Table 30.

—[Section 5.6.1] Summary of Findings: Systemic Thrombolytic Therapy vs Anticoagulation Alone in Patients With Acute PE^{a-d,273,309,310,314,315}

Outcomes	No. of Participants (Studies), Follow-up	Quality of the Evidence (GRADE)	Relative Effect (95% CI)	Anticipated Absolute Effects
				Risk With No Systemically Administered Thrombolytic Therapy	Risk Difference With Systemically Administered Thrombolytic Therapy (95% CI)
Mortality	847 (12 studies), 30 d	Lowe-h due to risk of bias and imprecision	RR 0.7 (0.37-1.31)	Lowi,j
				11 per 1,000	3 fewer per 1,000 (from 7 fewer to 3 more)
				Highi,j
				89 per 1,000	27 fewer per 1,000 (from 56 fewer to 28 more)
Recurrent PE	801 (9 studies), 30 d	Lowe-h due to risk of bias and imprecision	RR 0.7 (0.4-1.21)	57 per 1,000	17 fewer per 1,000 (from 34 fewer to 12 more)
Major bleeding	847 (12 studies), 10 d	Moderatee,f,h,k due to risk of bias and imprecision	RR 1.63 (1-2.68)l	Lowm
				1 per 1,000	1 more per 1000 (from 0 more to 2 more)
				Highm
				62 per 1,000	39 more per 1,000 (from 0 more to 104 more)

The basis for the assumed risk (eg, the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). Working group grades of evidence are as follow: High quality, further research is very unlikely to change our confidence in the estimate of effect; moderate quality, further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate; low quality, further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; very-low quality, we are very uncertain about the estimate. See Table 1 and 3 legends for expansion of abbreviations.

^aOne study included exclusively patients with hemodynamic compromise (shock), six excluded them, whereas the rest either included a number of such patients or did not specify related eligibility criteria. Of studies not restricted to patients with hemodynamic compromise (n = 11), only three were clearly restricted to patients with right ventricular dysfunction; the rest either did not specify related eligibility criteria or included both patients with and without right ventricular dysfunction. As a result, it was not possible to perform reliable categorization of studies to conduct subgroup analyses based on the presence or absence of right ventricular dysfunction or hemodynamic compromise.

^bStudies included patients at low risk for bleeding.

^cIncluded studies that used different thrombolytic agents with varying doses and durations of administration; no statistical heterogeneity was noted.

^dThrombolysis was in addition to anticoagulation (most of the studies used heparin followed by warfarin; three studies used warfarin only).

^eReport of methodologic quality was poor in most studies. Of the 12 eligible studies, allocation was concealed in five, three were single blind (outcome assessor), six were double blind, and three were not blinded. Most studies did not report on missing outcome data. None of the studies were stopped early for benefit. For the increase in bleeding with thrombolytic therapy, quality of evidence is increased from low to moderate because there is high quality evidence of this association in patients with myocardial infarction and the indirectness of this evidence to patients with PE is minor.

^fI² = 0%.

^gCI includes values suggesting both benefit and no effect or harm; small number of events.

^hInverted funnel plots suggestive of possible publication bias in favor of thrombolytics.

ⁱRecurrent PE stratification based on the simplified Pulmonary Embolism Severity Index validated in the RIETE (RegistroInformatizado de la Enfermedad Tromboembólica) cohort.²⁶²

^jSome studies suggested that the baseline risk of mortality in patients with hemodynamic instability is as high as 30%.²⁷⁴ In that case, the absolute number of deaths associated with thrombolytics would be 90 fewer per 1,000 (from 189 fewer to 93 more).

^kCI includes values suggesting both harm and no effect; small number of events.

^lMajor bleeding risk stratification derived from the RIETE cohort.³⁰ The median risk of bleeding over the first 10 d reported in the eligible trials was 3.1%. In that case, the absolute number of major bleeding events with thrombolysis would be 20 more per 1,000 (from 0 more to 52 more).

^mIndirect evidence from studies of thrombolysis for myocardial infarction and acute stroke provide more precise estimates of increase major bleeding with thrombolytics use.