Absolute risk reduction

Absolute reduced mortality by 5% Absolute risk reduction 10% (100 of 1000 patients died) in placebo and 5% (50 of 1000) in drug A group. 

Increased patient survival from 10% to 5% Absolute risk reduction From 10% to 5%... 

The ratio of the absolute risk reduction to the control group incidence (%) ... 

Recent publications on major clinical trials whose implications will involve a recommendation to change clinical practice have included summary statistics that quantify the risk of benefit or harm that may occur if the results of a given trial are strictly applied to an individual patient or to a representative cohort. Four simple calculations will enable the non-statistician to answer the simple question How much better would my chances be (in terms of a particular outcome) if I took this new medicine, than if I did not take it . These calculations are the relative risk reduction, the absolute risk reduction, the number needed to treat, and the odds ratio (see Box 6.3). 

The effects of coenzyme Q10 on coronary artery disease and chronic stable angina are modest but appear promising. A theoretical basis for such benefit could be metabolic protection of the ischemic myocardium. Double-blind, placebo-controlled trials have demonstrated that coenzyme Q10 supplementation improved a number of clinical measures in patients with a history of acute myocardial infarction (AMI). Improvements have been observed in lipoprotein a, high-density lipoprotein cholesterol, exercise tolerance, and time to development of ischemic changes on the electrocardiogram during stress tests. In addition, very small reductions in cardiac deaths and rate of reinfarction in patients with previous AMI have been reported (absolute risk reduction 1.5%). 

The major features of treatment guidelines concern indications for treatment, the particular treatments to be used, and in the case of biomedical risk factors, target levels following intervention. Figure 2 shows how these aspects are informed by clinical trials. In particular, net benefit depends on the absolute risk reduction (related to both baseline risk and relative risk reduction) and safety of the treatment. The greater the risk of the patient group or individual for future events, the greater is the absolute risk reduction with therapy (Fig. 3). Health policy decisions are informed not only by outcome data but also by cost-effectiveness analyses, Cost-effectiveness in turn relates to the absolute benefits that are observed. 

COMET (32) NYHA class ll-IV LVEF < 35% at least 1 admission for cardiovascular reason per year 3029 Carvedilol, 25-mg twice/day vs. Metoprolol tartrate, 50-mg/day Hazard ratio 0.83 in favor of carvedilol (P = 0.0017) absolute risk reduction 6%... 

RALES (92) NYHA III-IV LVEF < 35% Treatment with ACE inhibitors and loop diuretics 1663 Spironolactone, 25-mg daily, vs. placebo Significant reduction of all causes of mortality absolute risk reduction 11 % lower risk of hospitalization for worsening HF... 

CHARM-Added (47) NYHA ll-IV LVEF < 0.40 adjunctive to ACE inhibitors 2548 Candesartan, 32 mg/ day vs. placebo Absolute risk reduction 4% trend toward lower in all cause mortality (P = 0.086)... 

Two studies evaluated the effects of lipid-lowering therapy on clinical endpoints in the leg. The Program on the Surgical Control of the Hyperlipidemias was a randomized trial of partial ileal-bypass surgery for the treatment of hyperlipidemia in 838 patients (9). After five years, the relative risk (RR) of an abnormal ankle-brachial index value (ABI) was 0.6 (95% Cl, 0.4 to 0.9, absolute risk reduction, 15% points, p < 0.01), and the RR of claudication or limb-threatening ischemia was 0.7 (95% Cl, 0.2 to 0.9, absolute risk reduction, 7% points, p < 0.01), as compared with the control group. 

In a subgroup of patients treated with simvastatin in the Scandinavian Simvastatin Survival Study, the RR of new claudication or worsening of preexisting claudication was 0.6 (95% Cl, 0.4 to 0.9, absolute risk reduction, 1.3% points), as compared with patients randomly assigned to placebo (12). 

Finally, the RUTH study (Raloxifene Use for the Heart)38 was a placebo-controlled clinical trial following over 10,000 postmenopausal women with coronary heart disease (CHD) or with multiple risk factors for CHD.44 16 This trial demonstrated 44% reduced incidence of invasive breast cancer versus placebo, with 0.6% absolute risk reduction,47 thus confirming the findings from MORE and CORE, while also demonstrating that raloxifene did not increase or decrease risk for coronary events or stroke. However, there was an increase in stroke mortality and incidence of venous thromboembolic events (VTEs) as compared to placebo, already seen in MORE, which resulted in a recommendation that raloxifene should not be used for the prevention or reduction of the risk of cardiovascular disease.21... 

HDL-cholesterol levels are increased by 4—8% (Maron et al., 2000). These changes in plasma lipids are claimed to reduce the risk of major coronary events by around 30%. However, this value is misleading because it refers to the relative risk of CHD the absolute risk reduction is only about 2%. 

Fig. 18.2. The absolute risk reduction (ARR) at five years of ipsilateral ischemic stroke (top) and any stroke or death (bottom) with surgery in European Carotid Surgery Tria centers in which the median delay from last symptomatic event to randomization was <50 days (fast centers) compared with centers with a longer delay (slow centers) (Rothwell 2005a). Data are shown separately for patients with moderate (50-69%) and severe (70-99%) carotid stenosis. Cl, confidence interval.

Fig. 27.4. Absolute risk reduction (ARR) with surgery in the five-year risk of ipsilateral carotid territory ischemic stroke and any stroke or death within 30 days after trial surgery according to predefined subgroup variables in an analysis of pooled data from the two largest randomized trials of endarterectomy versus medical treatment for recently symptomatic carotid stenosis (Derived form Rothwell et ai. 2004b), Cl, confidence interval.

A fuller description of die methods used in the APT overview can be found elsewhere (8), but Figures 27.1 and 27.2 respectively summarise the derivation of a proportional od leduction and corresponding absolute risk reduction. In Figure 27.1 the overall typical odds ratio for patients with a prior MI is the ratio of the odds of a serious vascular event among patients allocated antiplatelet treatment to the corresponding odds among control patients. This typical odds ratio of 0.75 corresponds to a typical odds reduction of 25%. 

Overall, antiplatelet therapy produced a 13% (95% Cl 5-20%) proportional reduction in the odds of a vascular event, corre onding to an absolute risk reduction of only about one vascular event avoided per 1000 patients treated per year (Table 24.2 (a)). As in the ofiier low risk trials, the risk of MI was reduced in both TPT and HOT in TPT the rate of all (i.e. fotal or non-fetal) ischemic heart disease was reduced by 20% (95% Cl 1 -35%) and in HOT the rate of all MI was reduced by 36% (95% Cl 15-51%). But, alfiiough antiplatelet therapy appeared to reduce the risk of ischemic stroke, it also appeared to increase the risk of hemonhagic stroke overall in TPT there was a non-significant 3% (95% Cl -45-35%) reduction in the rate of all stroke and in HOT there was a nonsignificant 2% (95% Cl -24-22%) reduction in the rate of all stroke. As in the other low risk trials, there was no overall effect on vascular death or on all-cause mortality (52,53). 

To make clinical decisions, readers of therapeutic studies need to know how many patients must be treated (and for how long) to obtain one desired result /number needed to treut/. This is the inverse (or reciprocal) of absolute risk reduction. 

In the second analysis, data from 14 studies of the efficacy of celecoxib in osteoarthritis or rheumatoid arthritis in 11 007 patients were pooled (80,81). Gastrointestinal complications (bleeding, obstruction, or perforation) occurred in 0.2% of the patients per year of exposure to celecoxib and in 1.7% per year of exposure to traditional NSAIDs. The absolute risk reduction was 1.5% (Cl = 0.4, 2.6). This study, too, had some limitations. In fact, ulcer complication was not the specified end-point of the studies that were pooled, and about 15% of celecoxib-treated patients took a dose below that indicated for arthritis. 

A series of trials in elderly hypertensive subjects has shown a very pronounced reduction in cardiac events as a result of treatment based on thiazide diuretics. In the European Working Party on Hypertension in the Elderly (EWPHE) trial (13), total cardiovascular deaths were reduced by 38%, all cardiac deaths by 43%, and deaths due to myocardial infarction by 60%. Benefits in the Systolic Hypertension in the Elderly Program (SHEP) included a reduction in fatal and non-fatal myocardial infarction of 25% and major cardiovascular events of 32% (14) and were seen in those with and without electrocardiographic abnormalities at entry. The risk of heart failure was also reduced in patients taking chlortalidone-based therapy (15). Relative risk was similar in patients with and without non-insulin dependent diabetes meUitus absolute risk reduction was twice as great in the diabetic subjects (16). The Swedish Trial of Old Patients with Hypertension (STOP-Hypertension) reported a significant reduction in myocardial infarction and all-cause mortahty (17). In the MRC Trial in elderly adults (18), diuretic treatment reduced coronary events by 44% and fatal cardiovascular events by 35%. 

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