levels).”

Tools for Practice 2013: “Fibrates: Statin’s Trusty Sidekick or Lackluster Fallback?” http://www.acfp.ca/Portals/0/docs/TFP/20131007_090323.pdf

“When used alone, fibrates reduce non-fatal coronary events, but have no effect on mortality or other CV events, including stroke. Current evidence suggests fibrates provide no advantage when added to statin therapy.”

InfoPOEM: “Statins but not fibrates associated with lower risk of pancreatitis” http://www.ncbi.nlm.nih.gov/pubmed/22910758

statins significantly reduced risk of pancreatitis, where as fibrates did not

Statin dosing and efficacy

Cochrane 2014: “Statins for the primary prevention of cardiovascular disease” http://summaries.cochrane.org/CD004816/statins-for-the-primary-prevention-of-cardiovascular-disease

“All-cause mortality was reduced by statins (OR 0.86, 95% CI 0.79 to 0.94); as was combined fatal and non-fatal CVD RR 0.75 (95% CI 0.70 to 0.81), combined fatal and non-fatal CHD events RR 0.73 (95% CI 0.67 to 0.80) and combined fatal and non-fatal stroke (RR 0.78, 95% CI 0.68 to 0.89). Reduction of revascularisation rates (RR 0.62, 95% CI 0.54 to 0.72) was also seen. [...] Evidence available to date showed that primary prevention with statins is likely to be cost-effective and may improve patient quality of life. Recent findings from the Cholesterol Treatment Trialists study using individual patient data meta-analysis indicate that these benefits are similar in people at lower (< 1% per year) risk of a major cardiovascular event.”

InfoPOEM: “Statins of modest benefit for low- to moderate-risk persons (NNT ~ 80)”  http://www.ncbi.nlm.nih.gov/pubmed/21989464

for a patient group with a mean 10-year risk of cardiovascular death or MI around 6.2%, the NNT for all-cause mortality was 80, for any MI was 72, and for any stroke was 97 over 10 years of statin treatment

InfoPOEM: “Statins for hyperlipidemia reduce all-cause mortality”  http://www.ncbi.nlm.nih.gov/pubmed/20934984

for patients with hyperlipidemia (LDL 180 mg/dL or 4.6mmol/L), and a mean follow up of 2.7 years, number needed to treat [NNT] to reduce 1 death = 67

Tools for Practice 2012: “How does high dose statin compare to low dose in people with heart disease?” http://www.acfp.ca/Portals/0/docs/TFP/20120522_090852.pdf

“In patients with coronary heart disease, using high dose statins (compared to low-moderate dose) prevents one CHD event for every 91 patients but results in one in 47 patients discontinuing therapy due to adverse events.

However, low-moderate dose statin (compared to placebo) provides 2-3 times greater benefit than increasing to high dose statin. Therefore, getting and keeping patients on any statin is key, with dose adjusted up to tolerable levels”

Statin side effects

InfoPOEM: “Does statins cause cognitive decline?” http://www.ncbi.nlm.nih.gov/pubmed/24000778

No. Statins are not associated with cognitive decline. Actually, in patients without baseline cognitive impairment, statin use is associated with slower cognitive decline.

Tools for Practice 2013: “Statin-Induced Diabetes: Too Sweet a Deal?” http://www.acfp.ca/Portals/0/docs/TFP/20130527_014005.pdf

“Statins modestly increase blood glucose, which leads to 1 in 250 or so patients crossing the “diabetic threshold” over 5 years. Pre-existing elevated sugars, other diabetes risk factors or higher doses may slightly increase the risk. This should not change statin prescribing as they reduce cardiovascular events and all-cause mortality in appropriate patients.”

Additional tests

InfoPOEM: “CRP of little value for risk stratification” http://www.ncbi.nlm.nih.gov/pubmed/23034020

“In patients with an intermediate 10-year risk of a cardiovascular event (10% – 20%), you would have to screen more than 440 with a C-reactive protein (CRP) test to prevent 1 [cardiovascular] event. This test is quite expensive: in the neighborhood of $100 or more at many laboratories (LOE = 2a)

(Originally published on February 1, 2014)

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.)